慢性乙型肝炎丙氨酸转氨酶低于2倍正常上限者的肝组织学改变

目的 通过肝组织活检评价慢性乙型肝炎患者丙氨酸转氨酶(ALT)低于2倍正常上限(2×ULN)者的肝组织病理学特征，为临床抗病毒治疗提供客观依据。方法 2005年10月至2010年8月四川省人民医院感染科肝脏组织活检患者。肝脏组织活检纳入标准：①HBsAg阳性持续6个月以上；②HBeAg阳性者，HBV DNA≥103拷贝/ml,HBeAg阴性者，HBV DNA≥104拷贝/ml;③AIT＜2×UIN持续6个月以上，且未使用任何保肝降酶药；④既往未接受过任何抗病毒治疗，包括干扰素和核苷类似物；⑤愿意接受肝活检。肝脏组织活检前查血常规、凝血酶原时间、生化、乙型肝炎病毒标志物、HBV DNA定量，常规B型超声定位，肝组织活检评价炎症坏死分级范围和纤维化程度。比较各因素与肝脏炎症和纤维化之间的关系。结果 符合诊断标准病例共383例，其中男性240例，女性143例，年龄16～59岁，平均年龄28.0岁。肝脏炎症G0期2例(0.5％)、G1期165例(43.1％)、G2期191例(49.9％)、(3期25例(6.5％)、G4期0例(0.0％)，≥G2期占56.4％。肝脏纤维化S0期103例(26.9％)、S1期265例(69.2％)、S2期13例(3.4％)、S3期2例(0.5％)、S4期0例(0.0％),肝脏纤维化≥S2期仅3.9％。不同年龄、AIT水平、HBV DNA水平和H BeAg状态与肝脏炎症严重程度发生率相关(P＜0.05)。肝纤维化程度仅与年龄、ALT水平及HBeAg状态相关(P＜0.05)，HBV DNA水平与肝纤维化发生率无明显相关性(P＞0.05)。结论 ALT低于2×ULN患者大多数有明显的肝脏炎症和不同程度的肝纤维化，建议应通过肝活检了解肝损伤程度作为评价是否具有抗病毒治疗的指征。

Liver histological changes in chronic hepatitis B patients with alanine aminotransferase lower than two times the upper limit of normal

Objective To assess the liver histopathological characteristics of chronic hepatitis B (CHB) patients with alanine aminotransferase(ALT)lower than 2 times the upper limit of normal (ULN) through liver biopsy, and try to provide subjective evidence for clinical anti-viral treatment.Methods From October 2005 to August 2010, patients accepted liver biopsy in department of infectious disease, Sichuan provincial people's hospital were enrolled. The criteria for liver biopsy was as follow, (1) HBsAg-positive for more than 6 months, (2) HBeAg-positive patients with HBV DNA ≥103 copies/ml or HBeAg-negative patients with HBV DNA≥ 104copies/ml, (3) ALT was lower than 2 times ULN for more than 6 months,and without any hepatic protectants, (4) never accepted any antiviral treatment before, including IFN or nucleoside analogues, (5) willing to accept liver biopsy. Before liver biopsy, routine blood test, prothrombin time, liver function test, hepatitis B antigen and antibody test, HBV DNA quantification were examined. The biopsy position was located under routine ultrasound, liver biopsy were performed to assess the grading of inflammation and necrosis and the degree of fibrosis. The correlation between all the factors and liver inflammation and fibrosis were analyzed. Results Totally 383 cases (240 males and 143 females) met the diagnostic criteria, aged from 16 to 59 years old and the mean age was 28.0 years old. Cases of liver inflammation in G0, G1, G2, G3andG4 grade was 2 cases (0.5％), 165 cases (43.1％), 191 cases (49.9％), 25 cases (6.5 ％ ) and 0 cases (0 ％ ) respectively, cases≥G2 grade accounted 56.4 ％ of total. Meanwhile,stage of fibrosis in S0, S1, S2, S3 and S4 was 103 cases (26.9％), 265 cases (69. 2％), 13 cases (3.4％), 2 cases (0.5％) and 0 cases (0％) respectively, percentage of liver fibrosis in S2stage and over was only 3.9％. The occurrence of serious liver inflammation was associated with age, ALT levels, HBV DNA levels and HBeAg status (P＜0.05). There was no obvious association between HBV DNA level and liver fibrosis (P＞0.05). Conclusions There were obvious liver inflammation and different degree of liver fibrosis in CHB patients with alanine aminotransferase(ALT)lower than 2 times ULN. The degree of liver injury assessed by liver biopsys is recommended as an evaluation for the necessary of anti-viral therapy.