GBV-C in HIV-HCV Coinfection, Low Liver–Related Mortality But High Overall Mortality

Abstract

We read with interest the recent article by Berzseyni et al indicating a reduction in hepatitis C virus (HCV)-related advanced liver disease, but not mortality, in association with GB virus-C (GBV-C) in human immunodeficiency virus (HIV) coinfected patients in the highly active antiretroviral therapy era.1Berzsenyi M.D. Bowden D.S. Kelly H.A. et al.Reduction in hepatitis C-related liver disease associated with GB virus C in human immunodeficiency virus coinfection.Gastroenterology. 2007; 133: 1821-1830Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar These are encouraging findings given that end-stage liver disease–related outcomes have been increasingly recognized as the main cause of mortality in HIV coinfected individuals.2Stapleton J. A new variable influencing HCV-related liver disease in HIV-HCV coinfected individuals?.Gastroenterology. 2007; 33: 2042-2043Abstract Full Text Full Text PDF Scopus (5) Google Scholar The strengths of this study include the strict inclusion criteria requiring both HIV positivity and HCV RNA positivity on stored samples collected ≥18 months apart, and exclusion of confounding host-mediated variables for liver disease progression, such as alcohol. GBV-C has previously been associated with improved overall survival in some3Kaiser T. Tillmann H.L. GB virus C infection: is there a clinical relevance for patients infected with the human immunodeficiency virus?.AIDS Rev. 2005; 7: 3-12PubMed Google Scholar but not all studies evaluating HIV-1 infected populations.4Zhang W. Chaloner K. Tillmann H.L. et al.Effect of early and late GBV-C viremia on survival of HIV infected individuals: A meta-analysis.HIV Medicine. 2006; 7: 173-180Crossref PubMed Scopus (92) Google Scholar Although this study noted a decrease in cirrhosis-free survival in GBV-C–infected patients, overall or liver-related mortality was not reduced in these patients in univariate modeling. However, the study notes that 10 of 25 deaths were liver related with 9 of 10 occurring in the GBV-C–negative group. Analyzing mortality rates according to liver or non–liver-related death using Fisher's exact test indicates no significant difference between the GBV-C–negative and active GBV-C group for overall mortality (16/114 vs 9/44; P = 1.0) or liver related death (9/107 vs 1/32; P = .45), but there is a significant difference toward higher non–liver-related mortality (7/105 vs 8/43; P = .038) in the GBV-C–positive population. Could this relate to a higher incidence of HIV/AIDS-related deaths in this group, which would be in contrast to previous findings in relation to GBV-C in HIV-1 infected patients? The duration of HCV infection has been defined based on date of diagnosis, but could only have been estimated in a proportion of these patients with documented blood exposure or during the 1st year of intravenous drug use. In addition, patients who potentially met inclusion criteria but had died before January 1996 were not included. Thus, using the starting point for survival analysis as time of diagnosis of HIV or HCV may have inadvertently introduced a length-time bias. Analysis starting at the date of inclusion into the prospective follow-up from 1996 onward would reduce the effect of such nonmonitored time before inclusion into the follow-up. In this regard it would be informative to know the CD4 cell count at entry into the prospective follow-up. Additional data should include the patients' CD4 nadir. Finally, because only 27% of the patients were biopsied, information regarding liver disease severity at baseline should be provided and included in multivariate modeling. Using the APRI index may be a feasible option in this regard as these biochemical values should be available. Reduction in Hepatitis C–Related Liver Disease Associated With GB Virus C in Human Immunodeficiency Virus CoinfectionGastroenterologyVol. 133Issue 6PreviewBackground & Aims: It has been reported that GB virus C infection (GBV-C) leads to improved morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. However, GBV-C has no effect on the course of liver disease in hepatitis C virus (HCV) monoinfection. The aim of the study was to determine the influence of GBV-C infection on liver disease in patients with HCV/HIV coinfection. Methods: Data on 158 HCV/HIV patients were collected from January 1996 to October 2005. Two plasma specimens, collected at least 18 months apart, were tested for GBV-C RNA by reverse transcription-polymerase chain reaction with primers to the NS5B gene and confirmed using E2 gene primers and sequencing. Full-Text PDF ReplyGastroenterologyVol. 134Issue 7PreviewWe thank Tillmann, Patel, and McHutchison for their comments regarding our recently published work in Gastroenterology showing that GBV-C RNA is associated with a reduction in the severity of HCV-related liver disease but not mortality in HIV coinfected subjects.1 Full-Text PDF