Hypergammaglobulinemia is a strong predictor of disease progression, hepatocellular carcinoma, and death in patients with compensated cirrhosis.

Background & Aims: The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long-lasting follow-up. Methods: Two hundred and seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63years, range 34-81) were analysed. All patients were followed up for a median time of 96months (range 21-144) through periodically performed clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic examinations. Results: During the follow-up, 97 individuals (36%) were clinically stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%) progressed towards C-P class B/C without developing cancer. One hundred and thirty-one patients (48%) died or underwent liver transplantation. Multivariate regression analysis showed that clinical stability was significantly associated with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8gr/dL (P = .01). HCC development was significantly associated with younger age (P = 01) and serum gamma globulin values 1.8 gr/dL (P<.001). C-P score progression was associated with oesophageal varices (P < .001), lower serum albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P = .02). Death was associated with younger age (P < .001) and hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan-Meier's survival test confirmed that gammaglobulinemia 1.8 g/dL was a significant predictor of death (P < .02, and P < .01 respectively). Conclusions: Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk of disease progression, HCC development and death.