I read with interest the report by Patel et al regarding the prevalence of coronary artery disease (CAD) in alcoholic cirrhosis. The investigators reviewed retrospectively 420 subjects with liver failure due to alcoholic cirrhosis and other causes. A 2-group comparison was made regarding the prevalence of angiographic evidence of CAD. The investigators found a lower prevalence of CAD in patients with alcoholic cirrhosis compared to patients with nonalcoholic cirrhosis, which included viral cirrhosis, biliary cirrhosis, cryptogenic cirrhosis, and nonalcoholic steatohepatitis (NASH) in their cohort of patients.

Several studies have shown that consumption of moderate alcohol (<30 g/day) prevents nonfatal and fatal CAD, although controversy remains on the direct effect of alcohol consumption on CAD. Furthermore, the consequences of severe consumption of alcohol on CAD are totally unknown.

Patel et al’s observation of a lower prevalence of CAD in the alcoholic group might not correctly reflect alcohol-related cardioprotection, because their study included patients with NASH and cryptogenic cirrhosis, which are known risk factors for CAD and accounted for 1/3 of their control group (97 of 295).

In parallel with global recognition of nonalcoholic fatty liver disease (NAFLD) and NASH, the prevalence of NAFLD and NASH has accelerated in the past 20 years, and irreversible liver failure due to NASH or NAFLD has become a leading indication for liver transplantation. Because of a lack of appropriate diagnostic tools and accurate diagnosis of NAFLD or NASH, which contributes to unawareness of disease until the late stages, previous studies have found that most transplant recipients misdiagnosed as having “cryptogenic cirrhosis” had NAFLD or NASH. The pathophysiology of NAFLD and NASH is strongly related to metabolic syndrome (including diabetes, hypercholesterolemia, hypertension, and obesity), which is a highly arthrogenic condition and a substantial risk factors for CAD. Kadayifci et al reported in 2008 that the prevalence of coronary angiographic evidence of CAD was significantly higher in a group of patients with NASH (21.6%), compared to 3.3% prevalence of CAD with other causes of cirrhosis. Also, Mirbagheri et al found that NAFLD was the strongest independent risk factor for angiographic evidence of CAD, with an odds ratio of 8.48. NAFLD-associated elevations of liver enzymes were found to be associated with increased risk for CAD in the Third National Health and Nutrition Examination Survey (NHANES III) in the United States. Also, a prospective observational study with 1637 healthy volunteers found that NAFLD is a strong predictor of CAD. Therefore, although some data have suggested that cirrhosis has a protective effect against CAD, NAFLD- and NASH-related cirrhosis has a greater proclivity to develop atherosclerosis.

Because of the high prevalence of CAD in patients with NASH and part of the cryptogenic cirrhosis group, the inclusion of patients with NASH and cryptogenic cirrhosis in the nonalcoholic group may have increased the incidence of CAD in Patel et al’s control group. My group’s unpublished data on >100,000 transplant recipients from the Standard Transplant Analysis and Research database, provided by the Organ Procurement and Transplantation Network and the United Network for Organ Sharing, disclosed no difference in the prevalence of CAD when comparing alcoholic patients with a viral hepatitis group. Therefore, the exclusion of patients with NASH and cryptogenic cirrhosis from the nonalcoholic group may be necessary to draw the conclusion that invasive coronary angiography may not be necessary in alcoholic liver disease.