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 . 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 .
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 , 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 . 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 .
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 .
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.
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