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Study identifies changing trends in PBC incidence, mortality
A new study has identified a higher mortality rate among males with primary biliary cholangitis (PBC) and a lower sex ratio in disease prevalence than previously thought, according to findings published online in the journal Scientific Reports.
Investigators analyzed inpatient data from 2000 to 2009 for PBC patients in Denmark and in the Italian province of Lombardia. In the Lombardia cohort, 2,970 PBC patients were identified, with a female to male ratio of 2.3:1. In the Denmark population, 722 cases were identified, with a female to male ratio of 4.2:1, reported Dr. Ana Lleo from the Humanitas Clinical and Research Center in Rozzano, Italy, and her coauthors.
Among the Lombardia patients, survival at 1, 5, and 10 years was significantly higher for females (89%, 95% confidence interval, 88%-91%; 77%, 95% CI, 75%-78%; and 67%, 95% CI, 65%-70%, respectively) than for males (78%, 95% CI, 75%-80%; 55%, 95% CI, 52%-59%; and 47%, 95% CI, 43%-51%, respectively). Findings were similar in the Denmark cohort, with female patients having higher survival rates (survival at 1, 5, and 10 years of 90%, 87%-92%; 73%, 95% CI, 69%-77%; and 60%, 95% CI, 53%-67%, respectively) than males (72%, 95% CI, 63%-79%; 42%, 95% CI, 32%-51%; and 27%, 95% CI, 14%-43%, respectively), the authors reported.
The study findings question long-held beliefs on PBC, the authors said. Hepatologists should be aware that “male PBC patients have higher mortality than [do] their female counterparts, such that close clinical follow-up and checking adherence to therapy are strongly recommended,” Dr. Lleu and colleagues concluded.
Read the full article in Scientific Reports: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872151.
A new study has identified a higher mortality rate among males with primary biliary cholangitis (PBC) and a lower sex ratio in disease prevalence than previously thought, according to findings published online in the journal Scientific Reports.
Investigators analyzed inpatient data from 2000 to 2009 for PBC patients in Denmark and in the Italian province of Lombardia. In the Lombardia cohort, 2,970 PBC patients were identified, with a female to male ratio of 2.3:1. In the Denmark population, 722 cases were identified, with a female to male ratio of 4.2:1, reported Dr. Ana Lleo from the Humanitas Clinical and Research Center in Rozzano, Italy, and her coauthors.
Among the Lombardia patients, survival at 1, 5, and 10 years was significantly higher for females (89%, 95% confidence interval, 88%-91%; 77%, 95% CI, 75%-78%; and 67%, 95% CI, 65%-70%, respectively) than for males (78%, 95% CI, 75%-80%; 55%, 95% CI, 52%-59%; and 47%, 95% CI, 43%-51%, respectively). Findings were similar in the Denmark cohort, with female patients having higher survival rates (survival at 1, 5, and 10 years of 90%, 87%-92%; 73%, 95% CI, 69%-77%; and 60%, 95% CI, 53%-67%, respectively) than males (72%, 95% CI, 63%-79%; 42%, 95% CI, 32%-51%; and 27%, 95% CI, 14%-43%, respectively), the authors reported.
The study findings question long-held beliefs on PBC, the authors said. Hepatologists should be aware that “male PBC patients have higher mortality than [do] their female counterparts, such that close clinical follow-up and checking adherence to therapy are strongly recommended,” Dr. Lleu and colleagues concluded.
Read the full article in Scientific Reports: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872151.
A new study has identified a higher mortality rate among males with primary biliary cholangitis (PBC) and a lower sex ratio in disease prevalence than previously thought, according to findings published online in the journal Scientific Reports.
Investigators analyzed inpatient data from 2000 to 2009 for PBC patients in Denmark and in the Italian province of Lombardia. In the Lombardia cohort, 2,970 PBC patients were identified, with a female to male ratio of 2.3:1. In the Denmark population, 722 cases were identified, with a female to male ratio of 4.2:1, reported Dr. Ana Lleo from the Humanitas Clinical and Research Center in Rozzano, Italy, and her coauthors.
Among the Lombardia patients, survival at 1, 5, and 10 years was significantly higher for females (89%, 95% confidence interval, 88%-91%; 77%, 95% CI, 75%-78%; and 67%, 95% CI, 65%-70%, respectively) than for males (78%, 95% CI, 75%-80%; 55%, 95% CI, 52%-59%; and 47%, 95% CI, 43%-51%, respectively). Findings were similar in the Denmark cohort, with female patients having higher survival rates (survival at 1, 5, and 10 years of 90%, 87%-92%; 73%, 95% CI, 69%-77%; and 60%, 95% CI, 53%-67%, respectively) than males (72%, 95% CI, 63%-79%; 42%, 95% CI, 32%-51%; and 27%, 95% CI, 14%-43%, respectively), the authors reported.
The study findings question long-held beliefs on PBC, the authors said. Hepatologists should be aware that “male PBC patients have higher mortality than [do] their female counterparts, such that close clinical follow-up and checking adherence to therapy are strongly recommended,” Dr. Lleu and colleagues concluded.
Read the full article in Scientific Reports: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872151.
FROM SCIENTIFIC REPORTS
New HCV test approach could cut costs, streamline diagnosis
Substituting a less-expensive hepatitis C core antigen test into the standard two-step process for diagnosing active hepatitis C virus (HCV) infection could streamline and cut the cost of HCV detection.
The standard two-step approach – detection of HCV antibodies followed by nucleic acid testing (NAT) as a marker for HCV viremia – may be improved by replacing NAT with the HCV core antigen (HCVcAg) test, according to the results of a study published in Annals of Internal Medicine.
Dr. J. Morgan Freiman, of the Boston Medical Center, and her colleagues conducted a systematic literature review to identify 44 case-control, cross-sectional, cohort, or randomized trials that compared any of five HCVcAg screening tests with a NAT reference standard.
The investigators performed a meta-analysis to assess the sensitivity (proportion of samples with a positive NAT and HCVcAg) and specificity (proportion of samples with a negative NAT and HCVcAg) associated with the five HCVcAg tests, as well as how they correlated with NAT-derived HCV RNA levels greater than 3,000 IU/mL.
The two best-performing HCVcAg tests of the five assessed were the Abbott ARCHITECT HCV Ag and the Ortho HCV Ag ELISA, based on their sensitivity (93.4%and 93.2%, respectively), specificity (98.8% and 99.2%, respectively), and positive (80.6 and 116.5, respectively) and negative (0.06 and 0.06, respectively) likelihood ratios.
Although limited data were available, the results of three quantitative studies showed that Abbott ARCHITECT HCVcAg was well correlated with HCV RNA levels greater than 3,000 IU/mL.
“This systematic review concludes that a well-performing HCVcAg test can achieve similar diagnostic accuracy to NAT for identification of active HCV infection when the viral load exceeds 3,000 IU/mL,” Dr. Freiman and her colleagues noted.
HCVcAg testing should be researched further as a potentially viable and less-expensive alternative to NAT, the investigators said, with the goal of simplifying detection at the point of care and increasing the rate of patient diagnosis (Ann Intern Med. 2016 Jun 21; doi: 10.7326/M16-0065).
The National Institutes of Health funded the study. Dr. White disclosed grant support from the funding source. Dr. Ongarello and Dr. Denkinger reported relationships with the Foundation for Innovative New Diagnostics. No additional authors reported conflicts of interest.
Substituting a less-expensive hepatitis C core antigen test into the standard two-step process for diagnosing active hepatitis C virus (HCV) infection could streamline and cut the cost of HCV detection.
The standard two-step approach – detection of HCV antibodies followed by nucleic acid testing (NAT) as a marker for HCV viremia – may be improved by replacing NAT with the HCV core antigen (HCVcAg) test, according to the results of a study published in Annals of Internal Medicine.
Dr. J. Morgan Freiman, of the Boston Medical Center, and her colleagues conducted a systematic literature review to identify 44 case-control, cross-sectional, cohort, or randomized trials that compared any of five HCVcAg screening tests with a NAT reference standard.
The investigators performed a meta-analysis to assess the sensitivity (proportion of samples with a positive NAT and HCVcAg) and specificity (proportion of samples with a negative NAT and HCVcAg) associated with the five HCVcAg tests, as well as how they correlated with NAT-derived HCV RNA levels greater than 3,000 IU/mL.
The two best-performing HCVcAg tests of the five assessed were the Abbott ARCHITECT HCV Ag and the Ortho HCV Ag ELISA, based on their sensitivity (93.4%and 93.2%, respectively), specificity (98.8% and 99.2%, respectively), and positive (80.6 and 116.5, respectively) and negative (0.06 and 0.06, respectively) likelihood ratios.
Although limited data were available, the results of three quantitative studies showed that Abbott ARCHITECT HCVcAg was well correlated with HCV RNA levels greater than 3,000 IU/mL.
“This systematic review concludes that a well-performing HCVcAg test can achieve similar diagnostic accuracy to NAT for identification of active HCV infection when the viral load exceeds 3,000 IU/mL,” Dr. Freiman and her colleagues noted.
HCVcAg testing should be researched further as a potentially viable and less-expensive alternative to NAT, the investigators said, with the goal of simplifying detection at the point of care and increasing the rate of patient diagnosis (Ann Intern Med. 2016 Jun 21; doi: 10.7326/M16-0065).
The National Institutes of Health funded the study. Dr. White disclosed grant support from the funding source. Dr. Ongarello and Dr. Denkinger reported relationships with the Foundation for Innovative New Diagnostics. No additional authors reported conflicts of interest.
Substituting a less-expensive hepatitis C core antigen test into the standard two-step process for diagnosing active hepatitis C virus (HCV) infection could streamline and cut the cost of HCV detection.
The standard two-step approach – detection of HCV antibodies followed by nucleic acid testing (NAT) as a marker for HCV viremia – may be improved by replacing NAT with the HCV core antigen (HCVcAg) test, according to the results of a study published in Annals of Internal Medicine.
Dr. J. Morgan Freiman, of the Boston Medical Center, and her colleagues conducted a systematic literature review to identify 44 case-control, cross-sectional, cohort, or randomized trials that compared any of five HCVcAg screening tests with a NAT reference standard.
The investigators performed a meta-analysis to assess the sensitivity (proportion of samples with a positive NAT and HCVcAg) and specificity (proportion of samples with a negative NAT and HCVcAg) associated with the five HCVcAg tests, as well as how they correlated with NAT-derived HCV RNA levels greater than 3,000 IU/mL.
The two best-performing HCVcAg tests of the five assessed were the Abbott ARCHITECT HCV Ag and the Ortho HCV Ag ELISA, based on their sensitivity (93.4%and 93.2%, respectively), specificity (98.8% and 99.2%, respectively), and positive (80.6 and 116.5, respectively) and negative (0.06 and 0.06, respectively) likelihood ratios.
Although limited data were available, the results of three quantitative studies showed that Abbott ARCHITECT HCVcAg was well correlated with HCV RNA levels greater than 3,000 IU/mL.
“This systematic review concludes that a well-performing HCVcAg test can achieve similar diagnostic accuracy to NAT for identification of active HCV infection when the viral load exceeds 3,000 IU/mL,” Dr. Freiman and her colleagues noted.
HCVcAg testing should be researched further as a potentially viable and less-expensive alternative to NAT, the investigators said, with the goal of simplifying detection at the point of care and increasing the rate of patient diagnosis (Ann Intern Med. 2016 Jun 21; doi: 10.7326/M16-0065).
The National Institutes of Health funded the study. Dr. White disclosed grant support from the funding source. Dr. Ongarello and Dr. Denkinger reported relationships with the Foundation for Innovative New Diagnostics. No additional authors reported conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: The diagnostic rate of chronic hepatitis C virus may be increased by point of care hepatitis C virus core antigen assessment.
Major finding: For patients with chronic HCV infection and viral loads exceeding 3,000 IU/mL, an HCVcAg screen performed as well as nucleic acid testing.
Data sources: Case-control, cross-sectional, cohort, or randomized trials that compared any of five HCVcAg tests with a NAT reference standard.
Disclosures: The National Institutes of Health funded the study. Dr. White disclosed grant support from the funding source. Dr. Ongarello and Dr. Denkinger reported relationships with the Foundation for Innovative New Diagnostics. No additional authors reported conflicts of interest.
HCV patients had distinct mucosal microbiome
SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.
The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.
Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.
“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”
Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.
Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).
“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.
“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”
The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.
SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.
The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.
Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.
“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”
Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.
Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).
“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.
“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”
The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.
SAN DIEGO – Patients with hepatitis C virus (HCV) infections had distinct duodenal mucosal microbiomes and greater intestinal permeability, compared with healthy controls and patients with other chronic liver diseases, Dr. Ashok Raj reported.
The findings might one day lead to therapies that aim to restore or normalize the microbiomes of patients with HCV, Dr. Raj said in an interview at the annual Digestive Disease Week.
Chronic liver disease (CLD) has been linked to dysbiosis, or abnormal shifts of the microbiome. But most studies have focused on fecal specimens, and “recent evidence suggests that the mucosal microbiota differ from fecal microbiota,” said Dr. Raj, a gastroenterologist and hepatologist at Princess Alexandra Hospital in Brisbane, Australia, and a PhD candidate at the University of Queensland at Brisbane.
“The small-intestinal mucosal microbiota are of particular interest to us,” Dr. Raj explained. “Anatomically, all the blood from this region of the gut drains into the portal vein and flows directly to the liver. Because of small-intestinal permeability, either bacteria or their products could travel to the liver and contribute to disease. But very little is known about this microbiota in CLD.”
Therefore, Dr. Raj and his associates sequenced bacterial DNA from mucosal biopsies of the second part of the duodenum from 38 prospectively recruited endoscopy patients with CLD and 13 healthy controls. The researchers also evaluated dietary habits, intestinal permeability, hepatic stiffness based on transient elastography, and the presence of metabolic syndrome, as measured by the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 Consensus criteria. The CLD group included 28 men and 10 women aged 36-82 years, including 16 patients with HCV, 10 patients with nonalcoholic fatty liver disease, 7 patients with fatty liver disease, 3 patients with autoimmune hepatitis, and 2 patients with hepatitis B virus infection. The controls were between 24 and 73 years old, and 70% were women.
Sequencing of bacteria DNA revealed significant differences between patients and controls, particularly among patients with HCV, Dr. Raj said. The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of CLD (P less than .01 for both comparisons). Furthermore, HCV patients had significantly greater small-intestinal permeability (mean ± SD log lactulose to rhamnose ratio, 1.57 ± 0.27) than controls (1.21 ± 0.25; P less than .01) or patients with other CLDs (1.24 ± 0.39; P = .01).
“Additionally, for the HCV patients, dietary fat intake showed a moderately strong positive correlation with intestinal permeability,” Dr. Raj said (r = 0.58; P = .03). “These findings are in keeping with animal models, which have shown that dietary fat can change the microbiota and also increase intestinal permeability.” However, the multivariate analysis found no links between microbial characteristics and hepatic stiffness or metabolic syndrome – perhaps because most patients were “at the cirrhotic end of the spectrum, reflecting their indication for endoscopy,” or because “these relationships are subtler and require larger sample numbers,” he said.
“Patients with HCV may have a unique small-intestinal microbiome,” Dr. Raj concluded. “These patients had higher intestinal permeability, and it is possible that the microbiota have a part to play in that.” Exactly how microbiota and gut permeability contribute to disease remains unclear, but pathology in the small intestine could help explain some features of the HCV trajectory, such as extrahepatic manifestations or variations in disease progression, he added. “Future studies may lead to targeting the small-intestinal gut microbiome to modulate and even treat HCV.”
The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.
AT DDW® 2016
Key clinical point: Patients with hepatitis C virus infection had unique mucosal microbiomes, compared with controls or patients with other chronic liver diseases.
Major finding: The HCV patients not only had significantly less microbial diversity (P less than .02), but the overall changes in their microbiota were significant enough for them to cluster separately from controls and from patients with other types of chronic liver disease (P less than .01 for both comparisons).
Data source: Bacterial DNA sequencing of duodenal mucosal biopsies from 38 patients with chronic liver diseases and 10 controls.
Disclosures: The study was funded by a postgraduate award from the government of Australia and by the Princess Alexandra Hospital Research Foundation. Dr. Raj had no disclosures.
HCV regimen found safe, effective in patients with severe renal disease
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
A 12-week regimen achieved sustained viral response for 90% of patients with genotype 1 hepatitis C virus (HCV) infection and stage 4 or 5 chronic kidney disease (CKD), researchers reported in the April issue of Gastroenterology.
“The regimen is well tolerated, though ribavirin use may require a reduction or interruption to manage anemia,” said Dr. Paul Pockros at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates. The second phase of the study will evaluate the regimen in treatment-experienced CKD patients and those with compensated cirrhosis, they said.
The regimen contained ombitasvir, paritaprevir, ritonavir, and dasabuvir.
Between 8% and 44% of hemodialysis patients are HCV positive, and CKD is known to heighten the risk of HCV-associated cirrhosis, hepatocellular carcinoma, and liver-related death, the researchers noted. While sofosbuvir is cleared renally, ombitasvir, paritaprevir, ritonavir, and dasabuvir undergo hepatic metabolism and needed no dose adjustment in phase I studies of patients with mild, moderate, or severe renal impairment. To further investigate the safety and efficacy of these direct-acting antivirals in patients with severe kidney disease, the researchers performed a single-arm, open-label, multicenter study of 20 treatment-naive, noncirrhotic, HCV-infected adults with stage 4 CKD (estimated glomerular filtration rate, 15-30 mL/min per 1.73 m2) or stage 5 (eGFR, less than 15 mL/min per 1.73 m2 or requiring hemodialysis). Patients received once-daily ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) plus dasabuvir (250 mg) for 12 weeks. The 13 patients with genotype 1a infections also received once-daily ribavirin (200 mg). Most patients were black men with stage 5 CKD, and 14 were on hemodialysis, the researchers said (Gastroenterology. 2016 Apr 16. doi: 10.1053/j.gastro.2016.02.078).
All 20 patients completed treatment, and 18 (90%) achieved sustained viral response (SVR) at posttreatment week 12 (SVR12; 95% confidence interval, 70%-97%). No patients developed hepatic decompensation, the researchers said. The most common adverse effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%). Anemia developed only in patients receiving ribavirin and was more pronounced than in phase III studies of this regimen, the researchers said. Hemoglobin levels dropped an average of 1.38 plus or minus 1.54 g/dL among patients who received ribavirin, compared with 0.02 plus or minus 0.9 g/dL among patients who did not receive ribavirin. There was one case of grade 3 anemia related to incorrect dosing of ribavirin; the lowest measured hemoglobin level was 7.0 g/dL, which improved to more than 10 g/dL after stopping ribavirin and starting erythropoietin treatment. This patient also achieved SVR12. The other eight patients who developed anemia also stopped ribavirin, although three were able to resume it after their hemoglobin levels improved.
Of the two patients who did not achieve SVR12, one relapsed 4 weeks after treatment, and one died of cardiac arrest 14 days after treatment. The patient who died had a history of hypertension; his hemoglobin level was stable (9-11 g/dL) during the last 6 weeks of treatment, and was 10 g/dL at admission, suggesting that ribavirin-induced anemia did not cause the cardiac event, the investigators said.
“The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with DAA [direct-acting antiviral] therapy but who may not yet have seen sufficient data to initiate DAA therapy in patients with ESRD [end-stage renal disease],” the researchers concluded. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent the end-stage sequelae of HCV. How treatment of HCV infection affects early or intermediate stages of CKD and how achievement of SVR impacts strategies for kidney transplantation in patients with ESRD require more study.”
AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
FROM GASTROENTEROLOGY
Key clinical point: Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir cured 90% of patients with hepatitis C virus infection and severe or end-stage renal disease.
Major finding: The rate of SVR12 was 90% (95% CI, 70%-97%).
Data source: A single-arm, open-label, multicenter trial of 20 noncirrhotic genotype 1 HCV-infected adults with stage 4 or 5 chronic kidney disease.
Disclosures: AbbVie makes the regimen and sponsored the study. Dr. Pockros and six coinvestigators disclosed financial relationships with AbbVie and numerous other pharmaceutical companies. Seven coinvestigators reported being employed by AbbVie.
Race predicts poor outcomes in people with liver cancer
Black patients with hepatocellular carcinoma (HCC) have shorter survival and more adverse clinical features at diagnosis than do non-Hispanic whites and other races, according to a single-center review.
Blacks were at a 33% increased risk of death because of HCC, compared with non-Hispanic whites, and were diagnosed at a later stage with larger tumors. Thus, they were less likely to be eligible for curative transplantation, said Dr. Patricia D. Jones of the University of Miami, who presented her findings during a teleconference in advance of the annual Digestive Disease Week.
“We found that race was the strongest predictor of survival in a diverse sample of patients diagnosed with HCC,” said lead author Dr. Jones, who is also on the staff of the Sylvester Comprehensive Cancer Center at the university.
“Most research on racial disparity in medical illness comes from large retrospective databases such as SEER [Surveillance, Epidemiology, and End Results], which represents 28% of the U.S. population. Florida is excluded from the SEER database, but Florida has a diversity of patients as well as a diversity of practitioners. More than 50% of our study sample was born outside of the U.S.,” Dr. Jones explained.
The study included 999 patients diagnosed with HCC at the University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospitals between 2005 and 2014.
Based on a review of patient records, median survival following a diagnosis of HCC was 301 days for black patients, compared with 534 days for non-Hispanic whites and 437 days for Hispanics.
An analysis showed that median tumor size in blacks was 5.2 cm, compared with 3.9 cm in whites. “This seems like a small difference, but tumor size greater than 5 cm excludes a patient from transplantation, which is curative,” she said. “Larger tumor size also suggests inadequate screening and lack of access to medical care.”
After adjustment for factors such as alcohol use, tobacco use, insurance, and age at diagnosis, non-Hispanic whites had a 25% reduced risk of death and Hispanics, a 21% reduced risk of death, compared with black patients. Black patients were also significantly more likely to have hepatitis B virus (HBV), compared with non-Hispanic whites (24.1% vs. 7%, respectively; P less than .01), which increases the risk of developing HCC.
“Hepatitis B virus can be prevented by vaccination. This may be an underlying issue in this population,” according to Dr. Jones.
Patients who were eligible for and went on to have a liver transplant had a 66% reduction in death, compared with those who did not. Only 11.9% of black patients had a liver transplant, compared with 33.3% of non-Hispanic whites. When adjusted for transplant, the survival gap between races was narrowed. Among transplant recipients, non-Hispanic whites had an 8% reduction in risk of death and Hispanics, a 7% reduction, compared with blacks.
Dr. Jones and her coinvestigators plan to conduct further research to explore risk factors for HCC among their diverse patient population and identify opportunities to maximize education and screening.
One limitation of this study, she said, is that some information may be missing in studies based on records, and the severity of underlying liver disease was not known.
“Because this is a single-center study, we have the ability to go back and get more detailed information to understand racial disparities. For example, we can continue to review the charts of these patients to determine medical conditions and comorbidities,” she said. “So far, the factors that have emerged are socioeconomic, related to access to care and insurance.”
Dr. Jones had no relevant financial disclosures.
Black patients with hepatocellular carcinoma (HCC) have shorter survival and more adverse clinical features at diagnosis than do non-Hispanic whites and other races, according to a single-center review.
Blacks were at a 33% increased risk of death because of HCC, compared with non-Hispanic whites, and were diagnosed at a later stage with larger tumors. Thus, they were less likely to be eligible for curative transplantation, said Dr. Patricia D. Jones of the University of Miami, who presented her findings during a teleconference in advance of the annual Digestive Disease Week.
“We found that race was the strongest predictor of survival in a diverse sample of patients diagnosed with HCC,” said lead author Dr. Jones, who is also on the staff of the Sylvester Comprehensive Cancer Center at the university.
“Most research on racial disparity in medical illness comes from large retrospective databases such as SEER [Surveillance, Epidemiology, and End Results], which represents 28% of the U.S. population. Florida is excluded from the SEER database, but Florida has a diversity of patients as well as a diversity of practitioners. More than 50% of our study sample was born outside of the U.S.,” Dr. Jones explained.
The study included 999 patients diagnosed with HCC at the University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospitals between 2005 and 2014.
Based on a review of patient records, median survival following a diagnosis of HCC was 301 days for black patients, compared with 534 days for non-Hispanic whites and 437 days for Hispanics.
An analysis showed that median tumor size in blacks was 5.2 cm, compared with 3.9 cm in whites. “This seems like a small difference, but tumor size greater than 5 cm excludes a patient from transplantation, which is curative,” she said. “Larger tumor size also suggests inadequate screening and lack of access to medical care.”
After adjustment for factors such as alcohol use, tobacco use, insurance, and age at diagnosis, non-Hispanic whites had a 25% reduced risk of death and Hispanics, a 21% reduced risk of death, compared with black patients. Black patients were also significantly more likely to have hepatitis B virus (HBV), compared with non-Hispanic whites (24.1% vs. 7%, respectively; P less than .01), which increases the risk of developing HCC.
“Hepatitis B virus can be prevented by vaccination. This may be an underlying issue in this population,” according to Dr. Jones.
Patients who were eligible for and went on to have a liver transplant had a 66% reduction in death, compared with those who did not. Only 11.9% of black patients had a liver transplant, compared with 33.3% of non-Hispanic whites. When adjusted for transplant, the survival gap between races was narrowed. Among transplant recipients, non-Hispanic whites had an 8% reduction in risk of death and Hispanics, a 7% reduction, compared with blacks.
Dr. Jones and her coinvestigators plan to conduct further research to explore risk factors for HCC among their diverse patient population and identify opportunities to maximize education and screening.
One limitation of this study, she said, is that some information may be missing in studies based on records, and the severity of underlying liver disease was not known.
“Because this is a single-center study, we have the ability to go back and get more detailed information to understand racial disparities. For example, we can continue to review the charts of these patients to determine medical conditions and comorbidities,” she said. “So far, the factors that have emerged are socioeconomic, related to access to care and insurance.”
Dr. Jones had no relevant financial disclosures.
Black patients with hepatocellular carcinoma (HCC) have shorter survival and more adverse clinical features at diagnosis than do non-Hispanic whites and other races, according to a single-center review.
Blacks were at a 33% increased risk of death because of HCC, compared with non-Hispanic whites, and were diagnosed at a later stage with larger tumors. Thus, they were less likely to be eligible for curative transplantation, said Dr. Patricia D. Jones of the University of Miami, who presented her findings during a teleconference in advance of the annual Digestive Disease Week.
“We found that race was the strongest predictor of survival in a diverse sample of patients diagnosed with HCC,” said lead author Dr. Jones, who is also on the staff of the Sylvester Comprehensive Cancer Center at the university.
“Most research on racial disparity in medical illness comes from large retrospective databases such as SEER [Surveillance, Epidemiology, and End Results], which represents 28% of the U.S. population. Florida is excluded from the SEER database, but Florida has a diversity of patients as well as a diversity of practitioners. More than 50% of our study sample was born outside of the U.S.,” Dr. Jones explained.
The study included 999 patients diagnosed with HCC at the University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospitals between 2005 and 2014.
Based on a review of patient records, median survival following a diagnosis of HCC was 301 days for black patients, compared with 534 days for non-Hispanic whites and 437 days for Hispanics.
An analysis showed that median tumor size in blacks was 5.2 cm, compared with 3.9 cm in whites. “This seems like a small difference, but tumor size greater than 5 cm excludes a patient from transplantation, which is curative,” she said. “Larger tumor size also suggests inadequate screening and lack of access to medical care.”
After adjustment for factors such as alcohol use, tobacco use, insurance, and age at diagnosis, non-Hispanic whites had a 25% reduced risk of death and Hispanics, a 21% reduced risk of death, compared with black patients. Black patients were also significantly more likely to have hepatitis B virus (HBV), compared with non-Hispanic whites (24.1% vs. 7%, respectively; P less than .01), which increases the risk of developing HCC.
“Hepatitis B virus can be prevented by vaccination. This may be an underlying issue in this population,” according to Dr. Jones.
Patients who were eligible for and went on to have a liver transplant had a 66% reduction in death, compared with those who did not. Only 11.9% of black patients had a liver transplant, compared with 33.3% of non-Hispanic whites. When adjusted for transplant, the survival gap between races was narrowed. Among transplant recipients, non-Hispanic whites had an 8% reduction in risk of death and Hispanics, a 7% reduction, compared with blacks.
Dr. Jones and her coinvestigators plan to conduct further research to explore risk factors for HCC among their diverse patient population and identify opportunities to maximize education and screening.
One limitation of this study, she said, is that some information may be missing in studies based on records, and the severity of underlying liver disease was not known.
“Because this is a single-center study, we have the ability to go back and get more detailed information to understand racial disparities. For example, we can continue to review the charts of these patients to determine medical conditions and comorbidities,” she said. “So far, the factors that have emerged are socioeconomic, related to access to care and insurance.”
Dr. Jones had no relevant financial disclosures.
Key clinical point: Blacks with hepatocellular carcinoma have worse survival and more adverse clinical features than whites.
Major finding: Blacks were 33% more likely to die of hepatocellular carcinoma than were whites. Median survival from time of diagnosis was 301 days for blacks, compared with 534.5 days for non-Hispanic whites.
Data source: A retrospective analysis of 999 patients treated at a single center.
Disclosures: Dr. Jones had no relevant financial disclosures.
Tacrolimus worsens IBD post liver transplant for primary sclerosing cholangitis
SAN DIEGO – A retrospective study provides insight as to why some patients have a milder versus a more severe course of inflammatory bowel disease (IBD) after liver transplant for primary sclerosing cholangitis (PSC).
Recurrent PSC, prolonged use of steroids, and cancer development after liver transplant were associated with a milder course of IBD, but tacrolimus use was associated with increased IBD flare post transplant.
“The course of IBD is highly variable after liver transplant for PSC. PSC is associated with IBD in 60% to 90% of patients, and IBD worsens in about 30% of PSC-IBD patients after transplant. We wanted to explore the risk factors for worsening IBD in this setting,” Dr. Mohamad Mouchli of the Mayo Clinic in Rochester, Minn., explained at the annual Digestive Disease Week.
For purposes of this study, progression of IBD was defined as the need for escalation of medical therapy, compared with before liver transplant, or need for colectomy for medically refractory IBD.
The study population included patients with PSC-IBD who underwent liver transplant for noncholangiocarcinoma indications at the Mayo Clinic from 1998 to 2012. Patients were followed through February 2015.
The investigators screened 373 patients: After exclusions for cancer, no IBD at transplant, and pretransplant colectomy, 151 patients with an intact colon were left and formed the basis of further analysis.
Median age at transplant was 46 years and two-thirds of the patients were male. Transplant-related variables included the following: 23% experienced allograft failure, 36% had recurrent PSC, 25.2% had CMV infection, 19.2% were retransplanted, 22.5% developed cancer after liver transplant, and 52.3% had acute cellular rejection.
Before transplant, 69 patients had quiescent IBD with no therapy and 62 were maintained on 5-aminosalicylates. Post transplant, despite transplant-related immunosuppression, 56 patients (37.1%) required escalation of therapy, 87 patients (57.6%) had a stable course, and 8 patients (5.3%) improved.
Risk of IBD progression at 1, 5, and 10 years was 4%, 18.5%, and 25.5%, respectively. Thirty-five patients underwent colectomy after transplant: the 1-, 5-, and 10-year risks of colectomy were 2%, 9.3%, and 17.2%, respectively. Fourteen percent of patients required anti–tumor necrosis factor therapy after transplant.
On multivariate analysis, tacrolimus exposure emerged as a risk factor for progression of IBD. Tacrolimus immunosuppression was twice as likely as cyclosporine-based immunosuppression to lead to IBD progression. By contrast, recurrent PSC, use of steroids for longer than 6 months, and cancer development after liver transplant were protective of IBD progression.
No association was found between progression of IBD and transplant-related infection or mismatch, immunosuppression with mycophenolate or azathioprine, or IBD-related factors such as pretransplant IBD status or empirical initiation of 5-aminosalicylates within 4 months of liver transplant. During the question-and-answer session following his presentation, Dr. Mouchli was asked whether these results justify prophylactic colectomy. He said that could be considered in patients with active IBD before transplant, but on a case-by-case basis.
SAN DIEGO – A retrospective study provides insight as to why some patients have a milder versus a more severe course of inflammatory bowel disease (IBD) after liver transplant for primary sclerosing cholangitis (PSC).
Recurrent PSC, prolonged use of steroids, and cancer development after liver transplant were associated with a milder course of IBD, but tacrolimus use was associated with increased IBD flare post transplant.
“The course of IBD is highly variable after liver transplant for PSC. PSC is associated with IBD in 60% to 90% of patients, and IBD worsens in about 30% of PSC-IBD patients after transplant. We wanted to explore the risk factors for worsening IBD in this setting,” Dr. Mohamad Mouchli of the Mayo Clinic in Rochester, Minn., explained at the annual Digestive Disease Week.
For purposes of this study, progression of IBD was defined as the need for escalation of medical therapy, compared with before liver transplant, or need for colectomy for medically refractory IBD.
The study population included patients with PSC-IBD who underwent liver transplant for noncholangiocarcinoma indications at the Mayo Clinic from 1998 to 2012. Patients were followed through February 2015.
The investigators screened 373 patients: After exclusions for cancer, no IBD at transplant, and pretransplant colectomy, 151 patients with an intact colon were left and formed the basis of further analysis.
Median age at transplant was 46 years and two-thirds of the patients were male. Transplant-related variables included the following: 23% experienced allograft failure, 36% had recurrent PSC, 25.2% had CMV infection, 19.2% were retransplanted, 22.5% developed cancer after liver transplant, and 52.3% had acute cellular rejection.
Before transplant, 69 patients had quiescent IBD with no therapy and 62 were maintained on 5-aminosalicylates. Post transplant, despite transplant-related immunosuppression, 56 patients (37.1%) required escalation of therapy, 87 patients (57.6%) had a stable course, and 8 patients (5.3%) improved.
Risk of IBD progression at 1, 5, and 10 years was 4%, 18.5%, and 25.5%, respectively. Thirty-five patients underwent colectomy after transplant: the 1-, 5-, and 10-year risks of colectomy were 2%, 9.3%, and 17.2%, respectively. Fourteen percent of patients required anti–tumor necrosis factor therapy after transplant.
On multivariate analysis, tacrolimus exposure emerged as a risk factor for progression of IBD. Tacrolimus immunosuppression was twice as likely as cyclosporine-based immunosuppression to lead to IBD progression. By contrast, recurrent PSC, use of steroids for longer than 6 months, and cancer development after liver transplant were protective of IBD progression.
No association was found between progression of IBD and transplant-related infection or mismatch, immunosuppression with mycophenolate or azathioprine, or IBD-related factors such as pretransplant IBD status or empirical initiation of 5-aminosalicylates within 4 months of liver transplant. During the question-and-answer session following his presentation, Dr. Mouchli was asked whether these results justify prophylactic colectomy. He said that could be considered in patients with active IBD before transplant, but on a case-by-case basis.
SAN DIEGO – A retrospective study provides insight as to why some patients have a milder versus a more severe course of inflammatory bowel disease (IBD) after liver transplant for primary sclerosing cholangitis (PSC).
Recurrent PSC, prolonged use of steroids, and cancer development after liver transplant were associated with a milder course of IBD, but tacrolimus use was associated with increased IBD flare post transplant.
“The course of IBD is highly variable after liver transplant for PSC. PSC is associated with IBD in 60% to 90% of patients, and IBD worsens in about 30% of PSC-IBD patients after transplant. We wanted to explore the risk factors for worsening IBD in this setting,” Dr. Mohamad Mouchli of the Mayo Clinic in Rochester, Minn., explained at the annual Digestive Disease Week.
For purposes of this study, progression of IBD was defined as the need for escalation of medical therapy, compared with before liver transplant, or need for colectomy for medically refractory IBD.
The study population included patients with PSC-IBD who underwent liver transplant for noncholangiocarcinoma indications at the Mayo Clinic from 1998 to 2012. Patients were followed through February 2015.
The investigators screened 373 patients: After exclusions for cancer, no IBD at transplant, and pretransplant colectomy, 151 patients with an intact colon were left and formed the basis of further analysis.
Median age at transplant was 46 years and two-thirds of the patients were male. Transplant-related variables included the following: 23% experienced allograft failure, 36% had recurrent PSC, 25.2% had CMV infection, 19.2% were retransplanted, 22.5% developed cancer after liver transplant, and 52.3% had acute cellular rejection.
Before transplant, 69 patients had quiescent IBD with no therapy and 62 were maintained on 5-aminosalicylates. Post transplant, despite transplant-related immunosuppression, 56 patients (37.1%) required escalation of therapy, 87 patients (57.6%) had a stable course, and 8 patients (5.3%) improved.
Risk of IBD progression at 1, 5, and 10 years was 4%, 18.5%, and 25.5%, respectively. Thirty-five patients underwent colectomy after transplant: the 1-, 5-, and 10-year risks of colectomy were 2%, 9.3%, and 17.2%, respectively. Fourteen percent of patients required anti–tumor necrosis factor therapy after transplant.
On multivariate analysis, tacrolimus exposure emerged as a risk factor for progression of IBD. Tacrolimus immunosuppression was twice as likely as cyclosporine-based immunosuppression to lead to IBD progression. By contrast, recurrent PSC, use of steroids for longer than 6 months, and cancer development after liver transplant were protective of IBD progression.
No association was found between progression of IBD and transplant-related infection or mismatch, immunosuppression with mycophenolate or azathioprine, or IBD-related factors such as pretransplant IBD status or empirical initiation of 5-aminosalicylates within 4 months of liver transplant. During the question-and-answer session following his presentation, Dr. Mouchli was asked whether these results justify prophylactic colectomy. He said that could be considered in patients with active IBD before transplant, but on a case-by-case basis.
AT DDW® 2016
Key clinical point: Tacrolimus exposure was an independent risk factor for IBD progression after liver transplant in patients with PSC-IBD.
Major finding: Tacrolimus immunosuppression was twice as likely as cyclosporine-based immunosuppression to lead to worsening IBC post liver transplant.
Data source: Retrospective study of the natural history of IBD following liver transplant in 151 patients with PSC-IBD.
Disclosures: Dr. Mouchli had no financial disclosures to report.
Initiative dramatically raises HCV screening, treatment
A hepatitis C awareness initiative dramatically raised the rate of HCV screening and treatment in a large American Indian population – the ethnic group with the highest rate of HCV infection and HCV-related mortality in the United States, according to a report published May 13 in Morbidity and Mortality Weekly Report.
Cherokee Nation Health Services undertook the effort in 2012 to improve detection and management of HCV. It included a reminder in eligible patients’ electronic health records (EHRs) to offer screening; HCV education for primary care physicians and other health care providers; establishment of an HCV registry to monitor the clinical care of patients who initiated antiviral treatment; and outreach efforts by public health nurses to HCV patients, including home visits.
In 2014, an additional initiative was implemented to expand services for the rapidly increasing number of patients diagnosed as having HCV. This allowed a transition from having a single clinic staffed by only one caregiver with expertise in HCV management to five clinics staffed by three physicians, two nurse practitioners, and two pharmacists with HCV expertise, said Dr. Jorge Mera, director of infectious diseases, Cherokee Nation Health Services, Tulsa, Okla., and his associates.
An analysis of deidentified data in the HCV registry and EHRs showed that 92,012 patients aged 20 years and older had at least one visit with Cherokee Nation Health Services after the program was implemented, between October 2012 and July 2015. The proportion of this patient population that was tested for HCV antibodies rose fivefold, from 3.6% to 18.2% during the study period. A total of 715 patients were antibody positive, and 388 of them were found to have chronic HCV infection. Approximately 60% of these patients initiated antiviral treatment, and approximately 90% of them achieved a sustained virologic response and were essentially cured, Dr. Mera and his associates said (MMWR. 2016 May 13;65[18]:461-6).
The program included a component that particularly targeted baby boomers – patients born between 1945 and 1965 – for HCV screening. Across the Indian Health Service clinics in 34 states that adopted this component of the program, such screening increased fourfold in this high-risk population during the study period (MMWR. 2016 May 13;65[18]:467-9).
These efforts, the first of their kind in the United States, may help eliminate hepatitis C as a health disparity for American Indian/Alaska Native populations and also may serve as a model for other health care settings, the investigators added.
A hepatitis C awareness initiative dramatically raised the rate of HCV screening and treatment in a large American Indian population – the ethnic group with the highest rate of HCV infection and HCV-related mortality in the United States, according to a report published May 13 in Morbidity and Mortality Weekly Report.
Cherokee Nation Health Services undertook the effort in 2012 to improve detection and management of HCV. It included a reminder in eligible patients’ electronic health records (EHRs) to offer screening; HCV education for primary care physicians and other health care providers; establishment of an HCV registry to monitor the clinical care of patients who initiated antiviral treatment; and outreach efforts by public health nurses to HCV patients, including home visits.
In 2014, an additional initiative was implemented to expand services for the rapidly increasing number of patients diagnosed as having HCV. This allowed a transition from having a single clinic staffed by only one caregiver with expertise in HCV management to five clinics staffed by three physicians, two nurse practitioners, and two pharmacists with HCV expertise, said Dr. Jorge Mera, director of infectious diseases, Cherokee Nation Health Services, Tulsa, Okla., and his associates.
An analysis of deidentified data in the HCV registry and EHRs showed that 92,012 patients aged 20 years and older had at least one visit with Cherokee Nation Health Services after the program was implemented, between October 2012 and July 2015. The proportion of this patient population that was tested for HCV antibodies rose fivefold, from 3.6% to 18.2% during the study period. A total of 715 patients were antibody positive, and 388 of them were found to have chronic HCV infection. Approximately 60% of these patients initiated antiviral treatment, and approximately 90% of them achieved a sustained virologic response and were essentially cured, Dr. Mera and his associates said (MMWR. 2016 May 13;65[18]:461-6).
The program included a component that particularly targeted baby boomers – patients born between 1945 and 1965 – for HCV screening. Across the Indian Health Service clinics in 34 states that adopted this component of the program, such screening increased fourfold in this high-risk population during the study period (MMWR. 2016 May 13;65[18]:467-9).
These efforts, the first of their kind in the United States, may help eliminate hepatitis C as a health disparity for American Indian/Alaska Native populations and also may serve as a model for other health care settings, the investigators added.
A hepatitis C awareness initiative dramatically raised the rate of HCV screening and treatment in a large American Indian population – the ethnic group with the highest rate of HCV infection and HCV-related mortality in the United States, according to a report published May 13 in Morbidity and Mortality Weekly Report.
Cherokee Nation Health Services undertook the effort in 2012 to improve detection and management of HCV. It included a reminder in eligible patients’ electronic health records (EHRs) to offer screening; HCV education for primary care physicians and other health care providers; establishment of an HCV registry to monitor the clinical care of patients who initiated antiviral treatment; and outreach efforts by public health nurses to HCV patients, including home visits.
In 2014, an additional initiative was implemented to expand services for the rapidly increasing number of patients diagnosed as having HCV. This allowed a transition from having a single clinic staffed by only one caregiver with expertise in HCV management to five clinics staffed by three physicians, two nurse practitioners, and two pharmacists with HCV expertise, said Dr. Jorge Mera, director of infectious diseases, Cherokee Nation Health Services, Tulsa, Okla., and his associates.
An analysis of deidentified data in the HCV registry and EHRs showed that 92,012 patients aged 20 years and older had at least one visit with Cherokee Nation Health Services after the program was implemented, between October 2012 and July 2015. The proportion of this patient population that was tested for HCV antibodies rose fivefold, from 3.6% to 18.2% during the study period. A total of 715 patients were antibody positive, and 388 of them were found to have chronic HCV infection. Approximately 60% of these patients initiated antiviral treatment, and approximately 90% of them achieved a sustained virologic response and were essentially cured, Dr. Mera and his associates said (MMWR. 2016 May 13;65[18]:461-6).
The program included a component that particularly targeted baby boomers – patients born between 1945 and 1965 – for HCV screening. Across the Indian Health Service clinics in 34 states that adopted this component of the program, such screening increased fourfold in this high-risk population during the study period (MMWR. 2016 May 13;65[18]:467-9).
These efforts, the first of their kind in the United States, may help eliminate hepatitis C as a health disparity for American Indian/Alaska Native populations and also may serve as a model for other health care settings, the investigators added.
FROM MORBIDITY and MORTALITY WEEKLY REPORT
Key clinical point: A new program dramatically raised the rate of HCV screening and treatment in a large American Indian population – the ethnic group with the highest rate of HCV infection and HCV-related mortality in the United States.
Major finding: The proportion of adults tested for HCV antibodies rose fivefold, from 3.6% to 18.2%, during the study period.
Data source: An observational cohort study involving 92,012 adults who had at least 1 visit to Cherokee Nation Health Services between October 2012 and July 2015.
Disclosures: The sponsor of this study was not specified, and potential financial conflicts of interest were not provided. The authors were affiliated with Cherokee Nation Health Services, the U.S. Centers for Disease Control and Prevention, the University of Oklahoma Health Sciences Center, the Oklahoma City Veterans Affairs Medical Center, the Indian Health Service, and the Northwest Portland (Ore.) Area Indian Health Board.
FDA publishes draft guidance for developing HCV antivirals
The U.S. Food and Drug Administration has issued revised draft guidance intended to foster the development of direct-acting antiviral drugs to treat chronic hepatitis C virus infection.
The guidance, developed by the FDA’s Center for Drug Evaluation and Research, delineates the drug development process from the preinvestigational new drug application through the new drug application and postmarketing stages.
According to the FDA, the draft guidance, when finalized, will represent the current thinking of the agency on development of direct-acting antivirals and clinical trial designs, but is not binding on the FDA or the public. It explicitly states that industry may use an alternative approach to drug development if it “satisfies the requirements of the applicable statutes and regulations.” For the purposes of drug development, the FDA defines direct-acting HCV antivirals as drugs that “interfere with specific steps in the HCV replication cycle through a direct interaction with the HCV genome, polyprotein, or its polyprotein cleavage products.”
The guidance does not address the development of drugs that target host functions necessary for viral replication or immune-based drugs for the treatment of HCV infection, including new interferon drugs or therapeutics “without antiviral mechanisms intended to mitigate or reverse clinical or pathophysiological outcomes” of chronic HCV infection, such as prevention of hepatocellular carcinoma or reversal of fibrosis.
Once the draft guidance has been published in the Federal Register, the FDA will accept comments and suggestions at www.regulations.gov for 60 days.
On Twitter @richpizzi
The U.S. Food and Drug Administration has issued revised draft guidance intended to foster the development of direct-acting antiviral drugs to treat chronic hepatitis C virus infection.
The guidance, developed by the FDA’s Center for Drug Evaluation and Research, delineates the drug development process from the preinvestigational new drug application through the new drug application and postmarketing stages.
According to the FDA, the draft guidance, when finalized, will represent the current thinking of the agency on development of direct-acting antivirals and clinical trial designs, but is not binding on the FDA or the public. It explicitly states that industry may use an alternative approach to drug development if it “satisfies the requirements of the applicable statutes and regulations.” For the purposes of drug development, the FDA defines direct-acting HCV antivirals as drugs that “interfere with specific steps in the HCV replication cycle through a direct interaction with the HCV genome, polyprotein, or its polyprotein cleavage products.”
The guidance does not address the development of drugs that target host functions necessary for viral replication or immune-based drugs for the treatment of HCV infection, including new interferon drugs or therapeutics “without antiviral mechanisms intended to mitigate or reverse clinical or pathophysiological outcomes” of chronic HCV infection, such as prevention of hepatocellular carcinoma or reversal of fibrosis.
Once the draft guidance has been published in the Federal Register, the FDA will accept comments and suggestions at www.regulations.gov for 60 days.
On Twitter @richpizzi
The U.S. Food and Drug Administration has issued revised draft guidance intended to foster the development of direct-acting antiviral drugs to treat chronic hepatitis C virus infection.
The guidance, developed by the FDA’s Center for Drug Evaluation and Research, delineates the drug development process from the preinvestigational new drug application through the new drug application and postmarketing stages.
According to the FDA, the draft guidance, when finalized, will represent the current thinking of the agency on development of direct-acting antivirals and clinical trial designs, but is not binding on the FDA or the public. It explicitly states that industry may use an alternative approach to drug development if it “satisfies the requirements of the applicable statutes and regulations.” For the purposes of drug development, the FDA defines direct-acting HCV antivirals as drugs that “interfere with specific steps in the HCV replication cycle through a direct interaction with the HCV genome, polyprotein, or its polyprotein cleavage products.”
The guidance does not address the development of drugs that target host functions necessary for viral replication or immune-based drugs for the treatment of HCV infection, including new interferon drugs or therapeutics “without antiviral mechanisms intended to mitigate or reverse clinical or pathophysiological outcomes” of chronic HCV infection, such as prevention of hepatocellular carcinoma or reversal of fibrosis.
Once the draft guidance has been published in the Federal Register, the FDA will accept comments and suggestions at www.regulations.gov for 60 days.
On Twitter @richpizzi
Hepatitis Outlook: April 2016
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.
Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.
A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.
Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.
A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.
Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.
Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission.
A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.
A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.
New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.
Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.
Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.
Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.
As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.
A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.
Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.
Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.
A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.
A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.
A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.
Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.
A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.
Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.
A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.
Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.
Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission.
A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.
A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.
New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.
Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.
Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.
Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.
As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.
A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.
Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.
Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.
A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.
A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.
A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.
Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.
A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.
Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.
A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.
Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.
Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log10 IU/mL to interrupt mother-to-infant transmission.
A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.
A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.
New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.
Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.
Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.
Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.
As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.
A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.
Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.
Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.
A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.
A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.
A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.
On Twitter @richpizzi
Cirrhosis 30-day readmissions down 40% with quality improvement initiative
Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.
For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.
Source: American Gastroenterological Association
“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).
The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.
The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.
Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).
The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).
Dr. Tapper and his coauthors reported having no disclosures.
Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.
For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.
Source: American Gastroenterological Association
“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).
The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.
The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.
Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).
The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).
Dr. Tapper and his coauthors reported having no disclosures.
Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.
For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.
Source: American Gastroenterological Association
“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).
The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.
The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.
Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).
The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).
Dr. Tapper and his coauthors reported having no disclosures.
Key clinical point: Care protocols implemented by electronic decision support reduced 30-day readmissions of patients with cirrhosis by 40% in an inpatient liver unit.
Major finding: The drop was likely driven by fewer readmissions for hepatic encephalopathy (HE): the 30-day HE readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of quality improvement.
Data sources: The prospective study evaluated 824 patients who were admitted 1,720 times to the liver unit of Beth Israel Deaconess Medical Center, Boston.
Disclosures: Dr. Tapper and his coauthors reported having no disclosures.
