Non-alcoholic Steatohepatitis and Cancer
Section snippets
Retrospective studies: hepatocellular carcinoma arising in cryptogenic cirrhosis
NASH is associated closely with insulin resistance and several features of the metabolic syndrome [9]. Compelling evidence for an association between NASH and HCC comes from studies examining the risk for HCC and conditions linked strongly to NASH, mainly obesity and diabetes (Table 1) [10], [11], [12], [13]. Unfortunately, fat storage and the necroinflammation that characterize NASH no longer may be present in liver specimens when patients develop cirrhosis independently of obesity, so
Case reports of hepatocellular carcinoma in non-alcoholic steatohepatitis or non-alcoholic steatohepatitis–related cirrhosis
The relevant clinical and histologic characteristics of the 16 cases of HCC associated with NASH reported in the literature to date are summarized in Table 2[14], [18], [19], [20], [21], [22], [23], [24], [25], [26]. Most patients were male, and age at diagnosis ranged from 56 to 74 (mean, 66.7), consistent with the HCC-CC series. As expected, one or more features of the metabolic syndrome invariably were associated with the diagnosis of NASH, most frequently obesity and diabetes. In half of
Prospective studies on non-alcoholic steatohepatitis and hepatocellular carcinoma
The natural history of NAFLD has been assessed by serial liver biopsies and by cohort studies examining the clinical outcomes of NAFLD patients. These studies are limited by the long and asymptomatic clinical course of the disease and by its high prevalence in the general population. The biopsy studies usually involve small numbers of highly selected subjects and have a short-term follow-up. None of them report the onset of HCC in NAFLD, consistent with the slow progression of liver damage in
Obesity and hepatocellular carcinoma
Obesity now is recognized widely as a significant risk factor for the development of many types of cancer (Fig. 2). A recent mortality study by the American Cancer Society [32] followed approximately 900,000 United States adults from 1982 to 1998 and registered more than 57,000 cancer deaths, demonstrating that increased body weight is associated with higher cancer mortality. Among the heaviest members of the cohort (BMI≥35 kg/m2), death rates from all cancers combined were 52% higher for men
Mechanisms of carcinogenesis
Most cases of HCC are diagnosed in patients affected by long-standing cirrhosis. It is not clear, however, whether or not the neoplastic process begins during cirrhosis or starts at earlier stages of liver disease. In fact, steatosis per se and the pathophysiologic mechanisms of NASH might have carcinogenic potential (Fig. 3). During the neoplastic process, epithelial hyperplasia and dysplasia generally precede cancer by many years [53]. Although in humans, HCC never has been diagnosed in a
Summary
The literature on HCC in NASH is small and derived mostly from retrospective studies and case reports. The long, indolent clinical course of the disease has limited prospective studies so far. The available studies suggest that HCC is a rare, worrisome complication of NAFLD that may be of increasing importance in the coming years because of the rising incidence of the metabolic syndrome and its components. Patients who have NASH-related cirrhosis carry a substantial risk for early development
References (70)
- et al.
Primary liver cancer: worldwide incidence and trends
Gastroenterology
(2004) - et al.
Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status
Am J Gastroenterol
(2003) The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease
Clin Liver Dis
(2004)- et al.
Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship?
Dig Liver Dis
(2004) - et al.
Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma
Gastroenterology
(2002) - et al.
NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States
Hepatology
(2002) - et al.
Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis
Hepatology
(2002) - et al.
Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study
Hepatology
(2000) - et al.
Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values
Hepatology
(2003) - et al.
Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history?
Am J Gastroenterol
(2000)
Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis
J Hepatol
The natural history of nonalcoholic fatty liver disease: a clinical histopathological study
Am J Gastroenterol
Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C
Hepatology
The natural history of nonalcoholic fatty liver disease: a population-based cohort study
Gastroenterology
The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease
J Hepatol
Obesity and cancer risk: a Danish record-linkage study
Eur J Cancer
Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus
Hepatology
The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans
Am J Gastroenterol
Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma
Gastroenterology
Obesity and hepatocellular carcinoma
Gastroenterology
Induction of apoptosis by tumor suppressor genes and oncogenes
Semin Cancer Biol
Mitochondrial adaptations to obesity-related oxidant stress
Arch Biochem Biophys
An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis
Biochem Pharmacol
GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide. Version 1.0
Rising incidence of hepatocellular carcinoma in the United States
N Engl J Med
Risk factors for the rising rates of primary liver cancer in the United States
Arch Intern Med
Review article: the changing epidemiology of hepatocellular carcinoma in Canada
Aliment Pharmacol Ther
Viral pathogenesis of hepatocellular carcinoma in the United States
Hepatology
Obesità and diabetes as a risk factor for hepatocellular carcinoma
Liver Transpl
The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years
Hepatology
Italian Multicentre Cooperative project on nutrition in liver cirrhosis. Nutritional status in cirrhosis
J Hepatol
Hepatocellular carcinoma arising in non-alcoholic steatohepatitis
Pathol Int
Lipid-rich clear cell hepatocellular carcinoma arising in non-alcoholic steatohepatitis in a patient with diabetes mellitus
J Submicrosc Cytol Pathol
Hepatocellular carcinoma with nonalcoholic steatohepatitis
J Gastroenterol
Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma
J Hepatol
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