Elsevier

Clinics in Liver Disease

Volume 11, Issue 1, February 2007, Pages 191-207
Clinics in Liver Disease

Non-alcoholic Steatohepatitis and Cancer

https://doi.org/10.1016/j.cld.2007.02.006Get rights and content

Hepatocellular carcinoma (HCC) is part of the natural history of non-alcoholic steatohepatitis (NASH). A significant proportion of people who have cryptogenic cirrhosis develop HCC. NASH-related cirrhosis carries a substantial risk for early HCC development. Diagnosis of HCC often is made at first referral; the tumor usually is large with multiple localizations. Patients who have obesity or diabetes are at risk for HCC and a variety of cancers. Given the epidemic of obesity and diabetes, the incidence of NASH-related HCC is expected to increase. In addition to developing new diagnostic tools and pharmacologic therapies, efforts should be directed at preventing non-alcoholic fatty liver disease.

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

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