Ascitis y encefalopatía, causas de muerte y supervivencia del paciente por cirrosis alcohólica y su influencia inmunológica

Abstract

Introduction: Liver cirrhosis is mainly observed in patients with excessive and prolonged alcohol consumption, being the final stage of progressive chronic liver disease. Ascites, the most common decompensating manifestation in patients with liver cirrhosis, is related to two main pathogenic mechanisms: portal hypertension and renal sodium retention. Also, hepatic encephalopathy is another complication that occurs in cirrhotic patients, along with ascites, varicose hemorrhage, and spontaneous bacterial peritonitis; predominantly due to complications of portal hypertension, where the prognosis of cirrhosis progressively deteriorates. Objective: To know the incidence, main sociodemographic characteristics, complications, causes of deaths and survival of patients with alcoholic cirrhosis (AC) undergoing liver transplantation, as well as the genetic profile KIR/HLA of these patients who develop ascites or encephalopathy prior to transplantation. All this in order to find biomarkers that help to predict the development of these pre-transplant complications in alcoholic patients that prevent their development and improve patient survival both in the short and long term. Patients and methods: Study carried out in 281 male patients with AC who underwent liver transplantation, who presented ascites (n=162) and encephalopathy (n=91) to different degrees, as the main pre-transplant complication. All clinical, analytical and radiological data were collected from the patient&apos;s medical history. Genomic DNA was extracted from peripheral blood and KIR/HLA genotyping was performed by PCR-SSO. Statistical analysis was performed with SPSS 20.0. Comparisons were made using the X2-square test and the two-tailed Fisher test. A level of P <0.05 was accepted as statistically significant. To determine survival, the Kaplan-Meier test was applied. To establish the prognosis of patients with AC, three indices were used: Child-Pugh, MELD and ALBI. Results: The mean age of patients with AC was 53.63±0.495 years. The analysis of biochemical parameters showed lower albumin values (3.34±0.62mg/dl) in cirrhotic patients with ascites (P=0.0009); slightly elevated INR values, presenting differences between patients with or without associated ascites (P=0.038). Creatinine increased with greater severity of encephalopathy, with higher values in type III encephalopathy (1.77±1.57 mg/dl; P=0.015). The frequency of KIR2LD2+, KIR2DS2+ and KIR2DS5+ genes were decreased in the healthy population compared to cirrhotic patients (P=0.013, P=0.006 and P=0.033, respectively). Equally, it occurs in patients depending on the development or not of encephalopathy. The frequency of KIR2DL2+ gene decreases in patients with type I ascites (43.8%) compared to the healthy control population (63.3%) (P=0.036), in addition to presenting differences between patients with and without associated encephalopathy (P=0.008). The frequency of KIR3DL1+ gene is decreased among patients with ascites versus patients without ascites (P=0.048). Analysis of HLA-C epitopes showed fewer CA patients without C1 ligand compared to the healthy population (P=0.015). The C2C2 genotype was significantly higher in patients with cirrhosis than in controls (23.5% vs 15.3%; P=0.015). Significantly decreases the KIR2DL3+/C1+ combination and increases the KIR2DS4+/C1+ combination in patients with cirrhosis compared to the healthy control group (P=0.010 and P=0.013, respectively). There was a significantly higher representation of KIR2DS1+/C2+ and KIR2DS5+/C2+ combinations in patients with grade I encephalopathy compared to grade II patients (P=0.043 and P=0.038, respectively). The distribution of the KIR genes according to the main causes of death showed significant differences in patients with KIR2DL5+ encephalopathy (P=0.045), with a higher representation in deaths due to liver graft failure. KIR3DL1- and KIR2DS1+ patients have very low survival due to liver graft failure. Cirrhotic KIR2DS3- patients showed longer survival compared to other types of death. Finally, KIR2DS4+ patients showed superior survival in patients with liver graft rejection. Conclusions: Alcoholic cirrhosis is a growing cause of morbidity and mortality in the most developed countries. The absence of the KIR2LD2+/S2- genes and the presence of the KIR2DS5+ gene seem to predispose to the development of alcoholic cirrhosis. The decrease in the combination of the KIR2DL3+ gene with the C1+ ligand could influence the development of alcoholic cirrhosis, whereas the combination of KIR2DS4+ with the C1+ ligand could be considered a protective factor against alcoholic cirrhosis. Decreased KIR2DL2+/3DL1+ genes could be predisposing factors for ascites. The decrease in KIR2DL3+ could be a protective factor against the development of encephalopathy, while the lack of the C1+ epitope and the C2C2 genotype could be considered a susceptibility factor for encephalopathy. Patient survival was affected in those patients with the KIR3DL1, KIR2DS1, KIR2DS4, and KIR2DS4 genes.