Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry.

BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. APPROACH AND RESULTS: We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. CONCLUSIONS: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.

Poor Outcomes of Cirrhosis due to Nonalcoholic Steatohepatitis Compared With Hepatitis B After Decompensation With Ascites.

INTRODUCTION: Decompensation with ascites portends a poor prognosis in cirrhosis. The aim of this study was to compare the outcomes of patients with nonalcoholic steatohepatitis (NASH) with hepatitis B virus (HBV) cirrhosis after decompensation with ascites. METHODS: We conducted a retrospective study to evaluate the outcomes of patients with NASH and HBV cirrhosis who were admitted to hospital for first-onset ascites from January 1, 2004, to June 30, 2015. They were followed up until death, liver transplantation, or loss to follow up. RESULTS: Patients with NASH had lower median (interquartile range) Model for End-Stage Liver Disease score (11 [9-14] vs 14 [11-17], P < 0.001). Over 60 months, patients with NASH cirrhosis had higher cumulative incidence of dilutional hyponatremia (P < 0.001) and refractory ascites (P = 0.028). They also had higher cumulative incidence of cirrhosis-related deaths and liver transplantation compared with HBV cirrhosis (65.7%; [95% confidence interval (CI) 53.6-75.4] vs 42.5% [95% CI 32.4-55.2], P = 0.008). Multivariable competing risk analysis showed that NASH (subdistribution hazard ratio [sHR] 1.88 [95% CI 1.14-3.11], P = 0.014), non-Chinese ethnicity (sHR 1.63 [95% CI 1.06-2.50], P = 0.027), history of hepatocellular carcinoma (sHR 1.76 [95% CI 1.05-2.95], P = 0.033), estimated glomerular filtration rate <60 mL/min/1.73 m2 (sHR 1.70 [95% CI 1.09-2.65], P = 0.020), and Model for End-Stage Liver Disease score ≥15 (sHR 3.26 [95% CI 2.11-5.05], P < 0.001) were independent predictors of poor transplant-free survival. DISCUSSION: Patients with decompensated cirrhosis due to NASH had much poorer prognosis compared with HBV with more complications and greater healthcare resource utilization. Greater awareness is necessary for early diagnosis of NASH before decompensation.