Non-alcoholic steatohepatitis

Liver diseases Alcoholic hepatitis (A), hepatitis B and C (A), non-alcoholic steatohepatitis (A), liver transplantation (A), Wilson s disease (A)... 

HBV, hepatitis B HCV, hepatitis C IAP, inhibitor of apoptosis protein DBM, IAP binding motifs INCA, inhibitory CARD NASH, non-alcoholic steatohepatitis PCD, programmed cell death PCI, pan-caspase inhibitor OA, osteoarthritis RA, rheumatoid arthritis Smac, second mitochondria-derived activator of caspases TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. 

Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for nondiabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005 21 871-9. 

Thiazolidinediones cause recruitment and conversion of pre-adipocytes into adipocytes and are therefore adi-pogenic (75). In 18 patients without diabetes, mean age 46 years, who took pioglitazone 30 mg/day for 48 weeks for non-alcoholic steatohepatitis, there was a mean weight gain of 3.5 kg in 72% (76). Similarly, in 91 patients with type 2 diabetes who took pioglitazone 30 or 45 mg/day for... 

Causes of cirrhosis can usually be identified by the patient s history combined with serological and histological investigation. Alcoholic liver disease and hepatitis C and B are the most common causes of cirrhosis. The association of excessive alcohol consumption with liver disease has been recognised for centuries. After the identification of the hepatitis C vims and of non-alcoholic steatohepatitis in obese patients with diabetes, the diagnosis of cirrhosis without an apparent cause (cryptogenic cirrhosis) is rarely made. Genetic causes of cirrhosis include haemochromatosis and Wilson s disease. 

Epidemiological studies have identified a number of factors that contribute to the risk of developing cirrhosis. Regular (moderate) alcohol consumption, age older than 50 years, and male gender are examples that increase cirrhosis risk in chronic hepatitis C infection, and older age, obesity, insulin resistance or type 2 diabetes, hypertension and hyperlipidaemia in non-alcoholic steatohepatitis. 

Non-alcohol steatohepatitis Fat build-up in the liver eventually causes scar tissue associated with diabetes, protein malnutrition, obesity and coronary artery disease. Treatment with corticosteroid medications. Biopsy is needed for full diagnosis. 

Non-alcoholic fatty liver disease (NAFID) and non-alcoholic steatohepatitis (NASH)... 

Patient 1 Non-alcoholic steatohepatitis Mild hepatitis without cirrhosis... 

Xiang-Sheng F, Feng J (2006) Cisapride decreasing orocecal transit time in patients with non-alcoholic steatohepatitis. Hepatobiliary Pancreat Dis Int 5 534-537. 

Tilg H, Diehl A M 2000 Cytokines in alcoholic and non-alcoholic steatohepatitis. New England Journal of Medicine 343 1467-1476 Trauner M et al 1998 Molecular pathogenesis of cholestasis. New England Journal of Medicine 339 1217-1227... 

Causes of fatty liver are manifold, and combinations of causes quite common. Acquired causes are by far the most frequent, but there are also rare causes, e.g. coeliac disease (9, 25), parenteral nutrition. (28, 29) Congenital metabolic disorders can also lead to the development of a fatty liver, as in the case of a rare thesaurismosis. It is of considerable therapeutic and prognostic importance to differentiate between an alcoholic fatty liver (AFL) and alcoholic steatohepatitis (ASH) (s. pp 529, 531) as well as between non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH). (2, 20, 24, 36) (s. tabs. 31.5-31.7)... 

In 1980 the term non-alcoholic steatohepatitis (NASH) was introduced by J. Ludwig et al. to denote chronic liver disease with increased enzymatic activity and the histological picture of alcohol-induced hepatitis. (60) The histological feature itself was described by H. Thaler as early as 1962 in his paper Fatty liver and its relationship to cirrhosis . (76) Over the following years, transition from a diabetic fatty liver into cirrhosis was reported (S. Iron et al., 1979) as well as from an obesity-induced fatty liver into cirrhosis (M. Adler et al., 1979). 

Histologically, non-alcoholic steatohepatitis shows moderate to high-grade, mainly macrovesicular fatty degeneration of the liver cells with inflammatory infiltrates and formation of fibrosis. Cirrhosis frequently develops. Despite the morphological similarity to alcohol-induced fatty liver hepatitis, there is no (noteworthy) alcohol consumption involved in NASH. Viral or autoimmune hepatitis are not detectable either. There are no or only moderate subjective complaints. The transaminases are normal or slightly increased. NASH is mostly associated with obesity and/or type II diabetes, thus NASH is regarded as the hepatic manifestation of a metabolic syndrome. 

Fig. 31.7 Non-alcoholic steatohepatitis (NASH) Hydropic degenerated hepatocytes with Mallory s hyaline (- ) l)mphocytic and granulocytic infiltration as well as activated Kupffer cells (HE)...

Haemosiderosis can be found in several chronic liver diseases, such as chronic hepatitis (especially HVC leading to a reduced response rate to a-interferon), late-stage cirrhosis, spontaneous or surgical portal-systemic shunts, and non-alcoholic steatohepatitis. 

Angulo, R, Keach, J.C., Batts, K.R, Lindord, K.D. Independent predictors of liver fibrosis in patients with non-alcoholic steatohepatitis. Hepatology 1999 30 1356-1362... 

C. M. Recurrence of non-alcoholic steatohepatitis in a liver transplant recipient. Liver Transpl. Surg. 1997 3 174-176... 

George, D.K., Goldwurm, S., MacDonald, G.A., Cowley, L.L., Walker, NJ., Ward, P.J., Jazwinska, E.C., Powell, LW. Increased hepatic iron concentration in non-alcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998 114 311 — 318... 

Itoh, S., Yougel, T., Kawagoe, K. Comparison between non-alcoholic steatohepatitis and alcoholic hepatitis. Amer. J. Gastroenterol. 1987 82 650-654... 

James, O., Day, C. Non-alcoholic steatohepatitis another disease of affluence. Lancet 1999 353 1634-1636... 

Liangpunsakul, S., Chalasani, N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis J. Clin. Gastroenterol. 2003 37 340-343... 

Sorbi, D., Boynton, J., Lindor, KJ>. The ratio of aspartate aminotransferase to alanine aminotransferase potential value in differentiating non-alcoholic steatohepatitis from alcoholic Hver disease. Amer. J. Gastroenterol. 1999 94 1018-1021... 

Neonatal adrenoleucodystrophia Nieman-Pick disease Non-alcoholic steatohepatitis Porphyria cutanea tarda Seip-Lawrence syndrome Thalassaemia Tyrosinosis (type I)... 

Mori T, Ohta M, Nakagawa Y, Hayashi K, Sobajima J, Okuda M, Mochi T, Shimamoto K, Kagawa K, Okanoue T, Kashima K. A case report of non-alcoholic steatohepatitis associated with tiopronin-induced liver injury. Acta Hepatol Jpn 1990 31 449-53. 

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