Hepatitis C Viral Load and Its Correlation with Histologic Grade of Inflammation and Ultrastructural Features.
Stephanie D Norwood, Gurdip Sidhu, Nicholas Cassai, Guang-Yu Yang. Northwestern University Feinberg School of Medicine, Chicago, IL; New York University School of Medicine & New York VA Hospital, NY
Background: The host immune response induced by the hepatitis C virus (HCV) plays a predominant role in the pathogenesis of HCV, leading to inflammation, fibrosis, and sometimes eventual cirrhosis. Whether or not HCV directly causes cytopathic injury is not clear. In our previous study, we showed that HCV induces unique ultrastructural organelles called autophagosomes. In the present study, we further examine the relationship of HCV viral load to both the histologic grade of inflammation and stage of fibrosis as well as the electron microscopic (EM) findings in liver biopsies of HCV patients.
Design: 30 cases of HCV hepatitis liver biopsies were collected and the histologic grading of HCV hepatitis was determined using the following parameters on a scale of 0-4: portal inflammation (PI), piecemeal necrosis (PN) and stage of fibrosis. EM was also performed and the amount of HCV-induced autophagosomes graded on a scale of 0-3. HCV viral load (VL) was obtained and patients were categorized as having either a high VL (HVL) with >500,000 copies/mL or low VL (LVL) with <500,000 copies/mL. The histologic and EM findings were then compared between the 2 groups.
Results: 9/30 (30%) cases had a LVL (2000-370,000 copies/mL) and 21/30 (70%) cases had a HVL (540,000->5,000,000 copies). Of the LVL cases, 44% (4/9) had a PN grade of ≥2, 33% (3/9) had a PI grade of ≥2, 22% (2/9) had a stage of fibrosis ≥2, and 67% (6/9) had ≥2+ autophagosomes. Of the HVL cases, 67% (14/21) had a PN grade of ≥2, 76% (16/21) had a PI grade of ≥ 2, 62% (13/21) had a stage of fibrosis ≥2, and 86% (18/21) had ≥2+ autophagosomes. Overall, the HVL cases showed an increase in PN, PI, fibrosis, and autophagosome formation. The differences between the LVL and HVL cases were statistically significant for PI (p<0.0419).
Conclusions: Our results indicate the severity of portal inflammation is significantly correlated with HCV viral load. Although autophagosomes are a unique ultrastructural cytopathic change, the number of autophagosomes formed does not appear to be associated with viral load. Our results suggest the host immune-mediated inflammatory process together with direct viral cytopathic change is the crucial pathogenic process of hepatitis C.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 283, Wednesday Morning