ABSTRACT
CONTEXT: Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood. OBJECTIVE: To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system. MAIN OUTCOME MEASURE: Incidence of composite outcome of ESLD, HCC, or death. RESULTS: Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95) per 1000 person-years (P < .001). In multivariable negative binomial regression, fibrosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all-cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P = .009); F3, 3.18 (95% CI, 1.47-6.88; P = .003); and F4, 3.57 (95% CI, 2.06-6.19; P < .001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR, 0.27; 95% CI, 0.19-0.38; P < .001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P = .23). In contrast, no events were observed in the 51 patients with sustained virologic response (n = 36) and relapse (n = 15), including 19 with significant fibrosis. CONCLUSION: In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.
Subject(s)
Coinfection , End Stage Liver Disease/mortality , HIV Infections/drug therapy , HIV Infections/mortality , Hepatitis C/complications , Liver Cirrhosis/classification , Adult , Antiviral Agents/therapeutic use , Baltimore/epidemiology , Biopsy , Carcinoma, Hepatocellular/mortality , Disease Progression , Female , HIV Infections/complications , Humans , Incidence , Liver/pathology , Liver Cirrhosis/mortality , Liver Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
OBJECTIVES: To define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease. DESIGN: This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years). METHODS: Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression. RESULTS: A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9). CONCLUSION: Over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression.
