Refers to the end stage of a chronic liver disease in which its underlying etiology remains unknown after extensive clinical, serological, and pathological evaluations have been performed.
Represents a significant and increasing indication for liver transplantation in the United States.
Prevalence rate ranges from 5% to 30% in patients with cirrhosis in earlier studies but has decreased to an estimated 5% with advances in testing.
Metabolic causes including nonalcoholic fatty liver dis- ease (NAFLD) and nonalcoholic steatohepatitis (NASH), metabolic syndrome, type 2 diabetes, and obesity have identified more commonly in comparison with other well-described etiologies of chronic viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis, and alcoholic liver disease.
Work-up for chronic viral hepatitis, autoimmune conditions, alcohol abuse, toxin exposure, vascular and biliary tract diseases, congenital causes, and progression of NAFLD/NASH must be ruled out.
It is important to determine the specific cause of cirrhosis in view of the impli- cations in the management of patients and the long- term outcomes including liver transplantation.
Histological assessment is important, because specific tissue diagnosis can detect clinically silent advanced disease and provide an assessment of grade and fibrosis.
When the etiology of cirrhosis is identified with NAFLD/NASH, aggressive management of metabolic comorbidities such as type 2 diabetes mellitus, dyslipidemia, and obesity is important and may be helpful, because no particular proven treatment or drug has been developed for fatty liver disease
NASH risk factors such as obesity and metabolic syndrome should be suspected when evaluation renders no identifiable causes despite presence of metabolic syndrome in the cirrhotic patient.
Patients with NASH and cryptogenic cirrhosis with low Model for End-Stage Liver Disease scores have slower progression in their clinical course and are less likely to be liver transplant recipients when compared with those with hepatitis C virus–associated cirrhosis
Diagnostic features include:
Elevated serum liver enzymes (AST, ALT, GGT)
Imaging study with evidence of fatty content and minimal to no alcohol intake
Negative results for viral hepatitis, autoimmune disease, congenital liver disease, and any other plausible explanation
Liver biopsy with evidence of fatty content with or without inflammation or fibrosis and minimal to no alcohol intake.
Management efforts include: weight loss, physical exercise, diet with calories restriction.
Following liver transplant studies have shown a low prevalence of recurrent disease, favorable outcomes, and survival comparable with other recipients.
However, some studies suggest chronic rejection and postoperative mortality rates were higher and survival rates at 5, 10, and 15 years were lower than other etiologies.
A retrospective study revealed higher recurrence of cryptogenic cirrhosis and in post-transplant patients and was associated with the presence of metabolic syndrome, hypertension, and use of insulin.