The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options
Author(s): ,
Zachary Goodman
Affiliations:
Inova Fairfax Hospital, Falls Church, VA, USA
,
Jaime Bosch
Affiliations:
IDIBAPS, University of Barcelona, Barcelona, Spain
,
Nezam H. Afdhal
Affiliations:
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
,
Andrew Muir
Affiliations:
Duke Clinical Research Institute, Durham, NC, USA
,
Robert P. Myers
Affiliations:
Gilead Sciences, Inc., Foster City, CA, USA
,
G. Mani Subramanian
Affiliations:
Gilead Sciences, Inc., Foster City, CA, USA
,
Bryan McColgan
Affiliations:
Gilead Sciences, Inc., Foster City, CA, USA
,
Raul Aguilar Schall
Affiliations:
Gilead Sciences, Inc., Foster City, CA, USA
,
Mitchell L. Shiffman
Affiliations:
Liver Institute of Virginia, Richmond, VA, USA
,
Stephen Caldwell
Affiliations:
University of Virginia, Charlottesville, VA, USA
,
Anna Mae Diehl
Affiliations:
Duke Clinical Research Institute, Durham, NC, USA
,
Manal F. Abdelmalek
Affiliations:
Duke Clinical Research Institute, Durham, NC, USA
,
Vlad Ratziu
Affiliations:
Hôpital Universitaire Pitié-Salpêtrière, Paris, France
,
Stephen A. Harrison
Affiliations:
Pinnacle Clinical Research, San Antonio, TX, USA
,
Arun J. Sanyal
Affiliations:
Virginia Commonwealth University, Richmond, VA, USA
,
Maria Stepanova
Affiliations:
Inova Fairfax Hospital, Falls Church, VA, USA
Zobair Younossi
Affiliations:
Inova Fairfax Hospital, Falls Church, VA, USA
Corresponding author. Address: Betty and Guy Beatty Center for Integrated Research, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA 22042, USA; Tel.: +1 (703) 776 2540; fax: +1 (703) 776 4386.
EASL LiverTree™. Younossi Z. Dec 1, 2018; 256777
Dr. Zobair Younossi
Dr. Zobair Younossi
Contributions Biography
Journal Abstract
References
Graphical abstract

Graphical abstract

Patients with cryptogenic cirrhosis or NASH cirrhosis had similar clinical and demographic profile. Cryptogenic cirrhosis was associated with advanced fibrosis and a higher risk of liver-related decompensation or death. Cryptogenic cirrhosis may be a more advanced type of liver disease associated with the NAFLD spectrum. New research is required to address the lack of treatment options for cryptogenic cirrhosis.

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.

Keyword(s)
NAFLD, NASH, Outcomes, Fatty liver, Cryptogenic cirrhosis
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