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Interferon-free HCV treatment can lead to herpesvirus reactivation, experts say
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Interferon-free direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection can cause reactivation of herpesvirus, said the authors of a multicenter case series published in the November issue of Clinical Gastroenterology and Hepatology.
Reactivation occurred in 10 of 576 (2%) patients treated at three hospitals in Spain, reported Dr. Christie Perello of Puerta de Hierro University Hospital in Madrid, together with her associates. Clinicians who treat HCV should maintain a high degree of clinical suspicion for latent herpesvirus infection, particularly when patients are older or have undergone liver transplantation, and should consider varicella zoster virus vaccination before beginning DAA therapy in nontransplant patients, they said.
In all, 2% of patients had herpesvirus reactivations a median of 8 weeks after starting an interferon-free DAA regimen. Seven patients had cirrhosis, three were liver transplant recipients, and all achieved a sustained viral response. Seven patients were receiving sofosbuvir with ledipasvir, either with or without ribavirin; two patients were receiving ombitasvir with paritaprevir and ritonavir plus dasabuvir, with or without ribavirin; and one patient was receiving sofosbuvir with simeprevir plus ribavirin. Median age was 67 years. Seven cases involved cutaneous herpes, two involved ocular herpes, and one was herpes labialis. Two patients developed postherpetic neuralgia requiring gabapentin or pregabalin therapy, and one developed keratouveitis that was treated with valacyclovir (1 g every 8 hours for 7 days). Two other patients also received valacyclovir, three received famciclovir, and the remaining four received acyclovir. When the study was published, one patient, a 68-year-old male with postherpetic neuralgia, had residual symptoms even after undergoing antiviral therapy and nerve ablation. This patient was a liver transplantee and therefore was immunosuppressed, but like the others, he only developed herpesvirus reactivation after starting DAA HCV treatment, the researcher said.
In contrast, there were no reactivations among historical controls during a median of 37 months of follow-up. “Even when a causal relationship is not definitive, based on the temporal association and recent experience we conclude that the incidence of herpesvirus reactivation may be increased among patients on interferon-free regimens,” the researchers concluded. “More research is necessary in this new field because unexpected events might be arising in patients treated with direct-acting antivirals.”
The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Key clinical point: Latent herpesvirus infection may reactivate with interferon-free direct-acting antiviral treatment for chronic hepatitis C virus infection.
Major finding: In all, 2% of recipients of these regimens had herpesvirus reactivation a median of 8 weeks after starting treatment. Historical controls had no documented reactivations.
Data source: A multicenter retrospective study of 576 HCV-infected patients treated with interferon-free DAA regimens and 230 historical matched controls.
Disclosures: The investigators did not report funding sources. Dr. Perello had no disclosures. Four coinvestigators reported ties to Gilead, Bristol-Myers Squibb, AbbVie, Merck Sharp & Dohme, and Janssen.
Selected liver-transplant patients thrive off immunosuppression
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – Three-fifths of pediatric liver-transplant recipients who were doing well enough to attempt weaning from their immunosuppression regimen succeeded in getting off immunosuppression and staying off for more than a year. In the process, they also significantly improved their health-related quality of life.
“Health-related quality of life domains associated with social interactions, worry, and medications improved” in pediatric liver recipients who had undergone immunosuppression withdrawal, Saeed Mohammad, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.
Patients who succeeded in staying off immunosuppressant drugs for at least 2 years after they first began ratcheting down their regimen showed better quality of life scores compared with their scores at baseline, and also compared with the scores of other pediatric liver transplant patients who unsuccessfully tried coming off immunosuppression.
Not every pediatric liver transplant patient should attempt withdrawing immunosuppression, cautioned Dr. Mohammad, a pediatric gastroenterologist at Northwestern University in Chicago. “To be successful withdrawal of immunosuppression needs to be in selected patients; not every patient is a good candidate.”
The Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH) study ran at 11 U.S. center and one center in Toronto during October 2012 through June 2014. Pediatric liver transplant recipients were eligible to start a 9-10 month graduated withdrawal from their immunosuppression regimen if they met several criteria of stability including no rejection episode over at least the prior 12 months, normal laboratory-test results, no autoimmune disease and no problems detected in a liver biopsy. The prospective study enrolled 88 patients who averaged 10 years old. Patients underwent comprehensive examinations and laboratory testing at baseline and again several times during the subsequent 2 years including assessment of several quality of life measures.
During follow-up, 35 of the 88 patients (40%) developed symptoms of rejection and had to go back on immunosuppression. Most of these patients developed their rejection symptoms early during immunosuppression weaning, but a few patients failed later including one patient who failed 22 months after starting immunosuppression withdrawal, Dr. Mohammad said. Researchers from the iWITH study first reported these results at the American Transplant Congress in June 2016.
The quality of life findings reported by Dr. Mohammad came from assessments at baseline, after 12 months, and after 24 months, and included 30 of the patients who resumed immunosuppression and 48 patients who remained off immunosuppression for 2 years. All of these 78 patients had relatively robust quality of life profiles at baseline. Their scores for both physical and social subscales as well as for total score were significantly superior to the average scores for a large number of primarily U.S. pediatric liver transplant patients in the SPLIT database. Dr. Mohammad called the patients who attempted immunosuppression discontinuation as the “creme de la creme” of pediatric liver transplant patients in terms of their clinical status.
Analysis of scores after 2 years compared with baseline showed statistically significant improvements among patients who stayed off immunosuppression for the domains of social function, treatment attitudes and compliance, communication, and worry. A comparison of changes in quality of life scores from baseline to 2 years showed that patients who stayed off immunosuppression had improvements in several of their scores while patients who went back onto immunosuppression had on average a small deterioration of their scores.
Dr. Mohammad had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point: Selected pediatric liver-transplant patients who successfully weaned off immunosuppression responded with significantly improved quality of life scores.
Major finding: Patient and parent treatment satisfaction improved by 6-7 points when patients stopped immunosuppression and fell by 2-3 points when they did not.
Data source: iWISH, a multicenter study with 88 enrolled patients.
Disclosures: Dr. Mohammad had no disclosures.
Frailty stratifies pediatric liver disease severity
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
MONTREAL – A newly devised measurement of frailty in children effectively determined the severity of liver disease in pediatric patients and might serve as a useful, independent predictor of outcomes following liver transplantations in children and adolescents.
The adapted pediatric frailty assessment formula is a “very valid, feasible, and valuable tool” for assessing children with chronic liver disease, Eberhard Lurz, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology and Nutrition. “Frailty captures an additional marker of ill health that is independent of the MELD-Na [Model for End-Stage Liver Disease–Na] and PELD,” [Pediatric End-Stage Liver Disease] said Dr. Lurz, a pediatric gastroenterologist at the Hospital for Sick Children in Toronto.
The idea of frailty assessment of children with liver disease sprang from a 2014 report that showed a five-item frailty index could predict mortality in adults with liver disease who were listed for liver transplantation and that this predictive power was independent of the patients’ MELD scores (Am J Transplant. 2014 Aug;14[8]:1870-9). That study used a five-item frailty index developed for adults (J Gerontol A Biol Sci Med Sci. 2001;56[3]:M146-57).
Dr. Lurz came up with a pediatric version of this frailty score using pediatric-oriented measures for each of the five items. To measure exhaustion he used the PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale; for slowness he used a 6-minute walk test; for weakness he measured grip strength; for shrinkage he measured triceps skinfold thickness; and for diminished activity he used an age-appropriate physical activity questionnaire. He prespecified that a patient’s scores for each of these five measures are calculated by comparing their test results against age-specific norms. A patient with a value that fell more than one standard deviation below the normal range scores one point for the item and those with values more than two standard deviations below the normal range score two points. Hence the maximum score for all five items is 10.
Researchers at the collaborating centers completed full assessments for 71 of 85 pediatric patients with chronic liver disease in their clinics, and each full assessment took a median of 60 minutes. The patients ranged from 8-16 years old, with an average age of 13. The cohort included 36 patients with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) who were listed for liver transplantation.
The median frailty score of the CCLD patients was 3 and the median score for those with ESLD was 5, a statistically significant difference that was largely driven by between-group differences in fatigue scores and physical activity scores. A receiver operating characteristic curve analysis by area under the curve showed that the frailty score accounted for 83% of the difference between patients with CCLD and ESLD, comparable to the distinguishing power of the MELD-Na score. Using a cutoff on the score of 6 or greater identified patients with ESLD with 47% sensitivity and 98% specificity, and this diagnostic capability was independent of a patient’s MELD-Na or PELD score.
The five elements that contribute to this pediatric frailty score could be the focus for targeted interventions to improve the outcomes of patients scheduled to undergo liver transplantation, Dr. Lurz said.
Dr. Lurz had no relevant financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: The pediatric frailty score identified patients with end-stage liver disease with sensitivity of 47% and specificity of 98%.
Data source: A series of 71 pediatric patients with liver disease compiled from 17 U.S. and Canadian centers.
Disclosures: Dr. Lurz had no relevant financial disclosures.
Hepatitis Outlook: August 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.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
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.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
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.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
Ombitasvir, paritaprevir, ritonavir, and dasabuvir in CKD patients with HCV
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak) achieved sustained viral response in 90% of patients with noncirrhotic chronic hepatitis C virus (HCV) genotype 1 infection and comorbid stage 4 or 5 chronic kidney disease, according to a small, single-arm, industry-sponsored trial reported in the November issue of Gastroenterology.
Adverse effects were usually mild or moderate, and serious adverse effects were considered unrelated to treatment, Paul Pockros, MD, at Scripps Clinic and Scripps Translational Science Institute in La Jolla, Calif., and his associates reported in Gastroenterology. No patients stopped direct-acting antivirals because of adverse effects, although nearly half had to interrupt or discontinue ribavirin because of worsening anemia. “The results of this study are important for hepatologists, gastroenterologists, and infectious disease specialists who are accustomed to treating HCV-infected patients with direct-acting antiviral therapy but who may not yet have seen sufficient data to initiate [it] in patients with end-stage renal disease,” the researchers said. “Nephrologists, who may not be accustomed to treating HCV, should also be aware that treatment options may now be available that can help prevent end-stage sequelae of HCV.”
All patients completed treatment, and 18 (90%) achieved sustained viral response (95% confidence interval, 70%-97%). The most common adverse events were anemia (45% of patients), fatigue (35%), diarrhea (25%), and nausea (25%). Among the two patients who did not achieve sustained viral response, one relapsed and the other died. The relapse occurred in a 49-year-old black man on hemodialysis who took about 91% of his medication doses, compared with about 97% for the rest of the cohort, the investigators said. This patient also had to interrupt ribavirin after his hemoglobin level dropped below 10 g/dL. The death occurred in a 60-year-old male hemodialysis patient who had hypertensive nephropathy and developed hypertensive urgency and cardiomyopathy soon after finishing treatment. His death, although considered unrelated to HCV treatment, underscores the need for close monitoring and collaboration between physicians treating HCV and nephrologists, the researchers said.
Most patients in this study were in stage 5 chronic kidney disease. However, the median baseline hemoglobin level was relatively high at 12 g/dL, implying that these patients would tolerate ribavirin better than would those with more pronounced anemia, the researchers noted. Nonetheless, 9 of 13 patients had to interrupt discontinue ribavirin because of worsening anemia. “Therefore, this study does not provide guidance for chronic kidney disease patients with much lower baseline hemoglobin levels, who might not tolerate even a small decrease,” the investigators cautioned.
AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
FROM GASTROENTEROLOGY
Key clinical point: Twelve weeks of ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin was relatively well tolerated and cured most genotype 1 chronic hepatitis C virus infections in patients with severe or end-stage renal disease.
Major finding: All patients completed treatment and 18 (90%) achieved sustained viral response. The most common adverse effect was anemia (45% of patients).
Data source: A single-arm, multicenter study of 20 treatment-naive, noncirrhotic adults with HCV genotype 1 infection and stage 4 or 5 chronic kidney disease.
Disclosures: AbbVie makes Viekira Pak and sponsored the study. Dr. Pockros disclosed ties to AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.
Fulminant HBV reactivation associated with HCV treatment
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.
HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.
“The mechanism through which HBV reactivation occurs with DAAs is currently unknown. These medicines are not known to cause immunosuppression, but HBV reactivation may result from a complex interplay of host immunologic responses in the setting of infection with two hepatitis viruses.”
In response to the findings, the FDA will require a black box warning on all DAA medications. Before prescribing the drugs, clinicians should screen patients for evidence of current or prior HBV infection. Patients with evidence of current or prior HBV infection should be monitored for HBV surface antigen and HBV DNA, as well as serum aminotransferase bilirubin levels, and watched for signs of hepatitis flare or HBV reactivation during and after DAA treatment. Suspected cases should be reported to FDA MedWatch.
The reactivations occurred within 4-8 weeks of beginning a DAA, the FDA said. “A common sequence of events was initiation of DAA-based HCV treatment, rapid drop of HCV RNA to undetectable levels within 1-2 weeks after normalization of transaminase levels (if they were elevated), followed by a rise in HBV DNA with or without increase in transaminases between weeks 4 and 8.”
Half of the patients did eventually receive HBV antiviral treatment (tenofovir or entecavir). Treatment data were absent on six patients. The remaining six patients did not receive HBV treatment, for unclear reasons.
In eight cases, the initial transaminase increase was interpreted as a DAA drug reaction and the medicine was discontinued. These patients either failed to improve or deteriorated, prompting concerns about HBV reactivation. FDA couldn’t find any commonalities in the cases.
“The patients who developed HBV reactivation were heterogeneous in terms of HCV genotype. These patients were also heterogeneous in terms of baseline HBV disease, fitting into three general categories of patients: those with detectable HBV viral load (seven), those with positive HB surface antigen and undetectable HBV viral load (four), and those with negative HB surface antigen and undetectable HBV viral load (three).”
For the remaining 10 patients, HB surface antigen status was either not known or baseline HBV could not be interpreted.
Key clinical point:
Major finding: HBV reactivation has been reported in 24 patients since 2013.
Data source: Reports were made to the FDA MedWatch system.
Disclosures: No conflicts of interest were reported.
Simple interventions markedly improve hepatitis care
Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.
Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.
To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).
Among their findings:
• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.
• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.
• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.
• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).
• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.
The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.
This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.
But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.
John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.
But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.
John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.
But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.
John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.
Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.
To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).
Among their findings:
• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.
• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.
• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.
• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).
• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.
The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.
Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.
Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.
To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).
Among their findings:
• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.
• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.
• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.
• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).
• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.
The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.
Key clinical point: Several simple, inexpensive operational interventions substantially improve care for viral hepatitis.
Major finding: Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (relative risk, 3.70).
Data source: A meta-analysis of 56 studies worldwide assessing interventions to improve HBV and HCV care.
Disclosures: The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.
Nonalcoholic fatty liver disease estimated to cost $103 billion annually
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.
Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.
Their models, which were calibrated against real-world prevalence rates, predicted an estimated 58 million prevalent cases and 12 million new cases of NAFLD each year in the US alone (Hepatology. 2016 Sep 26. doi: 10.1002/hep.28785).
The models also incorporated the transition of patients between nine health states, from NAFLD through nonalcoholic steatohepatitis (NASH) to NASH fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, posttransplant, and death.
They forecast an overall prevalence of 64 million cases of NAFLD annually in the United States, which includes more than 5.5 million prevalent cases – and 600,000 incident cases – of NASH. The number of incident cases of NAFLD were highest in the patients aged 45-64 years, while the incident cases of NASH and hepatocellular carcinoma peaked in the patients aged 65 years and older.
The results were proportionally similar for the four European countries, although when it came to the analysis of economic burden, researchers found the direct costs of NAFLD were much higher in the United States.
Overall, NAFLD costs $103 billion each year in the United States, compared with EU 27.7 billion in Germany, France, and Italy, and GBP 5.24 billion in the United Kingdom. The authors attributed these greater costs to a larger population, as well as higher costs of managing disease-related complications.
“However, if we assume the annual rate of increase in the costs due to NAFLD to parallel the annual growth in the prevalence of obesity in the United States since 1994, the expected 10-year burden of NAFLD could increase substantially – to an estimated $1.005 trillion in the United States and EU334 billion in the Europe-4,” they noted.
Total costs were highest in the group aged 45-65 years, but per-patient costs were highest in the group aged 65 years and older, which the authors said reflected the higher proportion of these patients in more advanced stages of disease.
The authors also argued that these cost estimates do not take into account the societal costs related to the loss of quality years of life to NAFLD and its complications.
“By assigning a monetary value to societal costs and adding these to the annual direct cost of NAFLD for the United States and the Europe-4, the total annual cost of NAFLD can be estimated at $292.19 billion and EU227.84 billion, respectively,” they wrote. “Furthermore, these cost calculations do not take into account other indirect costs of NAFLD, which are related to work-productivity loss and its economic impact.”
The study was partly funded by Gilead Sciences. Four authors declared consultancies and advisory positions for the pharmaceutical industry, including Gilead.
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.
Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.
Their models, which were calibrated against real-world prevalence rates, predicted an estimated 58 million prevalent cases and 12 million new cases of NAFLD each year in the US alone (Hepatology. 2016 Sep 26. doi: 10.1002/hep.28785).
The models also incorporated the transition of patients between nine health states, from NAFLD through nonalcoholic steatohepatitis (NASH) to NASH fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, posttransplant, and death.
They forecast an overall prevalence of 64 million cases of NAFLD annually in the United States, which includes more than 5.5 million prevalent cases – and 600,000 incident cases – of NASH. The number of incident cases of NAFLD were highest in the patients aged 45-64 years, while the incident cases of NASH and hepatocellular carcinoma peaked in the patients aged 65 years and older.
The results were proportionally similar for the four European countries, although when it came to the analysis of economic burden, researchers found the direct costs of NAFLD were much higher in the United States.
Overall, NAFLD costs $103 billion each year in the United States, compared with EU 27.7 billion in Germany, France, and Italy, and GBP 5.24 billion in the United Kingdom. The authors attributed these greater costs to a larger population, as well as higher costs of managing disease-related complications.
“However, if we assume the annual rate of increase in the costs due to NAFLD to parallel the annual growth in the prevalence of obesity in the United States since 1994, the expected 10-year burden of NAFLD could increase substantially – to an estimated $1.005 trillion in the United States and EU334 billion in the Europe-4,” they noted.
Total costs were highest in the group aged 45-65 years, but per-patient costs were highest in the group aged 65 years and older, which the authors said reflected the higher proportion of these patients in more advanced stages of disease.
The authors also argued that these cost estimates do not take into account the societal costs related to the loss of quality years of life to NAFLD and its complications.
“By assigning a monetary value to societal costs and adding these to the annual direct cost of NAFLD for the United States and the Europe-4, the total annual cost of NAFLD can be estimated at $292.19 billion and EU227.84 billion, respectively,” they wrote. “Furthermore, these cost calculations do not take into account other indirect costs of NAFLD, which are related to work-productivity loss and its economic impact.”
The study was partly funded by Gilead Sciences. Four authors declared consultancies and advisory positions for the pharmaceutical industry, including Gilead.
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect over 64 million people each year in the United States, leading to medical costs of more than $100 billion, according to a new analysis.
Using a steady-state prevalence model, Zobair M. Younossi, MD, MPH, from the Center for Liver Diseases at Inova Fairfax (Va.) Hospital, and his coauthors, sought to estimate the prevalence and economic burden of NAFLD in the United States, Germany, France, Italy, and the United Kingdom.
Their models, which were calibrated against real-world prevalence rates, predicted an estimated 58 million prevalent cases and 12 million new cases of NAFLD each year in the US alone (Hepatology. 2016 Sep 26. doi: 10.1002/hep.28785).
The models also incorporated the transition of patients between nine health states, from NAFLD through nonalcoholic steatohepatitis (NASH) to NASH fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, posttransplant, and death.
They forecast an overall prevalence of 64 million cases of NAFLD annually in the United States, which includes more than 5.5 million prevalent cases – and 600,000 incident cases – of NASH. The number of incident cases of NAFLD were highest in the patients aged 45-64 years, while the incident cases of NASH and hepatocellular carcinoma peaked in the patients aged 65 years and older.
The results were proportionally similar for the four European countries, although when it came to the analysis of economic burden, researchers found the direct costs of NAFLD were much higher in the United States.
Overall, NAFLD costs $103 billion each year in the United States, compared with EU 27.7 billion in Germany, France, and Italy, and GBP 5.24 billion in the United Kingdom. The authors attributed these greater costs to a larger population, as well as higher costs of managing disease-related complications.
“However, if we assume the annual rate of increase in the costs due to NAFLD to parallel the annual growth in the prevalence of obesity in the United States since 1994, the expected 10-year burden of NAFLD could increase substantially – to an estimated $1.005 trillion in the United States and EU334 billion in the Europe-4,” they noted.
Total costs were highest in the group aged 45-65 years, but per-patient costs were highest in the group aged 65 years and older, which the authors said reflected the higher proportion of these patients in more advanced stages of disease.
The authors also argued that these cost estimates do not take into account the societal costs related to the loss of quality years of life to NAFLD and its complications.
“By assigning a monetary value to societal costs and adding these to the annual direct cost of NAFLD for the United States and the Europe-4, the total annual cost of NAFLD can be estimated at $292.19 billion and EU227.84 billion, respectively,” they wrote. “Furthermore, these cost calculations do not take into account other indirect costs of NAFLD, which are related to work-productivity loss and its economic impact.”
The study was partly funded by Gilead Sciences. Four authors declared consultancies and advisory positions for the pharmaceutical industry, including Gilead.
FROM HEPATOLOGY
Key clinical point:
Major finding: Models have predicted an estimated 58 million prevalent cases and 12 million new cases of nonalcoholic fatty liver each year in the United States.
Data source: Analysis using a steady-state prevalence model calibrated with real-world prevalence data.
Disclosures: The study was partly funded by Gilead Sciences. Four authors declared consultancies and advisory positions for the pharmaceutical industry, including Gilead.
Direct-acting antivirals: One of several keys to HCV eradication by 2030
Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.
Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.
Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new 
Success in meeting the WHO challenge will hinge largely on the dramatic scale-up of new oral DAAs, according to Simone Lanini, MD, an epidemiologist at the National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, in Rome, and his coauthors. They’ve written a detailed analysis of all available tools and impending obstacles in the global fight against the virus.
With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.
DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.
Access to these therapies, however, remains at issue.
“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”
Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.
There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.
Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.
Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
[email protected]
On Twitter @whitneymcknight
Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.
Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.
Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new
Success in meeting the WHO challenge will hinge largely on the dramatic scale-up of new oral DAAs, according to Simone Lanini, MD, an epidemiologist at the National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, in Rome, and his coauthors. They’ve written a detailed analysis of all available tools and impending obstacles in the global fight against the virus.
With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.
DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.
Access to these therapies, however, remains at issue.
“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”
Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.
There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.
Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.
Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
[email protected]
On Twitter @whitneymcknight
Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.
Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.
Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new
Success in meeting the WHO challenge will hinge largely on the dramatic scale-up of new oral DAAs, according to Simone Lanini, MD, an epidemiologist at the National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, in Rome, and his coauthors. They’ve written a detailed analysis of all available tools and impending obstacles in the global fight against the virus.
With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.
DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.
Access to these therapies, however, remains at issue.
“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”
Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.
There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.
Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.
Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
[email protected]
On Twitter @whitneymcknight
Analysis yields ‘strong evidence’ for benefit of physical activity in NAFLD
Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.
“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”
Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).
After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”
Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.
The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”
The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.
*Content was updated on 10/25/2016
There has been tremendous interest in developing pharmacologic treatments for nonalcoholic steatohepatitis, especially in the Western world. There has not been significant enthusiasm for investigating exercise-based lifestyle modification as a primary treatment for NASH. Although the meta-analysis by Orci et al. included 28 studies, there are only 2 studies (combined, fewer than 100 patients) that examined the effect of exercise on liver histology in NASH and they both suggest that lifestyle modification consisting of exercise in addition to dietary modification improves liver histology in NASH. A seminal study was published by Vilar-Gomez et al. (Gastroenterology. 2015;149:367-78) that showed that a lifestyle modification consisting of reduction in caloric intake by 750 kcal/d along with low-intensity exercise (200 minutes of walking each week) led to significant improvement in liver histology, especially in those who lost at least 5% of their body weight.
Naga Chalasani, MD, AGAF, FACG, FAASLD, is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Purdue. He had no relevant conflicts.
There has been tremendous interest in developing pharmacologic treatments for nonalcoholic steatohepatitis, especially in the Western world. There has not been significant enthusiasm for investigating exercise-based lifestyle modification as a primary treatment for NASH. Although the meta-analysis by Orci et al. included 28 studies, there are only 2 studies (combined, fewer than 100 patients) that examined the effect of exercise on liver histology in NASH and they both suggest that lifestyle modification consisting of exercise in addition to dietary modification improves liver histology in NASH. A seminal study was published by Vilar-Gomez et al. (Gastroenterology. 2015;149:367-78) that showed that a lifestyle modification consisting of reduction in caloric intake by 750 kcal/d along with low-intensity exercise (200 minutes of walking each week) led to significant improvement in liver histology, especially in those who lost at least 5% of their body weight.
Naga Chalasani, MD, AGAF, FACG, FAASLD, is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Purdue. He had no relevant conflicts.
There has been tremendous interest in developing pharmacologic treatments for nonalcoholic steatohepatitis, especially in the Western world. There has not been significant enthusiasm for investigating exercise-based lifestyle modification as a primary treatment for NASH. Although the meta-analysis by Orci et al. included 28 studies, there are only 2 studies (combined, fewer than 100 patients) that examined the effect of exercise on liver histology in NASH and they both suggest that lifestyle modification consisting of exercise in addition to dietary modification improves liver histology in NASH. A seminal study was published by Vilar-Gomez et al. (Gastroenterology. 2015;149:367-78) that showed that a lifestyle modification consisting of reduction in caloric intake by 750 kcal/d along with low-intensity exercise (200 minutes of walking each week) led to significant improvement in liver histology, especially in those who lost at least 5% of their body weight.
Naga Chalasani, MD, AGAF, FACG, FAASLD, is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Purdue. He had no relevant conflicts.
Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.
“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”
Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).
After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”
Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.
The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”
The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.
*Content was updated on 10/25/2016
Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized controlled* trials published in the October issue of Clinical Gastroenterology and Hepatology.
“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”
Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).
After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”
Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.
The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”
The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.
*Content was updated on 10/25/2016
Key clinical point: Physical activity benefits measures of nonalcoholic fatty liver disease independently of diet.
Major finding: After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001).
Data source: A systematic review and meta-analysis of 28 randomized controlled trials comprising more than 16,000 patients.
Disclosures: The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The researchers had no disclosures.