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The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P ‫؍‬ .0001), lower serum albumin levels (P ‫؍‬ .0009), and higher serum HBV DNA levels (P ‫؍‬ .01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P ‫؍‬ .04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process. (HEPATOLOGY 1999;29: 1306-1310.)

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...

The role of alcohol intake in the occurrence of severe liver disease in chronic hepatitis C virus (HCV) carriers is still debated. A cross-sectional study has been conducted in 233 chronic hepatitis C virus carriers. Weekly self-reported alcohol consumption (SRAC) was evaluated, serum HCV RNA levels were measured by a branched DNA technique (Quantiplex 2.0) and HCV genotypes were determined. A liver biopsy was performed simultaneously and liver lesions were graded with the Knodell histological activity index. Data were examined by uni-and multivariate analyses. Alcohol consumption was relatively low (F 140 g/per week in 193/233 patients [80%]). We found a highly significant correlation between SRAC and serum HCV RNA levels (r ‫؍‬ .26, P ‫؍‬ .001). Fibrosis was significantly correlated with age and alcohol consumption. These results suggest that in HCV carriers, alcohol consumption, even with low alcohol intake, increases viremia and hepatic fibrosis. Chronic HCV carriers should be advised to avoid regular alcohol intake. (HEPATOLOGY 1998;27:1717-1722.)The natural course of HCV infection is probably modulated by several cofactors. The role of virus-related factors, namely genotypes and viremia has been extensively studied 1-7 but still remains debated. 8 Up to now, immunological factors were underestimated but several arguments implicate the role of immune response in the course of the disease. Environmental factors and particularly alcohol intake are probably major factors, 9-10 and the increased severity of the disease and the faster occurrence of cirrhosis in patients with HCV infection and heavy alcohol intake has been suggested in several studies. [11][12] Moreover relations between alcohol and the immune response have been suggested with other viral infections. 13 The aim of the present study is to describe the effect of moderate alcohol intake on serum HCV RNA levels and histological liver lesions in patients with chronic HCV infection.

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-

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There has been a revolution in the treatment of chronic hepatitis C. Several oral regimens combining direct-acting antivirals (DAAs) from different families [NS5B nucleotide inhibitors, NS5B non-nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI)] have been developed. These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less. As of 2016 several regimens will be approved with additive potencies, without cross-resistance and with a good safety profile. Remaining issues will include increasing screening and access to care so that HCV may become the first chronic viral infection eradicated worldwide. This review summarizes results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection and discusses future perspectives.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.