By Liz Highleyman

Introduction

Current standard therapy for chronic hepatitis C is a combination of pegylated interferon (Pegasys or PegIntron) plus ribavirin. HCV genotype 1 -- which is most common in the U.S. -- is the most difficult to treat, with sustained virological response (SVR) rates around 50% with 48 weeks of therapy; genotype 4 is thought to be similar to genotype 1. Genotypes 2 and 3 respond better, with SVR rates reaching 70%-80% or higher with 24 weeks of therapy.

But HCV genotype 5, which is seen most often in parts of Africa, and genotype 6, which predominates in Southeast Asia, are rare in the U.S. and Europe, and their treatment has not been as extensively studied.

Worldwide distribution of HCV genotypes 1 to 6.

Source: Clinical Gastroenterol Hepatol 3: S97.

Genotypes 5 and 6 in Germany

In the first presentation, Dietrich Hueppe and colleagues assessed demographic characteristics, transmission risk factors, and medical care for genotype 5 and 6 chronic hepatitis C patients in Germany, based on a nationwide non-interventional study conducted by the Association of German Gastroenterologists in Private Practice in cooperation with Roche.

From March 2003 through September 2008, a total of 19,153 patients were included in the cohort, and 7266 treatments were recorded. The analysis presented at DDW looked at data from 32 individuals with genotype 5 and 29 with genotype 6. As a proportion of all hepatitis C cases, the prevalence of these genotypes was very low at 0.17% and 0.15%, respectively.

With regard to patient characteristics, genotype 5 patients were slightly older than those with genotype 6 (50 vs 45 years, respectively). Most genotype 6 patients (79%) were men -- and in most cohorts, men make up a majority of genotype 1, 2, and 3 patients as well -- but genotype 5 patients were more likely to be women (59%).

Looking at transmission routes, 56% of genotype 5 patients and 10% of those with genotype 6 cited blood transfusion as a risk factor, while 3% and 10%, respectively, cited other medical procedures. 13% of genotype 5 and 17% of genotype 6 patients reported injection drug use, and 3% and 17%, respectively, cited sexual transmission risk factors. For 28% of genotype 5 and 38% of genotype 6 patients, the transmission route was unknown.

Approximately 60% of these individuals had various comorbidities. Cardiovascular disease, thyroid disease, diabetes, and thrombocytopenia were predominant among genotype 5 patients, while hepatitis B virus and HIV coinfection were most frequent among those with genotype 6.

Within this cohort, 17 individuals with each genotype were treated with pegylated interferon plus ribavirin. The mean duration of therapy for both genotypes was 41 weeks; 69% of genotype 5 patients and 41% with genotype 6 received at least 80% of the cumulative prescribed doses of the 2 drugs for 48 weeks. Two patients (12%) with each genotype discontinued therapy prematurely.

A majority of patients (75% with genotype 5; 50% with genotype 6) achieved rapid virological response (RVR), or undetectable HCV RNA at treatment week 4. Almost all (94% and 100%, respectively) achieved early virological response (EVR) at week 12, but some experienced viral rebound, so the end-of-treatment (EOT) response rate was 82% for both genotypes. Some additional patients relapsed after completing therapy, resulting in SVR rates of 65% for genotype 5 and 59% for genotype 6.

"Genotype 5 and genotype 6 patients differed in their baseline demographic and virological characteristics," the investigators concluded. "However SVR rates between both genotypes were comparable and seem to be superior to [those of] genotype 1 patients."

Center of Gastroenterology, Herne, Germany; Center of Gastroenterology, Dortmund, Germany; Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; Center for Liver and Infectious Diseases, Stuttgart, Germany; Center of Gastroenterology, Goettingen, Germany; Hospital of Johannes-Gutenberg-Universitaet, Mainz, Germany; Center of Gastroenterology, Hannover, Germany; Center of Gastroenterology, Kassel, Germany; Center of Gastroenterology, Augsburg, Germany; Center of Gastroenterology, Paderborn, Germany; Center of Gastroenterology and Liver Center, Berlin, Germany; Meddata GmbH, Schkeuditz, Germany; Center of Gastroenterology, Berlin, Germany; Justus-Liebig-Universitaet, Giessen, Germany; Hepatitis/HIV/CF, Roche Pharma AG, Grenzach-Wyhlen, Germany.

Genotype 6 in Viet Nam

In the second study, Thuy Pham and Dat Ho looked at treatment response among individuals with HCV genotype 6 in Viet Nam.

The analysis included 75 patients, 42 of them treatment-naive and 33 who had received previous unsuccessful therapy with conventional interferon. All participants were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 15 mg/kg/day weight-adjusted ribavirin for 48 weeks.

SVR rates were 69% for treatment-naive patients and 61% for the treatment-experienced group. At 72 weeks, 74% and 64%, respectively, achieved ALT and AST normalization. Younger age and AST/ALT ratio < 1 were the factors that predicted sustained response. Baseline HCV RNA only influenced sustained response in patients with previous treatment failure. Most people who experienced RVR went on to achieve SVR.

Based on these findings, the researchers concluded, "Patients with chronic hepatitis C genotype 6 who have never been treated or have failed with standard interferon showed good responses when treated by peginterferon alfa-2a combined with ribavirin."

"The sustained viral response was better than that of genotype 1," they continued, recommending that further studies be done to determine whether treatment duration might be shortened for genotype 6 patients.

Hepatology, Medic Medical Center, Ho Chi Minh, Viet Nam.

6/19/09

Reference

D Hueppe, E Zehnter, S Mauss, and others. Efficacy and Tolerability of Peginterferon Alfa-2a (40KD) (PEG) and Ribavirin (RBV) in Genotype 5 and 6 Patients with Chronic Hepatitis C Under Real Life Conditions. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract M1794.

TT Phamand DT Ho. Pegylated Interferon Alfa-2a Plus Ribavirin in Chronic Hepatitis C Patients with Genotype 6. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract M1795.