May 14, 2013

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

Published on: 2013-05-14

Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy.Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications.

Methods: We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles.

In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies.

Results: Limited data is available on the neuropsychiatric adverse effectsof DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions.

Triazolam, oral midazolam, St. John's Wort, carbamazepine and pimozide, are contraindicated with DAAs.

DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized.

Conclusions: Although DAAs do not add significant neuropsychiatric risk, the potentialfor DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.

Author: Sanjeev SockalingamAlice TsengPierre GiguereDavid Wong
Credits/Source: BMC Gastroenterology 2013, 13:86


Central team discuses Hepatitis-C endemic with Director SKIMS

Last Update: May 14th, 2013 - IST

SRINAGAR, Kashmir -- A special team of doctors deputed by government of India to assess Hepatitis-C endemic in Kokernag area of South Kashmir held a meeting at Sher-e-Kashmir Institute of Medical Sciences Soura on Tuesday.

The team which has been deputed to Kashmir on the instructions of Union Health Minister Ghulam Nabi Azad held the meeting with director SKIMS Dr. Showkat A. Zargar. In the meeting there was exhaustive

In a statement to KNS Public Relations Officer (PRO) SKIMS Kulsoom Bhat said during the meeting discussion to devise a methodology to administer the treatment for endemic was done.

“The meeting was preceded by an exhaustive exchange of views with SKIMS experts from department of gastroenterology, microbiology, immunology and community medicine. Besides financial support Director SKIMS stressed for strengthening of lab at SKIMS and provide required infrastructure both in center and peripheries to ensure better treatment to the patients,” she said.

Associate Professor, Department of Gastroenterology Dr Mushtaq Ahmad Khan gave a comprehensive presentation about the disease prevalent in the areas including Takiya Magam Sonbrari and Zalangam in Kokenag block.

He informed preliminary analysis shows Takiya magma constitutes 62.5% HCV positive, Sonabrari 27.4 percent and 5.26 percent from Zalangam. “The overview and analysis suggests there is immediate need to arrest the spread of infection and treatment of the infected individuals. Experts pressed for treatment of 776 infected patients who suffer chronic hepatitis C which will help to reduce the viral load and spread of infection. The team was informed the treatment is costly and the people being poor can’t afford the treatment ranging from 1.5-3 lakhs/individual depending on the genotype of the virus and weight of the patient,” the PRO said.

Experts from SKIMS while expressing their concern said there should be extensive surveillance and screening for HCV to know the quantum of infection, source of infection and mode of spread and manifestation of the infection and vigorous awareness and health education programs.

The team comprising Dr. S.K Sarin, Director Institute of Liver and Biliary Sciences, Dr. L S Chauhan Director NCDC, New Delhi, Dr. S.K Acharya HOD Gastroenterology AIIMS, New Delhi, Dr. B.D Athani, MS Safdarjang Hospital, Dr Sandeep Tyagi, Army R&R Hospital, New Delhi earlier visited the affected district to assess the situation on ground.


Antiretrovirals Linked to Liver Fibrosis

Daniel M. Keller, PhD

May 14, 2013

AMSTERDAM, the Netherlands — Despite hepatitis B virus suppression provided by current drugs, many patients coinfected with hepatitis B and HIV have advanced liver fibrosis, according to new research.

"Of the patients we had liver biopsies on, 31 of 53 — more than half — had advanced fibrosis, bridging fibrosis, or cirrhosis. That was despite their hepatitis B being reasonably controlled," said Richard Sterling, MD, chief of hepatology at Virginia Commonwealth University in Richmond. "Liver enzymes were not that high, and most patients had low or undetectable hepatitis B DNA."

Dr. Sterling cited 2 possible reasons for this. "Many of these patients could have been on older antiretroviral therapy that included lamivudine, which we know is not a good long-term drug for hepatitis B. As a result, over time their liver disease progressed sort of under the radar of their HIV provider," he explained.

"We also know that hepatitis B liver disease is immune mediated," he added. "Perhaps immune reconstitution, when their HIV therapy was just starting, actually caused more liver disease, unbeknownst to the HIV provider."

Hepatitis B is prevalent in about 8% to 10% of patients infected with HIV and is controlled with some of the same drugs. However, few patients are biopsied, so little is known about liver disease in this population.

To learn more, Dr. Sterling and colleagues conducted a retrospective analysis of coinfected patients who had undergone liver biopsy. He presented the results here at the International Liver Congress 2013.

The researchers compared demographic and clinical characteristics of patients with and without advanced fibrosis. In 95% of patients, the level of HIV RNA was undetectable. In 30%, the level of hepatitis B DNA was undetectable; in 35%, it was below 1000 IU/mL. In 62%, the test for hepatitis B e antigen was positive.

Patients with advanced fibrosis had lower levels of hepatitis B DNA (P = .03) than those without advanced fibrosis, and more were on antiretroviral therapy (P = .02). For those with advanced fibrosis, there was a trend toward higher levels of aspartate transaminase (P = .08) and lower CD4 counts (P = .08).

There were no differences between patients with and without advanced fibrosis in terms of HIV RNA level, hepatitis B antigen status, the specific drugs used to treat hepatitis B, or the proportion with low or undetectable levels of hepatitis B DNA.

"The important thing is that the hepatitis B DNA was undetectable in the same proportion of patients who had mild disease and who had advanced disease," Dr. Sterling said. However, median levels were lower in the group with advanced fibrosis. "It's not clear whether they were lower because those patients were being treated and their hepatitis B was suppressed, or whether the virus count was lower because their disease was worse. We don't know which came first," he noted.

A high proportion of coinfected patients had advanced fibrosis despite hepatitis B suppression. Dr. Sterling explained that liver histology needs to be studied in a larger group of patients to define the spectrum of liver disease and to find biomarkers that predict advanced disease.

Limitations of this study were its retrospective nature and the selection bias of patients undergoing biopsy.

"I think the bottom line with hepatitis B is that it's forgotten but not gone," he said. Up to half of patients can have advanced fibrosis, despite having well-controlled HIV and, "on paper, not looking too bad as far as their hepatitis B, alanine transaminase, and DNA," he explained, "which certainly puts them at higher risk for developing hepatic decompensation and hepatocellular carcinoma."

Fabien Zoulim, MD, PhD, who was asked by Medscape Medical News to comment on the findings, said he agrees that coinfected patients can have advanced fibrosis even when hepatitis B has been suppressed. He is medical director of the Department of Hepatology at the Hospices Civils de Lyon, and scientific director of the Department of Immunology and Virology of an INSERM unit in Lyon, France, and was not involved with this study.

"The problem is that we don't know how long these patients have been treated, how many lines of antiviral therapy they've gone through. Have they failed an antihepatitis B regimen in the past?... I think it's difficult to make a good interpretation of their results" in light of these uncertainties, Dr. Zoulim explained.

Besides the question of whether hepatitis B was well controlled in the past, there is an issue of liver toxicity from previous antiretroviral treatments. "Some of these regimens in the past may have been toxic for the liver, and this may have induced liver fibrosis," Dr. Zoulim said. "This type of information is really important to know."

Dr. Zoulim advises that treating physicians get a very good assessment of the severity of liver disease in coinfected patients. That can involve noninvasive tests such as FibroScan or blood markers if the patients appear well. For abnormal liver function tests, he would do a biopsy because of the variety of conditions associated with older antiretroviral therapies and the hepatitis B itself, he explained.

With newer treatment regimens, the situation is "getting much better than it was 5 years ago," he said. For coinfected patients who start first-line treatment today, "I wouldn't predict major problems."

Dr. Sterling has disclosed no relevant financial relationships. Dr. Zoulim reports being is a consultant to Gilead, BMS, and Roche.

International Liver Congress 2013: 48th Annual Meeting of the European Association for the Study of the Liver (EASL). Abstract 429. Presented April 25, 2013.


Liver transplantation reduced fatigue among patients with primary biliary cirrhosis

Provided by
Carbone M. J Hepatol. 2013;doi:10.1016/j.jhep.2013.04.017.

May 14, 2013

Patients with primary biliary cirrhosis who underwent liver transplantation experienced a significant and persistent reduction in fatigue symptoms, although almost half continued to experience fatigue in a recent study.

Researchers administered a 40-item quality of life questionnaire to 49 adult liver transplant (LT) recipients with primary biliary cirrhosis (PBC), along with 31 matched controls without PBC and 124 patients with PBC who did not undergo LT (n=124). Questionnaires were completed at baseline and at 6, 12 and 24 months after LT. Fatigue responses were evaluated, with scores of 11 or lower indicating no fatigue, 12-28 mild, 29-39 moderate and 40 or greater severe fatigue.

Among 31 evaluable patients who underwent LT, lower fatigue scores were observed post-transplant during follow-up (40.7 ± 11.4 vs. 27.7 ± 9.5 at 6 months, 28.7 ± 10.1 at 12 months and 26.2 ± 10.1 at 24 months post-transplant; P<.0001). This improvement occurred regardless of MELD score, and fatigue scores also were better among transplant recipients compared with nonrecipients with PBC (31.1 ± 11.6; P=.03). Scores at 24 months, however, were higher among transplant recipients than controls without PBC (17.8 ± 5.9; P<.0001).

Moderate to severe fatigue (scores of 29 or greater) was observed in 44% of the cohort, including 47% of patients with low MELD scores, at 24 months. Severe fatigue was observed in 12% of LT recipients at 12 months and 6% at 24 months post-transplant.

“We have shown that fatigue improves after LT,” the researchers concluded. “However, almost half of the patients fatigued before transplant remained significantly fatigued at 2 years after transplant. … These findings raise concerns regarding the appropriateness of transplantation as a treatment modality for fatigue alone in PBC, balanced against the real risk of mortality and morbidity from the transplant procedure itself. With improving long-term transplantation outcomes, we should focus more on the long-term improvement of the quality of life after LT. Further studies on fatigue in transplant recipients … are clearly warranted in order to confirm these findings.