132例家族聚集性慢性乙型肝炎病毒感染者影响自然病程进展的相关因素分析*

doi:10.3969/j.issn.1672-5069.2016.01.011

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎病毒感染者自然病程进展规律及其与感染持续时间、血清HBV DNA载量、HBeAg状态和脾脏厚度的关系。方法2007年1月至2010年8月就诊于中国医科大学附属盛京医院感染病科的家族聚集性慢性乙型肝炎病毒感染者132例,常规行肝组织活检病理学检查,采用化学发光法检测血清HBV标记物;采用荧光定量PCR法检测血清HBV DNA;使用西门子S200二维彩超诊断仪测量脾脏厚度。结果在132例慢性乙型肝炎患者中,年龄≥30岁患者肝组织炎症评分≥5分和纤维化评分≥3分发生率分别为33.3%和38.4%,显著高于年龄<30岁组（14.9%和14.8%,P<0.05）;肝功能正常组肝组织炎症评分≤4分和纤维化评分≤2分发生率分别为92.0%和92.0%,肝功能异常组为53.6%和16.74%（P<0.05）;肝功能反复异常>1年的患者肝组织炎症评分≥5分和纤维化评分≥3分发生率分别为42.8%和51.5%,显著高于肝功能异常≤1年组（31.9%和31.9%,P<0.05）;血清HBV DNA载量为3~5 lg copies/ml组肝组织炎症评分为≤4分和纤维化评分为≤2分发生率分别为50.0%和27.8%,显著高于病毒载量<3 lg copies/ml组（P<0.05）;血清HBeAg阴性组纤维化评分在3~4分和≥5分发生率分别为23.1%和20.5%,显著高于HBeAg阳性组的11.8%和9.7%（P<0.05）;血清HBeAg阳性与否与肝组织炎症无显著相关性（P>0.05）;脾脏厚度≥4 cm组肝组织炎症≥5分和纤维化评分≥5分发生率分别为76.9%、7.7%和76.9%,显著高于脾脏厚度<4 cm组的16.0%、3.4%和5.9%（P<0.05）;多因素分析发现脾脏厚度与肝组织炎症（t=2.153）和纤维化程度（t=4.654）呈显著独立正相关（P=0.033）;血清HBV DNA载量与肝组织纤维化程度（t=-2.826）也呈独立相关（P=0.005）。结论家族聚集性的慢性乙型肝炎病毒感染者肝组织炎症和纤维化程度与感染持续时间成正相关,年龄大于30岁时更易出现肝脏疾病的进展。肝功能异常时间越长肝脏炎症和纤维化改变越显著。脾脏厚度与肝组织炎症和纤维化程度具有独立正相关。血清HBV DNA载量为1×10³~10⁵copies/ml时肝组织炎症和纤维化改变更显著。

关键词: 慢性乙型肝炎, HBV, DNA, HBeAg, 纤维化

Abstract: Objective To illuminate the relationship between natural progressive course of chronic hepatitis B virus infection and the factors such as the time of infection,serum HBV DNA load,HBeAg status,and thickness of spleen. Method 132 patients with chronic hepatitis B infected with family cluster were enrolled in Shengjing hospital affiliated to China Medical University from January 2007 to August 2010. Liver biopsy,serum HBV markers and HBV DNA were routinely obtained. Results The prevalence of hepatic inflammation score≥5 and fibrosis score≥3 were 33.3% and 38.4% in patients aged >30 years old,significantly higher than 14.9% and 14.8% in age ≤30 years group（P<0.05）;The prevalence of inflammation score≤4 and fibrosis score ≤2 were 92.0% and 92.0% in individuals with normal liver function group, significantly higher than 53.6% and 16.74% in with abnormal liver function group（P<0.05）; The prevalence of inflammation score≤4 and fibrosis score ≤2 were 100.0% and 83.3% in patients with serum HBV DNA load <3 lg copies/ml,much higher than in patients with serum HBV DNA load >3 lg copies/ml;There was no statistical difference in hepatic inflammation score between patients with serum HBeAg-negative and HBeAg-postive group;The patients with spleen thickness≥4 cm had higher hepatic inflammation and fibrosis score than in with spleen thickness<4 cm（P<0.05）;In multivariate analysis,the spleen thickness（P=0.033） and serum HBV DNA（P<0.01） had independent positive correlation to liver inflammation and fibrosis. Conclusion The time of infection has positive correlation to the severity of liver inflammation and fibrosis in patients with chronic hepatitis B virus infection with family cluster. It shows up the progress of liver disease go ahead when age is greater than 30 years old;The abnormal liver function continues,the more serious liver inflammation and fibrosis stands;Spleen thickness has independent positive correlation to liver inflammation and fibrosis;It is more serious in liver inflammation and fibrosis when serum HBV DNA load are in the range of 1×10³~10⁵ copies/ml;Serum HBeAg-negative chronic hepatitis B patients with a family cluster may have more serious liver fibrosis than in serum HBeAg-positive ones.

Key words: Chronic hepatitis B, HBV DNA, HBeAg, Inflammation, Fibrosis

郭素娟, 李娟, 李智伟. 132例家族聚集性慢性乙型肝炎病毒感染者影响自然病程进展的相关因素分析*[J]. 实用肝脏病杂志, 2016, 19(1): 41-44.

Guo Sujuan, Li Juan, Li Zhiwei. Natural progressive course of chronic hepatitis B virus infection in 132 patients with chronic hepatitis B virus infection with family cluster[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(1): 41-44.

参考文献

[1] Centers for Disease Control and Prevention. Viral hepatitis:statistics and surveillance. http://www.cdc.gov/hepatitis/statistics.htm. Accessed January 2010.
[2] Chen CJ,Yang HI,Su J,et al. REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA,2006,295:65-73.
[3] Iloeje UH,Yang HI,Su J,et al. The risk evaluation of viral load elevation and associated liver disease cancer-in HBV （the REVEAL-HBV） study group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology,2006,130:678-686.
[4] Lai CL,Yuen MF. The natural history of chronic hepatitis B. J Viral Hepat,2007,14 （Suppl 1）,6-10.
[5] Yang HI,Lu SN,Liaw YF,et al. Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med,2002,347:168-174.
[6] Yuen MF,Tanaka Y,Mizokami M,et al. Role of hepatitis B virus genotypes B and C,core promoter and precore mutations on hepatocellular carcinoma:a case control study. Carcinogenesis,2004,25:153-159.
[7] Yuen MF,Yuan HJ,Wong DK,et al. Prognostic determinants for chronic hepatitis B in Asians:therapeutic implications. Gut,2005,54:1610-1614.
[8] Alexander JV,Tin NT,Iser D,et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers:Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology,2010,6（51）:1933-1944.
[9] Chen YC,Chu CM,Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology,2010,51（2）:435-444.
[10] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志,2011,14（2）：81-89.
[11] Ishak K,Baptista A,Bianchi L,et al. Histological grading and staging of chronic hepatitis. J Hepatol,1995,22:696-699.
[12] Manno M,Camma C,Schepis F,et al. Natural history of chronic HBV carriers in northern Italy:morbidity and mortality after 30 years. Gastroenterology,2004,127:756-763.
[13] Kim HC,Nam CM,Jee SH,et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases:prospective cohort study. BMJ,2004,328:983.
[14] Anna SF,Lok B,McMahon J. Chronic hepatitis B:Update 2009. AASLD practice guidelines. Hepatology,2009,50（9）:1-36.
[15] European Association for the Study of the Liver. EASL Clinical Practice Guidelines:Management of chronic hepatitis B. J Hepatol,2009,50:115-123.