Effect on Hepatic Morphology of Treatment of Obesity by Fasting, Reducing Diets and Small-Bowel Bypass

Drenick, Ernst J.; Simmons, Fred A.; Murphy, James A.

doi:10.1056/nejm197004092821502

Cited by 269 publications

(82 citation statements)

References 16 publications

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“…Additionally, two studies have examined caloric restriction alone in overweight or obese subjects. 12,13 One study by Drenick et al 12 showed normalization of histology in 9 of 14 patients who were able to lose weight and maintain weight loss over a 17-month period. Additionally, a small, retrospective cohort study of overweight patients showed that a 10% weight reduction achieved on a 600-800 calorie/day diet for a mean of 16 months resulted in improvement in liver enzymes and hepatosplenomegaly; however, no follow-up liver biopsies were carried out.…”

Section: Discussionmentioning

confidence: 99%

Orlistat for overweight subjects with nonalcoholic steatohepatitis

Fecht²,

et al. 2009

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The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index ‫؍‬ >27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 ؎ 9.0 (standard deviation) years and mean body mass index was 36.4 ؎ 6.3 kg/m 2 . Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >5% body weight (n ‫؍‬ 24) compared to <5% body weight (n ‫؍‬ 17) correlated with improvement in insulin sensitivity (P ‫؍‬ 0.001) and steatosis (P ‫؍‬ 0.015). Comparing subjects who lost >9% of body weight (n ‫؍‬ 16), to those that did not (n ‫؍‬ 25), improved insulin sensitivity (P < 0.001), adiponectin (P ‫؍‬ 0.03), steatosis (P ‫؍‬ 0.005), ballooning (P ‫؍‬ 0.04), inflammation (P ‫؍‬ 0.045), and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P ‫؍‬ 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >9% also achieved improved hepatic histologic changes. (HEPATOLOGY 2009;49:80-86.)

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Section: Discussionmentioning

confidence: 99%

Orlistat for overweight subjects with nonalcoholic steatohepatitis

Fecht²,

et al. 2009

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“…55 Early studies demonstrated that weight reduction due to fasting or low-calorie diets is associated with reduced steatosis, but that a transient increase in the degree of hepatocellular degeneration and focal necrosis may also occur. 95 In a more recent study, a rapid weight loss of 34 + 9 kg with a very-low-calorie formula diet resulted in a significant improvement of fatty change, but 24% of the patients developed slight portal inflammation or fibrosis. 96 While improvement generally occurs after gradual weight reduction, histological lesions of steatohepatitis may deteriorate after rapid weight loss.…”

Section: Reversibility After Weight Lossmentioning

confidence: 96%

Obesity and liver disease

Scheen

Luyckx

2002

Best Practice & Research Clinical Endocrinology & Metab

119

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Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.

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“…These typically reveal improved biochemical parameters but variable changes in histology. 6,[147][148][149][150][151][152][153][154][155] Histologic exacerbation has been observed when the rate of weight loss exceeded 1.6 g/wk. Higherintensity exercise regimens are probably more effective in producing significant metabolic changes.…”

Section: Managementmentioning

confidence: 99%