No abstract

Graft dysfunction associated with autoimmune phenomena has been recently described in liver transplant recipients without previous autoimmune disease. However, the natural history, diagnostic criteria, and definitive therapeutic approach of de novo autoimmune hepatitis (de novo AIH) are poorly understood. We report 12 cases of de novo AIH 27.9 ؎ 24.5 months after liver transplantation: the outcome of 7 patients treated with steroids is compared with a group of 5 nontreated patients. Nontreated patients lost the graft after 5.8 ؎ 2.6 months from de novo AIH onset. All treated patients were alive after 48.4 ؎ 14 (29-65) months from de novo AIH onset, and none of them lost the graft. However, 5 patients relapsed in relation to steroid tapering. All patients presented an atypical antiliver/ kidney cytosolic autoantibody, associated to classical autoantibodies in 10 cases. Histological study showed several degrees of lobular necrosis and inflammatory infiltrate. HLA antigen frequencies and matching were compared with 2 control groups (16 orthotopic liver transplantation [LTX] patients without de novo AIH and 929 healthy blood donors); de novo AIH patients showed a higher prevalence of HLA-DR3 (54.5% vs. 25.9%, P ‫؍‬ .04) than healthy controls, which was not observed in LTX patients without de novo AIH. In conclusion, this new disease should be included in the differential diagnosis of unexplained graft dysfunction. In addition, treatment with steroids results in a dramatically improved outcome. However, maintenance therapy is usually required. (HEPATOLOGY 2002;35:349-356.)

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for EndStage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02-1.08; P ‫؍‬ .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00-1.06; P ‫؍‬ .05) so that each 1-mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic T he Model for End-Stage Liver Disease (MELD) score, initially developed for survival prediction of patients undergoing the transjugular intrahepatic portal systemic shunt (TIPS) procedure, 1 has been subsequently validated in an increasingly heterogeneous population of patients with cirrhosis as a very good tool to rank patients according to their short-term risk of death. [2][3][4][5] In the initial validation of the MELD score, individual complications of portal hypertension (ascites, spontaneous bacterial peritonitis, variceal bleeding, and encephalopathy) were added to the model, producing only minimal improvement in its discriminative ability. 2 However, each individual portal hypertensionrelated complication is only one aspect of the underlying pathophysiological mechanism, the portal hypertensive syndrome. Re-evaluation of the role of portal hypertension indexes in such predictive scores has been suggested, as portal hypertension has been described as the third parameter most frequently found to be a significant predictor of survival in cirrhosis. 6 Interestingly, after dividing patients in categories according to MELD score, 1-year mortality within each category was higher among patients with portal hypertension-related complications.

Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

Bacterial infections are frequent, life-threatening complications in cirrhotic patients. This study investigated in vivo neutrophil migration and phagocytic activity in cirrhotic patients with advanced liver disease, in liver transplant recipients, and in healthy volunteers, by use of the skin window technique. Complement receptor type III (CR3) expression was also measured in blood and elicited neutrophils. Neutrophil migration to skin windows and neutrophil in vivo phagocytosis of heat-killed Escherichia coli were significantly decreased in cirrhotic patients compared with healthy controls. Neutrophil migration and phagocytosis were decreased in cirrhotic patients with previous episodes of bacterial infection compared with noninfected patients. Expression of CR3 in circulating neutrophils was significantly higher in cirrhotic patients, whereas it was significantly reduced in elicited neutrophils of cirrhotic patients with previous bacterial infection. These data suggest that deficient neutrophil recruitment to the infection site and impaired phagocytic activity may contribute to bacterial infections in cirrhotic patients with advanced liver disease.