Liver Cells May Die More Quickly in HIV/HCV Coinfection (DDW, May 2000)

     Andrew H. Talal, Herman Yee, Douglas T. Dieterich, Weill Med Coll of Cornell Univ, New York, NY; New York Univ Med Ctr, New York, NY.

  Andy Talal from Cornell suggests in this study that liver cells may die more quickly in coinfected individuals than in those with HCV or uninfected. He says this may explain why HIV accelerates HCV progression.

  Hepatocyte apoptosis is increased in hepatitis C virus (HCV) infection. The human immunodeficiency virus-1 (HIV-1) increases CD4+ T cell proliferation and apoptosis. However, the effect of HCV/HIV-1 co-infection on hepatic parenchymal and mononuclear cell proliferation and apoptosis has not been evaluated. Therefore, we performed immunohistochemistry on hepatic tissue obtained from 7 HCV mono-infected, 7 HCV/HIV-1 co-infected, and 3 seronegative (uninfected) individuals. 5mm thick tissue-sections were stained with antibodies to detect lymphocyte subsets (CD3+, CD4+, and CD8+), proliferative (Ki-67+) and apoptotic (caspase-3+) cells. The mean number of cells per high power field was computed after counting five randomly selected microscopic fields (x40). 13/14 infected subjects had grade 1-2 necroinflammatory activity and stage 1-2 hepatic fibrosis.

Comparing virus infected to seronegative individuals, the mean CD3+ T cell number was significantly increased (32.4 vs. 15.9, p < 0.05). The mean number of CD4+ (2.8 vs. 4.5) and CD8+ (16.2 vs. 10.1) T cells did not differ significantly between the two groups. Comparing HCV/HIV-1 co-infected and HCV mono-infected individuals, the mean number of CD8+ (19.6 vs. 12.8, p < 0.05) T cells was significantly increased while the number of CD4+ T cells did not differ significantly between the two groups. Comparing virus-infected to seronegative individuals, the mean number of proliferating (3.4 vs. 0.4, p < 0.05) and apoptotic (0.8 vs. 0.0, p < 0.001) cells was also increased. Comparing HCV/HIV-1 co-infected and HCV mono-infected individuals, the number of proliferating and apoptotic cells were greater but did not differ significantly. Viral infection with HCV increases hepatic cell turnover when compared to seronegative individuals.

Talal concluded dual infection with HCV and HIV-1 further increases hepatic cellular turnover and may partially explain the accelerated course of liver disease in the HCV/HIV-1 co-infected individuals.

 Cellular changes in uninfected, HCV mono-infected, and HCV/HIV-1 co-infected subjects:


CD3+ CD4+ CD8+ Ki67+ Caspase-3+
Normal 15.9    5.9 4.5 7.7 10.1 3.2 0.4 0.4 0.0
HCV 31.8 16.0 3.2 3.2 12.8 6.3 2.9 2.4 0.7 0.5
HCV/HIV-1   32.5    6.8   2.5 0.7 19.6 4.0 3.9 2.1 0.9 0.3