Wang Chia C, Lim Lei Y, Deubner Heike, Tapia Kenneth, Lau Agnes W Y, Manansala Jaime, Krows Meighan, Shuhart Margaret C, Kowdley Kris V
Department of Medicine, University of Washington, Seattle, WA 98104-2499, USA.
J Clin Gastroenterol. 2008 Aug;42(7):820-6. doi: 10.1097/MCG.0b013e318156feef.
This study examines the prevalence and correlates of significant liver fibrosis among patients with immunotolerant hepatitis B.
Adults with chronic hepatitis B infection acquired early in life often have normal serum alanine aminotransferase (ALT) activity and high serum hepatitis B virus deoxyribonucleic acid loads (HBV DNA), known as "immunotolerant" hepatitis B.
We conducted a cross-sectional study of 28 hepatitis B patients with serum HBV DNA titer >10 copies/mL, positive hepatitis B envelope antigen, and persistently normal serum ALT in a tertiary care setting. Liver biopsies were reviewed by a single pathologist who was blinded to other data. The prevalence of significant hepatic fibrosis was determined using the hospital-defined upper limit of normal for ALT and 2 more stringent criteria proposed by recent studies. Statistical analyses were conducted to identify factors associated with hepatic fibrosis.
The prevalence of stage 2 fibrosis using the hospital laboratory, more stringent, and most stringent definitions of normal serum ALT, was 32%, 32%, and 13%, respectively, corresponding to negative predictive values of 68%, 68%, and 88%, respectively. Age greater than 30 years (P=0.035), grade 2 liver inflammation (P=0.005), and lower serum HBV DNA level (mean 7.45 vs. 8.42 log10 copies/mL, P<0.001) were independently associated with stage 2 fibrosis on liver biopsy.
These results highlight the need to use stringent definitions of normal serum ALT when making clinical decisions for patients with chronic hepatitis B. Older age and lower serum HBV DNA level predict significant hepatic fibrosis on biopsy. Our findings may guide decisions regarding liver biopsy among patients with immunotolerant hepatitis B.
本研究调查免疫耐受期乙型肝炎患者中显著肝纤维化的患病率及其相关因素。
幼年时感染慢性乙型肝炎的成年人通常血清丙氨酸氨基转移酶(ALT)活性正常,血清乙肝病毒脱氧核糖核酸载量(HBV DNA)高,即所谓的“免疫耐受期”乙型肝炎。
我们在一家三级医疗机构对28例血清HBV DNA滴度>10拷贝/mL、乙肝e抗原阳性且血清ALT持续正常的乙型肝炎患者进行了横断面研究。肝活检由一位对其他数据不知情的病理学家进行复查。使用医院定义的ALT正常上限以及近期研究提出的另外两个更严格的标准来确定显著肝纤维化的患病率。进行统计分析以确定与肝纤维化相关的因素。
采用医院实验室定义、更严格定义以及最严格定义的正常血清ALT时,2期纤维化的患病率分别为32%、32%和13%,相应的阴性预测值分别为68%、68%和88%。年龄大于30岁(P=0.035)、2级肝脏炎症(P=0.005)以及较低的血清HBV DNA水平(平均7.45对8.42 log10拷贝/mL,P<0.001)与肝活检2期纤维化独立相关。
这些结果强调在对慢性乙型肝炎患者做出临床决策时,需要使用严格的正常血清ALT定义。年龄较大和血清HBV DNA水平较低可预测活检时显著肝纤维化。我们的研究结果可能为免疫耐受期乙型肝炎患者肝活检决策提供指导。