Catherine Fleming

Hepatitis C Virus and Human Immunodeficiency Virus Coinfection in an Urban Population: Low Eligibility for Interferon Treatment

One hundred eighty human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients were prospectively evaluated for suitability for interferon and ribavirin therapy. Of the 149 patients with chronic HCV infection who completed the evaluation, 44 (30%) were eligible for treatment and 105 (70%) were ineligible, with the main barriers being missed clinic visits, active psychiatric illness, active drug or alcohol use, decompensated liver disease, or medical illness.

Noninvasive Markers of Liver Fibrosis Are Highly Predictive of Liver-Related Death in a Cohort of HCV-Infected Individuals With and Without HIV Infection

OBJECTIVES:Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality.METHODS:We assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child–Pugh–Turcotte (CPT) and model of end-stage liver disease (MELD) scores.RESULTS:A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86–0.96), CPT 0.91 (0.79–0.96), APRI 0.88 (0.80–0.93), Fib-4 0.87 (0.77–0.92), MELD 0.84 (71–0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT.CONCLUSION:Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD.

HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease.

Background:Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression. To date, few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts. The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with and without HIV infection. Methods:A sample of 97 subjects (40 HCV/HIV-coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing prospective cohort study was evaluated. Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria. Noninvasive markers of fibrosis studied included international normalized ratio, platelet count, aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and YKL-40. Results:The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection. Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed, this may be related to the small sample size. Conclusions:The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects. These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study.

Health-Related Quality of Life of Patients with HIV Disease: Impact of Hepatitis C Coinfection

Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations.

Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV.

Persons with human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV‐specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4‐enriched, liver‐infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon γ (IFN‐γ), tumor necrosis factor α (TNF‐α), and interleukin (IL) 10 was determined using enzyme‐linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN‐γ or TNF‐α in response to HCV or recall antigens. However, there was a significant increase in IL‐10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV‐specific IL‐10 cytokine response that may have implications for HCV‐related disease progression. (HEPATOLOGY 2004;40:125–132.)