慢性肝病患者乙型肝炎病毒C基因启动子变异对病毒复制水平及肝功能损害的影响

目的 :探讨乙型肝炎病毒慢性感染 C基因启动子 (BCP)变异对病毒复制水平及肝功能损害程度的影响。方法 :采用PCR微板核酸杂交结合 EL ISA检测显示技术 ,检测 74例乙型肝炎病毒慢性感染者 BCP区核苷酸 (nt) 176 2碱基 A→ T和176 4碱基 G→ A联合突变。结果 :在 74例乙型肝炎病毒慢性感染者中检出 BCP区 T176 2 A 176 4突变 2 4例 (32 .4 % ) ,BCP变异阳性组的 HBVDNA水平 (10 8.2 992± 0 .86 6 5拷贝 / m l)显著高于 BCP变异阴性组的水平 (10 7.1 737± 1 .1 539拷贝 / ml) (P <0 .0 0 1) ;BCP变异组的肝功能损害程度较非变异组明显。结论 :BCP变异可引起 HBV致病力增强 ,复制水平提高 。

Liver disease in pregnancy

Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

Six Minute Walk Test to assess functional capacity in chronic liver disease patients

AIM: To examine the utility of Six Minute Walk Test (6MWT) in patients with chronic liver disease (CLD). METHODS: Two hundred and fifty subjects between the ages of 18 and 80 (mean 47) years performed 6MWT and the Six Minute Walk Distance (6MWD) was measured. RESULTS: The subjects were categorized into four groups. Group A (n = 45) healthy subjects (control); group B (n = 49) chronic hepatitis B patients; group C (n = 54) chronic hepatitis C patients; group D (n = 98) liver cirrhosis patients. The four groups differed in terms of 6MWDs (P < 0.001). The longest distance walked was 421 ± 47 m by group A, then group B (390 ± 53 m), group C (357 ± 72 m) and group D (306 ± 111 m). The 6MWD correlated with age (r = -0.482, P < 0.01), hemoglobin (r = +0.373, P < 0.001) and albumin (r = +0.311, P < 0.001) levels. The Child-Pugh classification was negatively correlated with the 6MWD in cirrhosis (group D) patients (r = -0.328, P < 0.01). At the end of a 12 mo follow-up period, 15 of the 98 cirrhosis patients had died from disease complications. The 6MWD for the surviving cirrhotic patients was longer than for non-survivors (317 ± 101 vs 245 ± 145 m, P = 0.021; 95% CI 11-132). The 6MWD was found to be an independent predictor of survival (P = 0.024). CONCLUSION: 6MWT is a useful tool for assessing physical function in CLD patients. We suggest that 6MWD may serve as a prognostic indicator in patients with liver cirrhosis.

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

AIM： To test the psychometric properties of a Chinese [（Hong Kong） HK] translation of the chronic liver disease questionnaire （CLDQ）. METHODS： A Chinese （HK） translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B （CriB） patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese （HK） SF-36 Health Survey Version 2 （SF-36v2）. RESULTS： Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two （Fatigue and Systemic Symptoms） subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION： The Chinese （HK） CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties,

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

METHODS： Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled, Liver stiffness was obtained noninvasively by using Fibroscan （Echosens, Paris, France）, The date of blood transfusion was obtained by interview, Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement （LSM）. Patients were stratified into four groups based on the duration of infection （17-29 years; 30-39 years; 40-49 years; and 50-70 years）. The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS： A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis （225 with HCC and 291 without）. The patients were 244 men and 272 women, with a mean age of 67.8 ±9.5 years. The median liver stiffness was 14.3 kPa （25.8 in HCC group and 7.6 in non HCC group）. The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC （r = 0.132, P = 0.024） but not in patients with HCC （r = -0.103, P = 0.123）. Liver stiffness was significantly higher in patients with HCC than in those without in each duration group （P 〈 0.0001）. The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion （P 〈 0.0001）, duration of infection （P = 0.0015）, and heavy alcohol consumption （P = 0.043）CONCLUSION： Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.

Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B

AIM:To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B(CHB).METHODS:We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d.The biochemical response,as assessed by serum alanine aminotransferase(ALT) activity,virologic response,as assessed by serum hepatitis B virus DNA(HBV DNA) titer,serologic response,as assessed by hepatitis B e antigen(HBeAg) status,and virologic breakthrough with genotypic mutations were assessed.RESULTS:Two-hundred and fifty-four patients [clevudine(n = 118) vs entecavir(n = 136)] were enrolled.In clevudine-treated patients,the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96(80.9% and 91.2% in the entecavir group,respectively),the mean titer changes in serum HBV DNA were-6.03 and-6.55 log 10 copies/mL(-6.35 and-6.86 log 10 copies/mL,respectively,in the entecavir group),and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1%(74.4% and 83.8%,respectively,in the entecavir group).These results were similar to those of entecavir-treated patients.The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine,which was similar to patients treated with entecavir(22.8% and 27.7%,respectively).The virologic breakthrough in the clevudine group occurred in 9(7.6%) patients at weeks 48 and 15(12.7%) patients at week 96,which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M.There was no virologic breakthrough in the entecavir group.CONCLUSION:In antiviral-naive CHB patients,longterm treatment outcomes of clevudine were not inferior to those of entecavir,except for virologic breakthrough.

Treatment of chronic viral hepatitis with nitazoxanide and second generation thiazolides

Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevalence of IgG anti-HAV was 86.61%(854/986) in patients with chronic liver disease and was 88.13%(869/986) in age-and gendermatched patients from the Center for Health Promotion.The anti-HAV prevalence was 80.04%(405/506) in patients with chronic hepatitis B,86.96%(20/23) in patients with chronic hepatitis C,93.78%(422/450) in patients with HBV related liver cirrhosis,and 100%(7/7) in patients with HCV related liver cirrhosis.The anti-HAV prevalence according to the decade of age was as follows:20s(6.67%) ,30s(50.86%) ,40s(92.29%) ,50s(97.77%) ,and 60s(100%) .The antiHAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age.Multivariable analysis showed that age≥40 years,female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity. CONCLUSION:Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

Lnc-TCL6 is a potential biomarker for early diagnosis and grade in liver-cirrhosis patients

Background:Long non-coding RNAs(lncRNAs)have been applied as biomarkers in many diseases.However,scarce biomarkers are available in single lncRNA differential expression associated with different clinical stages of liver cirrhosis(LC).The aim of the study is to identify some lncRNAs that can serve as non-invasive sensitive biomarkers for early diagnosis and grade of LC.Methods:Blood lncRNA expression was evaluated in three independent cohorts with 305 participants including healthy controls,hepatitis B virus(HBV)carriers,and patients with chronic hepatitis B(CHB)or LC.First,candidate lncRNAs were screened by CapitalBiotech microarray to diagnose cirrhosis.Quantitative reverse-transcriptase polymerase chain reaction was then used to investigate the expression of selected lncRNAs in the whole group of cirrhosis and different Child–Pugh classes.Ultimately,the diagnostic accuracy of the promising biomarker was examined and validated via Mann–Whitney test and receiver-operating characteristics analysis.Results:Lnc-TCL6 was identified as a sensitive biomarker for early diagnosis of LC(Child–Pugh A)compared with healthy controls(area under the ROC curve[AUC]=0.636),HBV carriers(AUC=0.671),and CHB patients(AUC=0.672).Furthermore,lnc-TCL6 showed a favourable capacity in discriminating among different Child–Pugh classes(AUC:0.711–0.837).Compared with healthy controls,HBV carriers,and CHB patients,the expression of lnc-TCL6 was obviously up-regulated in Child–Pugh A patients and,conversely,significantly down-regulated in Child–Pugh C patients.Conclusions:Lnc-TCL6 is a novel potential biomarker for early diagnosis of LC and is a possible predictor of disease progression.