Impact of highly active antiretroviral therapy on the spectrum of liver disease in hcv-hiv coinfection

doi:10.1016/S1542-3565(04)00129-6

Clinical Gastroenterology and Hepatology

Volume 2, Issue 5, May 2004, Pages 432-439

Presented in part at Digestive Disease Week, Orlando, Florida, May 17–22, 2003.

https://doi.org/10.1016/S1542-3565(04)00129-6 Get rights and content

Abstract

$Background & Aims:$ Hepatitis C virus (HCV) coinfection is common in patients with human immunodeficiency virus (HIV) infection. The mortality associated with HIV has decreased dramatically with the introduction of highly active antiretroviral therapy (HAART). However, the impact of HAART, including protease inhibitors (PIs), nucleoside reverse-transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs), on the spectrum of HCV-related liver disease remains unclear. The purpose of this retrospective analysis is to determine the impact of PI and NNRTI use on liver histological characteristics in patients with stable HIV-HCV coinfection (n = 101) compared with HIV-uninfected controls with HCV infection (n = 302). $Methods:$ The majority of coinfected patients were men (75%), African American (82%), and had genotype 1 HCV (91%). Mean HIV load was 1.52 log copies/mL, 48% had undetectable HIV RNA and a mean CD4 count of 528 cells/μL, and 11% had a CD4 count < 200 cells/μL. Both mean alanine aminotransferase (ALT) level (83 U/L; 54% had a normal ALT level) and Knodell Histological Activity Index score (7.04; 33% had advanced fibrosis) were similar to those of our control population. Ninety-three percent of patients were administered a mean of 3 antiretroviral medications: NRTIs in 98%, NNRTIs in 45%, and PIs in 54%. $Results:$ There were no significant differences in biochemical or histological parameters between patients administered or not administered PIs or NNRTIs. $Conclusions:$ In this uncontrolled retrospective analysis, we were unable to show a significant impact of either PI or NNRTI use on the spectrum of liver disease.

Section snippets

Patient populations

A cross-sectional retrospective cohort analysis of consecutive coinfected patients evaluated by the Hepatology Section at the Virginia Commonwealth University Health System from 1997 to 2002 was performed. The control group consisted of a cohort of consecutive patients with chronic HCV infection without antibodies to HIV (anti-HIV) with similar risk factors evaluated during the same period. Inclusion criteria for coinfected patients were the presence of anti-HIV, and, for both groups, the

Population studied

Clinical characteristics of 101 coinfected patients and 302 patients with chronic HCV infection are listed in Table 1. Mean age of the coinfected population was 43 years, 75% were men, and 82% were black. This reflected our urban HIV clinic population. Mean and median HIV titers were 1.52 and 1.76 log copies/mL; 48% had undetectable HIV RNA (<400 copies/mL). Mean and median CD4 counts were 528 and 503 cells/μL (range, 52–2332 cells/μL); only 11% had a CD4 count < 200 cells/μL. Mean and median

Discussion

Our study provides several important findings regarding patients with HCV-HIV coinfection on stable HAART. First, a significant proportion of coinfected patients have a normal ALT level. Although we did not observe a significant difference in inflammation or fibrosis between patients with elevated and normal ALT levels, this may have been caused by a small sample size resulting in a type 2 error. Furthermore, our analysis included ALT level at the time of biopsy. Whether these individuals had

Acknowledgements

The authors thank the staff and providers of the HIV clinic at Virginia Commonwealth University Health System for their support, referral, and care of these coinfected patients.

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2012, Zakim and Boyer's Hepatology
Similar progression of fibrosis between HIV/HCV-infected and hcv-infected patients: Analysis of paired liver biopsy samples
2010, Clinical Gastroenterology and Hepatology
Fibrosis progression might be accelerated in patients who are coinfected with human immunodeficiency virus (HIV) and HCV (HIV/HCV). However, no studies have directly compared fibrosis progression by paired liver biopsy between patients infected with HIV and HCV versus those infected with only HCV.
Liver biopsy samples were collected from patients with HIV/HCV (n = 306) and those with HCV; biopsies from 59 without a sustained virologic response (SVR) or cirrhosis were matched with those from patients with only HCV (controls) for initial fibrosis stage, demographics, and HCV treatment. For HIV/HCV patients, categorical variables at baseline and the area under the curve of continuous variables per unit time were analyzed for associations with fibrosis progression.
Liver biopsies from HIV/HCV patients had more piecemeal necrosis than controls (P = .001) and increased lobular inflammation (P = .002); HIV/HCV patients also had shorter intervals between liver biopsies (4.7 vs 5.9 years, P < .0001). Between the first and second biopsies, fibrosis remained unchanged or progressed 1 or 2 units in 55%, 18%, and 18% of HIV/HCV patients, respectively, compared with 45%, 30%, and 9% of controls. The fibrosis progression rate was similar between HIV/HCV and control patients (0.12 ± 0.40 vs 0.091 ± 0.29 units/y; P = .72). In paired biopsies from 66 patients, including those with SVR, there were no associations between fibrosis progression and demographics; numbers of CD4+ T cells; levels of aspartate aminotransferase or alanine aminotransferase; use of highly active antiretroviral therapy; response to HCV therapy (no treatment, SVR, or non-response); baseline levels of FIB-4; or histologic features including inflammation, fibrosis, or steatosis.
On the basis of analysis of liver biopsy samples, fibrosis progression was similar between HIV/HCV-infected and HCV-infected patients; no clinical or laboratory parameters predicted disease progression.
Effect of Human Immunodeficiency Virus and Antiretrovirals on Outcomes of Hepatitis C: A Systematic Review From an Epidemiologic Perspective
2007, Clinical Gastroenterology and Hepatology
Citation Excerpt :
All studies showed a trend toward an association between HIV co-infection and liver-related death, although only 4 reported a statistically significant adjusted risk estimate that ranged from 2.26 to 17.5.36,41,42,44 We identified 11 studies (2 were also presented in Table 1) in which co-infected patients were reported to receive a quantifiable amount of antiretroviral therapy (Table 2 and Supplementary Table 4).24,25,45–53 Seven used a cross-sectional study design, whereas the other 4 were retrospective cohort studies.
Background & Aims: We systematically reviewed the literature examining the association of human immunodeficiency virus (HIV) and antiretroviral therapy (ART) with liver disease in patients with hepatitis C virus (HCV) infection. Methods: PubMed was searched for studies examining hepatic fibrosis, cirrhosis, decompensated liver disease, hepatocellular carcinoma, and liver-related death. Thirty-nine reports (describing 34 unique studies) met inclusion criteria. Information was abstracted on study design, sampling frame, inclusion/exclusion criteria, sample size, results, and covariates used for adjustment. Because of the heterogeneity among study designs, a meta-analysis was not conducted. Results: Nine of the 12 cross-sectional studies showed a statistically significant association between HIV co-infection and fibrosis or cirrhosis, whereas 7 retrospective cohort studies were inconsistent. Six studies examined decompensated liver disease as the outcome: 5 of these found a significantly increased risk in patients with HIV co-infection. The 7 studies examining liver-related death showed a trend toward an association with HIV co-infection, although only 4 were statistically significant. Four studies examined the effect of HIV on hepatocellular carcinoma, 2 of which found no association. Of 10 studies that investigated the effect of ART on the risk of liver disease, half reported a significant protective association. Conclusions: HIV co-infection is associated with an increased risk of advanced liver disease in hepatitis C virus–infected patients. Data on hepatocellular carcinoma are sparse, but an association is plausible given the increased risk of advanced liver disease. In contrast, data for an effect of ART are plentiful, but findings are inconsistent. More robust studies are needed on this topic.
HIV-Associated Hepatobiliary Disease
2006, Zakim and Boyer's Hepatology
HIV Infection of hepatocytes results in a modest increase in hepatitis C virus expression in vitro
2014, PLoS ONE
Relationship between the genetic variation in interleukin 28B and response to antiviral therapy in patients with chronic hepatitis C
2012, Chinese Medical Journal

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Original articleImpact of highly active antiretroviral therapy on the spectrum of liver disease in hcv-hiv coinfection

Abstract

Section snippets

Patient populations

Population studied

Discussion

Acknowledgements

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Original article
Impact of highly active antiretroviral therapy on the spectrum of liver disease in hcv-hiv coinfection