慢性乙肝病毒感染者肝脏病理与临床特征研究

目的 探讨肝活检病理组织学对慢性乙型肝炎病毒（HBV）携带者和血清ALT轻度升高慢性乙型肝炎患者（CHB）的临床意义.方法 105例慢性HBV感染患者全部进行肝组织活检,并按血清ALT水平分为3组：ALT≤0.5×正常参考值上限（ULN）为A组,0.5×ULN＜ALT≤1×ULN为B组,1×ULN＜ALT＜2×ULN为C组;对3组肝脏炎症程度及纤维化程度比较,并对不同肝组织炎症程度、纤维化程度与患者基本情况的关系进行分析.结果 105例患者中炎症程度≥G2者占40.95%,其中ALT正常的患者有30.43%≥G2;纤维化程度≥S2者占26.67%,其中ALT正常的患者中≥S2者占17.39%.血清ALT及透明质酸随肝脏炎症程度加重及纤维化分期的增加而增加（P＜O.05）.结论 密切随访血清ALT和透明质酸可协助了解肝脏病变情况,肝脏病理学依据仍然是决定是否抗病毒治疗的有力依据.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化(S2～S4期),严重纤维化(S3～S4期)和肝硬化(S4期).以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线(ROC),计算曲线下面积(AUC),评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例(1.4%),S1期49例(23.1%),S2期66例(31.1%),S3期50例(23.6%),S4期44例(20.8%),即显著纤维化者(S2～S4期)160例(75.5%),严重纤维化者(S3～S4期)94例(44.3%),肝硬化者(S4期)44例(20.8%).FIB-4指数对3个判定点的AUC值分别为0.733(95%(CI:0.660～0.806,P<0.01)、0.746(95%CI:0.679～0.813,P<0.01)、0.756(95%CI:0.687～0.825,P<0.01).结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化(S2～S4期),严重纤维化(S3～S4期)和肝硬化(S4期).以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线(ROC),计算曲线下面积(AUC),评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例(1.4%),S1期49例(23.1%),S2期66例(31.1%),S3期50例(23.6%),S4期44例(20.8%),即显著纤维化者(S2～S4期)160例(75.5%),严重纤维化者(S3～S4期)94例(44.3%),肝硬化者(S4期)44例(20.8%).FIB-4指数对3个判定点的AUC值分别为0.733(95%(CI:0.660～0.806,P<0.01)、0.746(95%CI:0.679～0.813,P<0.01)、0.756(95%CI:0.687～0.825,P<0.01).结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化（S2～S4期）,严重纤维化（S3～S4期）和肝硬化（S4期）.以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线（ROC）,计算曲线下面积（AUC）,评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例（1.4%）,S1期49例（23.1%）,S2期66例（31.1%）,S3期50例（23.6%）,S4期44例（20.8%）,即显著纤维化者（S2～S4期）160例（75.5%）,严重纤维化者（S3～S4期）94例（44.3%）,肝硬化者（S4期）44例（20.8%）.FIB-4指数对3个判定点的AUC值分别为0.733（95%（CI：0.660～0.806,P〈0.01）、0.746（95%CI：0.679～0.813,P〈0.01）、0.756（95%CI：0.687～0.825,P〈0.01）.结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.     

Clinical use of liver biopsy for the diagnosis and management of inactive and asymptomatic hepatitis B virus carriers in Bangladesh

Patients with inactive chronic hepatitis B virus (HBV) infection are assumed to be free from liver disease. Accordingly, antiviral drug treatment is not recommended for these patients. However, the extent of liver damage in these patients has not been evaluated fully. The aim of this study was to evaluate the extent of liver damage in patients with inactive HBV. Liver biopsy was conducted in 141 inactive HBV carriers [HBeAg‐negative, low levels of HBV DNA (≤10,000 copies/ml) and normal levels of serum alanine aminotransferase (ALT)]. The extent of hepatic inflammation and fibrosis was evaluated in these patients by examining liver biopsy specimens. Although the patients were inactive HBV carriers, mild to moderate levels of necroinflammation (HAI necroinflammation score HAI‐N1 ≥ 7) were detected in 36 of 141 (26%) patients. Seventeen patients had a severe degree of hepatic fibrosis (HAI fibrosis score HAI‐F ≥ 3). A total of 10 patients had both considerable necroinflammation (HAI‐N1≥7) and severe fibrosis (HAI‐F ≥3). All 10 patients with significant hepatic inflammation and fibrosis were male and older than 25 years. However, all were HBeAg‐negative and expressed low levels of HBV DNA and normal ALT levels. The study demonstrates that features of liver damage were present in a considerable number of the patients. Assessment of liver biopsy specimens in a larger cohort of inactive HBV carriers is necessary to establish management guidelines for such patients. J. Med. Virol. 82:1350–1354, 2010. © 2010 Wiley‐Liss, Inc.     

Serum liver fibrosis markers discriminate significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase

Chronic liver inflammation caused by chronic hepatitis B virus (CHB) infection leads to liver cirrhosis and hepatocellular carcinoma. Recently, the role of alanine aminotransferase (ALT) as a predictor of liver inflammation has been questioned. The aim of this study was to investigate the utility of noninvasive fibrosis markers including hyaluronic acid (HA), collagen type IV (CIV), N-terminal propeptide of type III procollagen (PIIINP), and laminin (LN) in identifying significant liver inflammation in patients with CHB, especially in patients with normal or near-normal ALT. A total of 242 CHB patients who underwent liver biopsy were enrolled. The serum levels of ALT, aspartate aminotransferase, HA, CIV, PIIINP, and LN were quantified and the relationship between histological staging and serum markers was systematically analyzed. Serum CIV, PIIINP, HA, and LN levels increased significantly along with the increasing severity of liver inflammation. Multivariate analysis showed that CIV and LN were independently associated with significant inflammation. CIV, PIIINP, HA, and LN levels were found to have high diagnostic values for predicting significant inflammation in patients with CHB (area under the curve, AUC = 0.807, 0.795, 0.767, and 0.703, respectively). The combined index for the identification of significant inflammation, including CIV, PIIINP, HA, and LN levels, significantly improved diagnostic performance (AUC = 0.851). Moreover, the combined index also achieved excellent diagnostic accuracy (AUC = 0.861) in patients with CHB with normal or near-normal ALT. In conclusion, the combined index may be a strong indicator for discriminating significant liver inflammation, especially in patients with CHB with normal or near-normal ALT.     

Histological grading and staging in chronic hepatitis: its practical correlation

Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection or concomitant liver disease and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease.     

Influence of hepatitis G virus infection on liver disease

The influence of hepatitis G virus (HGV) infection on disease activity in hepatitis C related and unrelated liver disease was investigated in 254 individuals using an EIA polymerase chain reaction assay for HGV. One hundred patients had chronic hepatitis C, 26 primary biliary cirrhosis, and 30 alcoholic liver cirrhosis. In addition, 51 hepatitis B surface antigen (HBsAg)-positive and 47 anti-hepatitis C virus (HCV)-positive blood donors were screened. Hepatitis G virus was detected in 18% of patients with chronic hepatitis C, 13% of patients with alcoholic liver cirrhosis, 11 % of patients with primary biliary cirrhosis, 10% of anti-HCV-positive blood donors, and 2% of HBsAg-positive blood donors. Virus load and alanine aminotransferase (ALT) levels did not differ significantly in patients with HCV alone versus patients coinfected with HCV and HGV. However, mild liver fibrosis correlated with HGV coinfection. Hepatitis G virus did not influence ALT levels or liver damage in liver disease unrelated to viral infection.     

急、慢性乙型肝炎及乙肝肝硬化患者 肝功能及血脂水平分析

目的 分析急、慢性乙型肝炎、乙肝肝硬化患者血脂水平及患者血脂水平的变化情况。方法 选择2015年1月~2018年12月我院收治的急性乙型肝炎患者40例作为急性乙型肝炎组,慢性乙型肝炎患者44例作为慢性乙型肝炎组、乙肝肝硬化患者35例作为乙肝肝硬化组,采用回顾性调查方法比较急、慢性乙型肝炎及乙肝肝硬化患者肝功能及血脂水平。结果 急性乙型肝炎组与慢性乙型肝炎组在ALT、AST、TBIL、DBIL比较,差异有统计学意义（P＜0.05）;急性乙型肝炎组与乙肝肝硬化组在ALT、AST、ALB、TBIL、DBIL、PT、PTA、INR比较,差异有统计学意义（P＜0.05）;慢性乙型肝炎组与乙肝肝硬化组在ALT、AST、ALB、PT、PTA、INR比较,差异有统计学意义（P＜0.05）。急性乙型肝炎组TG高于慢性乙型肝炎组与乙肝肝硬化组,差异有统计学意义（P＜0.05）;慢性乙型肝炎组CHO水平高于急性乙型肝炎组与乙肝肝硬化组,差异有统计学意义（P＜0.05）;急性乙型肝炎组、慢性乙型肝炎组、乙肝肝硬化组在HDL-C、LDL-C间比较,差异无统计学意义（P＞0.05）。结论 急、慢性乙型肝炎及乙肝肝硬化患者血脂水平逐渐降低,以TG下降为主,与肝功能损伤有关,是评估乙型肝炎病程进展的一个重要指标。     

Management of hepatitis B in China

A randomised, multicentre, double-blind, placebo controlled trial was conducted in Chinese patients with chronic hepatitis B to compare the efficacy of once-daily lamivudine and placebo on serum HBV DNA, and to assess the long-term efficacy and safety of lamivudine. Patients received lamivudine 100 mg (n = 322) or placebo (n = 107) once daily for 12 weeks, and were then offered open-label lamivudine treatment for 2 years. Lamivudine therapy resulted in increased hepatitis B e antigen (HBeAg) loss and seroconversion (loss of HBeAg plus the development of antibodies to HBeAg) in patients with high baseline serum alanine aminotransferase (ALT) concentrations. At 2 years, loss of HBeAg was achieved by 27% (38/140), 38% (25/66) and 60% (9/15), and seroconversion was achieved by 17% (24/140), 24% (16/66) and 33% (5/15) of patients with baseline serum alanine aminotransferase (ALT) concentrations of >1 x upper limit of normal (ULN), >2 x ULN and >5 x ULN, respectively. With lamivudine treatment, serum HBV DNA decreased rapidly to very low concentrations and remained low throughout the 2 years of the study. At 1 year, 15% (43/295) of patients in the lamivudine group had developed YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. These patients derived clinical benefit with continued lamivudine therapy, demonstrated by serum HBV DNA and ALT concentrations below baseline, or normal serum ALT concentrations. Lamivudine was well tolerated and an effective once-daily oral therapy for Chinese patients with chronic hepatitis B with viral replication and liver disease.     

Hepatitis B e antigen seroconversion: effects of lamivudine alone or in combination with interferon alpha

Seroconversion of hepatitis B e antigen (HBeAg) is an important marker for resolution of active hepatitis B virus (HBV) infection and for a long-term positive response to treatment. Lamivudine, a nucleoside analogue, is the first effective oral treatment for chronic hepatitis B in patients with evidence of viral replication and liver disease. When appropriate patient groups are compared, treatment with lamivudine for 1 year leads to HBeAg seroconversion in a similar proportion of patients as a standard course of interferon (IFN) alpha therapy. Seroconversion increases during prolonged therapy (up to 3 years), and is sustained post-treatment in more than three-quarters of patients. Response rates are related to the pretreatment level of serum alanine aminotransferase (ALT) and reach 65% in those patients with serum ALT > 5 x upper limit of normal (ULN) after one year. For patients with pretreatment ALT > 2 x ULN, response was seen in 38% after one year, rising to 65% after 3 years. To date, combination with IFN and lamivudine has not been shown to confer additional benefit compared with lamivudine monotherapy. Lamivudine is effective and appropriate for use in a greater proportion of HBV infected patients than IFN alpha, particularly those infected at birth or in early childhood. Furthermore, because seroconversion after lamivudine is not normally associated with a severe flare of liver disease, as seen with IFN, it is more suitable for use in patients with active liver disease and cirrhosis. In conclusion, lamivudine is more suitable than IFN for a broad range of patients, including those with severe liver disease, recurrent flares, pre-core mutant HBV and those who have failed previously IFN treatment or are immunosuppressed. Lamivudine is also better tolerated than IFN.     

慢性乙型肝炎患者肝功能及血清HBeAg和HBV DNA载量与肝组织病理相关性的研究

目的 探讨慢性乙型肝炎患者肝功能、HBeAg及HBV DNA水平与肝组织病理炎症分级和纤维化分期的关系.方法 选择233例慢性乙型肝炎患者进行肝穿病理学检查,同时所有患者检测HBV DNA、HBeAg及肝功能,比较患者的肝功能、HBeAg及HBV DNA水平在不同病理炎症分级及纤维化分期中的差异情况.结果 不同的炎症分级患者中,ALT以C3组最高,G0～1组最低,各组间比较差异有统计学意义(P =0.016);TBil以G4组最高,G0～1组最低,各组间比较差异有统计学意义(P=0.000);HBV DNA载量各组间差异无统计学意义.不同的纤维化分期患者中,ALT各组间比较差异无统计学意义;TBil以S4组最高,S2组最低,各组间比较差异有统计学意义(P=0.039);HBV DNA载量各组间差异无统计学意义.炎症分级为G3～4的患者比例在HBeAg阳性组与阴性组差异无统计学意义.纤维化分期S3～4的患者比例在HBeAS阳性组(38%)比HBeAg阴性组(53%)低,两组差异有统计学意义(P=0.025).结论 慢性乙型肝炎患者血清HBV DNA水平的高低不能反映其肝脏炎症及纤维化程度,HBeAg阴性慢乙肝患者肝组织纤维化程度较高,TBil水平与肝组织炎症分级及纤维化分期均有良好的相关性,ALT水平与炎症分级有一定的关联性,但与纤维化分期无关.     

血清HBsAg与HBV DNA水平与乙肝患者肝纤维化程度的相关性分析

目的 探讨血清HBsAg与HBV DNA对乙肝患者肝纤维化的相关性分析.方法 选取2010年5月至2014年9月在我院进行治疗的100例肝脏穿刺活组织学检查的患者,根据肝脏炎症程度将患者分为G0-G1、G2、G3-G4三组,根据不同纤维化分期将患者分为S0-S1、S2、S3、S4四组,根据丙氨酸转氨酶(ALT)水平,将患者分为A1 (ALT≤40U/L)组、A2(40＜ALT≤80U/L)组,对不同分组患者进行血清HBsAg测定、HBV DNA测定及ALT测定,分析其含量与肝脏炎症程度及纤维化程度的相关性.结果 G0-G1组、G2组、G3-G4组HBsAg定量分别为(3.85±0.87)U/ml、(3.54±0.79) U/ml、(2.79 ±0.58) U/ml,三组间具有统计学差异(P＜0.05).G0-G1组、G2组、G3-G4组HBV DNA定量分别为(6.27±1.67) U/ml、(5.68±1.49) U/ml、(5.84±1.59) U/ml,三组间差异无统计学差异(P＞0.05).S0-S1组、S2组、S3组、S4组患者HBsAg定量分别为(3.95±0.93) U/ml、(3.62±0.86) U/ml、(3.55±0.62) U/ml、(3.35 ±0.54) U/ml,四组差异有统计学差异(P＜0.05).S0-S1组、S2组、S3组、S4组患者HBV DNA定量分别为(6.23±1.72) U/ml、(5.79±1.62U/ml)、(5.50±1.48) U/ml、(5.48±1.35U/ml),四组差异有统计学意义(P＜0.05).ALT水平与炎症程度及纤维化程度没有相关性(P＞0.05).结论 HBsAg、乙肝病毒随着肝纤维化程度的加重逐渐减低,血清HBsAg结合HBV DNA载量作为检测乙肝病毒感染者肝纤维化指标更为可靠.     

Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B

We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB). In this study, a total of 331 CHB patients from three cohorts who underwent liver biopsy were enrolled, and the Scheuer system was used for liver fibrosis classification. The combined score was derived by principal component analysis of key differentially expressed genes. For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842, and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801, and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase≥to≥platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression. In conclusion, the novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.     

Liver disease-significant improvement with lamivudine

The natural history of chronic hepatitis B virus (HBV) infection is highly variable, ranging from a benign course to one of shortened life expectancy. Liver histology represents an accurate tool for assessing progressive liver disease, and has been used in five recent Phase III clinical trials of the oral nucleoside analogue, lamivudine, 100 mg/day, in patients with chronic hepatitis B. Significant improvements in the Knodell histological activity index (HAI) score were reported with lamivudine, with greater decreases noted after 2 years of therapy, consistent with continued alanine transaminase (ALT) normalisation. Histological data showed that lamivudine therapy can resolve or lessen the progression of fibrosis, and reduce the progression to cirrhosis in patients with chronic hepatitis B. These trials also showed that lamivudine provoked significant enhancement of hepatitis B e antigen (HBeAg) seroconversion compared with placebo, and had a profound effect on serum HBV DNA, resulting in rapid suppression of viraemia. The emergence of variants with a mutation in the YMDD (tyrosine-methionine-aspartate-as-partate) motif did not cause significant worsening of the Knodell HAI score. In conclusion, lamivudine is the first oral antiviral therapy for the treatment of chronic hepatitis B. It reduces significantly the severity of liver disease and reduces progression to cirrhosis. In addition, because lamivudine is well tolerated it represents a viable therapeutic option that may improve the prognosis of patients with chronic hepatitis B.     

慢性HBV感染肝脏病理变化和生化ALT及病毒学关系

目的 探讨慢性HBV感染ALT、HBV DNA与肝脏病理的关系.方法 对81例慢性HBV感染患者检测血清ALT、HBV DNA.并进行肝活检病理检查.结果 肝脏炎症分级和纤维化分期与ALT明显相关(r值分别为0.683和0.419),与HBV DNA无相关性.随着肝脏炎症活动度和纤维化程度的加重,ALT有升高趋势(χ2趋势值分别为25.81和12.012),HBV DNA无升高趋势,而随着HBVDNA的升高,肝脏炎症活动度和纤维化程度并无加重趋势.肝组织HBsAg、HBcAg阳性组与阴性组的ALT、HBV DNA差异无统计学意义.结论 ALT与肝脏炎症活动度有明显相关性,仍是观察炎症变化的敏感指标,HBV DNA与肝组织炎症分级及纤维化分期无相关性.     

Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance

The long-term histological and virological outcomes of spontaneous circulating hepatitis C virus (HCV) clearance were studied in chronic liver disease. Between 1979 and 1984, three patients underwent laparoscopy for chronic non-A, non-B liver disease, and two were found to have cirrhosis and one with chronic active hepatitis. After HCV assays became available in 1990, they were positive persistently for HCV antibody without serum HCV RNA. Reductions of antibody levels to HCV core and/or nonstructural proteins were observed, and liver biopsies were undertaken between 1995 and 2000. Liver biopsies at 11-19 years after laparoscopy disclosed marked alleviation of liver inflammation and fibrosis in each case although a low grade of inflammation remained. The two patients with cirrhosis no longer showed histological features of cirrhosis, and the poor liver function in one patient had been ameliorated. Liver specimens from two patients were subjected to polymerase chain reaction to detect positive and negative HCV RNA strands and hepatitis B virus DNA. Only the positive HCV RNA strand was detected for one patient who had previously cirrhosis. Liver specimens were examined from another six nonviremic HCV-seropositive individuals without chronic liver disease. Five patients displayed low-grade liver inflammation without evident fibrosis, but none had any viral genome in the liver. These findings suggest that spontaneous circulating HCV clearance in chronic liver disease confers favorable liver histological outcome, although occult HCV infection persists. J. Med. Virol. 69:41-49, 2003.     

Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.

Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear. We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores. Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes. These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.     

慢性乙型肝炎患者肝组织p53的表达及其影响因素

目的探讨慢性乙型肝炎患者肝组织抑癌基因p53的表达及其影响因素。方法符合诊断标准的HBeAg阴性慢性乙型肝炎患者17例、HBeAg阳性慢性乙型肝炎患者31例。行血清学标志物及肝组织病理学检查。结果（1）HBeAg阴性组患者年龄较大、男性居多、HBVDNA水平偏低,三项指标均与HBeAg阳性组有统计学差异。血清学指标除Glo外,均无统计学差异。（2）两组患者肝脏病理学炎症及纤维化分期差异均无统计学意义;肝组织中p53阳性率及p53计分无统计学差异。（3）Logisticregression分析表明,只有肝脏纤维化分期（s）是p53阳性表达的危险因素,与S0-1相比,S≥2患者出现p53阳性的风险增高3．9倍。结论慢性乙型肝炎患者肝脏纤维化分期是其肝组织p53阳性表达的危险因素。     

Liver histopathology in patients with concurrent chronic hepatitis C and HIV infection

To investigate the influence of human immunodeficiency virus (HIV) coinfection on preexisting long-term chronic C hepatitis (HCV) 68 liver biopsies from 22 HIV/HCV-coinfected, 13 HIV and 33 HCV-monoinfected patients and 71 livers obtained at autopsy from 26 HIV/HCV-coinfected and 45 HIV-monoinfected patients were studied by histo- and immunohistochemistry. All HIV patients had reached the advanced stage of immunodeficiency (stage III CDC), except for 3 haemophiliacs (stage II CDC). HCV infection was associated with a higher degree of portal, periportal and lobular inflammation — regardless of whether there was concurrent HIV infection. HIV/HCV coinfection was associated with a significantly higher rate of granulocytic cholangiolitis than HCV and HIV monoinfection (P < 0.05), a histological feature uncommon in C hepatitis. In HIV/HCV coinfection cholestasis was a predominant histological feature. HCV monoinfection and HCV/HIV coinfection were associated with the highest fibrosis index. In HIV/HCV coinfection centrilobular fibrosis was significantly more marked than in HCV monoinfection (P < 0.05), suggesting an HIV associated fibrogenic effect. Patients with chronic C hepatitis showed a significantly increased rate of posthepatitic cirrhosis compared with the patients without HCV infection (P < 0.05). At autopsy, 10 of the 20 HIV/HCV-coinfected haemophiliacs had developed cirrhosis because of chronic C hepatitis, whereas cirrhosis was found in only 2 of 6 HIV/HCV-coinfected non-haemophiliacs (1 case of chronic B and C hepatitis, and 1 case of chronic alcohol abuse). No cirrhosis was observed in the 45 autopsy patients with HIV monoinfection. The findings suggest that HIV coinfection aggravates the course of preceding long-term chronic C hepatitis by a more marked (centrilobular) fibrosis. HIV/HCV-coinfected patients are threatened by a higher rate of posthepatitic cirrhosis —particularly in multitransfused haemophiliacs — and cholestatic hepatopathy.