Nonalcoholic steatohepatitis: an expanded clinical entity: Bacon BR, Farakvash MJ, Janney CG, Neuschwander-Tetri BA. Gastroenterology 1994; 107: 1103–1109

doi:10.1016/0270-9139(95)90482-4

Hepatology

Volume 21, Issue 6, June 1995, Pages 1742-1743

https://doi.org/10.1016/0270-9139(95)90482-4 Get rights and content

Abstract

Background/Aims: In the past, nonalcoholic steatohepatitis 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 virus-negative. Nineteen of 33 (58%) were men, 20 of 33 (61%) were non-obese, 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.

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Cited by (100)

The relationship between copper and steatosis in Wilson's disease
2013, Clinics and Research in Hepatology and Gastroenterology
The histological similarities seen in Wilson's disease (WD) and non-alcoholic steatohepatitis (NASH) led us to verify possible correlations between glucose and/or lipid and/or iron metabolism alterations and hepatic steatosis in WD patients.
Thirty-five WD patients (20 females, 15 males, mean age 40.1 ± 5.4 years), and 44 NASH patients (25 females, 19 males, mean age 42.8 ± 6.7 years) were enrolled in the study. BMI, total/HDL/LDL-cholesterol, triglycerides and glucose serum levels were established in all subjects. HOMA index was calculated. Percutaneous liver biopsy with quantitative evaluation of steatosis and copper tissue content was performed in all WD patients and in NASH control group.
Significant difference was seen in baseline serum levels of glucose, HOMA index, total cholesterol, triglycerides, and ferritin between the WD group and NASH group (P < 0.05) but steatosis scored was similar between two groups. No correlation between the level of steatosis and metabolic factors studied was highlighted. In WD, hepatic parenchymal copper concentration was 753 ± 65.3 mcg/g dry weight against 54.5 ± 16.9 mcg/g dry weight in NASH patients (P < 0.05). Higher liver copper concentrations were seen in patients with severe steatosis compared to those with mild (P = 0.004) and moderate, (P = 0.038) steatosis. Positive significant correlation between liver copper content and steatosis scores (r = 0.87; r² = 0.76) was observed.
The hepatic steatosis in WD is not induced by metabolic comorbidities but by the accumulation of copper in the liver tissue. The hypothesise that the metabolic alterations could be co-factors in the pathogenesis of steatosis in these patients cannot be excluded.
Serologic predictors of nonalcoholic steatohepatitis in a population undergoing bariatric surgery
2012, Surgery for Obesity and Related Diseases
Citation Excerpt :
Fibrosis is not considered necessary. Critics of this approach have stated that lobular inflammation and hepatocyte ballooning have no prognostic significance [17] and have argued against using a broad definition of NASH [27]. More recently, however, a systematic review (10 studies involving 221 patients) of the risk factors for the progression to fibrosis in patients with NASH demonstrated inflammation on the initial biopsy as an independent predictor of progression to advanced fibrosis [28].
Nonalcoholic steatohepatitis (NASH) is common in the morbidly obese. It is a condition that can lead to progressive fibrosis and cirrhosis. We determined the prevalence in a population undergoing bariatric surgery and evaluated the possible serologic predictors before the development of fibrosis.
Liver biopsies were taken from 370 consecutive patients who were undergoing laparoscopic bariatric surgery. The clinical and biochemical parameters were then assessed for correlation with the histologic features of nonalcoholic steatohepatitis.
Of the 370 patients, 68 (18%) were found to have NASH. Increased insulin resistance, alanine transaminase, and total bilirubin were independently associated with the presence of NASH. The presence of ≥2 of the 3 provided the best combination of sensitivity (.71) and specificity (.71) for predicting NASH.
Increased insulin resistance, alanine transaminase, and total bilirubin are serologic predictors for the presence of NASH before the development of fibrosis.
Effect of atorvastatin and diet on non-alcoholic fatty liver disease activity score in hyperlipidemic chickens
2010, Biomedicine and Pharmacotherapy
Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD), which includes from simple steatosis and steatohepatitis, to the most severe cirrhosis and carcinoma, which develops in the absence of excessive alcohol intake. NAFLD is the most common liver disorder in affluent societies. There is no proven treatment for NAFLD/NASH. One of the most frequent adverse effects of statins is an increase in hepatic aminotransferases. Studies that evaluate if the benefits of statins overcome the risks in NASH are lacking. The present study was conceived to explore the effect of both atorvastatin and diet on regression of steatohepatitis, using a chicken experimental model induced by a hyperlipidemic diet (HD). Plasma lipid levels, liver enzymes and hepatic histopathology, as well as image analysis were performed to determine changes in liver lipid deposits and inflammatory infiltration. Features of steatosis, cell-ballooning, and inflammation were scored to obtain the NAFLD activity score (NAS). A severe level of steatosis was found in animals fed on HD. Atorvastatin treated groups showed smaller size of lipid deposits and a lower level of inflammation than non-treated groups. Atorvastatin therapy induced a significant reduction of hepatocellular damage, even though in the animals which continuously received a hyperlipidemic diet. The combination of atorvastatin therapy and a standard diet produced the lowest decrease of NAS. Our results show that atorvastatin therapy not only decreased plasmatic levels of cholesterol and triglycerides, but also induced a reduction of liver steatosis, inflammation and hepatocellular damage, without increasing plasmatic amynotransferase levels.
Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment
2009, Epilepsy Research
Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls.
Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n = 23), CBZ (n = 22) and LTG (n = 23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n = 16).
Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p ≤ 0.049). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and γ-glutamyltransferase (γGT) were greatest in the CBZ group (p ≤ 0.043). Interestingly, serum fasting glucose, serum fasting insulin as well as the HOMA-IR did not differ significantly between groups.
In conclusion, VPA (and moderately CBZ) therapy is related to increased risk for ultrasonographic signs of fatty liver disease, emphasizing the importance of regular ultrasound measurements as well as monitoring of serum lipids and BMI during enzyme-modulating AED treatment.
Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: Implications for the pathogenesis of human nonalcoholic steatohepatitis
2007, American Journal of Pathology
Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. Here, we report a molecular aspect of this disease elucidated using rabbits fed a cholesterol-rich high-fat diet and exhibiting insulin resistance. The liver in this model showed steatohepatitis with fibrosis and high mRNA expression for some cytokines, heme oxygenase-1, transforming growth factor-β1, and collagen α1(I). Erythrocytes isolated from the model showed marked fragility and the externalization of phosphatidylserine (PS) on the outer leaflet of the membrane and were frequently engulfed by Kupffer cells/macrophages in the hepatic sinusoids. Expression of milk fat globule-epidermal growth factor (EGF)-factor 8, a PS-binding protein, was augmented in the liver. In culture, RAW 264.7 cells engulfed erythrocytes oxidized by tert-butyl hydroperoxide, a process that was inhibited by anti-milk fat globule-EGF-factor 8 antibody. In addition, PS-positive erythrocytes appeared entrapped in the model liver in ex vivo perfusion experiments. Finally, in specimens from NASH patients, the aggregation of erythrocytes in inflammatory hepatic sinusoids was notable. These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis.
Role of Magnetic Resonance Imaging in the Monitoring of Patients with Nonalcoholic Fatty Liver Disease: Comparison with Ultrasonography, Lipid Profile, and Body Mass Index
2020, Journal of Clinical and Experimental Hepatology
The aim of this study was to study the role of magnetic resonance imaging (MRI) in monitoring hepatic fat content in cases of nonalcoholic fatty liver disease (NAFLD).
41 adults (mean age: 39 years, 22 males; 19 females) with NAFLD were included after obtaining approval from the institutional ethics committee. The baseline clinical (weight, body mass index [BMI]) and biochemical parameters, fatty liver grade on ultrasonography (USG), and hepatic fat signal fraction (FSF) using dual-echo chemical shift imaging and proton density fat fraction on magnetic resonance spectroscopy (MRS-PDFF) were assessed, before and after intervention (dietary and lifestyle changes and oral vitamin E for six months). They were categorized into Group A (good compliance to intervention) and Group B (poor compliance), and the clinical and imaging parameters were compared between them.
After intervention, Group A (n = 30) showed significant reduction in BMI (28.35 ± 3.25 to 27.14 ± 3.24 kg/m²; P < 0.001), hepatic FSF (19.30 ± 9.09% to 11.18 ± 7.61%; P < 0.05), and MRS-PDFF (18.79 ± 8.53% to 10.64 ± 6.66%). In Group B (n = 11), there was significant increase in BMI (28.85 ± 2.41 to 29.31 ± 2.57 kg/m²; P < 0.001), hepatic FSF (18.96 ± 9.79% to 21.48 ± 11.80%; P < 0.05), and reduction in high-density lipoproteins (P < 0.05). Although there was good correlation between USG and MRS in quantifying liver fat (r = 0.84–0.87; P < 0.001), USG was unable to detect <5.3% change in hepatic fat. There was poor correlation between lipid profile and MRS-PDFF. Change in body weight significantly correlated with change in hepatic fat content (r = 0.76; P < 0.001).
MRI is useful in accurately quantifying and in monitoring hepatic fat content and is better than clinical and biochemical parameters and USG.

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Hepatology elsewhereNonalcoholic steatohepatitis: an expanded clinical entity: Bacon BR, Farakvash MJ, Janney CG, Neuschwander-Tetri BA. Gastroenterology 1994; 107: 1103–1109

Abstract

Gastroenterology

Gastroenterology

Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis

Am J Gastroenterol

Hepatology elsewhere
Nonalcoholic steatohepatitis: an expanded clinical entity: Bacon BR, Farakvash MJ, Janney CG, Neuschwander-Tetri BA. Gastroenterology 1994; 107: 1103–1109