Long-term outcome of chronic hepatitis C virus infection in a real-world setting: The German LOTOS study.

BACKGROUND & AIMS: There are few large-scale, prospective studies comparing liver-associated events in treated and untreated patients with CHC managed in routine clinical practice. METHODS: Patients with CHC were prospectively enrolled in a non-interventional study. Data from patients with available documentation who had either achieved a sustained virological response, or were non-responders, relapsers, or had virological breakthrough following treatment with peginterferon alfa-2a±ribavirin, or who had been diagnosed but never treated at least 3 years previously, and who remained under medical observation were analyzed. Primary endpoint was liver-associated events (composite of decompensation/liver failure, ascites, hepatocellular carcinoma, or liver transplant/placement on a transplant list). RESULTS: In all, 1444 eligible patients were identified. Mean follow-up was 4.7 (standard deviation; SD 1.1) years. Patients with sustained virological response had a lower incidence of liver-associated events vs non-responders, relapsers, or virological breakthrough and never treated patients (1.7% vs 4.7% and 4.7% respectively). The proportion of patients with cirrhosis increased from baseline in the non-responders, relapsers, or virological breakthrough (6.8%-10.5%) and never treated group (3.7%-8.4%), with an associated increase in severity, but was unchanged in the sustained virological response group (2.1%). Event-free survival was significantly higher in sustained virological response patients (P=.0082). CONCLUSIONS: In this "real-world" cohort, the achievement of sustained virological response almost eliminated liver-related morbidity and mortality compared with patients who failed to achieve sustained virological response and those who were untreated. Overall, the LOTOS cohort highlights the importance of timely and effective treatment for patients with CHC.

Pegylated interferon alpha-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients.

OBJECTIVES: HIV-coinfection accelerates the course of HCV-related liver disease. Since, highly active anti-retroviral therapy significantly improved survival of HIV-patients more coinfected patients develop end stage liver disease. Therefore, treatment options for chronic hepatitis C in HIV-coinfected patients need to be evaluated. METHODS: Efficacy and safety of pegylated interferon alpha-2b (peg IFN) plus ribavirin (RBV) was examined within this prospective, uncontrolled, multicentre trial. Patients received peg IFN (1.5 microg/kg) once weekly plus RBV 800 mg daily for 48 weeks for HCV genotypes (GT) 1/4 and 24 weeks for GT 2/3. RESULTS: One hundred and twenty-two patients were enrolled. Patients were predominantly male (68%) and former i.v. drug users (61%). Baseline characteristics (median) were as follows: age 39 years (range 23-58), CD4 count 494 cells/microl (range 150-1578/microl), HIV-RNA 2.3log copies/ml (range <1.7-5.4log copies/ml). 61% currently received anti-retroviral treatment. Fifty-six percent had HCV GT 1. EOT response was achieved by 52%. However, only 25% achieved sustained response (SR) due to a high relapse rate. SR rates were significantly higher among patients with GT 2/3 compared to those with GT 1/4 (44 vs. 18%). SR was observed in only one patient without early response (ER). Discontinuation rate was 30%, 21% discontinued due to adverse events. CONCLUSION: Peg IFN/RBV appears safe and effective in HIV/HCV-coinfected patients. GT 2/3 is associated with better SR. Lack of ER strongly predicts non-response. High relapse rates substantially reduce treatment success. In terms of toxicity neuro-psychiatric side effects frequently required treatment discontinuation.

A prospective controlled study of interferon-based therapy of chronic hepatitis C in patients on methadone maintenance.

We examined the feasibility of hepatitis C treatment in patients on opioid maintenance. One hundred patients with chronic hepatitis C, 50 on methadone maintenance, and 50 with no intravenous drug use or opioid maintenance for at least 5 years were prospectively matched for sex, age, hepatitis C virus (HCV) genotype and HCV RNA. The primary end point was undetectable HCV RNA at 24 weeks posttreatment. Treatment with peginterferon alfa-2b (1.5 microg/kg per week) and ribavirin (1000-1200 mg /day) was initiated for 24 weeks (HCV genotype 2, 3) or 48 weeks (HCV genotype 1, 4). Within the first 8 weeks of therapy, discontinuation due to noncompliance or patient request was observed in 22% (11/50) in the methadone group versus 4% (2/50) in the control group (P =.02). After 8 weeks, there was no significant difference in discontinuation due to noncompliance or patient request (4/39 [10%] vs. 4/48 [8%]). There was no difference in discontinuation of therapy because of viral failure or adverse events (10/50 methadone vs. 6/50 control, P =.41). At the end of treatment, 50% (25/50) in the methadone group and 76% (38/50) in the control group had undetectable HCV RNA (P =.01). Sustained viral response was 42% (21/50) in the methadone group and 56% (28/50) in the control group (P =.16). No serious psychiatric event occurred in either group. In conclusion, peginterferon and ribavirin seem reasonably safe and sufficiently effective in patients on methadone maintenance. Patients discontinuing therapy due to noncompliance or request did so early, thereby limiting the cost of an unsuccessful approach to treatment.