https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.28431

Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes

Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis

Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

Nonalcoholic fatty liver disease.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.29367

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element–binding proteins (SREBPs). SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1–4). In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles. The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice. These studies form the subject of this review.

/pdf/srebps-activators-of-the-complete-program-of-cholesterol-and-1sop601qwq.pdf

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.510310209

Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid.

Is there a role for liver biopsy in primary sclerosing cholangitis

The aim of this study was to determine if a relationship exists between nonalcoholic steatohepatitis (NASH) and serum levels of free fatty acids, choline deficiency, or celiac disease. Forty-seven patients with liver biopsy proven NASH were enrolled. Total serum free fatty acids and anti-endomysial antibodies were determined in all patients, while plasma free and phospholipid-bound choline were determined in 29 patients. Total serum free fatty acid concentration correlated significantly with female gender and serum albumin concentration. Patients with severe fibrosis on liver biopsy had significantly greater serum concentration of free fatty acids than patients without severe fibrosis. Plasma free and phospholipid-bound choline levels were normal and no significant correlation was found between the concentration of plasma free or phospholipid bound choline, and the severity of liver damage. Only one of the 47 patients with NASH had a positive titer for the anti-endomysial antibody. In conclusion, increased serum concentrations of free fatty acids were found in NASH and were associated with development of more severe liver disease. Neither choline deficiency nor celiac sprue by anti-endomysial antibody testing was associated with NASH.

Nutritional and metabolic considerations in the etiology of nonalcoholic steatohepatitis.

Bone disease in primary biliary cirrhosis: Independent indicators and rate of progression

Objective To determine outcomes in patients undergoing liver transplantation (LT) for metastatic neuroendocrine tumors (NETs). Design Retrospective analysis. Setting University of Kentucky Medical Center. Patients Patients undergoing LT performed for NET metastases from October 1, 1988, through January 31, 2008, were analyzed using the United Network for Organ Sharing database. Main Outcome Measure Patient survival. Results During the study period, 87 280 LTs were performed. One hundred fifty LTs were performed for metastatic NETs. Among those 150 patients undergoing LT, 51 patients (34.0%) had carcinoid, 6 had insulinoma (4.0%), 3 had glucagonoma (2.0%), 11 had gastrinoma (7.3%), and 9 had vasoactive intestinal peptide–secreting tumors (6.0%); an additional 70 (46.7%) had an unspecified NET. The mean (SE) age of the patients was 45.1 (12.5) years. The mean (SE) cold ischemic time was 8.9 (4.1) hours. One hundred forty-four patients were adults and 6 were children. Thirteen patients received another organ at the time of LT. During the same period, 4693 patients underwent transplantation for hepatocellular carcinoma. Overall, 1-, 3-, and 5-year survival rates for patients with NETs undergoing isolated LT were 81%, 65%, and 49%, respectively. No difference in survival was observed in patients with carcinoid vs noncarcinoid tumors (P = .84). No significant difference was observed in patient survival between those with metastatic NETs and those with hepatocellular carcinoma. Patients waiting for LT longer than 2 months had improved survival (P = .005). Conclusions Patients with liver metastases from NETs who were undergoing LT had long-term survival similar to that of patients with hepatocellular carcinoma. Longer wait times were associated with better outcomes in our series. Waiting for disease to stabilize before considering patients with liver metastases from NETs for transplantation may be appropriate. Excellent results can be obtained in highly selected patients.

https://jamanetwork.com/journals/jamasurgery/articlepdf/1107098/soa05101_953_958.pdf

Paul Angulo

Papers

Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid.

Is there a role for liver biopsy in primary sclerosing cholangitis

Nutritional and metabolic considerations in the etiology of nonalcoholic steatohepatitis.

Bone disease in primary biliary cirrhosis: Independent indicators and rate of progression

Liver Transplantation for the Treatment of Liver Metastases From Neuroendocrine Tumors: An Analysis of the UNOS Database