Lakshmi Alaparthi

Anti-adipocyte antibody response in patients with non-alcoholic fatty liver disease.

A significant number of autoantibodies have been reported in patients with non‐alcoholic fatty liver disease (NAFLD) patients. In the present study, our aim was to assess the role of disease and cell‐specific antibodies, namely anti‐adipocyte antibodies (anti‐AdAb) in patients with NAFLD and non‐alcoholic steatohepatitis (NASH).

Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct-Acting Antivirals for Hepatitis C

Sustained virologic response (SVR) after direct‐acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post‐SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR. Overall, 62% had improved liver stiffness that was consistent with regression of at least one stage of fibrosis. In the cirrhosis group, 48% showed fibrosis regression by at least two stages by TE (<9.5 kPa). In the F3 fibrosis group, 39% regressed by at least two stages (<7 kPa). The median time from SVR to regression by TE was 1 year. Fifteen patients with liver biopsies prior to SVR underwent a biopsy after SVR; 13 of these patients had improved liver stiffness (to <9.5 kPa). The post‐SVR liver biopsies of only 4 patients showed F1‐F2 while 11 patients showed F3‐F4; however, morphometry of the first 11 biopsied patients revealed that 10 patients had an average 46% decrease in collagen content. Conclusion: This is the first DAA study that also has paired liver biopsies showing fibrosis regression. After SVR is achieved, improvements in liver stiffness measured by TE are seen in a majority of patients with advanced fibrosis/cirrhosis within 2 years. TE improvements are overstated when compared to histologic staging but confirmed with morphometric analysis. It is unclear whether TE following SVR can reliably predict when patients no longer require advanced fibrosis/cirrhosis monitoring after SVR.

Mo1996 Inflammatory Cytokines Are Associated With Hepatic Steatosis and Fibrosis Measured by Computer-Assisted Morphometry (CAM) in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)

BACKGROUND: Systemic inflammation has been shown to play an important role in the development and progression of NASH and related fibrosis. AIM: To compare inflammationassociated cytokines with the degree of liver fibrosis and steatosis as measured by computerassisted morphometry (CAM). METHODS: Liver biopsies, clinical data and fasting serum samples had been collected after informed consent. Biopsies were semiquantitatively graded for histopathologic features, and digital images of Sirius red stained sections was used to determine the fraction of collagen and steatosis on a continuous scale by CAM. Serum from the time of liver biopsy was examined with a Bio-Plex Pro Human Cytokine 17-plex assay (Bio-Rad) run on a Bio-Plex 200 (Bio-Rad). RESULTS: 66 NAFLD subjects are included [22 (33.3%) male, 51 (76.6%) Caucasian, 23 (34.8%) diabetes mellitus, 28 (42.4%) with histologic NASH, and 5 (7.6%) with histologic cirrhosis]. The amount of collagen as measured by CAM correlated moderately with the semiquantitative stage of portal fibrosis (r = 0.49, p < 0.0001). The percentage of fat as measured by CAM highly correlated with semiquantitative grade of steatosis (r=0.74, p < 0.0001). Percentage of collagen as measured bymorphometry correlated with IL-1β and IL-7 (r = 0.37, p < 0.01; r = 0.39, p=0.001, respectively). On the other hand, TNF-α was positively associated with both percentage of fat (CAM) and grade of steatosis (r = 0.32, p < 0.01; r = 0.35, p < 0.01, respectively). CONCLUSIONS: These results show that CAM can provide a new dimension to standard histology with the capability of uncovering unsuspected associations with circulating biochemical markers, and may lead to a better understanding of pathogenetic mechanisms in liver disease