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 24 June 2018

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Question Time

HepatologyLiver diseases

Fatty liver and NASH

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Please submit a new question (maximum 100 words) to Please note that this service is only for medically qualified professionals, and not for the general public. The questions should ask a technical question about a topic in gastroenterology, hepatology or endsocopy. You may nominate the expert from our Global Academic Faculty whom you would like us to contact for the first reply. Don't forget to include your full name, city, country and your email address.

How is it possible to differentiate non-B, non-C cirrhosis from nonalcoholic steatohepatitis-related cirrhosis?

Muhammad Yousuf, Lahore, Pakistan  25 February 2003

I would prefer to designate "non-B, non-C" cirrhosis as "cryptogenic" cirrhosis. This indicates that there may be non-viral etiologies, such as drug-induced chronic liver disease or nonalcoholic steatohepatitis (NASH).

The contribution of NASH to cryptogenic cirrhosis appears to have been underestimated in the past. The features of insulin resistance, such as obesity and diabetes mellitus, have been demonstrated to be much more prevalent in patients with cryptogenic cirrhosis than in those with liver diseases of well-defined etiologies [1][2]. Furthermore, these features are more frequently observed in hepatocellular carcinoma (HCC) arising in patients with cryptogenic cirrhosis than in age- and sex-matched patients with HCC of alcoholic or viral origin [3].

The classic histology of NASH may disappear after the development of "burnt-out" cirrhosis, leaving behind the clinical presentation as the only clue to the cause of the liver disease. Furthermore, NASH has been shown to develop in liver recipients who underwent transplantation for cryptogenic cirrhosis [4], further suggesting the underestimated prevalence of NASH in the pre-transplant population.

Thus, I would phrase your question slightly differently (i.e. "How is it possible to diagnose NASH as the cause of cryptogenic cirrhosis?"). Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome that encompasses a broad spectrum ranging from simple steatosis alone to NASH [5]. This disease entity may be considered as an additional feature of the metabolic (or insulin resistance) syndrome that includes obesity, diabetes mellitus, dyslipidemia and hypertension.

The prevalence of NAFLD varies from 10% to 40%, based on estimates by various studies either focused on selected subpopulations or on population-based studies using liver biopsy, autopsy, radiological imaging or elevated liver chemistry tests [4].

NAFLD is an increasingly common liver disease in developed countries due to the rising prevalence of obesity. Steatohepatitis is common in markedly obese subjects in autopsy studies. The risk of steatohepatitis increases approximately 3-fold in those who have a history of type 2 diabetes mellitus. Dyslipidemia is found in up to 90% of patients with NASH.

Finally, the majority of unexplained aminotransferase elevations in the general US population are associated with central adiposity as well as various features of insulin resistance [6][7].

In summary, if your patient has central obesity, diabetes mellitus, dyslipidemia, and/or hypertension and all other viral, genetic, autoimmune, and drug-induced causes have been excluded, NASH is the likely diagnosis. Liver biopsy may or may not be helpful, since the pathologic features of NASH may not be evident in late (i.e. "burnt-out") NASH.


  1. Caldwell SH, Oelsner DH, Iezzoni JC, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999; 29: 664-9.
  2. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology 2000; 32: 689-92.
  3. Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134-40.
  4. Ong J, Younossi ZM, Reddy V, et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl 2001; 7: 797-801.
  5. Yu AS, Keeffe EB. Nonalcoholic fatty liver disease. Rev Gastroenterol Disord 2002; 2: 11-9.
  6. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124: 71-9.
  7. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferease levels in the United States. Am J Gastroenterol [In press].

Emmet B Keeffe, Stanford, CA, USA  25 February 2003

DISCLAIMER: Question Time is for information only and is not a substitute for specific medical advice and diagnosis from a medical practitioner. Neither the content providers nor the publisher accept any legal responsibility for nor make any warranty with respect to the views expressed or procedures outlined on the site.


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