Hepatocellular mitochondrial alterations in patients with chronic hepatitis C: Ultrastructural and biochemical findings

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with increased l ipoperoxidation, which may lead to interference with mitochondrial function with possible depletion of mitochondrial DNA (mtDNA). We correlated the ul tra structural findings of liver biopsy specimens with the lipoperoxidation markers and contents of mtDNA in chronic hepatitis C (CHC) patients with a different HCV genotype. METHODS: Liver biopsy samples obtained from 75 CHC patients were processed for histological and electron microscopic examination. Twenty-two subjects without known liver disease served as controls. Hepatic glutathione in its reduced (H-GSH) and oxidized (H-GSSG) forms were determined from biopsy spe cimens by high-performance liquid chromatography. Plasmatic and lymphocytic GSH and erythrocytic malonyldialdehyde (MDA) were also determined, along w ith the ratio between mtDNA and nuclear DNA (nDNA). RESULTS: Ultrastructural alterations of the mitochondria were documented in 23 patients with genotype Ib, compared with 15 patients with genotype 2a/2 c (p = 0.020) and seven patients with genotype 3a (p < 0.001). A significan t depletion of H-GSH and lymphocytic GSH, an increase of H-GSSG and MDA, an d a reduction of the mtDNA/nDNA ratio were documented in patients with geno type Ib, compared with patients with genotype 2a/2c and 3a and with control s. CONCLUSIONS: In patients with genotype 1b frequent ultrastructural alterati ons of the mitochondria may be observed, and the depletion of mtDNA in thes e patients may represent the expression of a greater impairment of the proc ess of oxidative phosphorylation. An increased production of free radicals in patients with genotype Ib may influence the evolution of the liver disea se by enhancement of the cytopathic effect of HCV. (Am J Gastroenterol 1999 ;94: 2198-2205. (C) 1999 by Am. Cell. of Gastroenterology).