Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) inS ubstantial advances have been made in the treatment of chronic hepatitis B (CHB) in the past decade. Several nucleos(t)ide analogues are currently approved for the treatment of hepatitis B virus (HBV) infection with a high efficacy in suppressing HBV replication. However, a long duration of treatment is needed to maintain viral suppression, and the major question of whether oral therapy can ever be stopped remains unanswered. 1 In parallel with analogues, the American Association for the Study of Liver Diseases practice guidelines have advocated pegylated interferon alfa-2a (PEG-IFN) as a potential first-line therapy in hepatitis B e antigen (HBeAg)-negative patients. 2 The advantages of PEG-IFN therapy include a limited treatment course, a high rate of HBeAg seroconversion (in HBeAg-positive patients), a 20% to 30% rate of sustained virological response (SVR), the potential for hepatitis B surface antigen (HBsAg) loss or seroconversion, and a lack of resistance development. 3 Nonetheless, the use of PEG-IFN currently accounts for

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In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

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The aim of the study was to determine the respective influence of pretreatment serum hepatitis C virus (HCV) RNA levels and HCV genotype on the response to interferon (IFN) alfa in patients with chronic hepatitis C. We retrospectively studied 141 patients with chronic hepatitis C included in two consecutive controlled trials of IFN alfa. A sustained response was observed in 28, a response followed by relapse in 43, and no response in 70 patients.Pretreatment serum HCV RNA quantitation with the branched DNA (bDNA) assay and HCV genotyping with reverse hybridization assay (LiPA) were performed in all patients. Seventy-four percent of the patients had detectable serum HCV RNA (43%, 77% and 84%) in the three groups of patients with sustained response, relapse, and no response, respectively (P = .005). Mean serum HCV RNA level were 1.4 f 6 x lo6, 4.8 f 6 x lo6, and 3.9 f 5 x lo6 genomeslml in patients with sustained response, response and relapse, and no response, respectively (P < .01). Genotype l b was found in 7%, 47%, and 46V0 of the patients in the three response groups, respectively. By univariate analysis, age, source, and duration of HCV infection, serum HCV RNA levels, and HCV genotypes were significantly different in the three response groups. By multivariate analysis, the only independent factors associated with sustained response were low serum HCV RNA levels and HCV genotype other than lb. Pretreatment serum HCV RNA levels and HCV genotype are the main and independent factors associated with sustained response to IFN therapy. (HEPATOLOGY 1995; 22:1050-1056 Abbreviations: HCV, hepatitis C virus; IFN, interferon; bDNA, branched DNA ALT, alanine transaminase. Diseases.Hepatitis C virus (HCV) has been shown to be the major causal agent of chronic non-A, non-B Although interferon (IFN) is currently the only effective antiviral agent for the treatment of chronic hepatitis c, 50% of the patients treated respond and only 20% have a sustained r e~p o n s e .~.~ The factors influencing the response to IFN therapy are unknown. Several pretreatment features have been reported to be useful in identifying patients with a high probability of response to IFN treatment, such as young age, source of infect i~n ,~ absence of cirrhosis, and short duration of the disease.8 The lack of reliability of these patient-related factors from one study to the other suggests that they do not markedly influence the response to IFN treatment and that virus-related factors might be crucial for response to IFN therapy. Indeed, several studies have shown that pretreatment serum HCV RNA levels and HCV genotype influence the response to IFN treatment.9-i5 However, many of these studies only included small numbers of patients and did not use multivariate analysis. Furthermore, the methods used to quantitate serum HCV RNA and to genotype HCV were not always standardized, leading to difficulties in interpreting the different studies. Two new approaches, branched DNA (bDNA) signal amplification, recently developed for serum HCV RNA quantificatio...

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In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P ‫؍‬ .012), higher total Knodell score (P ‫؍‬ .011), and poorer sustained response to interferon therapy (P ‫؍‬ .009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P ‫؍‬ .001). Necroinflamatory score was higher in HIV-positive patients (P ‫؍‬ .023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P ‫؍‬ .011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR ‫؍‬ 4.06, P ‫؍‬ .024) and in interferon-untreated patients (RR ‫؍‬ 4.76, P ‫؍‬ .001), independently of age at HCV infection (P ‫؍‬ .001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR ‫؍‬ 10.8, P ‫؍‬ .001) and in HIV-positive patients with CD4 cell count less than 200/mm 3 (RR ‫؍‬ 11.9, P ‫؍‬ .007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-

Hepatitis delta virus (HDV) can cause severe acute and chronic liver disease in patients infected by hepatitis B virus. Interferon alpha at high doses, although poorly efficient, is the only treatment reported to provide some benefit in chronic hepatitis delta. Pegylated interferon alpha (PEG-IFN) has not yet been evaluated. Treatment is usually monitored by the qualitative detection of HDV-RNA in serum. In this study, safety and efficacy of PEG-IFN were assessed in chronic hepatitis delta, and serum HDV-RNA kinetics were determined using quantitative RT-PCR. Fourteen patients with chronic hepatitis delta received subcutaneous PEG-IFN alpha-2b during 12 months (1.5 g/kg per week). Serum HDV-RNA was quantified at initiation and during the course of therapy, and during the posttreatment follow-up period, which ranged from 6 to 42 months (median 16 months). PEG-IFN alpha-2b was well tolerated, inducing no serious adverse effect. Sustained biochemical response was obtained in 8 patients (57%). At the end of treatment, 8 patients (57%) had achieved virological response (undetectable HDV-RNA). Sustained virological response throughout the posttreatment follow-up period was observed in 6 patients (43%). HDV-RNA kinetics were predictive of the response: after 3 months of PEG-IFN, HDV-RNA levels were significantly lower in the responders than in the nonresponders group (P ‫؍‬ .018). After 6 months of therapy, a negative HDV-RNA was predictive of sustained response (P ‫؍‬ .021). In conclusion, this preliminary study indicates that PEG-IFN alpha-2b is safe and efficient for treatment of chronic hepatitis delta. H epatitis delta virus (HDV) is a satellite RNA virus, which depends on the hepatitis B virus (HBV) for virion assembly and propagation. 1 HDV infection can cause severe acute and chronic liver disease, with a chronicity rate reaching 70% to 90% in cases of super-infection, 1-3 and a common progression to cirrhosis (60%-70%) accounting for frequent evolution to end-stage liver disease and hepatocellular carcinoma. 4,5 To date, treatment of chronic hepatitis delta relies on interferon alpha (IFN), but the efficacy is limited. 6 Antiviral drugs such as ribavirin, acyclovir, or famcyclovir are inefficient, 7,8 and anti-HBV drugs such as lamivudine, which efficiently reduce HBV viremia but not HBsAg levels have no effect on hepatitis delta, 9 even when associated to IFN. 10 Clevudine, which induces a reduction in the covalently closed circular DNA replication template levels could be useful in the treatment of chronic hepatitis delta but has only been evaluated in the woodchuck model for this indication. 11 The pegylated form of IFN (PEG-IFN), which has been proved to be more efficient than standard IFN in chronic hepatitis B and C, might improve the outcome of chronic hepatitis delta, but such treatment has not yet been evaluated. 12,13 The diagnosis of HDV infection usually relies on the detection of specific anti-HDV antibodies, with the presence of anti-HDV IgM reflecting ongoing viral replication. However, serologi...