Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and C

T-cell immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Th1 cytokines positively correlate with hepatic inflammation in chronic hepatitis B virus (HBV) infection. The pro-inflammatory, cytokines IL-6 and IL-18, are involved in viral clearance and in metabolic and viral hepatic diseases, respectively. The aim of this study was to evaluate the profile of Th1/Th2 cytokines in HCV and HBV hepatitis. HBV-infected patients showed higher plasma IFN-gamma levels than the HCV+ patients or the control group (p <0.0001). Plasma TNF-alpha and IL-2 were higher in HBV+ in comparison to HCV+ patients (p <0.001) or the control group (p <0.005). Plasma IL-6 and IL-18 were higher in both groups of patients compared to the control group (p <0.04). In HCV+ and HBV+ groups, IL-6 was positively correlated with the duration of the illness (p <0.01 and <0.001, respectively) and viral load (p <0.001 and <0.001, respectively), while IL-18 was positively correlated with serum ALT activity (p <0.01 and <0.001, respectively) and serum AST activity (p <0.01 and <0.001, respectively). We found that in HCV+ and HBV+ patients there are higher levels of Th1 cytokines, particularly in the course of chronic hepatitis B, and that IL-18 and IL-6 levels may have important roles as markers of both inflammation and hepatic injury, particularly in the course of hepatitis C.     

379例HCV感染者丙型肝炎病毒载量与抗HCV及肝功能指标的相关性分析

目的 探讨丙型肝炎患者HCV RNA载量与抗HCV及肝功能指标的相关性.方法 回顾分析2011年1月至2013年12月间在本院门诊,住院,体检中丙型肝炎抗体阳性病人,男150人,女229人,年龄32-87岁,应用实时荧光定量PCR检测HCV RNA病毒,全自动生化分析仪检测肝功能8项指标,按HCV RNA病毒载量数分HCV RNA阴性组,HCV RNA低中水平组,HCV RNA高水平组.结果 三组年龄分布比例经统计学检验无明显差异（P＞0.05）,但低中水平女性比例比男性略高;三组肝功能生化指标检测结果不完全相同（P ＜0.05或P＜0.01）,其中HCV RNA低中水平组和高水平组血清ALT、AST、GGT、ALP、TBIL与阴性组比较均有差异（P＜0.05或P＜0.01）;TP、ALB、DBIL三组间比较虽无明显统计学差异,但低中水平组和高水平组结果呈下降趋势,低中水平组和高水平组比较ALT、AST、TBIL也有明显差异（P＜0.05）,病毒载量越高ALT、AST的结果越高,经干扰素治疗后随载量的下降肝功能酶类指标也随之下降.结论 不论病毒载量的高低只要HCV RNA持续阳性,都可导致肝细胞的损害和肝功能的异常,临床应尽早进行抗病毒治疗.PCR实时荧光探针技术方法先进,技术成熟,结果稳定,能早期诊断HCV感染者,有助于临床早期抗病毒治疗,防止HCV传播和发展.     

67例慢性丙型肝炎治疗过程及随访中血清ALT、病毒载量及肝纤维化指标的变化

目的 观察聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎过程中肝功能、病毒复制及肝纤维化指标的改变情况.方法 检测67例慢性丙型肝炎患者在干扰素联合利巴韦林治疗开始（0周）、结束（48周）和停药12周（60周）时血清丙氨酸转氨酶（ALT）、丙肝病毒核糖核酸（HCV RNA）、透明质酸（HA）、Ⅲ型前胶原肽（PCⅢ）、Ⅳ型胶原（Ⅳ-C）和层粘连蛋白（LN）水平.结果 治疗后完全应答组（CR-S,43/67） ALT、HCV RNA及血清4项纤维化指标均显著下降（P ＜0.05或P＜0.01）,部分应答组（CR-R,13/67）和无应答组（NR,11/67） ALT、HCV RNA及血清4项纤维化指标变化不明显,反跳甚至更高.结论 聚乙二醇干扰素α-2b联合利巴韦林治疗慢性丙型肝炎约65％患者完全应答,随着肝细胞炎症的改善,病毒RNA滴度、肝纤维化指标水平明显下降,表明干扰素联合利巴韦林能抑制HCV RNA复制,调节机体免疫功能,减轻肝脏炎症反应,改善肝功能,减少肝纤维化.     

Adenosine deaminase activity in serum of patients with hepatitis -- a useful tool in monitoring clinical status.

BACKGROUND AND PURPOSE: The evaluation of adenosine deaminase (ADA) activity in sera of patients with hepatitis should be considered a useful tool in the monitoring of their clinical status. In this study, we aimed to determine the relationship between viral load, transaminase levels, and serum ADA levels in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients. METHODS: Seventy three patients with hepatitis B, 71 patients with hepatitis C and 40 healthy individuals were included. Patients with HBV and HCV infections were classified into 3 groups according to viral load. Serum ADA levels were investigated by colorimetric assays. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ADA levels of HBV- and HCV-infected patients were higher than those of the control group. These differences were statistically significant for the levels of all enzymes in HCV-infected patients (p<0.05), and all except AST (p>0.05) in HBV-infected patients. ADA levels of HBV-infected patients with high viral loads were higher than those in HBV-infected patients with intermediate and low viral loads, and the difference was detectably significant between patients with high and intermediate viral loads. Evaluation of HCV-infected patients according to viral load showed no statistically significant relationship between viral load and serum ADA, ALT, and AST levels (p>0.05). HBV- and HCV-infected patients with high ALT and AST levels showed statistically significantly higher levels of ADA than patients with normal ALT and AST levels (p<0.001). CONCLUSIONS: We suggest that serum ADA levels are associated more with the level of serum transaminases than viral load in HBV- and HCV-infected patients. In the treatment of patients with hepatitis, serum ADA levels should be considered a useful tool for the monitoring of liver condition.     

Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C

Occult hepatitis B virus (HBV) infection is common in chronic hepatitis C patient. However, its significance and consequences are still unclear. The aim of this study was to evaluate the prevalence of occult HBV among HCV chronic carriers in France and to assess its impact on liver histology and response to antiviral therapy. To this end a cohort of 203 patients with chronic hepatitis C without hepatitis B surface antigen (HBsAg) has been examined. Serum HBV-DNA was detected using a highly sensitive PCR with primers located in the S and X genes. HBV viraemia levels were further determined by real-time PCR. Results showed that 47 of 203 (23%) patients had occult HBV infection with a low HBV load (10(2)-10(4) copies/ml) but significantly higher HCV-RNA titers (P < 0.05). No significant difference in age, gender, serum ALT level, HCV genotypes, and the presence of anti-HBc was observed between patients with or without HBV-DNA. When compared histologically, patients with occult HBV infection had higher activity (A2-A3 in 53% vs. 38%, P < 0.01) and more advanced fibrosis (60% vs. 33%, P < 0.001) than HBV-DNA negative cases. Sustained response to combination therapy against Chronic hepatitis C was achieved in 11 (28%) of 40 HBV-DNA positive cases, compared with 65 (45%) of the 144 HBV-DNA negative cases (P < 0.05). Among the 144 HBV-DNA negative HCV patients those with genotype 1 responded less frequently to therapy as compared to other genotypes infected patients (38% vs. 55%, P < 0.05). Surprisingly, when considering all patients studied, irrespective to the HBV-DNA status no significant difference was observed in response to combination therapy regarding HCV genotypes (39% vs. 44%, P > 0.05). In conclusion, HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc. Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes.     

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.     

Association of human leucocyte antigen Class I (HLA-A and HLA-B) with chronic hepatitis C virus infection in Egyptian patients

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, ranging from 6% to 28% with an average of approximately 13.8% in the general population. It has been reported that human leucocyte antigen (HLA) alleles are associated with the outcome of HCV infection, but this associations showed ethnic and geographical differences. The objective of this study is to investigate the association between the frequencies of HLA Class I and chronic HCV infection in Egyptian patients and to find out whether there is a relation between certain HLA Class I antigens and HCV viral load, degree of fibrosis, activity and alanine aminotransferase (ALT) level. A case control study was conducted on 100 patients with chronic HCV infection and 150 healthy controls. HLA-A and HLA-B typing by complement-dependent micro-lympho-cytotoxicity assay was performed for both groups. HLA-A11 antigen was significantly increased in patients with chronic HCV infection versus controls (OR 3.98; 95% CI = 1.85-8.89; P = 0.001; and Pc = 0.021). HLA-B12, HLA-B13, HLA-B17 and HLA-B40 were higher in patients, and HLA-A32 and HLA-B14 were higher in controls, although the significance was lost after correction for multiple testing. HLA-A9 was significantly associated with low viral load (P = 0.008, Pc = 0.048). The results of this work implicate that HLA-A11 antigen may influence chronic HCV infection and may play a role in viral persistence. Different HLA Class I antigens are not associated with degree of liver fibrosis, grades of activity or level of ALT. However, HLA-A9 is associated with low HCV viral load in chronic HCV Egyptian patients.     

慢乙肝患者HBV-DNA和Pre-S1Ag及HBVM与肝脏功能的检测意义

目的:了解乙型肝炎病毒HBV-DNA、Pre-S1Ag、乙肝标志物(HBVM)和肝脏功能之间的关系及临床意义.方法:采用荧光定量聚合酶链式反应(FQ-PCR)和ELISA分别检测169例乙肝病人血清HBV-DNA含量和乙肝标志物及Pre-S1Ag与肝功能,并对结果进行对比分析.结果:各种不同类型乙肝HBsAg的阳性率均高于91.1%,HBeAg、Pre-S1Ag的阳性率随HBV-DNA拷贝数的升高而升高,但肝功能和HBV-DNA拷贝数之间不存在相关关系.结论:同时检测血清乙肝标志物、Pre-S1Ag、HBV-DNA和肝脏功能对临床HBV感染、复制及传染性的判断以及肝功能损伤程度均有重要意义.     

Description of liver disease in a cohort of HIV/HBV coinfected patients

BackgroundFactors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients.ObjectivesTo describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients.Study designWe followed-up 107 consecutive HIV/HBV coinfected patients. Clinical, biological and virological data were collected every 3 months. Liver-related mortality and a composite score were used to define advanced liver disease.ResultsThe patients were mainly sub-Saharan Africans (61%) or Europeans (33%). Forty-four percent of patients had liver biopsy, 78% of patients received lamivudine. Advanced liver disease (ALD) was diagnosed in 19/107 patients during follow-up (mean 4.8 years): 10 extensive fibrosis, 5 cirrhosis, 3 hepatocellular carcinoma resulting from cirrhosis, and 1 fulminant hepatitis following lamivudine withdrawal. Eleven patients died, 4 from HBV-related liver disease. In univariate analysis, male gender, mean HIV and HBV viral loads, and raised AST/ALT transaminases were associated with increased risk of ALD. The strongest associations, in a multivariate model, were mean AST transaminase and cumulated time receiving lamivudine, with a favourable effect. 39% of patients with increased mean AST presented with ALD, versus 7% when normal mean AST (Relative Risk 5.5).ConclusionsDuring HIV/HBV coinfection, transaminase levels are strongly associated with ALD. Normal mean AST has a high negative predictive value, contrary to previously reported data in HIV/HCV patients.     

Monitoring patients with chronic hepatitis during and after therapy

Hepatitis C is a major public health problem. General screening is not advisable and should be limited to risk groups. The gold standard for the assessment of disease severity is liver biopsy. AST and ALT do not correlate with histology. Serum HCV RNA by qualitative assay and HCV genotype should be determined prior to therapy. Response to antiviral therapy should be assessed by testing AST, ALT and qualitative HCV RNA. Repeat liver biopsy is not necessary. The incidence of HCC related to HCV infection is rising. Early detection by a cost effective screening program is essential. In patients with liver cirrhosis caused by hepatitis C, alpha fetoprotein and liver sonography should be done every 6 months. Upper GI endoscopy is recommended every 1-4 years in cirrhotic patients. Over 350 000 000 people are infected with HBV worldwide, and chronic HBV infection is the leading cause of liver cancer and tenth leading cause of death. HBs Ag, HBeAg and HBV DNA positive patients should be monitored for 6 months before treatment. Patients treated with antiviral therapy should be tested for HBAg, HBeAg and HBV DNA at the end of treatment and every 6 months thereafter to assess virologic response. Monitoring of serum HBV DNA is done by PCR. Patients treated with lamivudine should be tested for YMDD mutation. Ultrasound and AFP monitoring are recommended for detection of HCC, but results are not always reliable. Approximately 40% -70% of HIV infected patients have coinfection with HCV, HBV and HDV. HIV/HCV coinfected patients have an increased risk of progressive liver disease and should be treated accordingly.     

慢性HCV感染者外周血中髓样和浆样树突状细胞频数和表型研究

目的 探讨慢性HCV感染者外周血中髓样树突状细胞(mDC)和浆样树突状细胞(pDC)频数和表型的变化,并分析其与丙型肝炎临床指标间的相关性.方法 采用流式细胞术检测HCV感染者及健康对照外周血中mDC和pDC的频数及细胞表面共刺激分子HLA-DR、CD83、CD86、CD40和共抑制分子PD-L1的表达水平,并分析DC频数与HCV感染者血浆病毒载量、谷丙转氨酶(ALT)的相关性.结果 与健康对照组相比,HCV感染者外周血中mDC和pDC的频数明显降低(患者组分别为0.37±0.19和0.19±0.12,对照组为0.51±0.18和0.29±0.13,P＜0.05),且mDC频数与血浆HCV载量和血清ALT水平呈负相关(r=-0.5878,P＜0.0001;r=-0.4628,P=0.003).患者mDC和pDC表面共刺激分子HLA-DR、CD83、CD86、CD40以及共抑制分子PD-L1的表达均有不同程度升高,差别有统计学意义(共刺激分子P＜0.01,共抑制分子P＜0.05或0.01).结论 慢性HCV感染者外周血mDC和pDC频数下降,但DC表面共刺激分子和共抑制分子的表达均明显升高.该结果提示mDC数量的减少可能与HCV的慢性持续性感染有关.

Abstract：

Objective To explore the frequencies and phenotype of myeloid and plasmacytoid dendritic cells (mDC and pDC) in chronic HCV infection and to investigate the relationships between DC frequencies and HCV viral load and serum ALT level. Methods PBMC were isolated from chronic HCV infected patients and healthy control. Multi-color flow cytometry was used to analyze the frequencies and surface marker expression on mDC and pDC. The relationship between DC frequencies and viral load and ALT level was also calculated. Results In comparison with healthy control, frequencies of mDC and pDC in chronic HCV infection were significantly decreased (0. 37 ± 0. 19 and 0. 19 ± 0. 12 vs 0. 51 ± 0. 18 and 0. 29 ± 0.13, P＜0.05). The frequency of mDC was negatively correlated with HCV viral load (r= -0.5878, P ＜ 0. 0001 ) and serum ALT level ( r = - 0. 4628 , P = 0. 003 ). Both costimulatory markers ( HLA-DR, CD83, CD86, and CD40) and coinhibitory marker (PD-L1) expression on mDC and pDC in HCV infection were increased (P＜0.01 for costimulatory marker, P＜0.05 or F＜0.01 for coinhibitory marker). Conclusion The frequencies of mDC and pDC in chronic HCV infection were decreased, while the expression of costimulatory markers and coinhibitory marker were increased or not decreased in HCV infection. The decreased frequency of mDC was probably related to persistance of HCV infection.     

丙肝患者HCV病毒载量、HCV抗体与ALT、AST、前白蛋白的相关性分析

目的 探讨丙肝患者HCV抗体和HCV病毒核酸定量与ALT、AST、前白蛋白水平的相关性.方法 分别采用ELISA、RT-PCR法、速率法和免疫比浊法检测133例丙型肝炎患者血清抗HCV、HCV-RNA定量、ALT、AST和PA.数据处理采用Spss 13.0统计软件.结果 ALT、AST阳性率分别为69.9％和70.7％,组间比较x2=18.05,P＜0.01.PA浓度在HCV-RNA不同含量组别方差分析F=129.92,P＜0.001.前白蛋白水平随HCV核酸含量增高而逐渐降低,而ALT、AST阳性率则增高,组间PA比较,除1.0×10^5组和≥1.0×10^6组无差异外,其它各组差异均有统计学意义.结论 同时检测HCV抗体和HCV病毒核酸定量有助于丙型肝炎诊断;与转氨酶相比,血清PA水平的变化能更加灵敏、快速地反映肝脏损害程度.     

Low Rate of Adverse Hepatic Events Associated with Fosamprenavir/Ritonavir-Based Antiretroviral Regimens

Abstract

Purpose: To appraise the incidence of liver toxicity in a population of patients receiving fosamprenavir/ritonavir (FPV/r) with a high frequency of viral hepatitis co-infection. Method: 636 patients, 341 (54%) with HCV antibodies and 38 (5.6%) bearing serum HBsAg, were recruited. All of them received FPV/r 700/100 twice every day. 93 (27%) patients who tested positive for HCV antibodies showed an AST to platelet ratio index (APRI) higher than 1.5, consistent with significant liver fibrosis. Results: After a median (range) follow-up time of 6.91 (0.46–20.66) months, 3 (0.47%) patients developed grade ?3 ALT elevation. All the former patients were hepatitis virus co-infected, 2 with hepatitis C virus and 1 with hepatitis B virus. The frequency of grade ?3 ALT elevation in patients with HCV antibodies was 0.58% and in those harbouring HBsAg it was 2.63%. 4 (0.62%) patients suffered from a liver decompensation and 1 died due to a hepatic cause while on follow-up. No patients with APRI equal to or higher than 1.5 showed grade ?3 ALT elevation. Conclusion: The incidence of adverse hepatic events in patients receiving FPV/r including combinations seems to be low, even in subjects co-infected with hepatitis virus and in those with significant liver fibrosis.     

丙型病毒性肝炎患者血清瘦素的检测

研究丙肝患者血清leptin水平的变化。采用RIA检测65例丙肝组患者,80名对照组血清leptin水平,以及各种生化指标,比较各组的leptin水平以及leptin与各生化指标的相关性。结果显示慢性丙肝患者血清leptin水平较对照组明显升高(P<0.01);血清leptin水平与谷丙转氨酶(ALT)、谷草转氨酶(AST)呈显著性正相关(P<0.05);而与血糖(Glu)、总胆固醇(TC)无明显相关性(P>0.05)。慢性丙肝患者血清leptin水平升高且与肝脏炎症病变严重程度有关,leptin可以作为一个判断肝脏炎症严重程度的指标。     

Influence of hepatitis B virus virema upon serum aminotransferase activity in dialysis population

BACKGROUND: The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been one of the major advances in the management of patients with end-stage renal disease (ESRD). However, clinical and biochemical expression of HBV in dialysis patients have not been adequately addressed. Elevated values of serum aminotransferase activity are a sensitive measure of hepatocellular injury, but the role of HBV infection in the development of liver disease among dialysis patients has not been adequately analysed. Also, the clinical impact related to the virological characteristics of HBV in dialysis has not been evaluated. METHODS: Demographic, biochemical and virological data from 727 patients undergoing chronic dialysis in seven dialysis units in northern Italy were collected in order to assess the biochemical consequences related to the presence of HBV infection in this population. We have measured by RT-PCR technology the titers of HBV viremia in HBsAg positive patients receiving dialysis. RESULTS: Univariate analysis showed that AST and ALT values were significantly higher in HBsAg positive/HBV DNA positive than HBsAg negative patients on dialysis; AST, 22.86+/-31.34 vs. 14.19+/-9.7 IU/L (P=0.00001); and ALT, 25.07+/-41.59 vs. 13.9+/-41.59 IU/L (P=0.00001). In the subgroup of HBsAg positive patients, the frequency of detectable HBeAg in serum was 14.9% (7/47). The median value of HBV DNA in patients with detectable HBV DNA in serum was 2.160 x 10(3) copies/mL (range, 2.5 x 10(2)-4 x 10(6) copies/mL). HBsAg positive/HCV positive patients had higher aminotransferase activity than other subgroups (P=0.0001). Multivariate analysis showed a significant and independent association between detectable HBsAg/HBV DNA in serum and AST (P=0.00001) and ALT (P=0.0001) activity AST and ALT levels were lower in dialysis than healthy individuals--this finding persisted in age- and gender-matched comparisons. CONCLUSIONS: The HBV viral load in HBsAg positive patients receiving maintenance dialysis is not high. HBsAg positivity with detectable HBV DNA in serum is a strong and independent predictor of raised aminotransferase activity among dialysis patients. HBsAg positive patients had greater aminotransferase activity than HBsAg negative individuals even if both the groups had mean aminotransferase levels within the normal range considered for healthy population. Clinical trials aimed at identifying the best cut-off value to enhance the diagnostic yield of AST/ALT for detecting HBV in dialysis population are under way.     

恩替卡韦治疗高病毒载量HBeAg阳性慢性HBV携带者144周的临床观察

目的 评估恩替卡韦治疗高病毒载量HBeAg阳性慢性HBV携带者的疗效和安全性.方法 64例高病毒载量HBeAg阳性的慢性HBV携带者分为恩替卡韦治疗组(32例)和对照组(32例),治疗24、48、72、96、120、144周时检测肝功能、HBV-DNA(乙肝病毒的脱氧核糖核酸)、乙肝五项、肝纤维化四项、腹部彩超,观察治疗组患者达到血清学应答的比例、ALT变化比例、HBV-DNA低于检测值下限比例、肝纤维化值、观察两组患者的病情变化及指标差异,同时观察治疗过程中药物的安全性.计数资料采用x2检验,计量资料采用f检验.结果 两组各时间点比较,在0、24、48、72、96、120、144周时,ALT变化比例差异无统计学意义.HBV DNA低于检测值下限患者比例,差异有统计学意义.两组HBeAg阳性患者中HBeAg阴转率及HbeAg血清学转换率均为0.144周后治疗组患者的PCⅢ、HA、CIV值与对照组比较,0周与144周比较,差异有统计学意义,层黏连蛋白(LN)t=0.219,差异无统计学意义.腹部彩超结果显示,治疗组在96周检测到有门静脉、脾静脉增宽、脾厚大于正常值表现1例,对照组有2例出现.治疗组至144周有肝硬化1例,对照组有肝硬化2例,两组均未发现肝癌.结论 恩替卡韦治疗高病毒载量HBeAg阳性慢性HBV携带者的病毒学和肝纤维化指标效果均优于对照组,可进行抗病毒治疗,以减轻病毒对肝细胞损伤,降低肝纤维化、肝硬化的发生率.     

护肝合剂对肝星形细胞的活化及胶原表达的作用和机制

目的观察护肝合剂对肝损害模型大鼠血清TGF-β1的影响及护肝合剂含药血清对HSC—T6细胞的增殖、Ⅰ型胶原和Ⅲ型胶原的表达的影响,探讨该复方对肝纤维化的可能作用及其机制。方法设立正常组、护肝合剂组、模型组,采用卡介苗和脂多糖进行肝损害造模,然后观察3组ALT、AST和血清TGF-β1的变化。制备各组大鼠的血清,进行HSC-T6细胞的培养,采用MTT方法观察该细胞的增殖情况．并用RT—PCR的方法观察Ⅰ型胶原和Ⅲ型胶原的表达。结果模型组造模前后的ALT、AST及TGF-β1都显著升高（P〈0．01）,护肝合剂组上述指标较模型组显著下降（P〈0．01）,护肝合剂组的HSC-T6细胞增殖较模型组显著下降（P〈0．01）,且没有Ⅰ型胶原和Ⅲ型胶原的表达。结论护肝合剂能在一定程度上通过改善肝功能、降低TGF-β1水平抑制肝星形细胞的增殖,改善肝纤维化程度。     

Application strategies of serum HBV DNA detection in HBV infection patients: A retrospective study of 5611 specimens

The detection of hepatitis B virus (HBV) DNA plays a critical role in determining the level of viral replication in HBV-infected patients. However, how to select appropriate HBV DNA detection method, low-sensitivity (ls) and hypersensitivity (hs) remains unclear. In this study, hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), alanine transaminase (ALT), aspartate transaminase (AST), and hs HBV DNA titers in serum of 5611 cases with suspected HBV infection were reviewed. Besides, the dynamic changes of HBV DNA and HBsAg in 85 chronic hepatitis B (CHB) patients receiving peginterferon α (PegIFNα) or entecavir (ETV) were observed. The results showed the positive rate of HBV DNA was 32.8%, of which low viral load (20 to 500 IU/mL) accounted for 51.8%. In the 5611 cases, when the HBsAg was less than 1000 IU/mL, the proportion of low viral load was 76.3%. Moreover, in patients receiving antiviral treatment, when HBsAg was less than 2000 IU/mL (PegIFNα) or HBsAg was less than 3500 IU/mL (ETV), the proportion of patients with low viral load was 79.5% or 78.0%, respectively. We developed a strategy of serum HBV DNA detection in HBV-infected patients. When HBsAg was negative, HBV DNA detection should be unnecessary. When HBsAg was 0.05 to 1000 IU/mL, hs HBV DNA should be detected in patients with abnormal level of ALT, AST, or HBeAg. While HBsAg was greater than or equal to 1000 IU/mL, ls HBV DNA was recommended. Moreover, the cutoff value of HBsAg increased during antiviral therapy of CHB patients. In conclusion, hs HBV DNA is of great value in HBV-infected patients with low viral load. HBV DNA detection methods should be selected reasonably according to the levels of HBsAg, HBeAg, ALT, and AST.     

Prevention and treatment of hepatitis C in patients on dialysis

Nosocomial transmission of blood-borne pathogens, including hepatitis C virus infection, is the most common one in a dialysis center setting. The prevalence of HCV antibodies is by far higher in patients undergoing maintenance hemodialysis therapy than in those on peritoneal dialysis. Standard infection prevention measures in hospital settings and measures of infection prevention in dialysis units should be performed. They include serologic testing for HCV of every new patient in a dialysis unit as well as routine testing of all patients every six months. Hepatitis C therapy is recommended in patients on dialysis who have detectable HCV RNA, positive liver biopsy (portal or bridging fibrosis or moderate stage of necroinflammation), younger patients (less than 65 years), and transplantation candidates. When evaluating ALT, it should be kept in mind that ESRD patients have ALT levels lower than general population, making ALT level not relevant parameter of liver disease activity in these patients. Results of hepatitis C therapy with interferon alpha and peginterferon alpha are similar to those in the general population but with more common side effects, which may require therapy discontinuation. Due to the possibility of anemia, ribavirin is contraindicated in patients with ESRD. Around 30% of patients treated with peginterferon have sustained viral response, 25%-45% of them have end of treatment viral response, and 50%-80% have end of treatment biochemical response (ALT normalization). Numerous clinical trials have established that the decrease in HCV load and prolonged suppression of viral replication during interferon therapy significantly reduce hepatic inflammation and consequently postpone progression of fibrosis to cirrhosis.     

Hepatitis C plasma viral load is associated with HCV genotype but not with HIV coinfection

The influence of human immunodeficiency virus (HIV) coinfection and hepatitis C virus (HCV) genotype distribution on HCV viral load and alanine amino transferase (ALT) levels in chronically infected patients remains unclear. In the present study, serum samples from a group of haemophiliac patients were investigated retrospectively. HCV geno- and subtyping was carried out using the Inno line probe assay (Inno LIPA, Innogenetics, Zwijnaarde, Belgium) in 87 patients positive by HCV RT PCR. Of these patients, 31 (35.6%) were HIV coinfected. HCVRNA was quantified with the HCV Monitor kit (Roche, Basel, Switzerland) in 43 patients (22 HIV-negatives, 21 HIV-positives). The most prevalent genotypes were 1 (n = 52) and 3a (n = 16) followed by genotype 2 (n = 9) and 4 (n = 3). Mixed infections were detected in 7 patients. Of genotype 1 positive samples, 24 and 23 were classified as subtype a and b, respectively. Five samples could not be subtyped. Although higher mean values of ALT were observed in genotype 1 infected patients, there was no statistically significant association between HCV genotype or subtype and liver enzymes (P > 0.05). On the other hand, statistically significant higher HCV RNA titres were observed in haemophiliacs infected with HCV genotype 1 in comparison to those infected with other genotypes (P < 0.01). No relationship was found between the presence of HIV coinfection and viral load of HCV RNA. There was no evidence that HCV infection had a more severe outcome in HIV-positive patients who had been infected with HIV and HCV more than ten years ago, even in those with very low CD4+ cell counts. No clear association between high ALT levels and large amounts of viral RNA was observed. In conclusion, a large viral load is associated with HCV genotype 1 infection; HIV coinfection has no clear effect on the intensity of HCV replication. An ongoing prospective study will evaluate the respective role of viral load, genotype, HIV coinfection and ALT level in the response to interferon therapy. © 1996 Wiley-Liss, Inc.