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In This Issue:
• Short Treatment for Genotype 2/3 Patients
• Anti-HCV Treatment in Older Patients
• Hepatitis C Progression in Patients with Severe Liver Fibrosis
• Natural History of Hepatitis C in Genotype 4 Patients
• Liver Steatosis in HIV/HCV Coinfected Patients
• HCV Sexual Transmission
Short Treatment for Genotype 2/3 Patients
Because patients with genotype 2 or 3 HCV have a high sustained virological response (SVR) rate of approximately 80% using pegylated interferon plus ribavirin for 24 weeks, some experts have suggested that shorter treatment might be adequate for this population. As reported in the July 12, 2007 New England Journal of Medicine, M.L. Shiffman and colleagues conducted a non-inferiority study in which 1,469 genotype 2/3 patients were randomly assigned to receive 180 mcg pegylated interferon alfa-2a (Pegasys) once weekly plus 800 mg ribavirin daily for either 16 or 24 weeks. The study failed to demonstrate that the 16-week regimen was non-inferior to the 24-week regimen, given that the overall SVR rate was significantly lower among patients treated for 16 weeks (62%) compared with 24 weeks (70%). Likewise, the relapse rate was significantly higher in the 16-week group (31%) compared with the 24-week group (18%). However, among patients with baseline HCV RNA levels of 400,000 IU/mL or less, SVR rates were similar in both treatment arms (82% vs 81%). And among patients who achieved rapid virological response at week 4, SVR rates were 79% in the 16-week group and 85% in the 24-week group. “Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen,” the investigators concluded, but added that 16 weeks may be adequate for a carefully selected subset of patients.
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Anti-HCV Treatment in Older Patients
In the July 2007 American Journal Gastroenterology, G. Antonucci and colleagues reported the results of a study evaluating the effect of age on response to hepatitis C treatment. The researchers retrospectively reviewed the medical records of 153 chronic hepatitis C patients¾30 of whom (19.6%) were age 65 or older¾treated with pegylated interferon plus ribavirin. In multivariate analysis, all age groups over 40 had a similar likelihood of achieving SVR. However, those older than 40 were significantly less likely to achieve SVR compared with younger patients. Odds ratios for achieving SVR were 0.16 for those age 40-49, 0.13 for those age 50-64, and 0.21 for those 64 years and older. But while age had an effect on treatment response among individuals with HCV genotypes 1 or 4, those with genotypes 2 or 3 had similar SVR rates regardless of age. “The probability of good response to combination treatment with peginterferon alpha plus ribavirin is decreased for patients aged more than 40 years infected with genotype 1 or 4, but patients aged more than 65 had a similar rate of response to those aged 40-64 years,” the investigators concluded, adding that, “Combination treatment may be safely extended to elderly patients with no major contraindications.”
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Hepatitis C Progression in Patients with Severe Liver Fibrosis
As reported in the July 2007 Journal of Hepatology, A. Lawson and colleagues conducted a study to assess morbidity and mortality in 150 British hepatitis C patients with severe liver fibrosis (Ishak stage 4). Among the 131 subjects with no prior history of hepatic decompensation, 25% either died (25 patients) or received a liver transplant (eight patients), after a median interval of 42 months. Similarly, 25% (33 patients) were diagnosed with either hepatocellular carcinoma or hepatic decompensation after a median interval of 41 months. The probability of survival without liver transplantation was 97% at one year, 88% at three years, and 78% at five years. The overall prognosis was not affected by the Ishak stage of the initial biopsy, but the 19 patients with prior hepatic decompensation had worse prognosis, with 89% either dying (15 patients) or receiving a liver transplant (two patients). However, use of interferon-based combination therapy was associated with improved survival. “This study demonstrates that severe liver fibrosis (Ishak stage 4) secondary to hepatitis C is associated with a poor prognosis, that may be improved following combination antiviral treatment,” the researchers concluded.
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Natural History of Hepatitis C in Genotype 4 Patients
While research has shown that genotype 1 HCV is more difficult to treat and is associated with lower SVR rates than genotypes 2 or 3, less is known about genotype 4, which is seen with increasing frequency in Europe, though still uncommon in the United States. As reported in the July 2007 Journal of Viral Hepatitis, D. Roulot and colleagues conducted a retrospective study of 1,532 genotype 4 patients in France, including 1,056 subjects infected in that country, 227 immigrants infected in Egypt, and 249 infected in sub-Saharan Africa. They found that HCV subtypes 4a or 4d were most common among patients infected in France (where the predominant risk factor is injection drug use), while subtype 4a accounted for 93% of cases among patients infected in Egypt (where HCV transmission was predominantly related to parenteral treatment for parasites). In contrast, more than seven different genotype 4 subtypes were found among patients infected in sub-Saharan Africa. The investigators also determined that liver fibrosis was significantly less severe among patients infected in France or sub-Saharan Africa compared with Egypt. Among 242 patients treated with pegylated interferon plus ribavirin for 48 weeks, SVR rates were higher in patients infected in Egypt (55%) compared with those infected in France (40%) or sub-Saharan Africa (32%), and sustained response was more likely among patients with subtype 4a.
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Liver Steatosis in HIV/HCV Coinfected Patients
Several studies have shown that HIV/HCV coinfected patients have more rapid liver fibrosis progression than individuals with HCV alone, but less is known about liver steatosis in this population. As reported in the June 1, 2007 issue of AIDS, D. Neau and colleagues evaluated liver steatosis among 148 coinfected individuals in France. Overall, about two-thirds of patients (67%) had some degree of fat accumulation in their liver, including 30% who had moderate or worse steatosis. Steatosis was of the macrovesicular type in 41% of patients and mixed (macrovesicular and microvesicular) in 53%. Microvesicular steatosis is characteristic of drug-related liver toxicity, which can be caused by certain antiretroviral drugs used to treat HIV. Necroinflammatory activity was the only significant independent risk factor for steatosis. However, when necroinflammatory activity was omitted, HCV genotype 3 and higher body mass index were significantly associated with steatosis.
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HCV Sexual Transmission
Evidence continues to accumulate that HCV may be transmitted through sexual activity, especially among HIV positive men who have sex with men (MSM). In the July 15, 2007 Journal of Infectious Diseases, T.K. van de Laar and colleagues reported results from an analysis of an acute hepatitis C outbreak among gay men in Amsterdam in the Netherlands. The researchers performed retrospective HCV antibody screening of 1,836 MSM participating in an ongoing HIV cohort study. The incidence of HCV infection was 0.18 per 100 person-years (eight cases in 4,408 total person-years) among HIV positive men, compared with zero cases (in 7,807 total person-years) among HIV negative men. The researchers also found that the outbreak is relatively recent: after the year 2000, HCV incidence among HIV positive men increased about ten-fold, to 0.87 cases per 100 person-years. Men newly infected with HCV after 2000 reported high rates of ulcerative sexually transmitted infections (59%) and practicing “rough sexual techniques” (56%), but denied injection drug use. “The emergence of an MSM-specific transmission network suggests that HIV positive MSM with high-risk sexual behaviors are at risk for sexually acquired HCV,” the investigators concluded. They recommended that, “Targeted prevention and routine HCV screening among HIV positive MSM is needed to deter the spread of HCV.”
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