NATAP - DDW Liver Conference, San Diego, May 21-24 - Report 9

CHRONIC HEPATITIS C: ASSOCIATION OF FAT AND FIBROSIS

It has been considered that diabetes can cause fatty liver which in turn may lead to fibrosis and cirrhosis. This study reported that diabetes, glucose >99, and increased weight (BMI-body mass index) are associated with advanced fibrosis.

Christian A. Speer, Janus P. Ong, Terry L. Gramlich, Navdeep Boparai, Zobair M. Younossi, Cleveland Clin Fdn, Cleveland, OH.

Background:

Excessive hepatic fibrosis and its associated clinical features (obesity, DM, etc.) may enhance fibrogenesis of chronic hepatitis C (CHC).

Aim:

To determine if hepatic steatosis (fat accumulation in liver) and clinical characteristics of patients with non-alcoholic fatty liver disease (NAFL) are associated with advanced fibrosis of CHC.

Methods:

213 Patients with biopsy proven CHC were identified from our database (6/97 - 3/99). Clinico-demographic data were obtained from charts and from mail/telephone surveys. One hepatopathologist (TG) reviewed all pathologic specimens, using the modified HAI (Ishak et al. 1995) and NAFL pathologic protocol (Younossi et al. 1998).

Results:

The mean age was 47.7 ± 10. There were 152 (71%) males, 167 (78%) whites, 30 (14%) blacks, and 9 (4%) Hispanics. Patients were divided into three groups according to the degree of fibrosis. Group 1 - no fibrosis (n=21), Group 2 - mild fibrosis (Ishak 1,2,3)(n=109) and Group 3 - severe fibrosis (Ishak 4,5,6)(n=83). Group 3 patients were more likely to be diabetic (p<0.001) and have an abnormal blood glucose (p=0.003). There was a trend of increasing body mass index (BMI) from group 1 to group 3 (Group 1 - 27.6, Group 2 - 28.5, Group 3 - 29.1, p=0.067). Gender, ethnicity, genotype, viral load and ALT were similar in all 3 groups. Patients in group 3 had a higher degree of steatosis (p<0.001), periportal necrosis (p<0.001), macrovesicular steatosis (p=0.021), more inflammation (p=0.028) and ballooning degeneration (p=0.022). Moreover, patients with aggressive NAFL (Types 3 and 4) were more commonly seen in fibrosis group 3 (p<0.001). The following features were significantly (p<0.05) associated with advanced fibrosis (Ishak fibrosis grade 5 and 6) as compared to no fibrosis: Glucose > 99 - odds ratio (OR) 11.5 [confidence interval (CI) 1.4-96], Periportal necrosis - OR 28.8 (CI 8-101), portal inflammation - OR 12 (CI 1.2-126), and severe NAFL - OR 14.3 (CI 1.8-114).

  Conclusion:

(1) Elevated glucose, DM and BMI are associated with increased fibrosis in patients with CHC. (2)Hepatic steatosis and inflammation were likewise associated with increased fibrosis. (3) Interestingly, both DM and increased BMI, which are risk factors for hepatic steatosis, may also exert their fibrogenic effect on patients with CHC through mechanisms similar to NAFL.