Author information
1
Inova Fairfax Hospital, Falls Church, VA, USA. Electronic address: zobair.younossi@inova.org.
2
Inova Fairfax Hospital, Falls Church, VA, USA.
3
Virginia Commonwealth University, Richmond, VA, USA.
4
Pinnacle Clinical Research, San Antonio, TX, USA.
5
Hôpital Universitaire Pitié-Salpêtrière, Paris, France.
6
Duke Clinical Research Institute, Durham, NC, USA.
7
University of Virginia, Charlottesville, VA, USA.
8
Liver Institute of Virginia, Richmond, VA, USA.
9
Gilead Sciences, Inc., Foster City, CA, USA.
10
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
11
Inselspital, Bern University, Switzerland, and IDIBAPS, University of Barcelona, Barcelona, Spain.
Abstract
BACKGROUND:
Although patients with cryptogenic cirrhosis have been historically considered to have "burnt out" nonalcoholic steatohepatitis (NASH), some controversy remains. The aim 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 had similar age, gender, BMI, PNPLA3 rs738409 genotype, and prevalence of diabetes (p>0.05), but cryptogenic cirrhosis patients had higher serum fibrosis markers and greater collagen content and α-SMA expression on liver biopsy. As 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:
Patients with NASH and cryptogenic cirrhosis have similar demographics, but those 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 but is more progressive leading to advanced liver disease at a faster rate.