IgG and IgM Immunohistochemistry in Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) Liver Explants.

OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) can be difficult to distinguish in end-stage liver disease. Previous studies have shown that immunoglobulin G (IgG) and immunoglobulin M (IgM) immunostaining can differentiate AIH from PBC in needle core biopsy specimens, and we seek to extend these data to cirrhotic liver explants, in which the histology of AIH or PBC may be indiscernible. METHODS: Clinical data were reviewed for 20 patients with PBC cirrhosis and 16 with AIH cirrhosis. Immunohistochemistry for IgM and IgG was performed on representative blocks of explanted livers. Three high-power fields with the highest concentration of IgG- and IgM-positive plasma cells were counted and compared. RESULTS: The average number of IgM-positive plasma cells was significantly higher in PBC explants (7.3) than in AIH (1.8) (P = .001). There was no significant difference in the average number of IgG-positive plasma cells in PBC (2.5) and AIH (2.8) (P = .8). The IgG/IgM ratio was more likely to be less than 1.0 in PBC (17/20, 85%) compared with AIH (7/16, 44%) (P = .01). CONCLUSIONS: Our study demonstrates that the absolute number of IgM plasma cells is greater in explants of cirrhotic PBC compared with AIH. These findings may be helpful in the evaluation of cryptogenic cirrhosis.

Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis.

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver-related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol-associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow-up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD-cirrhosis and HCV-cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07-1.19 and aHR = 1.14, 95% CI = 1.08-1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07-1.30 and aHR = 1.08, 95% CI = 1.00-1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV-cirrhosis and ALD-cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.