摘要
AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.
AIM To evaluate the association between alpha-1antitrypsin deficiency （A1ATD） and hepatocellularcarcinoma （HCC） in patients with end-stage liver disease（ESLD）.METHODS： Patients with cirrhosis and ESLD referred tothe Cleveland Clinic Foundation for liver transplantationbetween 2003 and 2014 were included in the study （N =675）. ESLD was defined as having histological features ofcirrhosis and/or radiological evidence of cirrhosis in thecontext of portal hypertension （ascites, variceal bleeding,thrombocytopenia, or hepatic encephalopathy）. A1ATDwas diagnosed using phenotype characterization （MZor ZZ）, liver biopsy detection of PAS-positive diastaseresistant（PAS＋） globules, or both. Patients with othercauses of liver diseases such as hepatitis C virus （HCV）,alcoholic liver disease and non-alcoholic steatohepatitis（NASH） or NASH were also included in the study. HCCwas diagnosed by using imaging modalities, biopsyfindings, or explanted liver inspection. Follow-up timewas defined as the number of years from the diagnosisof cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow upvisit. The rate of HCC was assessed using time-tointervalanalysis for interval censored data.RESULTS： This study included 675 patients. 7% ofsubjects had A1ATD （n = 47）. Out of all subjects whodid not have A1ATD, 46% had HCV, 17% had alcoholicliver disease, 19% had NASH and 18% had anotherprimary diagnosis. Of the 47 subjects with A1ATD, 15had a primary diagnosis of A1ATD （PI＊ZZ phenotypeand PAS＋ globules）, 8 had a PI＊MZ phenotype alone,14 had PAS＋ alone, and 10 had both the PI＊MZphenotype and PAS＋. Median follow-up time was 3.4（25th, 75th percentiles： 1, 5.2） years. The overall rate ofhepatocellular carcinoma in all subjects was 29% （n =199）. In the A1ATD group, the incidence rate of HCCwas 8.5% compared to 31% in the group of patientswith other causes of cirrhosis （P = 0.001）. Patients withESLD due to A1ATD had the lowest yearly cumulativerate of hepatocellular carcinoma at 0.88% per yearcompared to 2.7% for those with HCV cirrhosis, 1.5%in patients with NASH and 0.9% in alcohol-induced liverdisease （P 〈 0.001）.CONCLUSION： Within this group of patients withESLD, there was no significant association betweenA1ATD and increased risk of HCC.
