Hepatic Decompensation in Antiretroviral-Treated Patients Co-Infected With HIV and Hepatitis C Virus Compared With Hepatitis C Virus–Monoinfected Patients: A Cohort Study

Original Research | 18 March 2014

Vincent Lo Re III, MD, MSCE; Michael J. Kallan, MS; Janet P. Tate, ScD; A. Russell Localio, PhD; Joseph K. Lim, MD; Matthew Bidwell Goetz, MD; Marina B. Klein, MD, MS; David Rimland, MD; Maria C. Rodriguez-Barradas, MD; Adeel A. Butt, MD, MS; Cynthia L. Gibert, MD, MS; Sheldon T. Brown, MD; Lesley Park, MPH; Robert Dubrow, MD, PhD; K. Rajender Reddy, MD; Jay R. Kostman, MD; Brian L. Strom, MD, MPH; and Amy C. Justice, MD, PhD

[+-] Article and Author Information

Ann Intern Med. 2014;160(6):369-379. doi:10.7326/M13-1829

Background: The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone.

Objective: To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART.

Design: Retrospective cohort study.

Setting: Veterans Health Administration.

Patients: 4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment–naive.

Measurements: Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.

Results: The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients.

Limitation: Observational study of predominantly male patients.

Conclusion: Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race.

Primary Funding Source: National Institutes of Health.

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Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion-acquired HCV infection

Liver Int. 2014 Feb 16. doi: 10.1111/liv.12502. [Epub ahead of print]

Zavaglia C¹, Silini E, Mangia A, Airoldi A, Piazzolla V, Vangeli M, Stigliano R, Foschi A, Mazzarelli C, Tinelli C.

Abstract

AIMS: Aim of the study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening.

METHODS: Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption.

RESULTS: The follow-up was 22 (SD 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24 - 38). The cumulative incidence of liver failure was 0.4% (95%CI: 0.1 - 3.1), 4.9% (95%CI: 2.6 - 9.3) and 16.2% (95%CI: 10.4 - 24.7) at 10, 20 and 30 years after blood transfusion, respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared with 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age, respectively (HR 5.5, 95%CI: 2.78-10.7, p<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR 1.12, 95% CI 1.08-1.16 per year of age, p<0.001, >36 compared to ≤24 years, HR 10.3, 95% CI 3.9-26.9, p<0.001) and male sex (HR 4.2, 95% CI 1.7-10, p=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development (HR 1.12 per year [95% CI: 1.08-1.16], p<0.001 and HR 5.4 [95% CI 2.2-13.2], p<0.001, respectively)

CONCLUSIONS: In patients with transfusion-acquired HCV infection, age at transfusion affect the risk for hepatic decompensation. Age at transfusion and male sex are also independent risk factors for HCC development. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: HCV , blood transfusion, chronic hepatitis C, hepatic decompensation, hepatocellular carcinoma

PMID: 24529078 [PubMed - as supplied by publisher]

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Antiretroviral Therapy Reduces the Rate of Hepatic Decompensation among HIV- and Hepatitis C Virus-Coinfected Veterans

Clin Infect Dis. 2013 Nov 27. [Epub ahead of print]

Anderson JP, Tchetgen EJ, Lo Re V 3rd, Tate JP, Williams PL, Seage GR 3rd, Horsburgh CR, Lim JK, Goetz MB, Rimland D, Rodriguez-Barradas MC,Butt AA, Klein MB, Justice AC.

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.

Abstract

Background. HIV coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure. Methods. We evaluated 10,090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying antiretroviral regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of one hospital discharge diagnosis or two outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HR) of hepatic decompensation, comparing initiation of ART to non-initiation. Results. We observed 645 hepatic decompensation events in 46,444 person-years of follow-up (incidence rate: 1.4 per 100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to non-initiators (HR=0.72, 95% CI: 0.54, 0.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline (assuming they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR=0.59, 95% CI: 0.43, 0.82). Conclusions. Initiation of ART significantly reduced the rate of hepatic decompensation by 28-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.

PMID: 24285848 [PubMed - as supplied by publisher]

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