Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States

Hu, Ke–Qin; Kyulo, Namgyal L.; Esrailian, Eric; Thompson, Kevin M.; Chase, Resa; Hillebrand, Donald J.; Runyon, Bruce A.

doi:10.1016/s0168-8278(03)00479-3

Cited by 130 publications

(113 citation statements)

References 35 publications

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“…It was reported that obesity and overweight is directly associated with hepatic steatosis in patients (34). Obesity-induced simple steatosis could develop into NASH and then to liver cirrhosis and hepatocellular carcinoma (35).…”

Section: Discussionmentioning

confidence: 99%

Binge Alcohol Consumption Aggravates Oxidative Stress and Promotes Pathogenesis of NASH from Obesity-Induced Simple Steatosis

Minato

Tsutsumi

Tsuchishima

et al. 2014

Mol Med

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The pathogenesis of nonalcoholic steatohepatitis (NASH) is a two-stage process in which steatosis is the "first hit" and an unknown "second hit." We hypothesized that "a binge" could be a "second hit" to develop NASH from obesity-induced simple steatosis. Thirty-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were administered 10 mL of 10% ethanol orally for 5, 3, 2, and 1 d/wk for 3 consecutive weeks. As control, male Otsuka Long-Evans Tokushima (OLET) rats were administered the same amount of alcohol. Various biochemical parameters of obesity, steatosis and NASH were monitored in serum and liver specimens in untreated and ethanol-treated rats. The liver sections were evaluated for histopathological alterations of NASH and stained for cytochrome P-4502E1 (CYP2E1) and 4-hydroxy-nonenal (4-HNE). Simple steatosis, hyperinsulinemia, hyperglycemia, insulin resistance, hypertriglycemia and marked increases in hepatic CYP2E1 and 4-HNE were present in 30-wk-old untreated OLETF rats. Massive steatohepatitis with hepatocyte ballooning was observed in the livers of all OLETF rats treated with ethanol. Serum and hepatic triglyceride levels as well as tumor necrosis factor (TNF)-α mRNA were markedly increased in all ethanol-treated OLETF rats. Staining for CYP2E1 and 4-NHE demonstrated marked increases in the hepatic tissue of all the groups of OLETF rats treated with ethanol compared with OLET rats. Our data demonstrated that "a binge" serves as a "second hit" for development of NASH from obesity-induced simple steatosis through aggravation of oxidative stress. The enhanced levels of CYP2E1 and increased oxidative stress in obesity play a significant role in this process.

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Section: Discussionmentioning

confidence: 99%

Binge Alcohol Consumption Aggravates Oxidative Stress and Promotes Pathogenesis of NASH from Obesity-Induced Simple Steatosis

Minato

Tsutsumi

Tsuchishima

et al. 2014

Mol Med

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“…24 This finding is supported by evidence that hepatic steatosis in patients with CHC is associated with hepatic inflammation and advanced stages of fibrosis. 21 Leptin also may mediate fibrogenesis. This satiety hormone has been shown to be profibrogenic and up-regulation of leptin signaling may lead to fibrosis progression.…”

Section: Increased Fibrosismentioning

confidence: 99%

Steatosis and Chronic Hepatitis C Infection: Mechanisms and Significance

Harrison

2005

Clinical Gastroenterology and Hepatology

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“…3,4 Alcohol abuse, hepatitis B virus (HBV) infection, and metabolic liver diseases have emerged as major determinants of clinical decompensation, development of hepatocellular carcinoma (HCC), and survival of patients with compensated cirrhosis. [5][6][7][8] However, lack of cohort enrollment and sufficiently long periods of follow-up might have limited the correct understanding of the natural history and prognostication of hepatitis C virus (HCV)-related cirrhosis-particularly when epiphenomena like ascites, jaundice, and encephalopathy are selected, all of which are indirect indicators of liver function not central to the disease process. 9 In 1986, a cohort of 417 HCCfree patients with compensated cirrhosis of different etiologies was enrolled into a surveillance program for HCC, whose secondary end point was clinical decompensation and patient survival.…”

mentioning

confidence: 99%

The natural history of compensated cirrhosis due to hepatitis C virus

et al. 2006

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Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA-seropositive patients with Child-Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations. During 114 months (range 1-199), hepatocellular carcinoma (HCC) developed in 68 (32%), ascites in 50 (23%), jaundice in 36 (17%), upper gastrointestinal bleeding in 13 (6%), and encephalopathy in 2 (1%), with annual incidence rates of 3.9%, 2.9%, 2.0%, 0.7%, and 0.1%, respectively. Clinical status remained unchanged in 154 (72%) and progressed to Child-Pugh class B in 45 (21%) and class C in 15 (7%). HCC was the main cause of death (44%) and the first complication to develop in 58 (27%) patients, followed by ascites in 29 (14%), jaundice in 20 (9%), and upper gastrointestinal bleeding in 3 (1%). The annual mortality rate was 4.0% per year and was higher in patients with other potential causes of liver disease than in those without them (5.7% vs. 3.6%; P ‫؍‬ .04). In conclusion, hepatitis C-related cirrhosis is a slowly progressive disease that may be accelerated by other potential causes of liver disease. HCC was the first complication to develop and the dominant cause for increased mortality.

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Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States

Cited by 130 publications

References 35 publications

Binge Alcohol Consumption Aggravates Oxidative Stress and Promotes Pathogenesis of NASH from Obesity-Induced Simple Steatosis

Binge Alcohol Consumption Aggravates Oxidative Stress and Promotes Pathogenesis of NASH from Obesity-Induced Simple Steatosis

Steatosis and Chronic Hepatitis C Infection: Mechanisms and Significance

The natural history of compensated cirrhosis due to hepatitis C virus

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