https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20701

Design and validation of a histological scoring system for nonalcoholic fatty liver disease

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.

Steatohepatitis: a tale of two "hits"?

https://www.aspe.vb.it/it/downloads/Brunt%20classificazione%20NASH.pdf

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20466

Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity

Nonalcoholic steatohepatitis: An expanded clinical entity

Background/Aims: In the past, nonalcoholic steatohep atitis has been described mostly in obese women with diabetes. The aim of this study was to describe a series of patients with nonalcoholic steatohepatitis with a different clinical profile. Methods: The clinical, biochemical, and histological features of 33 patients with nonalcoholic steatohepatitis seen from July 1990 to June 1993 were analyzed. Results: The mean age was 47 years. All patients were antibody to hepatitis C virusnegative. Nineteen of 33 (58%) were men, 20 of 33 (61%) were nonobese, 26 of 33 (79%) had normal glucose levels, and 26 of 33 (79%) had normal lipid levels. Fourteen of 33 (42%) had normal glucose and lipid levels and were not obese. Thirteen of 33 (39%) had pathological increases in fibrosis, 5 of whom had micronodular cirrhosis. Of these 13 with severe, progressive disease, 8 (62%) were women, 8 (62%) were obese, 4 (31%) were diabetic or had an elevated glucose level, and 3 (23%) had hyperlipidemia. Although serum iron studies (transferrin saturation and ferritin) were abnormal in 18 of 31(58%), no patient had hemochromatosis. Conclusions: Nonalcoholic steatohepatitis can be a severe, progressive liver disease leading to the development of cirrhosis. It should no longer be considered a disease predominantly seen in obese women with diabetes.

https://www.gastrojournal.org/article/0016-5085(94)90235-6/pdf

Nonalcoholic steatohepatitis: an expanded clinical entity

Concurrence of Histologic Features of Steatohepatitis with Other Forms of Chronic Liver Disease

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Christine G. Janney

Papers

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions

Nonalcoholic steatohepatitis: An expanded clinical entity

Nonalcoholic steatohepatitis: an expanded clinical entity

Concurrence of Histologic Features of Steatohepatitis with Other Forms of Chronic Liver Disease

Repetitive Self-Limited Acute Pancreatitis Induces Pancreatic Fibrogenesis in the Mouse