U.S. Hepatitis C Incidence Dropped 10-fold Over 2 Decades

The incidence of acute hepatitis C virus (HCV) infection in the U.S. has decreased dramatically over the past 25 years, falling from 7 to 0.7 cases per 100,000 people, according to a CDC study published in the February 14, 2011, Archives of Internal Medicine. In recent years nearly half of all new infections were attributable to injection drug use, but about a third had no identifiable risk factor.

DDW 2008: Pegylated Interferon (Pegasys) Continues to Suppress HBV, Adding Adefovir (Hepsera) Provides No Extra Benefit

Several nucleoside/nucleotide analogs are approved for the treatment of chronic hepatitis B virus (HBV) infection, but their long-term effectiveness is limited by the emergence of drug-resistant virus. Another approved hepatitis B therapy,pegylated interferon, works by modulating the immune response against the virus.

The multicenter Italian PEG for B study compared the safety and efficacy of pegylated interferon monotherapy vs pegylated interferon plus the nucleotide analog adefovir (Hepsera). The trial included 60 participants (67% men; median age 48 years) with chronic hepatitis B "e" antigen (HBeAg) negative infection.

All patients had HBV DNA viral loads of 104 copies/mL or greater, elevated alanineaminotransferase (ALT) levels, and compensated liver disease. The mean baseline HBV DNA level was 6.4 log copies/mL and the mean ALT level was 3.3 times the upper limit of normal. Individuals with hepatitis C virus (HCV) or HIV coinfection, as well as those with clinical signs of cirrhosis, were not included.

Participants were randomly assigned (1:1) to receive 180 mcg/week pegylated interferonalfa-2a (Pegasys) monotherapy or pegylated interferon plus 10 mg adefovir for 48 weeks, followed by 24 weeks of post-treatment observation. Baseline characteristics were comparable in both groups.

The primary study endpoint was sustained virological response (SVR), defined as serumHBV DNA < 104 copies/mL at the end of the post-treatment observation period.

Preliminary 24-week data from the study were presented at the European Association for the Study of the Liver (EASL) annual meeting in April 2007. More recently, at the Digestive Disease Week 2008 conference last month in San Diego, Paola Piccolo and colleagues presented longer-term, 48-week outcomes.

Results

• After 48 weeks of antiviral treatment, 69% of patients in the combination therapy group had undetectable HBV DNA, compared with 32% in thepegylated interferon monotherapy group (P < 0.01).

• ALT normalization occurred in 55% and 25%, respectively (P < 0.05). 

• At the end of post-treatment follow-up, about 80% of patients in both groups experienced virological relapse.

• 21% in the combination therapy group and 18% in the monotherapy group achieved SVR (not a significant difference).

• Mean post-treatment serum HBV DNA levels were about 5 log copies/mL in both groups.

• Post-treatment ALT levels increased to about 4 times the upper limit of normal in both groups.

• 1 patient in the combination therapy group, but none in the monotherapy arm, achieved hepatitis B surface antigen (HBsAg) loss. 

• In a multiple regression analysis, SVR was associated with a lower baseline fibrosis score. 

• 13% of participants in both groups discontinued therapy early due to adverse events. 

• Nearly 25% required pegylated interferon dose reduction to manage side effects.

"In HBeAg negative chronic hepatitis B, combination pegylated interferon plus adefovir treatment for 48 weeks is safe, and results in greater serum HBV DNA suppression and ALT normalization than pegylated interferon monotherapy," the study investigators concluded.

However, they added, "after 24 weeks of follow-up there is no difference in SVR and ALT levels between the two treatment regimens."

6/03/08

Reference

P Piccolo, L De Melia, F Bandiera, and others. Peginterferon alpha-2a plus adefovir dipivoxil vs. peginterferon alpha-2a monotherapy for 48 weeks in HBeAg-negative chronic hepatitis B: final results of the PEG for B randomized multicenter trial. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract 256.

Telaprevir Improves Treatment Outcomes for HIV/HCV Coinfected People

The experimental hepatitis C virus (HCV) protease inhibitor telaprevir, combined with pegyalted interferon plus ribavirin, reduced HCV viral load to undetectable levels in about 70% of HIV positive patients at weeks 4 and 12 in the first study of the drug in HIV/HCV coinfected people. Based on these eagerly awaited Phase 2 results, presented this week at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) in Boston, Vertex Pharmaceuticals plans to start a Phase 3 coinfection study later this year.

Sexual Transmission of Hepatitis C among HIV Positive Men in the U.S. and Australia

Nearly three-quarters of new hepatitis C virus (HCV) infections among HIV positive gay and bisexual men in the U.S. are likely due to sexual transmission, according to an analysis described in the January 31, 2011 advance online issue of Clinical Infectious Diseases. An Australian study published in the same issue found that sexual transmission accounted for a majority of cases among men who have sex with men, but injection drug use also played a role. These findings suggest that HIV positive people who have risky sex should undergo regular hepatitis C testing.

HCV Polymerase Inhibitor INX-189 Gets FDA Fast-Track Status, TMC649128 Enters Phase 1a Trial

The development of direct-acting antiviral agents active against hepatitis C virus (HCV) continues at a rapid pace. Two pharmaceutical companies this month announced progress in the development of investigational HCV polymerase inhibitors. Inhibitex said that it's candidate INX-189 has received "Fast Track" designation from the U.S. Food and Drug Administration (FDA), which allows for accelerated review and approval. Sweden's Medivir announced the start of the first human trial of its drug, TMC649128, in healthy volunteers.

Treatment of Recurrent Hepatitis C after Liver Transplantation

Hepatitis C patients with advanced liver disease may benefit from interferon-based therapy before receiving a liver transplant, but side effects are common and response rates are low, according to a systematic research review described in the January 2011 issue of Alimentary Pharmacology and Therapeutics. Injected antibodies do not prevent the new liver from becoming infected, but pegyalted interferon plus ribavirin can cures recurring HCV about 30% of the time.