The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options.

Abstract

BACKGROUND & AIMS:

Although patients with cryptogenic cirrhosis have historically been considered as having "burnt-out" non-alcoholic steatohepatitis (NASH), some controversy remains. The aim of this study was to compare outcomes of patients with cryptogenic cirrhosis and NASH-related cirrhosis from a cohort with longitudinal follow-up data.

METHODS:

Patients with cryptogenic cirrhosis or NASH cirrhosis were screened for a clinical trial. Patients with <5% hepatic steatosis regardless of other histologic features were considered to have cryptogenic cirrhosis. Clinico-laboratory data and adjudicated liver-related events (e.g. decompensation, qualification for transplantation, death) were available.

RESULTS:

A total of 247 patients with cirrhosis (55.3 ± 7.4 years, 37% male) were included; 144 had NASH cirrhosis and 103 had cryptogenic cirrhosis. During a median follow-up of 29 (IQR 21-33) months (max 45 months), 20.6% of patients had liver-related clinical events. Patients with NASH cirrhosis and cryptogenic cirrhosis were of a similar age and gender, as well as having a similar body mass index, PNPLA3 rs738409 genotype, and prevalence of diabetes (p >0.05). However, patients with cryptogenic cirrhosis had higher serum fibrosis markers and greater collagen content and α-smooth muscle actin expression on liver biopsy. Compared to cirrhotic patients with NASH, patients with cryptogenic cirrhosis experienced significantly shorter mean time to liver-related clinical events (12.0 vs. 19.4 months; p = 0.001) with a hazard ratio of 1.76 (95% CI 1.02-3.06).

CONCLUSIONS:

Populations with NASH and cryptogenic cirrhosis have similar demographics, but patients with cryptogenic cirrhosis have evidence of more active fibrosis and a higher risk of liver-related clinical events. Thus, we believe these patients belong to the same spectrum of disease, with cryptogenic cirrhosis representing a more advanced stage of fibrosis.

LAY SUMMARY:

Significant liver damage and cirrhosis of the liver may develop without a known cause - a liver disease referred to as cryptogenic cirrhosis. In this work we found that, in the presence of metabolic abnormalities, cryptogenic cirrhosis may actually be a part of the non-alcoholic fatty liver disease spectrum. Yet, it appears to be more progressive than typical non-alcoholic fatty liver disease, leading to advanced liver disease at a faster rate.

• Authors: Zobair Younossi, Maria Stepanova, Arun J Sanyal, Stephen A Harrison, Vlad Ratziu, Manal F Abdelmalek, Anna Mae Diehl, Stephen Caldwell, Mitchell L Shiffman, Raul Aguilar Schall, Bryan McColgan, G Mani Subramanian, Robert P Myers, Andrew Muir, Nezam H Afdhal, Jaime Bosch, Zachary Goodman
• Journal: Journal of hepatology (J Hepatol) Vol. 69 Issue 6 Pg. 1365-1370 (12 2018) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 30144554 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• ACTA2 protein, human
• Actins
• Collagen

Topics

• Actins (analysis)
• Aged
• Biopsy
• Collagen (analysis)
• Diabetes Mellitus (epidemiology)
• Disease Progression
• Female
• Fibrosis
• Follow-Up Studies
• Genotype
• Humans
• Liver (pathology)
• Liver Cirrhosis (congenital, epidemiology)
• Longitudinal Studies
• Male
• Metabolic Syndrome (epidemiology)
• Middle Aged
• Non-alcoholic Fatty Liver Disease (epidemiology)
• Outcome Assessment, Health Care
• Prevalence
• Prospective Studies