Soto B, Sánchez-Quijano A, Rodrigo L, et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis

Viral Hepatitis and AIDS Study Group, Virgen del Rocío University Hospital, Seville, Spain.
Journal of Hepatology (Impact Factor: 11.34). 02/1997; 26(1):1-5. DOI: 10.1016/S0168-8278(97)80001-3
Source: PubMed


To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C.
A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated.
Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05).
HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

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    • "Human immunodeficiency virus (HIV) accelerates the progression of human hepatitis C virus (HCV)-related liver disease in HIV/HCV co-infected patients (Balagopal et al., 2008; Benhamou et al., 1999; Soto et al., 1997; Thein et al., 2008). In general, the mean time from HCV infection to development of cirrhosis is about 30 years in mono-HCV-infected individuals, but in HIV/HCV coinfected patients the time of onset becomes significantly shorter (Benhamou et al., 1999; Macías et al., 2009; Mohsen et al., 2003; Pineda et al., 2007; Soto et al., 1997) and the occurrence of cirrhosis becomes more frequent (Bonacini et al., 2001; Ioannou et al., 2013; Mohsen et al., 2003; Parodi et al., 2007) than in mono-HCVinfected patients. However, the underlying mechanisms of the accelerated progression to liver fibrosis and cirrhosis due to HIV/HCV co-infection are not fully understood. "
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    ABSTRACT: HIV/HCV co-infection is characterized by higher serum HCV RNA loads compared with HCV monoinfection. However, the relationship between HIV and HCV replication remains to be clarified. HIV Vpr has been shown to play an essential role in HIV replication. In this study, we aimed to explore the role of Vpr in HCV replication and pathogenesis. We therefore used the genotype 2a full-length HCV strain JFH1 infection system and the genotype 1b full-length HCV replicon OR6 cell line to analyze the effects of Vpr on HCV replication. We found that Vpr promoted HCV 5' UTR activity, HCV RNA replication and HCV protein expression in two HCV infection cell models. Additionally, lymphocyte-produced Vpr significantly induced HCV 5' UTR activity and HCV replication in hepatocytes. We also found that Vpr up-regulated the expression of miR-122 by stimulating its promoter activity. Furthermore, a miR-122 inhibitor suppressed the Vpr-mediated enhancement of both HCV 5' UTR activity and HCV replication. In summary,our results revealed that the Vpr-upregulated expression of miR-122 is closely related to the stimulation of HCV 5' UTR activity and HCV replication by Vpr,providing new evidence for how HIV interacts with HCV during HIV/HCV co-infection.
    Journal of General Virology 04/2015; 96(8). DOI:10.1099/vir.0.000169 · 3.18 Impact Factor
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    • "Furthermore, HIV seroconversion and antiretroviral therapy (ART) initiation [Beld et al., 1998; John et al., 1998; Rutschmann et al., 1998; Ragni and Bontempo, 1999; Chung et al., 2002; Cooper and Cameron, 2002; Pett et al., 2002] are both associated with sustained increases in HCV RNA. The clinical course of HCV infection is also accelerated in patients co-infected with HIV and HCV, as they experience more advanced liver fibrosis, cirrhosis, and death than patients with HCV mono-infected [Soto et al., 1997; Lesens et al., 1999; Yee et al., 2000; Bica et al., 2001; Puoti et al., 2001; Ragni and Belle, 2001; Martinez- Sierra et al., 2003; Mohsen et al., 2003; Poynard et al., 2003; Tedaldi et al., 2003]. Further compounding the clinical management of HCV, HIV co-infection results in decreased response rates to HCV treatment compared to HCV mono-infection [DiMartino et al., 2001; Perez-Olmeda et al., 2003; Chung et al., 2004]. "
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    ABSTRACT: Viral diversity is an important predictor of hepatitis C virus (HCV) treatment response and may influence viral pathogenesis. HIV influences HCV variability in the plasma; however, limited data on viral variability are available from distinct tissue/cell compartments in patients co-infected with HIV and HCV. Thus, this exploratory study evaluated diversity of the hypervariable region 1 (HVR1) of HCV in the plasma and liver for 14 patients co-infected with HIV and HCV. Median intra-patient genetic distances and entropy values were similar in the plasma and liver compartments. Positive immune selection pressure was observed in the plasma for five individuals and in the liver for three individuals. Statistical evidence supporting viral compartmentalization was found in five individuals. Linear regression identified ALT (P = 0.0104) and AST (P = 0.0130) as predictors of viral compartmentalization. A total of 12 signature amino acids that distinguish liver from plasma E1/HVR1 were identified. One signature amino acid was shared by at least two individuals. These findings suggest that HCV compartmentalization is relatively common among patients co-infected with HIV and HCV. These data also imply that evaluating viral diversity, including drug resistance patterns, in the serum/plasma only may not adequately represent viruses replicating with in the liver and, thus, deserves careful consideration in future studies. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 08/2014; 86(8). DOI:10.1002/jmv.23968 · 2.35 Impact Factor
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    • "In the HAART era, the longevity of HIV infected individuals has significantly improved and chronic conditions such as HCV infection are emerging as important factors in morbidity and mortality [6] [7] [8]. HIV/HCV coinfected individuals develop the complications of HCV infection (i.e., cirrhosis of liver, end-stage liver disease, and hepatocellular carcinoma) more rapidly than those with HCV monoinfection [9] [10]. Similarly, some ISRN Gastroenterology studies have shown that the incidence of AIDS defining illnesses are increased among HIV/HCV infected individuals compared to those with HIV monoinfection [11] [12] [13], while others have not confirmed this [7] [13]. "
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    ABSTRACT: Background. Understanding the predictors of mortality in individuals with human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfection can be useful in management of these patients. Methods. We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for these analyses. Multivariate Cox-regression models were used to determine predictors of mortality. Results. Among 8,039 HIV infected veterans, 5251 (65.3%) had HCV coinfection. The all-cause mortality rate was 74.1 (70.4-77.9) per 1000 person-years (PY) among veterans with HIV/HCV coinfection and 39.8 (36.3-43.6) per 1000 PY for veterans with HIV monoinfection. The multivariable adjusted hazard ratio (95% confidence interval) of all-cause mortality for HCV infection was 1.58 (1.36-1.84). Positive predictors of mortality included decompensated liver disease (2.33 (1.98-2.74)), coronary artery disease (1.74 (1.32-2.28)), chronic kidney disease (1.62 (1.36-1.92)), and anemia (1.58 (1.31-1.89)). Factors associated with reduced mortality included HCV treatment (0.41 (0.27-0.63)) and higher CD4 count (0.90 (0.87-0.93) per 100 cells/ μ L higher count). Data were insufficient to make informative analyses of the role of HCV virologic response. Conclusion. HCV coinfection was associated with substantial increased risk of mortality among HIV infected veterans. HCV treatment was associated with significantly lower risk of mortality.
    04/2014; 2014:764540. DOI:10.1155/2014/764540
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