Abstract
BackgroundMitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients.MethodsWe carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk.ResultsThe study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups (p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups (p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values.ConclusionsEuropean mitochondrial haplogroups may influence the natural history of chronic hepatitis C.
Highlights
Mitochondrial DNA haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
74.9% were male, the median age was 40.7 years, 86% acquired HIV by injection drug use, 30.2% had prior AIDS-defining conditions, 81.5% were on combination antiretroviral therapy (cART), 12.3% reported a high intake of alcohol, the median baseline CD4+ T-cell count was 485 cells/mm3, 74.2% had an undetectable HIV viral load, 76.9% were infected by genotypes 1 or 4, and 78.4% had HCV RNA ≥ 500,000 IU/mL
In the multivariate analysis, haplogroup T was associated with an increased hazard of developing liver-related events (LREs) [adjusted SRH = 3.56; p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [adjusted subhazard ratio (aSHR) = 0.36; p = 0.105]
Summary
Mitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients. We lack predictive models to estimate the risk of fibrosis and clinical progression in individuals early on in their HCV infection, several factors are associated with increased risk of progression of liver fibrosis, including age, male gender, high alcohol intake, obesity, insulin resistance, type 2 diabetes, coinfection with human immunodeficiency virus (HIV) hepatitis B virus, and immunosuppressive therapy [3]. The macro-haplogroup JT is subdivided in haplogroups J (8% of the population) and T (9% of Europeans)
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