Christopher A. Aoki

Increased Soluble Leptin Receptor Levels in Morbidly Obese Patients With Insulin Resistance and Nonalcoholic Fatty Liver Disease

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMAIR) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.

The Evaluation of Patients with Hepatitis C Living in Rural California via Telemedicine

Patients with hepatitis C who live in rural and low socioeconomic communities often lack access to specialty care. Over the past 7 years, we have provided telemedicine consultations at the Peach Tree Clinic, located in rural northern California. We performed a retrospective analysis of our experience. During this time period we provided consultations for 103 patients with hepatitis C; 37% had cirrhosis, and 64% had never undergone therapy with interferon and ribavirin. Twenty-three percent of the patients were candidates for therapy. The most common contraindication to therapy was the severity of their disease and the risk of decompensation. Fifteen patients were evaluated for liver transplant; 2 were listed but none survived long enough to receive a liver transplant. Our data suggest that there is a large number of patients with hepatitis C and advanced liver disease living in rural communities, some of whom may need treatment or liver transplant. Telemedicine is an effective tool for identifying and treating patients with hepatitis C who live in rural communities.

Gene expression by PBMC in primary sclerosing cholangitis: Evidence for dysregulation of immune mediated genes

Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6) and membrane-spanning 4-domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

Decreasing disparity in liver transplantation among white and Asian patients with hepatocellular carcinoma : California, 1998-2005.

A preliminary study using national cancer surveillance data from 1998 through 2002 suggested that there were significant differences between non‐Hispanic whites (‘whites’) and Asian/Pacific Islanders (APIs) in the use of liver transplantation as a treatment for hepatocellular carcinoma (HCC).

41 – CYTOSKELETAL AUTOANTIBODIES/ANTI-ACTIN ANTIBODIES

ABSTRACT Anti-cytoskeleton antibodies were one of the first few autoantibodies to be discovered and have been found in a number of disease states. Further characterization of these autoantibodies has shown that these autoantibodies bind the principal components of microtubules, microfilaments, and intermediate filaments, which include actin, tubulin, keratin, vimentin, desmin, glial fibrillary acidic protein, peripherin, neurofilaments, alpha-internexin, and nuclear lamins. Because of their ubiquitous presence, cytoskeletal proteins are isolated from a number of different tissues and cells, and antibodies are detected using a variety of methods. Their significance is still under investigation but it has been suggested that they may be markers of ongoing tissue damage and non-specific B cell stimulation. Thus far, the presence of anti-cytoskeletal antibodies has not been shown to be pathogenic and is of limited clinical utility.