Hepatitis: Berk PD

Berk PD. · The Division of Digestive Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY. · Hepatology. · Pubmed #16447279 No free full text.

This publication has no abstract.

Berk PD. · No affiliation provided · Semin Liver Dis. · Pubmed #10895427 No free full text.

This publication has no abstract.

Bradbury MW, Berk PD. · Department of Medicine (Division of Liver Disease), Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1039, New York, NY 10029, USA. · Clin Liver Dis. · Pubmed #15331068 No free full text.

Abstract: Hepatic steatosis is a consequence of both obesity and ethanol use.Nonalcoholic steatosis (NASH) resemble alcoholic steatosis and steatohepatitis. Both exhibit increased hepatocellular triglycerides(TG), reflecting an increase in long chain fatty acids (LCFA). LCFA enter cells by both facilitated transport and passive diffusion. A driving force for both is the plasma unbound LCFA concentration ([LCFAu]). In both obese rodents and obese patients, adipocyte LCFA uptake via both facilitated transport and diffusion is increased. However, the LCFA uptake Vmax in hepatocytes is not increased in obese animals. Nevertheless, total LCFA uptake in obese rodents is increased ~3-fold, reflecting increased plasma LCFA concentrations. With advancing obesity, resistance to the antilipolytic effects of insulin results in increased lipolysis within the omental fat depot, a consequent further rise in portal venous LCFA, and an even greater rise in portal [LCFAu]. This causes a further increase in hepatocellular LCFA uptake, increased intracellular generation of reactive oxygen species (ROS), and transition from simple steatosis to NASH. By contrast, in rodent hepatocytes and in human hepatoma cell lines, ethanol up-regulates the LCFA uptake Vmax. Consequently, although plasma LCFA are unaltered, hepatocellular LCFA uptake in ethanol-fed rats is also increased~3-fold, leading to increased ROS generation and evolution of alcoholic hepatitis. Thus, while increased hepatic LCFA uptake contributes to the pathogenesis of both NASH and alcoholic hepatitis,the underlying mechanisms differ. Recognizing these mechanistic differences is important in developing strategies for both prevention and treatment of these conditions.

Twaddell WS, Lefkowitch J, Berk PD. · Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, USA. · Semin Liver Dis. · Pubmed #18293283 No free full text.

Abstract: An asymptomatic 70-year-old Hispanic woman with type 2 diabetes was found in 2004 to have an AST of 132 U/L, ALT 146 U/L, alkaline phosphatase 1107 U/L, total serum bilirubin 3.5 mg/dL, and albumin 2.9 g/dL. Viral hepatitis testing was negative. Serum IgG, IgA, and IgM were all elevated, antimitochondrial antibody was weakly positive, and antinuclear antibody was negative. Liver biopsy was reported to show "evolving cirrhosis with marked lymphoid hyperplasia." Although the indication was nowhere stated, she was prescribed ursodeoxycholic acid 500 mg b.i.d, on which her biochemical tests initially improved. One year later she developed itching and jaundice. Imaging studies revealed multiple gallstones. An MRCP was suggestive of cirrhosis with a questionable common bile duct stricture, and she underwent ERCP with removal of gallbladder and common bile duct stones and placement of a biliary stent. A periampullary mass, which proved to be a somatostatinoma, was excised in 2006 via an open laparotomy, at which the stent was removed and a second liver biopsy performed. It was reported as showing chronic active hepatitis, activity stage 2, and fibrosis grade 3 with bridging. Her subsequent course was complicated by recurrent bleeding from small bowel arteriovenous malformations. Seen for the first time at Columbia University Medical Center in January 2007, she complained of continuing pruritus. AST was 69 U/L, ALT 43 U/L, alkaline phosphatase 491 U/L, and total bilirubin 3.3 mg/dL. Serum albumin was 2.6 g/dL. Antinuclear antibodies, negative in 2004, were now positive at 1:320, and antimitochondrial M2 antibodies were strongly positive. Serum IgG and IgA, but NOT IgM, were elevated. Review of her outside liver biopsies revealed features of primary biliary cirrhosis (PBC) in the first, and of both PBC and autoimmune hepatitis (AIH) in the second. The patient exhibits an overlap syndrome, in which both histologic and serologic features of AIH evolved in a setting initially most suggestive of PBC alone. The phenomenon of autoimmune overlap syndromes is discussed.