The course of liver cirrhosis not preceded by viral hepatitis with p articular reference to toxic etiology]

The study was aimed at analysing the epidemiological structure of patients with liver cirrhosis without HBsAg treated in 1980-1988. There were 231 of such cases in this period of time. The most frequent cause of liver cirrhosis in patients under 60 years of life was chronic alcoholism whereas 40% of the diagnosed liver cirrhosis in older persons was of unclear etiology. Patients complaints, clinical examinations, and results of the laboratory tests were analysed. The course of the disease was more severe in alcohol-produced liver cirrhosis leading to the haemorrhage from esophageal varices in 36%, and coma in 8% of cases. Alcohol-produced liver cirrhosis promoted other complications such as: cancer of the liver, hepato-renal syndrome or encephalopathy. Liver cirrhosis of unclear etiology in the elderly may be a consequence of the prolonged exposition to environmental pollutants. More severe course of alcohol-produced liver cirrhosis may depend on simultaneous action of two harmful factors: alcohol and environmental pollutants.     

扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗乙型肝炎病毒感染失代偿期肝硬化的临床研究

目的:探讨扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗乙型肝炎病毒(HBV)感染失代偿期肝硬化的临床效果。方法:选取2015年6月～2019年6月期间我院收治的HBV感染失代偿期肝硬化患者73例,根据随机数字表法分为对照组(n=36)和研究组(n=37),对照组患者予以微生态制剂和恩替卡韦治疗,研究组则在对照组的基础上联合扶正化瘀胶囊治疗,比较两组患者疗效、T淋巴细胞亚群、肝功能[天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]以及肝纤维化指标[透明质酸(HA)、层黏连蛋白(LN)],记录两组乙肝表面e抗原(HBeAg)、乙肝病毒基因(HBV-DNA)转阴情况,记录两组不良反应发生情况。结果:研究组治疗6个月后的临床总有效率为91.89%(34/37),高于对照组的72.22%(26/36)(P0.05)。两组治疗6个月后AST、TBIL、HA、LN、CD8+~均下降,且研究组低于对照组(P0.05)。两组治疗6个月后CD4+~、CD4+~/CD8+~升高,且研究组高于对照组(P0.05)。两组治疗6个月后HBeAg、HBV-DNA转阴率比较无统计学差异(P0.05)。两组不良反应发生率对比未见统计学差异(P0.05)。结论:扶正化瘀胶囊联合微生态制剂和恩替卡韦治疗HBV感染失代偿期肝硬化疗效显著,虽在HbeAg、HBV-DNA转阴率方面未见明显改善,但可有效改善肝功能,减轻肝纤维化,提高机体免疫功能,且不增加不良反应发生率,安全性较好。     

阿德福韦酯联合拉米夫定治疗乙型肝炎DNA阳性肝硬化疗效观察

目的：探讨阿德福韦酯联合拉米夫定治疗HBV DNA阳性乙型肝炎肝硬化的疗效。方法：46例HBV DNA阳性乙肝肝硬化患者随机分为对照组及观察组。在保肝等对症治疗基础上,观察组22例患者联用阿德福韦酯与拉米夫定,对照组24例患者予阿德福韦酯,总疗程均为48周。结果：在治疗12周后,观察组与对照组HBV DNA转阴率分别为54.5%、20.8%（P〈0.05）,ALT复常率分别为63.6%、33.3%（P〈0.05）。治疗24周、48周后上述指标无统计学差异。两组患者未见明显药物不良反应。结论：阿德福韦酯联合拉米夫定治疗HBV DNA阳性乙型肝炎肝硬化起效快,降低病毒载量疗效佳,安全性好。     

Alcohol and the liver]

A biologic role of ethyl alcohol is analysed. The function of the liver in alcohol metabolism (90% of the total intake) in three oxidizing systems with the use of alcohol dehydrogenase, microsomal ethanol oxidizing system, and H2O2 catalase is described. Epidemiological data are given, clinical course of the alcohol-produced lesions to the liver starting from fatty degeneration, through the acute and chronic hepatitis, alcohol-produced cirrhosis up to the primary cancer of the liver are also presented in the light of authors experience.     

Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection.     

围手术期介入治疗对伽玛刀治疗肝癌肝硬化临床疗效及预后的影响

目的:探究围手术期介入治疗对伽玛刀治疗肝癌肝硬化临床疗效及预后的影响。方法:选取2013年1月～2015年1月在我院就诊的肝癌肝硬化患者共61例,按照随机数字表法分为对照组(30例)和观察组(31例),对照组患者仅进行伽玛刀治疗,观察组患者进行围手术期介入治疗联合伽玛刀治疗,比较两组患者治疗后的总有效率、治疗后1年和3年的生存率以及不良反应的发生情况。结果:观察组患者治疗后总有效率为77.4%,显著高于对照组(53.3%,P0.05);观察组治疗后1年和3年生存率分别为74.2%、45.2%,均显著高于对照组(53.3%、20.0%,P0.05);两组患者治疗后均发生不同程度的不良反应,但经对症治疗均有效好转,两组不良反应发生率比较差异无统计学意义(P0.05)。结论:围手术期介入治疗联合伽玛刀治疗肝癌患者可以有效提高治疗的总有效率以及治疗后1年和3年的生存率,且安全性好。     

Association of cytokine genetic polymorphism with hepatitis B infection evolution in adult patients

The infection by the hepatitis B virus (HBV) has different forms of evolution, ranging from self-limited infection to chronic hepatic disease. The objective of this study was to evaluate the influence of cytokine genetic polymorphisms in the disease evolution. The patients were divided into two groups, one with chronic HBV (n = 30), and the other with self-limited infection (n = 41). The genotyping for TNF (-308), TGFB1 (+869, +915), IL-10 (1082, -819, and -592), IL-6 (-174), and IFNG (+874) was accomplished by the PCR-SSP (polymerase chain reaction with sequence specific primers technique using the One Lambda kit. Although no statistically significant differences were found between the groups, the combination of TNF -308GG and IFNG +874TA was found in a lower frequency in chronic patients than in individuals with self-limited infection (26.7 versus 46.3%; P = 0.079; OR = 0.40; IC95% = 0.14-1.11). In chronic patients with histological alterations it was not observed the genotype TGFB1+869 C/C, against 24.4% in the self limited infection group (100 versus 75.6%; P = 0.096; OR = 7.67; IC95% = 0.42-141.63). Further studies in other populations, and evaluation of a greater number of individuals could contribute for a better understanding of the cytokine genetic polymorphism influence in HBV infection evolution.     

Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV

The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.     

Differences between the metabolic profiles of decompensated and compensated cirrhosis patients with Hepatitis B virus infections under high-performance liquid chromatography-mass spectrometry

To improve the grading and staging of liver cirrhosis among patients with HBV infection noninvasively, a high-performance liquid chromatography with mass spectrometry metabolomics method was used to investigate the potential metabolic biomarkers in the serum of patients with different degrees of hepatic cirrhosis. The results demonstrate that lysophosphatidyl choline (LPC) from positive electrospray ionization (ESI) mode, and fatty acids and bile acids from negative ESI mode play important roles in distinguishing decompensated from compensated cirrhosis. A total of 21 differential metabolites were found from the two groups of patients. LPCs, fatty acids, and taurocholic acid (TCA) 3-sulfate decreased in patients with decompensated cirrhosis, whereas other bile acids increased significantly. The levels of TCA 3-sulfate, LPC 16:0, and LPC 18:0 were significantly correlated with the stages of the decompensated cirrhosis, and they may serve as potential biomarkers for the stage assessment of liver cirrhosis in patients with HBV infections.     

Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients

Objective

Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP) at position -238 and -308 of the tumor necrosis factor alpha (TNF-α) and -592 of the interleukin-10 (IL-10) promotor genes) and of classical factors (age, alcohol, immunodepression, antirretroviral therapy) on the risk of liver cirrhosis in human immunodeficiency (HIV)-hepatitis C (HCV) virus coinfected patients.

Patients and Methods

Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis) and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load) and HCV-related (serum ALT concentration, HCV viral load, HCV genotype) characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α) and -592 of the interleukin-10 (IL-10) promotor genes were studied.

Results

Evolution time of the infection was 21 years in both patients’ groups (chronic hepatitis and liver cirrhosis). The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection), a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis.

Conclusion

It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position), above other factors previously accepted (age, gender, alcohol, immunodepression), on the evolution to liver cirrhosis among HIV-infected patients with established chronic HCV infections.     

UDP-glucuronosyltransferase 1A7 polymorphisms are associated with liver cirrhosis

Variations in the UDP-glucuronosyltransferase (UGT) 1A7 gene have been found to be related to the development of hepatocellular carcinoma (HCC). Since the pathogenesis of liver cirrhosis is not dissimilar to that of HCC, we hypothesized that UGT1A7 genetic polymorphisms may be associated with liver cirrhosis. PCR-restriction fragment length polymorphism was utilized to determine UGT for 1A7 genotypes for the 159 patients with liver cirrhosis and 263 gender/age matched controls. Simple logistic regression analysis revealed that significant risk factors for liver cirrhosis were (1) hepatitis B virus (HBV) infection, (2) hepatitis C virus (HCV) infection, (3) HBV infection plus HCV infection and (4) low-activity UGT1A7 genotypes. The results of further multivariate logistic regression confirmed these associations. Interaction of low-activity UGT1A7 genotypes and HBV (or HCV) infection produced an additive effect upon the risk for the development of liver cirrhosis [observed odds ratio (OR) (54.59) greater than the expected OR (18.05)]. UGT1A7 low/low genotype was also related to advanced liver cirrhosis (Child-Pugh classes C and/or B) (OR = 7.50, P = 0.009). This study demonstrates the novel findings that carriage of low-activity UGT1A7 genotypes represents a risk factor for the development and functional severity of liver cirrhosis.     

ARFI应用中射频及嵌入深度对肝脏弹性成像诊断准确性的影响

目的:分析应用声辐射力脉冲成像(Acoustic Radiation Force Impulse Imaging,ARFI)技术进行肝病诊断过程中不同探针及不同嵌入深度对其诊断准确性的影响。方法:于2012~2014年,选取经ARFI诊断过的98例丙型肝炎(Hepatitis C Virus,HCV)患者,对两种探针(凸阵探头C4-1 MHz和线阵探头L9-4 MHz)诊断下的相关数据进行前瞻性研究分析,并与瞬时弹性成像(Fibroscan)进行对比。对不同嵌入深度的ARFI弹性成像的变异性进行了系统评估。结果:根据Fibroscan成像结果,33例患者(34%)患有肝硬化,其余患者中27例(27%)患有严重的肝纤维化,38例(39%)未患。C4-1的传播速率平均为1.68±0.59 m/s,L9-4为1.93±0.76 m/s。两种探针检测结果彼此相关显著(P0.001,r=0.71),且二者均与Fibroscan结果显著相关(P0.001,r分别为0.79和0.81)。对于肝硬化或严重肝纤维化患者而言,L9-4探针诊断结果高于C4-1探针,差异具有统计学意义(P0.001)。在诊断肝硬化疾病中,C4-1和L9-4探针的AUROC值分别为0.97和0.91,截断水平分别为1.68和2.01 m/s。C4-1和L9-4嵌入深度分别为3~6 cm和2~3.5 cm。结论:线阵探头和凸阵探头在应用ARFI成像评估肝脏硬度中具有较高的准确性,相较而言,线阵探头诊断结果更高。且ARFI的测量操作不宜靠近肝被膜。     

双歧杆菌四联活菌片对乙肝相关慢加急性肝衰竭合并感染患者肠道菌群及免疫功能的影响

目的 分析双歧杆菌四联活菌片对乙肝相关慢加急性肝衰竭(HBV-ACLF)合并感染患者肠道菌群及免疫功能的影响,为该病的治疗提供参考.方法 选择2017年12月至2018年12月我院收治的106例HBV-ACLF合并感染患者,采用随机数字表法将其分为对照组(n=53)与研究组(n=53).对照组患者采用常规治疗,研究组患...     

病毒性肝炎HAV，HBV，HCV，HDV和HEV重叠感染的研究

采用ＥＬＩＳＡ法检测了１０８例乙型肝炎病毒（ＨＢＶ）感染者血清中的五种肝炎病毒──甲型（ＨＡＶ）、乙型（ＨＢＶ）、丙型（ＨＣＶ）、丁型（ＨＤＶ）和成型（ＨＥＶ）肝炎病毒的标志物,并采用ＰＣＲ技术检测了患者血清ＨＢＶＤＮＡ、ＨＣＶＲＮＡ及ＨＤＶＲＮＡ。结果五种肝炎病毒重叠感染者３５例（３２．４％）,单纯ＨＢＶ感染者７３例（６７．６％）。ＨＢＶ、ＨＡＶＭ重感染率为４．６％,ＨＢＶ、ＨＣＶ二重感染率为９．２％,ＨＢＶ、ＨＤＶＭ重感染率为１４．８％,ＨＢＶ、ＨＥＶ二重感染率为１．９％,ＨＢＶ、ＨＣＶ和ＨＤＶ三重感     

不同剂量易善复治疗肝硬化的疗效及安全性研究

目的:探讨不同剂量的多烯磷脂酰胆碱(易善复)对肝硬化的治疗效果及其安全性。方法:以2016年~2017年在我院就诊的70例单纯肝炎后肝硬化(VC)和酒精性肝硬化(AC)患者为研究对象,采用随机数字表法将其随机分为小剂量组和大剂量组,每组35例。小剂量组予易善复10 m L+5%葡萄糖注射液250 m L静滴,大剂量组予易善复20 m L+5%葡萄糖注射液250 m L静滴。观察两组治疗前后临床症状、血尿常规、肾功能、肝功能指标、腹腔彩超的变化情况。结果:两组患者治疗后肝功能指标谷丙转氨酶(ALT)、白蛋白(ALB)、总胆红素(TBIL)、谷草转氨酶(AST)、碱性磷酸酶(ALP)均较治疗前明显改善(P0.05),且大剂量组各项指标水平均明显优于小剂量组(P0.05);大剂量组治疗肝硬化的总有效率为88.6%,显著高于小剂量组的(68.6%,P0.05)。两组治疗过程中均未见明显药物副反应。结论:与小剂量易善复相比,大剂量易善复更能改善单纯肝炎后肝硬化和酒精性肝硬化患者的肝功能,提高药物疗效的同时不增加药物副反应,安全性高。     

甲、乙型肝炎联合疫苗接种恒河猴的初步观察

为了探索联合接种甲乙肝疫苗、实验性甲乙肝联合疫苗免疫恒河猴的安全性及免疫原性。实验中挑选了甲肝抗体阴性,乙肝两对半阴性,肝功能指标正常的健康恒河猴24只,随机分为10组。混合或分别接种,进行不同毒株的甲肝灭活疫苗与不同厂家的乙肝疫苗的配对效果比较。并接种了实验性甲乙肝联合疫苗;史克甲乙肝联合疫苗试验组。设甲肝单价灭活疫苗L8株、深圳乙肝单价疫苗作为对照。免疫方案0、4、24w。每只恒河猴接种lml。接种3d内,每天观察动物有无不良反应。接种1针和2针后4w内,每2w采集空腹静脉血,以后每4w采血1次检测抗HAV、抗HBs、ALT、AST直至40w。接种疫苗后4、8、24、28w穿刺肝组织做病理学检查。结果显示接种疫苗后3d内,所有恒河猴均无不良反应。ALT、AST无异常升高。4、8、24、28w肝组织无特殊病理改变。注射2针后4w,除3组外,其余各组抗HAV及抗HBs均阳转。3组抗HAV阳转时间迟至12w。全程免疫后12w(即40w),抗HAVGMT为258.75～37489.50mIU/ml;抗HBsGMT为8263.68～60008.064mIU/ml。甲乙肝疫苗联合免疫及实验性的甲乙肝联合疫苗接种恒河猴安全性及免疫原性均良好。     

Genotype Distribution of Vitamin D Receptor Polymorphisms among Indonesian Patients with Chronic Hepatitis B

Background:Chronic hepatitis B is a necro-inflammatory of the liver parenchyma caused by hepatitis B virus (HBV) infection leading to liver cirrhosis and hepatocellular carcinoma (HCC). Genetic variants including single nucleotide polymorphisms (SNPs) within genes regulating immune response may contribute to the progression of chronic hepatitis B (CHB) infection. This study aimed to examine the genotype distribution of vitamin D receptor (VDR) polymorphism among patients with CHB infection and to study its association with the development of cirrhosis and hepatoma.Methods:This cross-sectional study analysed 75 CHB patients, consisting of 36 CHB patients without cirrhosis, 25 CHB patients with cirrhosis, and 14 CHB patients with hepatoma. VDR polymorphism was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) method.Results:Alanine aminotransferase (ALT) and alpha fetoprotein (AFP) levels did not show any significant differences between study groups, but albumin levels in CHB patients with cirrhosis and hepatoma were significantly lower than CHB patients without cirrhosis (p< 0.05). In contrast, the bilirubin levels in CHB patients with cirrhosis was higher than in CHB patients’ cirrhosis. The most common genotypes of VDR polymorphisms were Ff (57.3%), TT (72%), aa (48%) and bb (74.7%) for Fok1, Taq1, Apa1 and Bsm1 respectively. There was no significant different in the genotype distribution of VDR polymorphism between CHB patients without cirrhosis and CHB with cirrhosis or hepatoma. Conclusion:This study suggest that VDR gene polymorphism may not contribute to the progression of CHB infection.Key Words: Cirrhosis, Hepatitis B, Hepatoma, Polymorphism, Vitamin D Receptor     

Blood amino acids in chronic HBsAg positive liver disease

Typical changes in blood aminoacid concentrations have been described in patients with severe liver disease. In this study we measured the serum amino acid levels, by Beckman Aminoacid Analyzer, in 11 healthy subjects and 24 HBsAg-positive patients with biopsy-proven liver disease (4 CPH, 10 CAH, 10 cirrhosis). A significant decrease in total aminoacids was observed in CAH and cirrhosis groups (-24% and -22% respectively). The three branched chain aminoacids (BCAA = val + leu + isoleu) were reduced by 24% (P less than 0.002) and 37% (P less than 0.001) in the CAH and cirrhosis groups respectively. Tyrosine was the only of the aromatic aminoacids (AAA) to increase in cirrhotics (+ 34%, P less than 0.02). The molar ratio BCAA/AAA was 3.6 in controls, 3.8 in CPH, 3.1 in CAH (P less than 0.025) and 1.9 in cirrhosis (P less than 0.001). A linear correlation was found between molar ratio BCAA/AAA and serum albumin in all patients (P less than 0.001). These results document the presence of specific quantitative changes in serum aminoacids of HBsAg positive patients, which appear related to severity of liver disease and comparable to the alterations described in non viral chronic liver disease.     

酒精性肝病合并HBV感染并发肝衰竭对NF-κB信号通路的影响

由于酗酒人数的增长,HBV感染合并酒精性肝病患者的数量在中国逐年增加,酒精性肝病与HBV感染会严重影响肝功能。目前中国已成为引起肝硬化的第二大病因。而乙型肝炎病毒感染合并酒精性肝病是最常见的,且会对肝脏造成严重的损伤。本实验的检测了NF-κB信号通路和IL-8、TNF-α和Cleaved caspase-3基因及蛋白的表达,结果表明,酒精性肝病合并HBV感染并发肝衰竭会激活NF-κB信号通路,并上调IL-8、TNF-α和Cleaved caspase-3基因和蛋白的表达,说明酒精性肝病合并HBV感染不仅对肝脏造成了极其严重的损伤,还造成肝脏组织或细胞炎症的发生和细胞凋亡及组织纤维化。通过以上的研究,本实验为揭示酒精性肝病合并HBV并发肝衰竭的分子机制,以及为后续研究酒精性肝病合并HBV并发肝衰竭的靶向治疗提供理论参考。