Published online Feb 28, 2017. doi: 10.3748/wjg.v23.i8.1458
Peer-review started: August 27, 2016
First decision: September 20, 2016
Revised: November 21, 2016
Accepted: January 18, 2017
Article in press: January 18, 2017
Published online: February 28, 2017
To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis.
A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.
At the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A.
Undiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.
Core tip: We evaluated the features and outcomes of cryptogenic cirrhosis (CC) compared to age- and Child-Pugh class-matched hepatitis C virus-related cirrhosis at baseline and over a 42-mo follow-up. At diagnosis, the median age of CC was 66 years and Child-Pugh classes A/B/C were 47%/31%/22%, respectively. Among CC cases higher prevalences of metabolic syndrome, overweight/obesity, high BMI, impaired glucose metabolism, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones were observed. Although in the two groups we detected a similar incidence of liver decompensation, hepatocellular carcinoma (HCC) and death, an earlier development of HCC was observed in CC. Age and Child-Pugh were predictors of death. Most CC cases are the consequence of undiagnosed nonalcoholic fatty liver disease.