Faculty Bibliography

Outbreaks of acute hepatitis C virus (HCV) infection are occurring in HIV-infected men who have sex with men. We evaluated risk factors and liver histopathology in 11 consecutively enrolled men with newly acquired HCV infection that was diagnosed on the basis of antibody seroconversion, new elevations in alanine aminotransferase level, and wide fluctuations in HCV RNA level. Ten patients reported unprotected anal intercourse, and 7 reported 'club-drug' use, including methamphetamine. Liver biopsy showed moderately advanced fibrosis (Scheuer stage 2) in 9 patients (82%). No cause of liver damage other than acute HCV infection was identified. The specific pathways leading to periportal fibrosis in HIV-infected men with newly acquired HCV infection require investigation

BACKGROUND: Prior research on adherence to hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence. AIMS: To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings. METHODS: One hundred and eighty patients on treatment for hepatitis C (23% coinfected with HIV) completed a cross-sectional survey at the site of their hepatitis C care. RESULTS: Seven per cent of patients reported missing at least one injection of pegylated interferon in the last 4 weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load. CONCLUSIONS: Self-reported dose non-adherence to hepatitis C treatment occurs frequently. Further studies of dose non-adherence (assessed by method other than self-report) and its relationship to HCV virological outcome are warranted

BACKGROUND/AIMS: Hepatic steatosis is caused by the complex interaction of host and viral factors, such as metabolic syndrome (MS), alcoholism and HCV genotype, and in HIV-HCV co-infected patients, antiretroviral therapy may also play a role. A large population of patients from the AIDS Pegasys Ribavirin International Co-infection Trial (APRICOT) had paired liver biopsies interpreted and graded for steatosis along with lipid measurements and anthropometric data. METHODS: We analyzed these patients to determine the prevalence of steatosis, baseline factors associated with steatosis, effect of steatosis in HCV therapy efficacy and the impact of anti-HCV treatment on steatosis. RESULTS: A total of 65/283 (23%) patients with paired biopsies were positive for steatosis. Patients with steatosis were significantly more likely to have HCV genotype 3, bridging fibrosis/cirrhosis, higher HCV RNA levels, increased triglycerides and lower cholesterol levels. The only different body measurement was neck circumference which was greater in patients with steatosis and significantly decreased from baseline during the study. Hip circumference was predictive of steatosis at baseline. CONCLUSIONS: Factors associated to the metabolic syndrome are important in co-infected patients. Treatment outcome affected steatosis in that viral eradication reduced steatosis in genotype 3 patients, but altogether steatosis did not affect efficacy of treatment in any genotype

Licensed oral agents for antiviral therapy in patients with chronic hepatitis B virus (HBV) infection include lamivudine, adefovir, entecavir, and telbivudine. Emtricitabine, tenofovir, and the combination of tenofovir plus emtricitabine in 1 tablet, which are licensed for the treatment of human immunodeficiency virus infection, are additional off-label options for treating HBV infection. Preventing HBV antiviral drug resistance to nucleoside/nucleotide analogues and appropriate management when resistance occurs has become a major focus in the management of chronic hepatitis B. HBV antiviral drug resistance may be best prevented by using an agent or combination of agents with a high genetic barrier to resistance, and 2 potent nucleoside and nucleotide drugs with different resistance profiles may prove to be the optimal first-line treatment for chronic hepatitis B. Frequent assessment of quantitative serum HBV DNA remains the best approach to early detection of resistance, and antiviral therapy should be modified as soon as resistance is detected. Results from several clinical trials have shown that the addition or substitution of newer antiviral agents can restore suppression of viral replication, normalize alanine aminotransferase levels, and reverse histologic progression in patients with resistance to lamivudine, but little information exists regarding the long-term benefits of second-line treatment regimens. Despite the substantial advances in treatment made to date, new agents with novel viral targets will be needed for patients who ultimately may fail second- or third-line therapy

OBJECTIVE: The impact of baseline CD4 status on hepatitis C virus (HCV) treatment response among patients with HIV/HCV coinfection was investigated using data from a randomized study of peginterferon alfa-2a (40KD) + ribavirin (Peg-IFN/RBV). METHODS: Of 860 patients treated with conventional interferon alfa-2a + ribavirin (IFN/RBV), peginterferon alfa-2a (40KD) + placebo (Peg-IFN), or Peg-IFN/RBV for 48 weeks, 857 patients had baseline CD4 data available and were included in the analysis. Efficacy and safety were analyzed according to baseline CD4 status as absolute cell count and proportion of total lymphocytes. RESULTS: Sustained virologic response (SVR) rates were highest with Peg-IFN/RBV across all CD4 strata. With Peg-IFN/RBV, SVR rates were independent of baseline CD4 in genotype 2/3 patients, but in genotype 1 patients, they tended to be higher with higher CD4 or CD4%. Frequencies of adverse events (AEs) and serious AEs were similar among treatment arms and CD4 strata. Withdrawal and dose reduction rates attributable to safety were highest with CD4 <200 cells/muL. CONCLUSIONS: Peg-IFN/RBV could be effective and well tolerated in HIV/HCV-coinfected individuals with stable HIV. With Peg-IFN/RBV, response tended to increase with higher CD4 counts in genotype 1; however, because of the paucity of patients with CD4 <200 cells/muL, these data require corroboration

An epidemic of acute hepatitis C is emerging among HIV-infected men who have sex with men (MSM), with a growing number of cases reported in the MSM population in the United States and Europe. We report a case of a 47-year-old HIV-infected MSM who sexually contracted acute hepatitis C and was treated with pegylated interferon and ribavirin for 24 weeks. After 4 weeks of therapy, the patient's HCV RNA level became undetectable and remained undetectable 1 year after the 24-week treatment course

BACKGROUND/AIMS: HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. RESULTS: HIV-positive patients were younger than controls (52 vs. 64 years, p<0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p<0.001), were more frequently symptomatic (51% vs. 38%, p=0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p=0.005), but a similar mean Child-Turcotte-Pugh score (7.0 vs. 7.5, p=0.05) and HCC staging score (Barcelona-Clinic-Liver-Cancer stages C+D in 50% vs. 58%, p=0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34 years after HCV infection, p=0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p=0.017), but median survival was similar (6.9 vs. 7.5 months, p=0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p<0.001), any proven therapy (HR, 2.19; p<0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p=0.010), Barcelona-Clinic-Liver-Cancer stages C+D (HR, 0.491; p<0.001), AST/ALT >or= 2.00 (HR, 0.597; p=0.001), AFP >or= 400 ng/mL (HR, 0.55, p=0.003), and platelets >or= 100,000/mm3 (HR, 0.651; p=0.012), but not HIV-serostatus (p=0.19). In HIV-infected patients without HCC therapy (n=33), median survival was longer with undetectable HIV RNA (<400 copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p=0.013). CONCLUSIONS: HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival

An international group of experienced hepatologists and virologists conducted a single-day workshop to review the management of patients with chronic hepatitis B receiving treatment with oral nucleosides or nucleotides. Guidelines regarding on-treatment management and available published data on the importance of serum hepatitis B virus (HBV) DNA as a marker of outcomes were reviewed. On-treatment monitoring strategies to define early virologic responses that might be predictive of better outcomes and a reduced risk of viral resistance were proposed for further study. This treatment plan, labeled the roadmap concept, recommends monitoring of serum HBV DNA levels to identify outcomes of therapy. Primary treatment failure was defined as a reduction of serum HBV DNA levels by less than 1 log10 IU/mL from baseline at week 12. Measurement of the HBV DNA level at week 24 was considered essential to characterize virologic responses as complete, partial, or inadequate. Complete virologic response was defined as negative HBV DNA by a sensitive assay (<60 IU/mL or <300 copies/mL); partial virologic response was defined as HBV DNA levels less than 2000 IU/mL (4 log10 copies/mL), and inadequate virologic response was defined as HBV DNA levels of 2000 IU/mL or greater (4 log10 copies/mL). Strategies are proposed for managing patients in each of these categories, depending in part on the rapidity with which HBV DNA suppression is achieved and the emergence of genotypic mutations that reduce the effectiveness of a specific drug. Future studies of the use of the roadmap concept in improving outcomes of chronic hepatitis B are warranted