Liver Disease

Rapid diagnostic and point-of-care tests for hepatitis C virus are accurate enough to be used in first-line HCV screening worldwide, according to results from the first systematic review of evidence on such tests.

Blood-based point-of-care tests (POCTs) had better sensitivity and specificity overall than did blood-based rapid diagnostic tests (RDTs), Sushmita Shivkumar of McGill University, Montreal, Quebec, and her colleagues reported.

POCTs do not require sample processing or refrigeration, and have a shelf life of 6 months or more. Rapid diagnostic tests, or RDTs, require refrigeration and sample processing. Manufactured by a variety of firms under various marketing names, all the tests can detect HCV infection in under 30 minutes, with many taking less than 5 minutes, according to the investigators, who conducted a meta-analysis of 18 studies evaluating the accuracy of one or more RDT or POCT, compared with standard assays (Ann. Intern. Med. 2012;157:558-66).

Ms. Shivkumar and her colleagues found blood-based POCTs (using serum, plasma, or whole blood) to be the most accurate of the tests evaluated in the included studies, showing 98.9% sensitivity with a 95% confidence interval [CI] of 94.5%-99.8% for whole blood and 96.8%-99.6% for serum or plasma). RDTs of serum or plasma had 98.4% sensitivity (95% CI 88.9%-99.8%). Specificity was highest in POCTs of serum or plasma at 99.7% (95% CI, 99.3%-99.9%), followed by POCTs of whole blood at 99.5% (95% CI, 97.5%-99.9%), RDTs of serum or plasma at 98.6% (95% CI, 94.9%-99.6%). POCTs for oral fluids had a sensitivity of 97.1% (95% CI, 94.7%-98.4%) and specificity of 98.2% (95% CI, 92.2%-99.6%).

POCTs and RDTs cannot distinguish between acute and chronic HCV infections, which is one of the reasons that public health organizations continue to favor conventional assays. The Food and Drug Administration currently approves the use of a single POCT for HCV, and for use only in nontraditional settings; in the United Kingdom and Canada such tests have not yet been approved.

However, by being fast, accurate, and cheaper than conventional tests, the rapid diagnostic and point-of-care tests offer "great potential for expanded first-line screening for hepatitis C infection and demonstrate the utility of blood-based singleton POCTs and of multiplex POCTs designed to provide integrated HIV and HCV screening of at-risk populations," Ms. Shivkumar and her associates wrote in their analysis. "Their rapid turnaround time limits loss to follow-up and facilitates early linkages."

The authors also concluded that their findings showed that the rapid and point-of-care tests could play a "substantial role" in expanded global screening initiatives for HCV.

The blood-based POCTs, besides being the most accurate, have the advantage of not requiring refrigeration, the investigators wrote. This feature is key in developing countries in Africa and Asia, where prevalence of HCV infection is highest.

Ms. Shivkumar and her colleagues noted several weaknesses in their meta-analysis, mostly related to the quality of studies included. Only three of the studies they evaluated were blinded, while four received industry funding; the conventional assays used as reference varied in the studies, and HCV genotype information was not collected in most.

The study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

Rapid diagnostic and point-of-care tests for hepatitis C virus are accurate enough to be used in first-line HCV screening worldwide, according to results from the first systematic review of evidence on such tests.

Blood-based point-of-care tests (POCTs) had better sensitivity and specificity overall than did blood-based rapid diagnostic tests (RDTs), Sushmita Shivkumar of McGill University, Montreal, Quebec, and her colleagues reported.

POCTs do not require sample processing or refrigeration, and have a shelf life of 6 months or more. Rapid diagnostic tests, or RDTs, require refrigeration and sample processing. Manufactured by a variety of firms under various marketing names, all the tests can detect HCV infection in under 30 minutes, with many taking less than 5 minutes, according to the investigators, who conducted a meta-analysis of 18 studies evaluating the accuracy of one or more RDT or POCT, compared with standard assays (Ann. Intern. Med. 2012;157:558-66).

Ms. Shivkumar and her colleagues found blood-based POCTs (using serum, plasma, or whole blood) to be the most accurate of the tests evaluated in the included studies, showing 98.9% sensitivity with a 95% confidence interval [CI] of 94.5%-99.8% for whole blood and 96.8%-99.6% for serum or plasma). RDTs of serum or plasma had 98.4% sensitivity (95% CI 88.9%-99.8%). Specificity was highest in POCTs of serum or plasma at 99.7% (95% CI, 99.3%-99.9%), followed by POCTs of whole blood at 99.5% (95% CI, 97.5%-99.9%), RDTs of serum or plasma at 98.6% (95% CI, 94.9%-99.6%). POCTs for oral fluids had a sensitivity of 97.1% (95% CI, 94.7%-98.4%) and specificity of 98.2% (95% CI, 92.2%-99.6%).

POCTs and RDTs cannot distinguish between acute and chronic HCV infections, which is one of the reasons that public health organizations continue to favor conventional assays. The Food and Drug Administration currently approves the use of a single POCT for HCV, and for use only in nontraditional settings; in the United Kingdom and Canada such tests have not yet been approved.

However, by being fast, accurate, and cheaper than conventional tests, the rapid diagnostic and point-of-care tests offer "great potential for expanded first-line screening for hepatitis C infection and demonstrate the utility of blood-based singleton POCTs and of multiplex POCTs designed to provide integrated HIV and HCV screening of at-risk populations," Ms. Shivkumar and her associates wrote in their analysis. "Their rapid turnaround time limits loss to follow-up and facilitates early linkages."

The authors also concluded that their findings showed that the rapid and point-of-care tests could play a "substantial role" in expanded global screening initiatives for HCV.

The blood-based POCTs, besides being the most accurate, have the advantage of not requiring refrigeration, the investigators wrote. This feature is key in developing countries in Africa and Asia, where prevalence of HCV infection is highest.

Ms. Shivkumar and her colleagues noted several weaknesses in their meta-analysis, mostly related to the quality of studies included. Only three of the studies they evaluated were blinded, while four received industry funding; the conventional assays used as reference varied in the studies, and HCV genotype information was not collected in most.

The study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

Rapid diagnostic and point-of-care tests for hepatitis C virus are accurate enough to be used in first-line HCV screening worldwide, according to results from the first systematic review of evidence on such tests.

Blood-based point-of-care tests (POCTs) had better sensitivity and specificity overall than did blood-based rapid diagnostic tests (RDTs), Sushmita Shivkumar of McGill University, Montreal, Quebec, and her colleagues reported.

POCTs do not require sample processing or refrigeration, and have a shelf life of 6 months or more. Rapid diagnostic tests, or RDTs, require refrigeration and sample processing. Manufactured by a variety of firms under various marketing names, all the tests can detect HCV infection in under 30 minutes, with many taking less than 5 minutes, according to the investigators, who conducted a meta-analysis of 18 studies evaluating the accuracy of one or more RDT or POCT, compared with standard assays (Ann. Intern. Med. 2012;157:558-66).

Ms. Shivkumar and her colleagues found blood-based POCTs (using serum, plasma, or whole blood) to be the most accurate of the tests evaluated in the included studies, showing 98.9% sensitivity with a 95% confidence interval [CI] of 94.5%-99.8% for whole blood and 96.8%-99.6% for serum or plasma). RDTs of serum or plasma had 98.4% sensitivity (95% CI 88.9%-99.8%). Specificity was highest in POCTs of serum or plasma at 99.7% (95% CI, 99.3%-99.9%), followed by POCTs of whole blood at 99.5% (95% CI, 97.5%-99.9%), RDTs of serum or plasma at 98.6% (95% CI, 94.9%-99.6%). POCTs for oral fluids had a sensitivity of 97.1% (95% CI, 94.7%-98.4%) and specificity of 98.2% (95% CI, 92.2%-99.6%).

POCTs and RDTs cannot distinguish between acute and chronic HCV infections, which is one of the reasons that public health organizations continue to favor conventional assays. The Food and Drug Administration currently approves the use of a single POCT for HCV, and for use only in nontraditional settings; in the United Kingdom and Canada such tests have not yet been approved.

However, by being fast, accurate, and cheaper than conventional tests, the rapid diagnostic and point-of-care tests offer "great potential for expanded first-line screening for hepatitis C infection and demonstrate the utility of blood-based singleton POCTs and of multiplex POCTs designed to provide integrated HIV and HCV screening of at-risk populations," Ms. Shivkumar and her associates wrote in their analysis. "Their rapid turnaround time limits loss to follow-up and facilitates early linkages."

The authors also concluded that their findings showed that the rapid and point-of-care tests could play a "substantial role" in expanded global screening initiatives for HCV.

The blood-based POCTs, besides being the most accurate, have the advantage of not requiring refrigeration, the investigators wrote. This feature is key in developing countries in Africa and Asia, where prevalence of HCV infection is highest.

Ms. Shivkumar and her colleagues noted several weaknesses in their meta-analysis, mostly related to the quality of studies included. Only three of the studies they evaluated were blinded, while four received industry funding; the conventional assays used as reference varied in the studies, and HCV genotype information was not collected in most.

The study was supported by grants from the Canadian Institutes of Health Research. None of the authors declared conflicts of interest.

The Centers for Disease Control and Prevention recommends that all Americans aged 47-67 years should be tested once for hepatitis C infection, according to a CDC statement published Aug. 16 online. The CDC proposed the recommendation in May 2012.

Data from previous studies suggest that the baby boomers, defined by the CDC as individuals born between 1945 and 1965, are at increased risk for hepatitis C for many reasons, including blood transfusions, hospital exposures, and a possible history of risky behaviors in their younger years. However, many people in this age group are amenable to hepatitis C testing if it is available to them.

Photo courtesy US Veterans Admin.

According to the CDC statement, "1 in 30 baby boomers has been infected with hepatitis C, and most don’t know it." This life-threatening infection has few symptoms and affects approximately 3.2 million U.S. adults, most of whom are baby boomers, according to the CDC. Hepatitis C is the leading cause of liver transplantation in the United States, and the virus causes serious liver diseases including cirrhosis and liver cancer.

The CDC said in the statement that a one-time hepatitis C test for all baby boomers could potentially identify more than 800,000 additional cases. If treated early, up to 75% of these individuals could be cured, avoiding the costs and serious complications associated with untreated hepatitis C infections. New therapies have recently improved the cure rate significantly.

The CDC encourages clinicians to promote hepatitis C testing to their baby boomer patients.

"Identifying these hidden infections early will allow more baby boomers to receive care and treatment, before they develop life-threatening liver disease," Dr. Kevin Fenton, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, said in the CDC statement. One-time hepatitis C testing for baby boomers "could potentially save tens of thousands of lives," he said.

The Centers for Disease Control and Prevention recommends that all Americans aged 47-67 years should be tested once for hepatitis C infection, according to a CDC statement published Aug. 16 online. The CDC proposed the recommendation in May 2012.

Data from previous studies suggest that the baby boomers, defined by the CDC as individuals born between 1945 and 1965, are at increased risk for hepatitis C for many reasons, including blood transfusions, hospital exposures, and a possible history of risky behaviors in their younger years. However, many people in this age group are amenable to hepatitis C testing if it is available to them.

Photo courtesy US Veterans Admin.

According to the CDC statement, "1 in 30 baby boomers has been infected with hepatitis C, and most don’t know it." This life-threatening infection has few symptoms and affects approximately 3.2 million U.S. adults, most of whom are baby boomers, according to the CDC. Hepatitis C is the leading cause of liver transplantation in the United States, and the virus causes serious liver diseases including cirrhosis and liver cancer.

The CDC said in the statement that a one-time hepatitis C test for all baby boomers could potentially identify more than 800,000 additional cases. If treated early, up to 75% of these individuals could be cured, avoiding the costs and serious complications associated with untreated hepatitis C infections. New therapies have recently improved the cure rate significantly.

The CDC encourages clinicians to promote hepatitis C testing to their baby boomer patients.

"Identifying these hidden infections early will allow more baby boomers to receive care and treatment, before they develop life-threatening liver disease," Dr. Kevin Fenton, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, said in the CDC statement. One-time hepatitis C testing for baby boomers "could potentially save tens of thousands of lives," he said.

The Centers for Disease Control and Prevention recommends that all Americans aged 47-67 years should be tested once for hepatitis C infection, according to a CDC statement published Aug. 16 online. The CDC proposed the recommendation in May 2012.

Data from previous studies suggest that the baby boomers, defined by the CDC as individuals born between 1945 and 1965, are at increased risk for hepatitis C for many reasons, including blood transfusions, hospital exposures, and a possible history of risky behaviors in their younger years. However, many people in this age group are amenable to hepatitis C testing if it is available to them.

Photo courtesy US Veterans Admin.

According to the CDC statement, "1 in 30 baby boomers has been infected with hepatitis C, and most don’t know it." This life-threatening infection has few symptoms and affects approximately 3.2 million U.S. adults, most of whom are baby boomers, according to the CDC. Hepatitis C is the leading cause of liver transplantation in the United States, and the virus causes serious liver diseases including cirrhosis and liver cancer.

The CDC said in the statement that a one-time hepatitis C test for all baby boomers could potentially identify more than 800,000 additional cases. If treated early, up to 75% of these individuals could be cured, avoiding the costs and serious complications associated with untreated hepatitis C infections. New therapies have recently improved the cure rate significantly.

The CDC encourages clinicians to promote hepatitis C testing to their baby boomer patients.

"Identifying these hidden infections early will allow more baby boomers to receive care and treatment, before they develop life-threatening liver disease," Dr. Kevin Fenton, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, said in the CDC statement. One-time hepatitis C testing for baby boomers "could potentially save tens of thousands of lives," he said.

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.

Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.

Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.

Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.

Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.

Serious adverse events associated with boceprevir should be reported to MedWatch or by phone at 800-332-1088.

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.

Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.

Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.

Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.

Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.

Serious adverse events associated with boceprevir should be reported to MedWatch or by phone at 800-332-1088.

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.

Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.

Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.

Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.

Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.

Serious adverse events associated with boceprevir should be reported to MedWatch or by phone at 800-332-1088.

ORLANDO – Treatment centers and surgeons tend to play to their strengths when choosing therapy for patients with well-compensated cirrhosis of the liver and early hepatocellular carcinoma, investigators reported at a symposium sponsored by the Society of Surgical Oncology.

Therapy for early HCC with well-compensated cirrhosis is controversial; there is little agreement on when resection, transplantation, or radiofrequency ablation becomes the best approach. Choice of therapy for early HCC often depends on the surgeon’s repertoire of techniques and the therapeutic services the hospital offers, based on the findings of a web-based survey of centers that had at least five HCC cases per year.

"This study demonstrates that nonclinical factors have an important effect of therapy for early HCC, and in particular the choice of therapy depends in part on the surgeon’s portfolio of techniques, as well as the availability of transplantation services," said Dr. Hari Nathan of the department of surgery at Johns Hopkins Hospital in Baltimore.

In a previous analysis of the data from their web-based survey, Dr. Nathan and colleagues found that surgeon specialty was more important than certain patient-specific factors when determining treatment choice (J. Clin. Oncol. 2011;29:619-25).

"Differences in choice of therapy for nontransplant and transplant surgeons were not the result of an across-the-board preference for one therapy vs. another. Rather, some clinical factors impacted surgeons differently, depending on their specialty," he said.

In the new analysis, the authors used the survey data to assess the effect of surgeon and hospital factors on the choice of therapy for early, well-compensated HCC, and the effect of regional liver transplantation services on the surgeon’s choice of therapy.

They defined early HCC according to the Milan criteria as a single tumor less than 5 cm in its largest dimension, or two to three tumors less than 3 cm. Cirrhosis was considered to be well compensated if it was Child-Pugh class A, with no varices, ascites, or encephalopathy.

They presented respondents with case scenarios factoring in age, tumor number and size, type of resection required, etiology of cirrhosis (hepatitis B or C, or alcoholic), biological MELD (Model for End-Stage Liver Disease) score, platelet count, and anticipated transplantation waiting time.

Of the 1,032 invitations they extended, 336 surgeons (33%) responded. Of the respondents, 284 (85%) were in academic practices and 52 (15%) were in community practices for a median of 10 years (range, 4-17 years). About two-thirds (65%) were trained in liver transplantation. Procedures performed for HCC included transplantation and radiofrequency ablation (41% of responders), transplantation alone (14%), or liver resection but not transplantation (45%). Asked which procedures were available at their primary hospital (regardless of whether the respondent performed them personally), 100% said that resections were available, and 99% said that ablations were available. In contrast, transplantations were available at 71% of respondents’ hospitals.

The authors found that neither years in practice, surgical oncology training, nor liver transplantation training had a significant effect on treatment choice. Similarly, regional transplantation variables – such as number of procedures, percentage of transplant recipients with HCC, 30th percentile of liver transplantation wait time, and severity of illness by median MELD score – did not significantly predict treatment choice.

There was, however, significant variation in therapeutic choice based on practice type, adjusted for case presentation, with surgeons in academic practices favoring transplantation 57% of the time, compared with 47% for those in community practice. Community-based surgeons were more likely to favor liver resection (45% vs. 38% for academic surgeons), and radiofrequency ablation (9% vs. 4%).

In regression analysis that controlled for clinical factors, they found that surgeons in academic setting were significantly less likely than community-based surgeons to recommend ablation over liver transplantation (relative risk ratio [RRR], 0.41; P = .01). When they looked at the effect of practice types’ controlling for surgeons’ specialties, however, the significance of the practice type on treatment choice disappeared.

Regression analysis also showed that "higher volume surgeons prefer transplantation over resection more strongly than lower-volume surgeons," Dr. Nathan said.

High-volume surgeons (defined as those performing 30 or more cases annually) were overwhelmingly transplantation surgeons; when the authors adjusted for whether the surgeon performed transplantations, the preference for transplantation disappeared.

Additionally, nontransplantation surgeons who worked at hospitals where transplantations were available were more likely to recommend transplantation over ablation, compared with surgeons working at nontransplantation hospitals.

"Interestingly, they also favored resection over radiofrequency ablation more strongly. This appeared to be a separate phenomenon than the one that we observed for the portfolio – that’s personally performed by each surgeon – and in regression analyses these effects were independent," he said.

Coauthor John F.P. Bridges, Ph.D., provided financial and administrative support for the study. Dr. Nathan reported no relevant financial disclosures.

ORLANDO – Treatment centers and surgeons tend to play to their strengths when choosing therapy for patients with well-compensated cirrhosis of the liver and early hepatocellular carcinoma, investigators reported at a symposium sponsored by the Society of Surgical Oncology.

Therapy for early HCC with well-compensated cirrhosis is controversial; there is little agreement on when resection, transplantation, or radiofrequency ablation becomes the best approach. Choice of therapy for early HCC often depends on the surgeon’s repertoire of techniques and the therapeutic services the hospital offers, based on the findings of a web-based survey of centers that had at least five HCC cases per year.

"This study demonstrates that nonclinical factors have an important effect of therapy for early HCC, and in particular the choice of therapy depends in part on the surgeon’s portfolio of techniques, as well as the availability of transplantation services," said Dr. Hari Nathan of the department of surgery at Johns Hopkins Hospital in Baltimore.

In a previous analysis of the data from their web-based survey, Dr. Nathan and colleagues found that surgeon specialty was more important than certain patient-specific factors when determining treatment choice (J. Clin. Oncol. 2011;29:619-25).

"Differences in choice of therapy for nontransplant and transplant surgeons were not the result of an across-the-board preference for one therapy vs. another. Rather, some clinical factors impacted surgeons differently, depending on their specialty," he said.

In the new analysis, the authors used the survey data to assess the effect of surgeon and hospital factors on the choice of therapy for early, well-compensated HCC, and the effect of regional liver transplantation services on the surgeon’s choice of therapy.

They defined early HCC according to the Milan criteria as a single tumor less than 5 cm in its largest dimension, or two to three tumors less than 3 cm. Cirrhosis was considered to be well compensated if it was Child-Pugh class A, with no varices, ascites, or encephalopathy.

They presented respondents with case scenarios factoring in age, tumor number and size, type of resection required, etiology of cirrhosis (hepatitis B or C, or alcoholic), biological MELD (Model for End-Stage Liver Disease) score, platelet count, and anticipated transplantation waiting time.

Of the 1,032 invitations they extended, 336 surgeons (33%) responded. Of the respondents, 284 (85%) were in academic practices and 52 (15%) were in community practices for a median of 10 years (range, 4-17 years). About two-thirds (65%) were trained in liver transplantation. Procedures performed for HCC included transplantation and radiofrequency ablation (41% of responders), transplantation alone (14%), or liver resection but not transplantation (45%). Asked which procedures were available at their primary hospital (regardless of whether the respondent performed them personally), 100% said that resections were available, and 99% said that ablations were available. In contrast, transplantations were available at 71% of respondents’ hospitals.

The authors found that neither years in practice, surgical oncology training, nor liver transplantation training had a significant effect on treatment choice. Similarly, regional transplantation variables – such as number of procedures, percentage of transplant recipients with HCC, 30th percentile of liver transplantation wait time, and severity of illness by median MELD score – did not significantly predict treatment choice.

There was, however, significant variation in therapeutic choice based on practice type, adjusted for case presentation, with surgeons in academic practices favoring transplantation 57% of the time, compared with 47% for those in community practice. Community-based surgeons were more likely to favor liver resection (45% vs. 38% for academic surgeons), and radiofrequency ablation (9% vs. 4%).

In regression analysis that controlled for clinical factors, they found that surgeons in academic setting were significantly less likely than community-based surgeons to recommend ablation over liver transplantation (relative risk ratio [RRR], 0.41; P = .01). When they looked at the effect of practice types’ controlling for surgeons’ specialties, however, the significance of the practice type on treatment choice disappeared.

Regression analysis also showed that "higher volume surgeons prefer transplantation over resection more strongly than lower-volume surgeons," Dr. Nathan said.

High-volume surgeons (defined as those performing 30 or more cases annually) were overwhelmingly transplantation surgeons; when the authors adjusted for whether the surgeon performed transplantations, the preference for transplantation disappeared.

Additionally, nontransplantation surgeons who worked at hospitals where transplantations were available were more likely to recommend transplantation over ablation, compared with surgeons working at nontransplantation hospitals.

"Interestingly, they also favored resection over radiofrequency ablation more strongly. This appeared to be a separate phenomenon than the one that we observed for the portfolio – that’s personally performed by each surgeon – and in regression analyses these effects were independent," he said.

Coauthor John F.P. Bridges, Ph.D., provided financial and administrative support for the study. Dr. Nathan reported no relevant financial disclosures.

ORLANDO – Treatment centers and surgeons tend to play to their strengths when choosing therapy for patients with well-compensated cirrhosis of the liver and early hepatocellular carcinoma, investigators reported at a symposium sponsored by the Society of Surgical Oncology.

Therapy for early HCC with well-compensated cirrhosis is controversial; there is little agreement on when resection, transplantation, or radiofrequency ablation becomes the best approach. Choice of therapy for early HCC often depends on the surgeon’s repertoire of techniques and the therapeutic services the hospital offers, based on the findings of a web-based survey of centers that had at least five HCC cases per year.

"This study demonstrates that nonclinical factors have an important effect of therapy for early HCC, and in particular the choice of therapy depends in part on the surgeon’s portfolio of techniques, as well as the availability of transplantation services," said Dr. Hari Nathan of the department of surgery at Johns Hopkins Hospital in Baltimore.

In a previous analysis of the data from their web-based survey, Dr. Nathan and colleagues found that surgeon specialty was more important than certain patient-specific factors when determining treatment choice (J. Clin. Oncol. 2011;29:619-25).

"Differences in choice of therapy for nontransplant and transplant surgeons were not the result of an across-the-board preference for one therapy vs. another. Rather, some clinical factors impacted surgeons differently, depending on their specialty," he said.

In the new analysis, the authors used the survey data to assess the effect of surgeon and hospital factors on the choice of therapy for early, well-compensated HCC, and the effect of regional liver transplantation services on the surgeon’s choice of therapy.

They defined early HCC according to the Milan criteria as a single tumor less than 5 cm in its largest dimension, or two to three tumors less than 3 cm. Cirrhosis was considered to be well compensated if it was Child-Pugh class A, with no varices, ascites, or encephalopathy.

They presented respondents with case scenarios factoring in age, tumor number and size, type of resection required, etiology of cirrhosis (hepatitis B or C, or alcoholic), biological MELD (Model for End-Stage Liver Disease) score, platelet count, and anticipated transplantation waiting time.

Of the 1,032 invitations they extended, 336 surgeons (33%) responded. Of the respondents, 284 (85%) were in academic practices and 52 (15%) were in community practices for a median of 10 years (range, 4-17 years). About two-thirds (65%) were trained in liver transplantation. Procedures performed for HCC included transplantation and radiofrequency ablation (41% of responders), transplantation alone (14%), or liver resection but not transplantation (45%). Asked which procedures were available at their primary hospital (regardless of whether the respondent performed them personally), 100% said that resections were available, and 99% said that ablations were available. In contrast, transplantations were available at 71% of respondents’ hospitals.

The authors found that neither years in practice, surgical oncology training, nor liver transplantation training had a significant effect on treatment choice. Similarly, regional transplantation variables – such as number of procedures, percentage of transplant recipients with HCC, 30th percentile of liver transplantation wait time, and severity of illness by median MELD score – did not significantly predict treatment choice.

There was, however, significant variation in therapeutic choice based on practice type, adjusted for case presentation, with surgeons in academic practices favoring transplantation 57% of the time, compared with 47% for those in community practice. Community-based surgeons were more likely to favor liver resection (45% vs. 38% for academic surgeons), and radiofrequency ablation (9% vs. 4%).

In regression analysis that controlled for clinical factors, they found that surgeons in academic setting were significantly less likely than community-based surgeons to recommend ablation over liver transplantation (relative risk ratio [RRR], 0.41; P = .01). When they looked at the effect of practice types’ controlling for surgeons’ specialties, however, the significance of the practice type on treatment choice disappeared.

Regression analysis also showed that "higher volume surgeons prefer transplantation over resection more strongly than lower-volume surgeons," Dr. Nathan said.

High-volume surgeons (defined as those performing 30 or more cases annually) were overwhelmingly transplantation surgeons; when the authors adjusted for whether the surgeon performed transplantations, the preference for transplantation disappeared.

Additionally, nontransplantation surgeons who worked at hospitals where transplantations were available were more likely to recommend transplantation over ablation, compared with surgeons working at nontransplantation hospitals.

"Interestingly, they also favored resection over radiofrequency ablation more strongly. This appeared to be a separate phenomenon than the one that we observed for the portfolio – that’s personally performed by each surgeon – and in regression analyses these effects were independent," he said.

Coauthor John F.P. Bridges, Ph.D., provided financial and administrative support for the study. Dr. Nathan reported no relevant financial disclosures.

More than half of a group of cirrhosis patients with portal vein thrombosis achieved recanalization with anticoagulation treatment maintained for at least 12 months.

"Moreover, when complete recanalization is achieved, therapy with anticoagulants should be maintained throughout life in order to prevent recurrent thrombosis," wrote Dr. María Gabriela Delgado and Dr. Susana Seijo along with their colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2012.01.012).

In the largest study to date to evaluate the safety and efficacy of anticoagulation for portal vein thrombosis in cirrhosis (for which there are no guidelines, according to the authors), the investigators looked at 55 patients with portal vein thrombosis and cirrhosis from four centers in Spain between June 2003 and September 2010.

All patients received anticoagulation according to the protocol of each hospital after the initiation of prophylaxis of variceal bleeding. For 31 patients, anticoagulation was indicated because of acute or subacute thrombosis, and in the remaining 24 patients, anticoagulation was started because of thrombosis progression.

Anticoagulant agents included low-molecular-weight heparin and vitamin K antagonists, wrote Dr. Delgado and Dr. Seijo, both of the University of Barcelona.

Over a mean 19 months of follow-up, half (n = 28) of the patients remained on anticoagulation until either the end of the study or liver transplant. The remaining 27 patients stopped treatment after a median of 6.3 months (range, 1-24 months).

A total of 33 patients achieved either complete or partial recanalization of the portal vein during the study period; 22 patients did not have a response.

There were three complete recanalizations that occurred within 1 month of anticoagulation initiation, and two patients achieved complete recanalization at month 12.

"Early initiation of anticoagulation therapy after the identification of thrombosis in an imaging study, especially in the first 2 weeks, was the only factor significantly associated with recanalization," wrote the authors.

A total of 17 patients had 30 clinical events during anticoagulation treatment. In 13 patients, these events were "liver related," according to the authors: six variceal bleeding episodes, eight new or worsening ascites cases, five hepatic encephalopathy cases, two spontaneous bacterial peritonitis cases, and two hepatocellular carcinoma cases (several patients had multiple events).

"Liver events were more frequent in patients not achieving recanalization (8/22) than in those achieving partial/complete recanalization (5/33)," added the investigators, though the difference between these groups did not reach significance (P = 0.1).

Non-liver-related events included five bleeding episodes, which the authors attributed to anticoagulation; one acute cholecystitis case; and one duodenal ulcer.

Overall, among the 11 total bleeding events (6 of which were liver related), the authors reported that all took place during the first year after starting anticoagulation, and five events occurred in the first 3 months of treatment.

Furthermore, the only significant predictor of bleeding was a platelet count below 50 × 10⁹/L (P = .018).

Six patients died, none of whom were receiving anticoagulation at the time of death.

Despite its retrospective design and the fact that no comparison group was available, this study shows that "recanalization can be achieved very early after starting anticoagulation treatment; however, those patients who do not present early recanalization may finally achieve it when long-term anticoagulation therapy is maintained," wrote the authors.

More importantly, anticoagulation is "relatively safe" in this population, they added, except in cases of severely depressed platelet counts.

The authors disclosed no conflicts of interest related to this study, and indicated that the research was supported by public grants.

More than half of a group of cirrhosis patients with portal vein thrombosis achieved recanalization with anticoagulation treatment maintained for at least 12 months.

"Moreover, when complete recanalization is achieved, therapy with anticoagulants should be maintained throughout life in order to prevent recurrent thrombosis," wrote Dr. María Gabriela Delgado and Dr. Susana Seijo along with their colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2012.01.012).

In the largest study to date to evaluate the safety and efficacy of anticoagulation for portal vein thrombosis in cirrhosis (for which there are no guidelines, according to the authors), the investigators looked at 55 patients with portal vein thrombosis and cirrhosis from four centers in Spain between June 2003 and September 2010.

All patients received anticoagulation according to the protocol of each hospital after the initiation of prophylaxis of variceal bleeding. For 31 patients, anticoagulation was indicated because of acute or subacute thrombosis, and in the remaining 24 patients, anticoagulation was started because of thrombosis progression.

Anticoagulant agents included low-molecular-weight heparin and vitamin K antagonists, wrote Dr. Delgado and Dr. Seijo, both of the University of Barcelona.

Over a mean 19 months of follow-up, half (n = 28) of the patients remained on anticoagulation until either the end of the study or liver transplant. The remaining 27 patients stopped treatment after a median of 6.3 months (range, 1-24 months).

A total of 33 patients achieved either complete or partial recanalization of the portal vein during the study period; 22 patients did not have a response.

There were three complete recanalizations that occurred within 1 month of anticoagulation initiation, and two patients achieved complete recanalization at month 12.

"Early initiation of anticoagulation therapy after the identification of thrombosis in an imaging study, especially in the first 2 weeks, was the only factor significantly associated with recanalization," wrote the authors.

A total of 17 patients had 30 clinical events during anticoagulation treatment. In 13 patients, these events were "liver related," according to the authors: six variceal bleeding episodes, eight new or worsening ascites cases, five hepatic encephalopathy cases, two spontaneous bacterial peritonitis cases, and two hepatocellular carcinoma cases (several patients had multiple events).

"Liver events were more frequent in patients not achieving recanalization (8/22) than in those achieving partial/complete recanalization (5/33)," added the investigators, though the difference between these groups did not reach significance (P = 0.1).

Non-liver-related events included five bleeding episodes, which the authors attributed to anticoagulation; one acute cholecystitis case; and one duodenal ulcer.

Overall, among the 11 total bleeding events (6 of which were liver related), the authors reported that all took place during the first year after starting anticoagulation, and five events occurred in the first 3 months of treatment.

Furthermore, the only significant predictor of bleeding was a platelet count below 50 × 10⁹/L (P = .018).

Six patients died, none of whom were receiving anticoagulation at the time of death.

Despite its retrospective design and the fact that no comparison group was available, this study shows that "recanalization can be achieved very early after starting anticoagulation treatment; however, those patients who do not present early recanalization may finally achieve it when long-term anticoagulation therapy is maintained," wrote the authors.

More importantly, anticoagulation is "relatively safe" in this population, they added, except in cases of severely depressed platelet counts.

The authors disclosed no conflicts of interest related to this study, and indicated that the research was supported by public grants.

More than half of a group of cirrhosis patients with portal vein thrombosis achieved recanalization with anticoagulation treatment maintained for at least 12 months.

"Moreover, when complete recanalization is achieved, therapy with anticoagulants should be maintained throughout life in order to prevent recurrent thrombosis," wrote Dr. María Gabriela Delgado and Dr. Susana Seijo along with their colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2012.01.012).

In the largest study to date to evaluate the safety and efficacy of anticoagulation for portal vein thrombosis in cirrhosis (for which there are no guidelines, according to the authors), the investigators looked at 55 patients with portal vein thrombosis and cirrhosis from four centers in Spain between June 2003 and September 2010.

All patients received anticoagulation according to the protocol of each hospital after the initiation of prophylaxis of variceal bleeding. For 31 patients, anticoagulation was indicated because of acute or subacute thrombosis, and in the remaining 24 patients, anticoagulation was started because of thrombosis progression.

Anticoagulant agents included low-molecular-weight heparin and vitamin K antagonists, wrote Dr. Delgado and Dr. Seijo, both of the University of Barcelona.

Over a mean 19 months of follow-up, half (n = 28) of the patients remained on anticoagulation until either the end of the study or liver transplant. The remaining 27 patients stopped treatment after a median of 6.3 months (range, 1-24 months).

A total of 33 patients achieved either complete or partial recanalization of the portal vein during the study period; 22 patients did not have a response.

There were three complete recanalizations that occurred within 1 month of anticoagulation initiation, and two patients achieved complete recanalization at month 12.

"Early initiation of anticoagulation therapy after the identification of thrombosis in an imaging study, especially in the first 2 weeks, was the only factor significantly associated with recanalization," wrote the authors.

A total of 17 patients had 30 clinical events during anticoagulation treatment. In 13 patients, these events were "liver related," according to the authors: six variceal bleeding episodes, eight new or worsening ascites cases, five hepatic encephalopathy cases, two spontaneous bacterial peritonitis cases, and two hepatocellular carcinoma cases (several patients had multiple events).

"Liver events were more frequent in patients not achieving recanalization (8/22) than in those achieving partial/complete recanalization (5/33)," added the investigators, though the difference between these groups did not reach significance (P = 0.1).

Non-liver-related events included five bleeding episodes, which the authors attributed to anticoagulation; one acute cholecystitis case; and one duodenal ulcer.

Overall, among the 11 total bleeding events (6 of which were liver related), the authors reported that all took place during the first year after starting anticoagulation, and five events occurred in the first 3 months of treatment.

Furthermore, the only significant predictor of bleeding was a platelet count below 50 × 10⁹/L (P = .018).

Six patients died, none of whom were receiving anticoagulation at the time of death.

Despite its retrospective design and the fact that no comparison group was available, this study shows that "recanalization can be achieved very early after starting anticoagulation treatment; however, those patients who do not present early recanalization may finally achieve it when long-term anticoagulation therapy is maintained," wrote the authors.

More importantly, anticoagulation is "relatively safe" in this population, they added, except in cases of severely depressed platelet counts.

The authors disclosed no conflicts of interest related to this study, and indicated that the research was supported by public grants.

SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

SAN DIEGO – Metformin may do double duty in diabetes patients by decreasing their risk of developing certain types of liver cancers in addition to reducing their blood sugar, studies have shown.

Treatment with the glucose-lowering drug was associated with a nearly 60% reduction in the risk of intrahepatic cholangiocarcinoma (ICC) among diabetes patients in one study presented at Digestive Disease Week 2012, while it was associated with a dose-dependant reduction of hepatocellular carcinoma (HCC) risk of about 7% annually in the second study.

Dr. Roongruedee Chaiteerakij of the Mayo Clinic in Rochester, Minn., and colleagues reviewed the records of 612 patients with ICC and 594 age-, gender-, ethnicity-, and residential area–matched controls who received care at Mayo between January 2000 and May 2010. Risk factors associated with ICC, according to multivariate models, include biliary tract disease, cirrhosis, diabetes, and smoking.

Interestingly, however, "the adjusted odds ratio for [ICC] for diabetic patients treated with metformin was comparable to nondiabetics, at 1.4, but it was significantly increased to 8.8 for diabetic patients not treated with metformin," Dr. Chaiteerakij said, noting that "the magnitude of the metformin-associated risk reduction was comparable to that shown in other cancers."

In the second study, designed to tease out a previously demonstrated relationship between HCC and metformin, Dr. Chun-Ying Wu of the National Yang-Ming University in Taipei, Taiwan, and colleagues identified 97,430 patients diagnosed with HCC between 1997 and 2008 and 194,860 age-, gender-, and physician visit date–matched controls from Taiwan’s National Health Insurance Research Database and evaluated the chemopreventive effects of metformin for different doses and durations of use.

The investigators also studied the in vitro effects of metformin on cell proliferation and cell cycle in HepG2 and HepB3 hepatocellular carcinoma cell lines. HepG2 and Hep3B cells were exposed to various concentrations of metformin for 48 hours and an MTT assay was then used to determine cell viability, calculated as a percentage of the viable vehicle-treated cells, Dr. Wu explained.

Relative to individuals without diabetes, the highest risk of HCC after adjustment for age, gender, and liver disease was observed in diabetic patients who did not take metformin, with an odds ratio of 1.95, followed by those who rarely used it, frequently used it, and regularly used it, with respective odds ratios of 1.74, 1.67, and 1.56, Dr. Wu reported. "In diabetic subjects, each incremental year increase in metformin use was associated with a nearly 7% reduction in the risk of developing [HCC]," he said. The in vitro studies were consistent with this observation. "Cell line studies showed an inhibition of hepatocyte proliferation and induction of cell cycle arrest at the G0-G1 phase associated with metformin in a dose-dependent manner."

Although the mechanism of action has not been fully elucidated, metformin, an activator of AMP-activated protein kinase, "may reduce circulating glucose and insulin levels and limit their systemic effects on the formation and development of tumors," Dr. Wu said in an interview. It also may reduce hepatic lipid accumulation, and by so doing interfere with the molecular events that contribute to the production of cancer cells in the liver, he said. By properly controlling glucose, metformin appears to help avoid or delay diabetes-associated complications, including liver cancer. As such, he concluded, "using metformin in diabetic patients to decrease the risk of hepatocellular carcinoma should be recommended."

Dr. Chaiteerakij and Dr. Wu reported having no relevant financial conflicts of interest.

Quality of care for ascites, the most common complication of cirrhosis, was found to be suboptimal at several Veterans Affairs medical centers, reported Dr. Fasiha Kanwal and colleagues in the July issue of Gastroenterology.

"In general, care targeted at diagnosis and treatment was more likely to meet standards than preventive care," wrote Dr. Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center, Houston.

"We also found a trend towards improved outcomes in patients who met recommended quality indicators," added the investigators, although these findings "can only be regarded as preliminary."

The authors studied records from 774 patients (mean age 54.7 years, 99% male) in a database comprising 3 VA medical centers and 15 affiliated clinics in the Midwest (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.03.038]).

All patients had at least two ICD-9 codes for cirrhosis or at least one code for cirrhosis with either a code for complications of cirrhosis or an aspartate aminotransferase to platelet ratio greater than 2. The patients were seen between January 2000 and December 2007.

The authors compared data on these patients to a set of class 1 ascites care quality indicators (QIs). These indicators were derived by using the RAND/University of California, Los Angeles (UCLA), Appropriateness Method, which had been previously published elsewhere (Clin. Gastroenterol. Hepatol. 2010;8:709-17).

If a patient had been hospitalized more than once, only the first hospitalization was assessed. The rate of adherence to each QI was expressed as a percentage of subjects who received the recommended care, among those who were eligible for the QI.

The first QI assessed the percentage of new-onset ascites patients who underwent abdominal paracentesis within 30 days of diagnosis. On this measure, the VA scored 50.6%. The second indicator was whether known ascites patients admitted with either ascites or hepatic encephalopathy underwent abdominal paracentesis during the index hospitalization. Just over half (57.6%) of patients met this criterion.

The next QI was more likely to be met: 89.3% of patients who underwent abdominal paracentesis received ascitic fluid cell count and differential. Another indicator that was met for a high percentage of patients addressed whether ascites patients with normal renal function received diuretics within 30 days of diagnosis – 82.8% met this criterion.

Similarly, among hospitalized patients with spontaneous bacterial peritonitis (SBP), 72.0% received antibiotics within 24 hours before or after ascitic fluid analysis.

However, just 30% of patients with SBP who survived and were discharged from the facility received long-term outpatient antibiotics (for secondary prophylaxis) within 30 days. And just under half (49.2%) of patients admitted with a GI bleed received antibiotics during the index hospitalization.

The final QI was associated with the worst compliance rate: just 22.2% of patients with ascitic fluid total protein levels less than 1 g/dL and serum bilirubin of greater than 2.5 mg/dL received long-term outpatient antibiotics (for primary prophylaxis) within –3 to 30 days of that test result.

Next, the authors assessed which demographic or other independent factors were associated with higher QI compliance. In general, they reported that better care was inversely related to a worsening liver disease. More specifically, they found that patients who saw a gastroenterologist received higher-quality care than those who did not (odds ratio, 1.33), as did patients who were seen at a VA facility with academic affiliation, versus unaffiliated centers (OR, 1.73).

Finally, in two exploratory analyses, the authors examined how adherence to the ascites QIs affected patient outcomes.

Not surprisingly, "we found that after adjusting for age, liver disease severity, and comorbidity, patients receiving suboptimum care had 37% higher odds of death and 35% higher odds of readmission during the 12-month follow-up compared to patients who received optimum ascites care," although these figures did not reach statistical significance.

This study was supported by the 2008 American Society of Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. The authors stated that they had no personal conflicts of interest.

Quality of care for ascites, the most common complication of cirrhosis, was found to be suboptimal at several Veterans Affairs medical centers, reported Dr. Fasiha Kanwal and colleagues in the July issue of Gastroenterology.

"In general, care targeted at diagnosis and treatment was more likely to meet standards than preventive care," wrote Dr. Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center, Houston.

"We also found a trend towards improved outcomes in patients who met recommended quality indicators," added the investigators, although these findings "can only be regarded as preliminary."

The authors studied records from 774 patients (mean age 54.7 years, 99% male) in a database comprising 3 VA medical centers and 15 affiliated clinics in the Midwest (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.03.038]).

All patients had at least two ICD-9 codes for cirrhosis or at least one code for cirrhosis with either a code for complications of cirrhosis or an aspartate aminotransferase to platelet ratio greater than 2. The patients were seen between January 2000 and December 2007.

The authors compared data on these patients to a set of class 1 ascites care quality indicators (QIs). These indicators were derived by using the RAND/University of California, Los Angeles (UCLA), Appropriateness Method, which had been previously published elsewhere (Clin. Gastroenterol. Hepatol. 2010;8:709-17).

If a patient had been hospitalized more than once, only the first hospitalization was assessed. The rate of adherence to each QI was expressed as a percentage of subjects who received the recommended care, among those who were eligible for the QI.

The first QI assessed the percentage of new-onset ascites patients who underwent abdominal paracentesis within 30 days of diagnosis. On this measure, the VA scored 50.6%. The second indicator was whether known ascites patients admitted with either ascites or hepatic encephalopathy underwent abdominal paracentesis during the index hospitalization. Just over half (57.6%) of patients met this criterion.

The next QI was more likely to be met: 89.3% of patients who underwent abdominal paracentesis received ascitic fluid cell count and differential. Another indicator that was met for a high percentage of patients addressed whether ascites patients with normal renal function received diuretics within 30 days of diagnosis – 82.8% met this criterion.

Similarly, among hospitalized patients with spontaneous bacterial peritonitis (SBP), 72.0% received antibiotics within 24 hours before or after ascitic fluid analysis.

However, just 30% of patients with SBP who survived and were discharged from the facility received long-term outpatient antibiotics (for secondary prophylaxis) within 30 days. And just under half (49.2%) of patients admitted with a GI bleed received antibiotics during the index hospitalization.

The final QI was associated with the worst compliance rate: just 22.2% of patients with ascitic fluid total protein levels less than 1 g/dL and serum bilirubin of greater than 2.5 mg/dL received long-term outpatient antibiotics (for primary prophylaxis) within –3 to 30 days of that test result.

Next, the authors assessed which demographic or other independent factors were associated with higher QI compliance. In general, they reported that better care was inversely related to a worsening liver disease. More specifically, they found that patients who saw a gastroenterologist received higher-quality care than those who did not (odds ratio, 1.33), as did patients who were seen at a VA facility with academic affiliation, versus unaffiliated centers (OR, 1.73).

Finally, in two exploratory analyses, the authors examined how adherence to the ascites QIs affected patient outcomes.

Not surprisingly, "we found that after adjusting for age, liver disease severity, and comorbidity, patients receiving suboptimum care had 37% higher odds of death and 35% higher odds of readmission during the 12-month follow-up compared to patients who received optimum ascites care," although these figures did not reach statistical significance.

This study was supported by the 2008 American Society of Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. The authors stated that they had no personal conflicts of interest.

Quality of care for ascites, the most common complication of cirrhosis, was found to be suboptimal at several Veterans Affairs medical centers, reported Dr. Fasiha Kanwal and colleagues in the July issue of Gastroenterology.

"In general, care targeted at diagnosis and treatment was more likely to meet standards than preventive care," wrote Dr. Kanwal, of the Michael E. DeBakey Veterans Affairs Medical Center, Houston.

"We also found a trend towards improved outcomes in patients who met recommended quality indicators," added the investigators, although these findings "can only be regarded as preliminary."

The authors studied records from 774 patients (mean age 54.7 years, 99% male) in a database comprising 3 VA medical centers and 15 affiliated clinics in the Midwest (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.03.038]).

All patients had at least two ICD-9 codes for cirrhosis or at least one code for cirrhosis with either a code for complications of cirrhosis or an aspartate aminotransferase to platelet ratio greater than 2. The patients were seen between January 2000 and December 2007.

The authors compared data on these patients to a set of class 1 ascites care quality indicators (QIs). These indicators were derived by using the RAND/University of California, Los Angeles (UCLA), Appropriateness Method, which had been previously published elsewhere (Clin. Gastroenterol. Hepatol. 2010;8:709-17).

If a patient had been hospitalized more than once, only the first hospitalization was assessed. The rate of adherence to each QI was expressed as a percentage of subjects who received the recommended care, among those who were eligible for the QI.

The first QI assessed the percentage of new-onset ascites patients who underwent abdominal paracentesis within 30 days of diagnosis. On this measure, the VA scored 50.6%. The second indicator was whether known ascites patients admitted with either ascites or hepatic encephalopathy underwent abdominal paracentesis during the index hospitalization. Just over half (57.6%) of patients met this criterion.

The next QI was more likely to be met: 89.3% of patients who underwent abdominal paracentesis received ascitic fluid cell count and differential. Another indicator that was met for a high percentage of patients addressed whether ascites patients with normal renal function received diuretics within 30 days of diagnosis – 82.8% met this criterion.

Similarly, among hospitalized patients with spontaneous bacterial peritonitis (SBP), 72.0% received antibiotics within 24 hours before or after ascitic fluid analysis.

However, just 30% of patients with SBP who survived and were discharged from the facility received long-term outpatient antibiotics (for secondary prophylaxis) within 30 days. And just under half (49.2%) of patients admitted with a GI bleed received antibiotics during the index hospitalization.

The final QI was associated with the worst compliance rate: just 22.2% of patients with ascitic fluid total protein levels less than 1 g/dL and serum bilirubin of greater than 2.5 mg/dL received long-term outpatient antibiotics (for primary prophylaxis) within –3 to 30 days of that test result.

Next, the authors assessed which demographic or other independent factors were associated with higher QI compliance. In general, they reported that better care was inversely related to a worsening liver disease. More specifically, they found that patients who saw a gastroenterologist received higher-quality care than those who did not (odds ratio, 1.33), as did patients who were seen at a VA facility with academic affiliation, versus unaffiliated centers (OR, 1.73).

Finally, in two exploratory analyses, the authors examined how adherence to the ascites QIs affected patient outcomes.

Not surprisingly, "we found that after adjusting for age, liver disease severity, and comorbidity, patients receiving suboptimum care had 37% higher odds of death and 35% higher odds of readmission during the 12-month follow-up compared to patients who received optimum ascites care," although these figures did not reach statistical significance.

This study was supported by the 2008 American Society of Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. The authors stated that they had no personal conflicts of interest.

SAN DIEGO  – Although the addition of telaprevir to peginterferon/ribavirin therapy for treatment of chronic hepatitis C exacerbates treatment-related side effects, the triple combination does not diminish patient quality of life relative to treatment with the peginterferon/ribavirin regimen alone, a study has shown.

In other words, adding the protease inhibitor "does not further diminish patient quality of life," lead investigator Dr. Zobair Younossi explained at the annual Digestive Disease Week. "The most important contributor to the quality of life measurement in interferon therapy is interferon itself, which is so overwhelming in terms of side effects, especially grade 4 and 5 effects, that it probably overshadows everything else," he said.

Photo courtesy US Dept. of Veterans Affairs

Studies have shown that the addition of telaprevir to standard peginterferon alfa-2a/ribavirin (PR) significantly improves treatment efficacy in treatment-naive patients with genotype 1 hepatitis C virus (HCV), but there is a perception that the additional side effect burden from adding telaprevir is prohibitive in some patients, said Dr. Younossi, chairman of the department of medicine at Inova Health System in Falls Church, Va.

Dr. Younossi and colleagues conducted post hoc analyses of data from the ADVANCE trial, in which adding telaprevir to the treatment mix significantly improved patients’ sustained virologic response compared with standard PR therapy.

In the ADVANCE study, 1,088 treatment naive HCV genotype 1 patients were assigned to one of three treatment arms: 48 weeks of standard PR therapy; 12 weeks of telaprevir plus 24 weeks PR; or 12 weeks of telaprevir plus 48 weeks of PR. Nearly 80% of patients in both telaprevir groups achieved sustained virologic response, compared with 46% of patients in the standard PR treatment group (N. Engl. J. Med. 2011;364:2405-16).

In terms of side effects, "across all phase III studies, the incidence of rash and anemia (which are the effects we’re talking about with the protease inhibitors) was 56% and 34%, respectively, among telaprevir-treated patients, and 36% and 17% in patients receiving standard treatment," Dr. Younossi said.

To assess whether and to what degree these increases played a role in patient quality of life, Dr. Younossi and colleagues analyzed the results of EQ-5D quality of life questionnaires completed at baseline and at weeks 4, 12, 24, 36, 48, and 72 by 722 patients. They derived a summary index by calculating the percentages of patients reporting problems for each of the five health-related quality of life dimensions measured (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).

After adjustment for age and sex, the baseline mean index values for the EQ-5D were 0.92 for the telaprevir plus 24-week PR group, 0.90 for the telaprevir plus 48-week PR group, and 0.91 for the 48-week PR-only group. The percentages of patients reporting any problems in each of the five qualitative dimensions at baseline were 8.2% for mobility, 2.0% for self-care, 12.9% for usual activities, 25.7% for pain/discomfort, and 25.6% for anxiety/depression, he said.

Across all the treatment groups, the EQ-5D index scores worsened during the first 12 weeks of treatment initiation. Specifically, mean values were 0.80 for the pooled-telaprevir groups and 0.83 for the PR-only group, according to Dr. Younossi.

Also, the respective percentages of patients in the pooled-telaprevir and PR-only groups reporting any problems at week 12 were 56% and 50% for usual activities, 51% and 42% for anxiety/depression, and 60% and 63% for pain/discomfort, he said. Change from baseline in terms of reported impact on mobility and self-care were small and not reported.

At week 48, the corresponding mean EQ-5D values were 0.93 for the telaprevir plus 24-week PR group, 0.83 for the telaprevir plus 48-week PR group, and 0.84 for the PR-only group.

By week 72 the EQ-5D index values returned to baseline levels, Dr. Younossi said.

Adjusted for age and sex, the mean EQ-5D index at week 72 was higher among the patients achieving sustained virologic response (SVR) compared with those who did not, with respective values of 0.90 and 0.86. "The 4% difference is within the range of published values for the minimal clinically important difference for the EQ-5D," he said.

Furthermore, at week 72, there were fewer patients among those who experienced SVR and reported problems in each dimension, compared with those who did not experience SVR.

At week 72, after adjustment for the index at baseline, patient age, sex, race, advanced liver disease, self-reported comorbidities, and the number of adverse events during treatment, only SVR was a positive predictor of the EQ-5D index. "We saw that [SVR] was a statistically significant and meaningful predictor of health-related quality of life," he said.

The study findings are consistent with the published research on the impacts of interferon-based regimens on health-related quality of life in this patient population, "and support the value of shorter treatment duration and [SVR] from a patient-reported outcomes perspective," said Dr. Younossi.

"We certainly cannot say that adding telaprevir causes fewer side effects. It’s clear there are more side effects, but it appears that the most troublesome side effects are related to the interferon therapy," he explained. When considered in the context of the improved SVR, "the burden of the increased incidence of anemia and rash associated with telaprevir, of which few cases are severe, appears to be outweighed by the overall treatment response."

This study was sponsored by Vertex. Dr. Younossi disclosed relationships with Biolex, Vertex, Salix, GlaxoSmithKline, and Tibotec.

SAN DIEGO  – Although the addition of telaprevir to peginterferon/ribavirin therapy for treatment of chronic hepatitis C exacerbates treatment-related side effects, the triple combination does not diminish patient quality of life relative to treatment with the peginterferon/ribavirin regimen alone, a study has shown.

In other words, adding the protease inhibitor "does not further diminish patient quality of life," lead investigator Dr. Zobair Younossi explained at the annual Digestive Disease Week. "The most important contributor to the quality of life measurement in interferon therapy is interferon itself, which is so overwhelming in terms of side effects, especially grade 4 and 5 effects, that it probably overshadows everything else," he said.

Photo courtesy US Dept. of Veterans Affairs

Studies have shown that the addition of telaprevir to standard peginterferon alfa-2a/ribavirin (PR) significantly improves treatment efficacy in treatment-naive patients with genotype 1 hepatitis C virus (HCV), but there is a perception that the additional side effect burden from adding telaprevir is prohibitive in some patients, said Dr. Younossi, chairman of the department of medicine at Inova Health System in Falls Church, Va.

Dr. Younossi and colleagues conducted post hoc analyses of data from the ADVANCE trial, in which adding telaprevir to the treatment mix significantly improved patients’ sustained virologic response compared with standard PR therapy.

In the ADVANCE study, 1,088 treatment naive HCV genotype 1 patients were assigned to one of three treatment arms: 48 weeks of standard PR therapy; 12 weeks of telaprevir plus 24 weeks PR; or 12 weeks of telaprevir plus 48 weeks of PR. Nearly 80% of patients in both telaprevir groups achieved sustained virologic response, compared with 46% of patients in the standard PR treatment group (N. Engl. J. Med. 2011;364:2405-16).

In terms of side effects, "across all phase III studies, the incidence of rash and anemia (which are the effects we’re talking about with the protease inhibitors) was 56% and 34%, respectively, among telaprevir-treated patients, and 36% and 17% in patients receiving standard treatment," Dr. Younossi said.

To assess whether and to what degree these increases played a role in patient quality of life, Dr. Younossi and colleagues analyzed the results of EQ-5D quality of life questionnaires completed at baseline and at weeks 4, 12, 24, 36, 48, and 72 by 722 patients. They derived a summary index by calculating the percentages of patients reporting problems for each of the five health-related quality of life dimensions measured (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).

After adjustment for age and sex, the baseline mean index values for the EQ-5D were 0.92 for the telaprevir plus 24-week PR group, 0.90 for the telaprevir plus 48-week PR group, and 0.91 for the 48-week PR-only group. The percentages of patients reporting any problems in each of the five qualitative dimensions at baseline were 8.2% for mobility, 2.0% for self-care, 12.9% for usual activities, 25.7% for pain/discomfort, and 25.6% for anxiety/depression, he said.

Across all the treatment groups, the EQ-5D index scores worsened during the first 12 weeks of treatment initiation. Specifically, mean values were 0.80 for the pooled-telaprevir groups and 0.83 for the PR-only group, according to Dr. Younossi.

Also, the respective percentages of patients in the pooled-telaprevir and PR-only groups reporting any problems at week 12 were 56% and 50% for usual activities, 51% and 42% for anxiety/depression, and 60% and 63% for pain/discomfort, he said. Change from baseline in terms of reported impact on mobility and self-care were small and not reported.

At week 48, the corresponding mean EQ-5D values were 0.93 for the telaprevir plus 24-week PR group, 0.83 for the telaprevir plus 48-week PR group, and 0.84 for the PR-only group.

By week 72 the EQ-5D index values returned to baseline levels, Dr. Younossi said.

Adjusted for age and sex, the mean EQ-5D index at week 72 was higher among the patients achieving sustained virologic response (SVR) compared with those who did not, with respective values of 0.90 and 0.86. "The 4% difference is within the range of published values for the minimal clinically important difference for the EQ-5D," he said.

Furthermore, at week 72, there were fewer patients among those who experienced SVR and reported problems in each dimension, compared with those who did not experience SVR.

At week 72, after adjustment for the index at baseline, patient age, sex, race, advanced liver disease, self-reported comorbidities, and the number of adverse events during treatment, only SVR was a positive predictor of the EQ-5D index. "We saw that [SVR] was a statistically significant and meaningful predictor of health-related quality of life," he said.

The study findings are consistent with the published research on the impacts of interferon-based regimens on health-related quality of life in this patient population, "and support the value of shorter treatment duration and [SVR] from a patient-reported outcomes perspective," said Dr. Younossi.

"We certainly cannot say that adding telaprevir causes fewer side effects. It’s clear there are more side effects, but it appears that the most troublesome side effects are related to the interferon therapy," he explained. When considered in the context of the improved SVR, "the burden of the increased incidence of anemia and rash associated with telaprevir, of which few cases are severe, appears to be outweighed by the overall treatment response."

This study was sponsored by Vertex. Dr. Younossi disclosed relationships with Biolex, Vertex, Salix, GlaxoSmithKline, and Tibotec.

SAN DIEGO  – Although the addition of telaprevir to peginterferon/ribavirin therapy for treatment of chronic hepatitis C exacerbates treatment-related side effects, the triple combination does not diminish patient quality of life relative to treatment with the peginterferon/ribavirin regimen alone, a study has shown.

In other words, adding the protease inhibitor "does not further diminish patient quality of life," lead investigator Dr. Zobair Younossi explained at the annual Digestive Disease Week. "The most important contributor to the quality of life measurement in interferon therapy is interferon itself, which is so overwhelming in terms of side effects, especially grade 4 and 5 effects, that it probably overshadows everything else," he said.

Photo courtesy US Dept. of Veterans Affairs

Studies have shown that the addition of telaprevir to standard peginterferon alfa-2a/ribavirin (PR) significantly improves treatment efficacy in treatment-naive patients with genotype 1 hepatitis C virus (HCV), but there is a perception that the additional side effect burden from adding telaprevir is prohibitive in some patients, said Dr. Younossi, chairman of the department of medicine at Inova Health System in Falls Church, Va.

Dr. Younossi and colleagues conducted post hoc analyses of data from the ADVANCE trial, in which adding telaprevir to the treatment mix significantly improved patients’ sustained virologic response compared with standard PR therapy.

In the ADVANCE study, 1,088 treatment naive HCV genotype 1 patients were assigned to one of three treatment arms: 48 weeks of standard PR therapy; 12 weeks of telaprevir plus 24 weeks PR; or 12 weeks of telaprevir plus 48 weeks of PR. Nearly 80% of patients in both telaprevir groups achieved sustained virologic response, compared with 46% of patients in the standard PR treatment group (N. Engl. J. Med. 2011;364:2405-16).

In terms of side effects, "across all phase III studies, the incidence of rash and anemia (which are the effects we’re talking about with the protease inhibitors) was 56% and 34%, respectively, among telaprevir-treated patients, and 36% and 17% in patients receiving standard treatment," Dr. Younossi said.

To assess whether and to what degree these increases played a role in patient quality of life, Dr. Younossi and colleagues analyzed the results of EQ-5D quality of life questionnaires completed at baseline and at weeks 4, 12, 24, 36, 48, and 72 by 722 patients. They derived a summary index by calculating the percentages of patients reporting problems for each of the five health-related quality of life dimensions measured (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).

After adjustment for age and sex, the baseline mean index values for the EQ-5D were 0.92 for the telaprevir plus 24-week PR group, 0.90 for the telaprevir plus 48-week PR group, and 0.91 for the 48-week PR-only group. The percentages of patients reporting any problems in each of the five qualitative dimensions at baseline were 8.2% for mobility, 2.0% for self-care, 12.9% for usual activities, 25.7% for pain/discomfort, and 25.6% for anxiety/depression, he said.

Across all the treatment groups, the EQ-5D index scores worsened during the first 12 weeks of treatment initiation. Specifically, mean values were 0.80 for the pooled-telaprevir groups and 0.83 for the PR-only group, according to Dr. Younossi.

Also, the respective percentages of patients in the pooled-telaprevir and PR-only groups reporting any problems at week 12 were 56% and 50% for usual activities, 51% and 42% for anxiety/depression, and 60% and 63% for pain/discomfort, he said. Change from baseline in terms of reported impact on mobility and self-care were small and not reported.

At week 48, the corresponding mean EQ-5D values were 0.93 for the telaprevir plus 24-week PR group, 0.83 for the telaprevir plus 48-week PR group, and 0.84 for the PR-only group.

By week 72 the EQ-5D index values returned to baseline levels, Dr. Younossi said.

Adjusted for age and sex, the mean EQ-5D index at week 72 was higher among the patients achieving sustained virologic response (SVR) compared with those who did not, with respective values of 0.90 and 0.86. "The 4% difference is within the range of published values for the minimal clinically important difference for the EQ-5D," he said.

Furthermore, at week 72, there were fewer patients among those who experienced SVR and reported problems in each dimension, compared with those who did not experience SVR.

At week 72, after adjustment for the index at baseline, patient age, sex, race, advanced liver disease, self-reported comorbidities, and the number of adverse events during treatment, only SVR was a positive predictor of the EQ-5D index. "We saw that [SVR] was a statistically significant and meaningful predictor of health-related quality of life," he said.

The study findings are consistent with the published research on the impacts of interferon-based regimens on health-related quality of life in this patient population, "and support the value of shorter treatment duration and [SVR] from a patient-reported outcomes perspective," said Dr. Younossi.

"We certainly cannot say that adding telaprevir causes fewer side effects. It’s clear there are more side effects, but it appears that the most troublesome side effects are related to the interferon therapy," he explained. When considered in the context of the improved SVR, "the burden of the increased incidence of anemia and rash associated with telaprevir, of which few cases are severe, appears to be outweighed by the overall treatment response."

This study was sponsored by Vertex. Dr. Younossi disclosed relationships with Biolex, Vertex, Salix, GlaxoSmithKline, and Tibotec.

SAN DIEGO – The U.S. incidence of hepatocellular carcinoma continues to soar, and will likely remain on that trajectory for at least a couple of decades, fed in large part by the obesity and type 2 diabetes epidemics, as well as by infections with hepatitis virus types C and B.

"I think rates will increase for another 10-20 years," predicted Dr. Alita Mishra, one of two researchers who reported results at the meeting from independent studies that documented increased rates of U.S. hepatocellular carcinoma (HCC) cases during the 2000s.

Greater vigilance is therefore needed to spot incident cases early, she said in an interview. While patients infected with hepatitis C virus who develop cirrhosis usually undergo routine, serial ultrasound screening for liver lesions, regular surveillance occurs less often in patients with cirrhosis who are infected with hepatitis B virus, or those with cirrhosis due to non-alcoholic fatty liver disease (NAFLD) secondary to obesity or type two diabetes. "Patients with cirrhosis should undergo regular HCC screening regardless of the underlying cause," Dr. Mishra said at the annual Digestive Disease Week.

One analysis, based on data collected by the Surveillance Epidemiology and End Results (SEER) registry of the National Cancer Institute, showed that U.S. HCC rates rose three-fold from 1975-2007, including a 33% rise during 1998-2007, Jessica A. Davila, Ph.D. reported at the meeting.

The second analysis, using data collected by the Nationwide Inpatient Sample (NIS), showed that the number of patients hospitalized with HCC per 100,000 hospital discharges jumped from 148 in 2005 to 213, said Dr. Mishra, a hospitalist at Inova Farifax (Va.) Hospital.

"HCC is rising because of hepatitis C viral infection, especially in people born during 1945-1965," Dr. Mishra said in an interview. Many of these people don’t know they are infected, and it usually takes decades for them to develop HCC.

The second big factor is the rising prevalence of obesity and type 2 diabetes. "Hepatitis C infections are now falling, so perhaps the rise in new HCC cases will eventually peak, but not if other factors like obesity and type 2 diabetes continue to push it up," she said.

"What is driving a lot of the increase is hepatitis C virus, and the high prevalence of hepatitis B virus in foreign-born Asians," said Dr. Davila, a clinical epidemiologist at the Houston VA Medical Center and Baylor College of Medicine in Houston.

"A lot also has to do with obesity and type 2 diabetes and their association with non-alcoholic fatty liver disease, especially in middle-aged, Hispanic women. I think we’ll see the greatest increase in HCC in women during the next 2 decades," Dr. Davila said. She also predicted increasing numbers of hepatitis C virus-driven HCC cases in the short term "as the [infected] cohort ages, increasing numbers will develop advanced fibrosis and eventually HCC," she said.

Dr. Davila’s study used data from SEER, which the National Cancer Institute began in 1973 to collect data on cancer cases from about 14% of the U.S. population in selected states and metropolitan areas. During 1975-2007, SEER tallied a total of 21,472 HCC cases, about 80% of which occurred in people aged 50-79 years, and about three-quarters of cases in men.

HCC incidence rose from 1.6 cases per 100,000 people during 1975-1977 to 4.8 per 100,000 in 2005-2007. Roughly a tripling of cases during the three decades occurred in both men and in women. The greatest increase occurred among people aged 50-59 years, which jumped nearly fivefold, from 2.6 per 100,000 in 1975-1977 to 12.6 per 100,000 in 2005-2007. The smallest rise was 2.4-fold among people aged 70-79 years.

By 2005-2007, the highest rate was among Asians, 10.3 per 100,000, followed by 8.2 per 100,000 in Hispanics, 7.5 per 100,000 in blacks, and 3.7/100,000 in whites (see table).

Dr. Mishra’s study used data collected in NIS by the federal Agency for Healthcare Research and Quality from about 1,000 hospitals in 44 states. The number of patients hospitalized with HCC (not confined to incident cases) rose from 9,537 in 2005 to 13,689 in 2009. During the 5-year period, in-hospital mortality of HCC cases dropped from 120 per 1,000 cases in 2005 to 95 per 1,000 cases in 2009, and the median length of stay fell by about 0.5 days.

Despite reduced hospitalized time, median hospital charges for each HCC hospitalized case rose from about $21,000 in 2005 to nearly $29,000 in 2009. Paralleling this increase was an uptick in the percent of cases having "major" or "extreme" illness, from 52% in 2005 to 63% in 2009, and the average number of comorbidities also rose steadily during the 5 years studied.

Hospitalized patients with HCC "are getting sicker, more complicated, and have more comorbidities," Dr. Mishra said. She also noted that the rate of liver transplants remained "very low" during the period studied.

Dr. Davila and Dr. Mishra reported having no conflicts of interest.

SAN DIEGO – The U.S. incidence of hepatocellular carcinoma continues to soar, and will likely remain on that trajectory for at least a couple of decades, fed in large part by the obesity and type 2 diabetes epidemics, as well as by infections with hepatitis virus types C and B.

"I think rates will increase for another 10-20 years," predicted Dr. Alita Mishra, one of two researchers who reported results at the meeting from independent studies that documented increased rates of U.S. hepatocellular carcinoma (HCC) cases during the 2000s.

Greater vigilance is therefore needed to spot incident cases early, she said in an interview. While patients infected with hepatitis C virus who develop cirrhosis usually undergo routine, serial ultrasound screening for liver lesions, regular surveillance occurs less often in patients with cirrhosis who are infected with hepatitis B virus, or those with cirrhosis due to non-alcoholic fatty liver disease (NAFLD) secondary to obesity or type two diabetes. "Patients with cirrhosis should undergo regular HCC screening regardless of the underlying cause," Dr. Mishra said at the annual Digestive Disease Week.

One analysis, based on data collected by the Surveillance Epidemiology and End Results (SEER) registry of the National Cancer Institute, showed that U.S. HCC rates rose three-fold from 1975-2007, including a 33% rise during 1998-2007, Jessica A. Davila, Ph.D. reported at the meeting.

The second analysis, using data collected by the Nationwide Inpatient Sample (NIS), showed that the number of patients hospitalized with HCC per 100,000 hospital discharges jumped from 148 in 2005 to 213, said Dr. Mishra, a hospitalist at Inova Farifax (Va.) Hospital.

"HCC is rising because of hepatitis C viral infection, especially in people born during 1945-1965," Dr. Mishra said in an interview. Many of these people don’t know they are infected, and it usually takes decades for them to develop HCC.

The second big factor is the rising prevalence of obesity and type 2 diabetes. "Hepatitis C infections are now falling, so perhaps the rise in new HCC cases will eventually peak, but not if other factors like obesity and type 2 diabetes continue to push it up," she said.

"What is driving a lot of the increase is hepatitis C virus, and the high prevalence of hepatitis B virus in foreign-born Asians," said Dr. Davila, a clinical epidemiologist at the Houston VA Medical Center and Baylor College of Medicine in Houston.

"A lot also has to do with obesity and type 2 diabetes and their association with non-alcoholic fatty liver disease, especially in middle-aged, Hispanic women. I think we’ll see the greatest increase in HCC in women during the next 2 decades," Dr. Davila said. She also predicted increasing numbers of hepatitis C virus-driven HCC cases in the short term "as the [infected] cohort ages, increasing numbers will develop advanced fibrosis and eventually HCC," she said.

Dr. Davila’s study used data from SEER, which the National Cancer Institute began in 1973 to collect data on cancer cases from about 14% of the U.S. population in selected states and metropolitan areas. During 1975-2007, SEER tallied a total of 21,472 HCC cases, about 80% of which occurred in people aged 50-79 years, and about three-quarters of cases in men.

HCC incidence rose from 1.6 cases per 100,000 people during 1975-1977 to 4.8 per 100,000 in 2005-2007. Roughly a tripling of cases during the three decades occurred in both men and in women. The greatest increase occurred among people aged 50-59 years, which jumped nearly fivefold, from 2.6 per 100,000 in 1975-1977 to 12.6 per 100,000 in 2005-2007. The smallest rise was 2.4-fold among people aged 70-79 years.

By 2005-2007, the highest rate was among Asians, 10.3 per 100,000, followed by 8.2 per 100,000 in Hispanics, 7.5 per 100,000 in blacks, and 3.7/100,000 in whites (see table).

Dr. Mishra’s study used data collected in NIS by the federal Agency for Healthcare Research and Quality from about 1,000 hospitals in 44 states. The number of patients hospitalized with HCC (not confined to incident cases) rose from 9,537 in 2005 to 13,689 in 2009. During the 5-year period, in-hospital mortality of HCC cases dropped from 120 per 1,000 cases in 2005 to 95 per 1,000 cases in 2009, and the median length of stay fell by about 0.5 days.

Despite reduced hospitalized time, median hospital charges for each HCC hospitalized case rose from about $21,000 in 2005 to nearly $29,000 in 2009. Paralleling this increase was an uptick in the percent of cases having "major" or "extreme" illness, from 52% in 2005 to 63% in 2009, and the average number of comorbidities also rose steadily during the 5 years studied.

Hospitalized patients with HCC "are getting sicker, more complicated, and have more comorbidities," Dr. Mishra said. She also noted that the rate of liver transplants remained "very low" during the period studied.

Dr. Davila and Dr. Mishra reported having no conflicts of interest.

SAN DIEGO – The U.S. incidence of hepatocellular carcinoma continues to soar, and will likely remain on that trajectory for at least a couple of decades, fed in large part by the obesity and type 2 diabetes epidemics, as well as by infections with hepatitis virus types C and B.

"I think rates will increase for another 10-20 years," predicted Dr. Alita Mishra, one of two researchers who reported results at the meeting from independent studies that documented increased rates of U.S. hepatocellular carcinoma (HCC) cases during the 2000s.

Greater vigilance is therefore needed to spot incident cases early, she said in an interview. While patients infected with hepatitis C virus who develop cirrhosis usually undergo routine, serial ultrasound screening for liver lesions, regular surveillance occurs less often in patients with cirrhosis who are infected with hepatitis B virus, or those with cirrhosis due to non-alcoholic fatty liver disease (NAFLD) secondary to obesity or type two diabetes. "Patients with cirrhosis should undergo regular HCC screening regardless of the underlying cause," Dr. Mishra said at the annual Digestive Disease Week.

One analysis, based on data collected by the Surveillance Epidemiology and End Results (SEER) registry of the National Cancer Institute, showed that U.S. HCC rates rose three-fold from 1975-2007, including a 33% rise during 1998-2007, Jessica A. Davila, Ph.D. reported at the meeting.

The second analysis, using data collected by the Nationwide Inpatient Sample (NIS), showed that the number of patients hospitalized with HCC per 100,000 hospital discharges jumped from 148 in 2005 to 213, said Dr. Mishra, a hospitalist at Inova Farifax (Va.) Hospital.

"HCC is rising because of hepatitis C viral infection, especially in people born during 1945-1965," Dr. Mishra said in an interview. Many of these people don’t know they are infected, and it usually takes decades for them to develop HCC.

The second big factor is the rising prevalence of obesity and type 2 diabetes. "Hepatitis C infections are now falling, so perhaps the rise in new HCC cases will eventually peak, but not if other factors like obesity and type 2 diabetes continue to push it up," she said.

"What is driving a lot of the increase is hepatitis C virus, and the high prevalence of hepatitis B virus in foreign-born Asians," said Dr. Davila, a clinical epidemiologist at the Houston VA Medical Center and Baylor College of Medicine in Houston.

"A lot also has to do with obesity and type 2 diabetes and their association with non-alcoholic fatty liver disease, especially in middle-aged, Hispanic women. I think we’ll see the greatest increase in HCC in women during the next 2 decades," Dr. Davila said. She also predicted increasing numbers of hepatitis C virus-driven HCC cases in the short term "as the [infected] cohort ages, increasing numbers will develop advanced fibrosis and eventually HCC," she said.

Dr. Davila’s study used data from SEER, which the National Cancer Institute began in 1973 to collect data on cancer cases from about 14% of the U.S. population in selected states and metropolitan areas. During 1975-2007, SEER tallied a total of 21,472 HCC cases, about 80% of which occurred in people aged 50-79 years, and about three-quarters of cases in men.

HCC incidence rose from 1.6 cases per 100,000 people during 1975-1977 to 4.8 per 100,000 in 2005-2007. Roughly a tripling of cases during the three decades occurred in both men and in women. The greatest increase occurred among people aged 50-59 years, which jumped nearly fivefold, from 2.6 per 100,000 in 1975-1977 to 12.6 per 100,000 in 2005-2007. The smallest rise was 2.4-fold among people aged 70-79 years.

By 2005-2007, the highest rate was among Asians, 10.3 per 100,000, followed by 8.2 per 100,000 in Hispanics, 7.5 per 100,000 in blacks, and 3.7/100,000 in whites (see table).

Dr. Mishra’s study used data collected in NIS by the federal Agency for Healthcare Research and Quality from about 1,000 hospitals in 44 states. The number of patients hospitalized with HCC (not confined to incident cases) rose from 9,537 in 2005 to 13,689 in 2009. During the 5-year period, in-hospital mortality of HCC cases dropped from 120 per 1,000 cases in 2005 to 95 per 1,000 cases in 2009, and the median length of stay fell by about 0.5 days.

Despite reduced hospitalized time, median hospital charges for each HCC hospitalized case rose from about $21,000 in 2005 to nearly $29,000 in 2009. Paralleling this increase was an uptick in the percent of cases having "major" or "extreme" illness, from 52% in 2005 to 63% in 2009, and the average number of comorbidities also rose steadily during the 5 years studied.

Hospitalized patients with HCC "are getting sicker, more complicated, and have more comorbidities," Dr. Mishra said. She also noted that the rate of liver transplants remained "very low" during the period studied.

Dr. Davila and Dr. Mishra reported having no conflicts of interest.

SAN DIEGO – Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a study has shown.

The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar.

"In fact, it seems the opposite may be true," said Dr. Kumar of Brigham and Women’s Hospital, Boston, referring to the results of her retrospective study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.

The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.

They identified all patients with biopsy-proven cirrhosis who had taken statins for a minimum of 3 months for treatment of dyslipidemia. A control population of cirrhosis patients not on statins was matched 2:1 for age, gender, and Child-Pugh class from the Partners HealthCare System Research Patient Data Registry, which includes demographic and diagnostic information on patients treated at Massachusetts General Hospital and Brigham and Women’s Hospital.

The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice (bilirubin greater than 2.5 mg/dL), hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome, Dr. Kumar explained.

The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and they used conditional logistic regression to assess mortality, she said.

Of 243 cirrhosis patients included in the analysis, 81 were statin users and 162 were matched controls. "In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C, and the MELD [Model for End-Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups," Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.62%) in the control group.

The control patients were followed for a mean of 1,503 days, and on Cox analysis, "statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46." Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients.

Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar. Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36, while coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.

There were no statistically significant differences in cause of death between the two groups, "however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver-related or cardiovascular causes than patients in the control group," said Dr. Kumar.

The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.

The retrospective design of the study limits the conclusions that can be taken from it. Specifically, "we can’t say that all patients with liver disease should be prescribed statins," Dr. Kumar said. "What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients." The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed.

Dr. Kumar disclosed no relevant financial conflicts of interest.

SAN DIEGO – Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a study has shown.

The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar.

"In fact, it seems the opposite may be true," said Dr. Kumar of Brigham and Women’s Hospital, Boston, referring to the results of her retrospective study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.

The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.

They identified all patients with biopsy-proven cirrhosis who had taken statins for a minimum of 3 months for treatment of dyslipidemia. A control population of cirrhosis patients not on statins was matched 2:1 for age, gender, and Child-Pugh class from the Partners HealthCare System Research Patient Data Registry, which includes demographic and diagnostic information on patients treated at Massachusetts General Hospital and Brigham and Women’s Hospital.

The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice (bilirubin greater than 2.5 mg/dL), hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome, Dr. Kumar explained.

The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and they used conditional logistic regression to assess mortality, she said.

Of 243 cirrhosis patients included in the analysis, 81 were statin users and 162 were matched controls. "In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C, and the MELD [Model for End-Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups," Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.62%) in the control group.

The control patients were followed for a mean of 1,503 days, and on Cox analysis, "statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46." Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients.

Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar. Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36, while coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.

There were no statistically significant differences in cause of death between the two groups, "however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver-related or cardiovascular causes than patients in the control group," said Dr. Kumar.

The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.

The retrospective design of the study limits the conclusions that can be taken from it. Specifically, "we can’t say that all patients with liver disease should be prescribed statins," Dr. Kumar said. "What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients." The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed.

Dr. Kumar disclosed no relevant financial conflicts of interest.

SAN DIEGO – Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a study has shown.

The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar.

"In fact, it seems the opposite may be true," said Dr. Kumar of Brigham and Women’s Hospital, Boston, referring to the results of her retrospective study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.

The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.

They identified all patients with biopsy-proven cirrhosis who had taken statins for a minimum of 3 months for treatment of dyslipidemia. A control population of cirrhosis patients not on statins was matched 2:1 for age, gender, and Child-Pugh class from the Partners HealthCare System Research Patient Data Registry, which includes demographic and diagnostic information on patients treated at Massachusetts General Hospital and Brigham and Women’s Hospital.

The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice (bilirubin greater than 2.5 mg/dL), hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome, Dr. Kumar explained.

The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and they used conditional logistic regression to assess mortality, she said.

Of 243 cirrhosis patients included in the analysis, 81 were statin users and 162 were matched controls. "In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C, and the MELD [Model for End-Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups," Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.62%) in the control group.

The control patients were followed for a mean of 1,503 days, and on Cox analysis, "statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46." Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients.

Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar. Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36, while coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.

There were no statistically significant differences in cause of death between the two groups, "however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver-related or cardiovascular causes than patients in the control group," said Dr. Kumar.

The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.

The retrospective design of the study limits the conclusions that can be taken from it. Specifically, "we can’t say that all patients with liver disease should be prescribed statins," Dr. Kumar said. "What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients." The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed.

Dr. Kumar disclosed no relevant financial conflicts of interest.