Clinical significance of hepatic derangement in severe acute espiratory syndrome

AIM: Elevation of alanine aminotransferase (ALT) level iscommonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient.METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death.RESULTS: Two hundred and ninety-four patients wereincluded in this study. Seventy (24%) patients had elevatedserum ALT on admission and 204 (69%) patients hadelevated ALT during the subsequent course of illness. Using peek ALT ＞5xULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peek ALT ＞5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95%CT 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severehepatitis had worse clinical outcome.     

Predictors of development and outcome in patients with acute respiratory distress syndrome due to tuberculosis.

OBJECTIVE: To study the predictors of development and determinants of outcome in patients with acute respiratory distress syndrome (ARDS) due to tuberculosis (TB). METHODS: Retrospective case-control study of demographic, clinical and laboratory data of hospitalised adult patients with active TB. RESULTS: Of 2733 TB patients treated during 1980-2003, 29 (1.06%; 1.21 patients/year; mean age 31.6 +/- 10.9 years; 16 males) developed ARDS (cases). Seven had pulmonary TB and 22 had miliary TB (MTB); 298 (mean age 32.0 +/- 14.2 years; 110 males) who did not develop ARDS constituted controls. Presence of MTB (OR 4.6, 95%CI 1.2-17.8; P = 0.02), duration of illness beyond 30 days at presentation (OR 177.9, 95%CI 39-811.7; P < 0.001), absolute lymphocyte count < 1625/ mm3 (OR 4.5, 95%CI 1.1-19.3; P = 0.04) and serum ALT > 100 IU (OR 15.7, 95%CI 3.0-81.1, P < 0.001) were independent predictors of ARDS development. Twelve cases died (41.4%). Patients with APACHE II score >18; those with APACHE II score <18 in the presence of hyponatraemia and PaO2/FIO2 ratio <108.5 were likely to die. CONCLUSIONS: In patients with TB, prolonged illness, MTB, absolute lymphocytopaenia and elevated ALT are independently associated with ARDS development. APACHE II score, serum sodium and PaO2/FIO2 ratio are determinants of outcome.     

ALT≤40U/L的HBeAg阴性慢性HBV感染者抗病毒治疗指征的无创指标分析

目的在肝组织病理的指导下探索ALT≤40 U/L的HBeAg阴性慢性HBV感染者抗病毒指征的无创指标。方法回顾性纳入2013年10月—2018年8月延安大学附属医院收治的已行肝活检的377例ALT≤40 U/L的HBeAg阴性慢性HBV感染者,入组患者中炎症活动度相似文献   

Genetic variants of interferon regulatory factor 5 associated with chronic hepatitis B infection

AIM To investigate possible effects of IRF5 polymorphisms in the 3' UTR region of the IFR5 locus on susceptibilityto hepatitis B virus(HBV) infection and progression of liver diseases among clinically classified Vietnamese patients.METHODS Four IFR5 SNPs(rs13242262 A/T, rs77416878 C/T, rs10488630 A/G, and rs2280714 T/C) were genotyped in clinically classified HBV patients [chronic hepatitis B(CHB). n = 99; liver cirrhosis(LC), n = 131; hepatocellular carcinoma(HCC), n = 149] and in 242 healthy controls by direct sequencing and Taq Man realtime PCR assays. RESULTS Comparing patients and controls, no significant association was observed for the four IFR5 variants. However, the alleles rs13242262 T and rs10488630 G contributed to an increased risk of liver cirrhosis(LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from 4 SNPs was observed frequently in LC compared to CHB patients(OR = 2.1, 95%CI: 1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB patients than in the other HBV patient groups(LC vs CHB: OR = 0.4, 95%CI: 0.2-0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P = 0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT, AST and bilirubin. CONCLUSION Our study shows that IFR5 variants may contribute as a host factor in determining the pathogenesis in chronic HBV infections.     

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found.     

Prevalence and etiology of elevated serum alanine aminotransferase level in an adult population in Taiwan

BACKGROUND: The prevalence and etiologies of elevated alanine aminotransferase (ALT) have geographic variations and they are rarely reported in Taiwan. Through a population-based screening study, the prevalence and etiologies of elevated ALT in an adult population of Taiwan were assessed. METHODS: A cross-sectional community study in a rural village of Taiwan was conducted in 3260 Chinese adults (age >or=18 years) undergoing ultrasonography (US), blood tests, and interviews with a structured questionnaire. The diagnostic criteria of non-alcoholic fatty liver disease (NAFLD) included alcohol intake <20 g/week for women or <30 g/week for men, negative hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, no known etiologies of liver disease, and US consistent with fatty liver. RESULTS: The prevalence of elevated ALT was 11.4% (372/3260). The probable cause of this elevation was excess alcohol consumption in 0.8%, HBV in 28.5%, HCV in 13.2%, both HBV and HCV in 2.2%, NAFLD in 33.6%, and unexplained cause in 21.8%. The etiologic distribution of elevated ALT was similar in both genders, although elevation was more common in men compared to women (17.3%vs 6.1%, P < 0.05). The prevalence of elevated ALT in NAFLD was 18.1% (125/691), and the positive predictive value was 33.6% (125/372). The development of NAFLD was related to increasing age (age between 40 years and 64 years, odds ratio [OR] 1.59, 95% confidence interval [CI]: 1.25-2.01; age >or= 65 years, OR 1.46, 95%CI: 1.08-1.96), fasting plasma glucose (FPG) >or= 126 mg/dL (OR 1.54, 95%CI: 1.11-2.14), body mass index (BMI) >or= 25 kg/m(2) (OR 5.01, 95%CI: 4.13-6.26), triglyceridemia >or= 150 mg/dL (OR 1.96, 95%CI: 1.58-2.42), and hyperuricemia (OR 1.50, 95%CI: 1.22-1.84). Elevated ALT was related to male gender, BMI >or= 25 kg/m(2), and triglyceridemia >or= 150 mg/dL in subjects without known etiologies of liver disease (all P < 0.05). CONCLUSIONS: Non-alcoholic fatty liver disease appears to be the commonest cause of elevated ALT and presumed liver injury in Taiwan. The development of NAFLD is closely associated with many metabolic disorders. Metabolic disorders are also related to elevated ALT in subjects without known etiologies of liver disease.     

Pathological evolution of hepatitis C virus-＂Healthy carriers＂

AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESULTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI） 〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLUSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.     

Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels

Chronic hepatitis B patients with high-normal serum ALT (levels of 0.5-1x upper limit of normal) are still at risk of liver disease progression. We thus investigated the correlation between serum ALT level and hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum ALT level (PNALT). Baseline clinical and virological features of 414 HBeAg-negative carriers, including 176 (42.5%) with low-normal ALT (levels of less than 0.5x upper limit of normal) and 238 (57.5%) with high-normal ALT, were compared. Compared with HBV carriers with low-normal ALT, those with high-normal ALT were older (41 vs. 37 years, P<0.001) and had a greater frequency of serum HBV DNA level>10(4) copies/ml (63.4% vs. 47.5%, P<0.001) as well as a higher prevalence of basal core promoter T1762/A1764 mutant (36.5% vs. 24.2%, P=0.01). Multivariate analysis showed that factors associated with a high-normal serum ALT level included male sex [odds ratio (OR), 1.82; 95% confidence interval (CI), 1.10-3.01, P=0.019], increasing age (OR, <30 years: 1, reference; 30-39 years: 2.43, 95% CI, 1.18-5.03, P=0.016; 40-49 years: 4.22, 95% CI, 1.99-8.93, P<0.001; >or=50 years: 4.06, 95% CI, 1.69-9.78, P=0.002) and serum HBV DNA level>10(4) copies/ml (OR, 1.83; 95% CI, 1.07-3.13, P=0.027). CONCLUSION: HBeAg-negative patients with persistently normal ALT are not a homogenous group, and those with high-normal ALT share some of the characteristics that have been associated with adverse long-term outcomes.     

Pathological evolution of healthy C virus-"Healthy carriers"

AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions.METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knedell score ≤ 3,with 2 liver biopsies and detectable HCVRNA were included.Markers of fibrosis progression were assessed.RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28)and 4 (95% CI: 2-16) years respectively.Alaninetransaminase (ALT) activity was normal in 43.4% of cases.50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16).The median difference in the necro-inflammation and fibrosis score between biopsies was low,1.5 and 0.0 respectively.Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load.A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) ＞25.Fibrosis progression correlated with the time interval between biopsies (P = 0.01).A significant progression of activity (1.7 vs 0.4,P＜0.05) or fibrosis (0.9 vs 0.0,P ＜ 0.01) was observed in patients with elevated ALT.There was a significant correlation between activity progression and fibrosis progression(P = 0.003).Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT,BMI＞25 and the time interval between 2 biopsies.CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion.Fibrosis progression is associated with elevated ALT and BMI ＞ 25.     

北京地区250例严重急性呼吸综合征患者临床分析

目的　探讨严重急性呼吸综合征 (SARS)的流行病学特征、临床表现、实验室检查、治疗及预后等特点。方法　回顾性分析北京地坛医院 2 50例SARS患者的临床资料。结果　 2 50例患者的平均年龄 (3 6± 16)岁 ,男 110例 (44 0 % ) ,女 14 0例 (56 0 % )。潜伏期平均 (8± 7)天。主要临床表现 :发热 (10 0 0 % )、咳嗽 (72 8% )、乏力 (70 0 % )。外周血白细胞计数降低者占 2 7 2 % ,淋巴细胞比例降低者占 64 2 %。CD+ 4和CD+ 8计数降低者分别占 91 4%、80 6%。动脉血氧饱和度 (SaO2 )低于 97%者162例 (64 8% )。血清丙氨酸转氨酶 (ALT)升高者 45 2 % ,天冬氨酸转氨酶 (AST)升高者 2 9 4% ,乳酸脱氢酶 (LDH)升高者 42 1% ,肌酸激酶 (CK)升高者 18 3 %。恢复期血清SARS病毒特异性抗体IgG阳性率 69 9%。采用综合治疗 ,使用抗生素、抗病毒药物、激素及免疫增强剂。需要呼吸支持者 196例 ,气管插管或切开机械通气支持治疗者 8例 ,重症患者 81例 (3 2 4% ) ,死亡 2 5例。结论　SARS传染性较强 ,中青年人群患病为主 ,有特征性临床表现 ,采用综合治疗 ,多数患者可取得较好疗效     

Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis study

AIM To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia.METHODS A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in Pub Med, Google Scholar, Science Direct, World Health Organization African Index Medicus and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems.RESULTS Twenty-nine studies from Somalia and Somali immigrants(United Kingdom,United States,Italy,Libya)with a combined sample size for each type of viral hepatitis[hepatitis A virus(HAV):1564,hepatitis B virus(HBV):8756,hepatitis C virus(HCV):6257,hepatitis D virus(HDV):375 and hepatitis E virus(HEV):278]were analyzed.The overall pooled prevalence rate of HAV was 90.2%(95%CI:77.8%to 96%).The HAV prevalence among different age groups was as follows:1 year old,61.54%(95%CI:40.14%to79.24%);1-10 years old,91.91%(95%CI:87.76%to94.73%);11-19 years old,96.31%(95%CI:92.84%to 98.14%);20-39 years old,91.3%(95%CI:83.07%to 95.73%);and40 years old,86.96%(95%CI:75.68%to 93.47%).The overall pooled prevalence of HBV was 18.9%(95%CI:14%to 29%).The overall pooled prevalence among subgroups of HBV was20.5%(95%CI:5.1%to 55.4%)in pregnant women;5.7%(95%CI:2.7%to 11.5%)in children;39.2%(95%CI:33.4%to 45.4%)in patients with chronic liver disease,including hepatocellular carcinoma(HCC);7.7%(95%CI:4.2%to 13.6%),12.4%(95%CI:6.3%to 23.0%)and 11.8%(95%CI:5.3%to 24.5%)in age groups20 years old,20-39 years old and40years old,respectively.The HBV prevalence among risk groups was 20%(95%CI:7.19%to 44.64%)in female prostitutes,21.28%(95%CI:7.15%to48.69%)in hospitalized adults,5.56%(95%CI:0.99%to 25.62%)in hospitalized children,60%(95%CI:31.66%to 82.92%)in patients with acute hepatitis,33.55%(95%CI:14.44%to 60.16%)in patients with ancylostomiasis,12.34%(95%CI:7.24%to 20.26%)in patients with leprosy and 20.19%(95%CI:11.28%to33.49%)in schistosomiasis patients.The overall pooled prevalence of HCV was estimated as 4.84%(95%CI:3.02%to 7.67%).The prevalence rates among blood donors,risk groups,children and patients chronic liver disease(including HCC)was 0.87%(95%CI:0.33%to 2.30%),2.43%(95%CI:1.21%to 4.8%),1.37%(95%CI:0.76%to 2.46%)and 29.82%(95%CI:15.84%to 48.98%),respectively.The prevalence among genotypes of HCV was 21.9%(95%CI:15.36%to 30.23%)in genotype 1,0.87%(95%CI:0.12%to 5.9%)in genotype 2,25.21%(95%CI:18.23%to 33.77%)in genotype 3,46.24%(95%CI:37.48%to 55.25%)in genotype 4,2.52%(95%CI:0.82%to7.53%)in genotype 5,and 1.19%(95%CI:0.07%to16.38%)in genotype 6.The overall pooled prevalence of HDV was 28.99%(95%CI:16.38%to 45.96%).The HDV prevalence rate among patients with chronic liver disease,including HCC,was 43.77%(95%CI:35.09%to 52.84%).The overall pooled prevalence of HEV was46.86%(95%CI:5.31%to 93.28%).CONCLUSION Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease.This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.     

Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C

In patients with chronic hepatitis C, alanine aminotransferase (ALT) levels do not accurately reflect the extent of liver inflammation. The discrepancy between ALT level and liver damage could be related to the mode of cell death. In the present study, we quantified serum levels of apoptotic cytokeratin 18 (CK-18) neoepitopes that are generated by activated caspases during apoptosis. Apoptotic CK-18 neoepitopes were quantified by enzyme linked immunosorbent assay in sera from patients with chronic hepatitis C and elevated ALT levels (n = 72), patients with chronic hepatitis C and persistently normal ALT levels (n = 27) and healthy controls (n = 19). Serum CK-18 neoepitope levels were strongly correlated with ALT (r = 0.659, P < 0.0001) and the histology activity index (r = 0.374, P < 0.001). Patients with chronic hepatitis C and persistently normal ALT levels had higher apoptotic CK-18 neoepitope levels than healthy controls (P = 0.03) but lower levels than patients with chronic hepatitis C and elevated ALT levels (P < 0.001). Highest serum CK-18 neoepitope levels were observed in patients with cirrhosis (P = 0.002). Hence apoptotic CK-18 neoepitopes in serum of patients with chronic hepatitis C are associated with ALT level and histological liver damage. Serum apoptotic CK-18 neoepitope levels are elevated both in patients with chronic hepatitis C and elevated ALT levels as well as in patients with normal ALT levels indicating that also patients with chronic hepatitis C and normal ALT have an increased hepatocyte loss by apoptosis.     

严重急性呼吸道综合征并发肝脏损害的临床特点与机制探讨

目的 探讨严重急性呼吸道综合征(SARS)并发肝脏损害的临床特点,分析其可能的原因,以进一步阐明SARS的发病机制,为临床治疗提供依据。方法 对154例SARS患者,观察了临床症状、体征、肝功能等。其中46例患者系统检测了血清白细胞介素(IL)-1 β、IL-2、IL—4、IL—6、IL—8、IL—10、肿瘤坏死因子(TNF)α、内毒素和甲～戊型肝炎病毒标志物。部分病例进行了肝脏B型超声和病理学检查。另有15例健康者及22例同期住院的慢性肝病患者作为对照。结果 37.7％的SARS患者入院时丙氨酸氨基转移酶(ALT)或/和天门冬氨酸氨基转移酶(AST)升高,其中43.1%轻度升高(<80 U/L),56.9%中度升高。肝功能异常以ATL单项增高为主(70.7％),其次为ALT与AST同时异常(22.4％),少数单纯AST增高。75.9％患者转氨酶在2周内恢复正常,有4例入院时转氨酶正常而在住院过程中升高。重型SARS患者转氨酶异常率显著高于轻型,x~2=19.28,P<0.05。住院期间24.0％患者血清白蛋白下降,28.6％前白蛋白降低,8.4％总胆红素升高,72.7％患者入院时肌酸激酶或(和)心肌型肌酸激酶同功酶异常。IL-1等6种白细胞介素与TNF—α在急性期均显著高于恢复期、正常对照组和慢性肝病组,t=1.67～6.48,P<0.05～0.01。ALT异常组IL-1 β、IL-6和IL-10显著高于ALT正常组,t-2.36～     

Normal vitamin D levels are associated with spontaneous hepatitis B surface antigen seroclearance

AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance.METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneous HBsAg seroclearance.RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (> 35 years) OR = 1.7 (95%CI: 1.25-2.8, P = 0.05), serum vitamin D levels (> 20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P = 0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P = 0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P = 0.04) were also associated with spontaneous HBsAg seroclearance.CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.     

拉米夫定治疗儿童慢性乙型肝炎疗效及安全性Meta分析

目的应用Meta分析评价拉米夫定治疗儿童慢性乙型肝炎(CHB)的疗效和安全性。方法计算机检索中英文数据库中有关拉米夫定治疗儿童CHB的临床随机对照试验。结果选中8项随机对照试验,包括1309例儿童CHB患者。Meta分析显示:拉米夫定组HBeAg阴转率、HBeAg血清学转换率和ALT复常率均明显高于安慰剂组:①HBeAg/抗HBe血清转换率:48周[OR=2.96,95%CI(1.71,5.12),P<0.001];②HBeAg阴转率:24周[OR=2.96,95%CI(1.71,5.12),P<0.001]。48周[OR=6.64,95%CI(3.47,12.7);Z=5.72,P<0.00001]。52周[OR=2.52,95%CI(1.44,4.42),P<0.01]。96周[OR=10.98,95%CI(3.26,37.05),P<0.001];③ALT复常率:12周[OR=2.84,95%CI(1.61,5.00),P<0.001]。24周[MD=4.56,95%C(I 1.46,14.28),P<0.01]。48周[OR=6.17,95%C(I 3.2,11.92),P<0.00001]。然而,在治疗12周和24周,患者HBV DNA阴转率与对照组比,差异无明显统计学意义[OR=56.66,95%CI(0.12,27661),P>0.05]、[OR=120.84,95%CI(0.67,21659.97),P>0.05],而在治疗48周[OR=66.02,95%CI(3.65,1195.7),P<0.01]、52周[OR=4.97,95%CI(2.35,10.51),P<0.0001]和96周[OR=46.92,95%CI(3.27,673.4),P<0.0001]时,HBV DNA阴转率明显提高。随访发现:拉米夫定治疗儿童CHB不影响正常的身高与体重的增长。结论拉米夫定可有效提高CHB患儿HBeAg阴转率、HBeAg血清学转换率和ALT复常率,治疗48周后HBVDNA阴转率才有明显提高。拉米夫定治疗儿童CHB,无明显的副作用,安全性较好。     

Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic Hepatitis B Patients: a Meta-Analysis Study

Background

Hepatitis B virus (HBV) infection is a serious global health problem that is associated with huge social and economic costs. Early antiviral drugs, such as interferon-α2b, peginterferon-α2a, lamivudine, and adefovir, all have their limitations (such as low responses or safety concerns) in clinical application. Telbivudine and entecavir are two of the latest nucleotide drugs and both have been shown to have potent viral suppression. However, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent results have been generated for efficacy between telbivudine and entecavir. Therefore, evidence-based medical data are required to compare the efficacies, in terms of virological and biochemical responses, and safety between telbivudine and entecavir.

Objectives

We aimed to compare the early antiviral efficacy and safety of telbivudine and entecavir in the treatment of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB).

Patients and Methods

A search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB patients treated with telbivudine and entecavir for 24 or 52 weeks, published before December 2011, was performed. Primary efficacy endpoint was the cumulative rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg seroconversion and adverse events. Meta-analysis was performed using the Review Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95% confidence intervals (CIs) using the fixed-or random-effects model.

Results

Six randomized controlled trials (RCTs) involving 555 patients were included. Telbivudine was associated with significantly higher rates of HBeAg disappearance (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25-2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 - 3.60), compared with entecavir. There was no difference between telbivudine and entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90 - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00).

Conclusions

Telbivudine is associated with significantly higher rates of HBeAg disappearance and HBeAg seroconversion than entecavir, whereas entecavir is superior to telbivudine in safety. Both drugs have similar efficacy on rates of cumulative undetectable HBV DNA and ALT normalization.     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.     

Clinical Values of Elevated Serum Cytokeratin-18 Levels in Hepatitis: A Meta-Analysis

Background:

As an important intermediate filament protein within liver cells, cytokeratin-18 (CK-18) has been confirmed as a potential indicator in various hepatitis progressions.

Objectives:

We sought to clarify the connection between serum CK-18 levels and hepatitis pathogenesis in the present meta-analysis.

Materials and Methods:

With the application of various computerized databases, including PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, China BioMedicine (CBM), China National Knowledge Infrastructure (CNKI), published papers that assessed the relationship between serum CK-18 levels and hepatitis were obtained. The main key words used are “Hepatitis”, “hepatitides”, “Cytokeratin-18”, “Keratin-18” and “CK-18”. Statistical analysis was conducted using the STATA software (version 12.0).

Results:

Eight case-control studies published between 2010 and 2014 were confirmed eligible, according to our selection criteria. The results of the meta-analysis showed that serum levels of CK-18 in hepatitis patients were higher compared to healthy controls (standardized mean difference (SMD) = 3.71, 95%CI: 2.27-5.14, P < 0.001). Subgroup analysis by ethnicity and disease implicated that high serum CK-18 levels might be a risk factor for non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC), and chronic hepatitis B (CHB) (all P < 0.05) among Asians (SMD = 2.89, 95%CI: 2.35-3.43, P < 0.001), Africans (SMD = 0.69, 95%CI: 0.12-1.26, P = 0.017), and Caucasians (SMD = 4.86, 95%CI: 1.82-7.89, P = 0.002).

Conclusions:

Serum CK-18 levels in hepatitis patients were higher, compared with healthy controls. Our results revealed the clinical values of CK-18, in combination with other apoptosis markers, in identifying the development of hepatitis.     

Effects of entecavir and lamivudine for hepatitis B decompensated cirrhosis: Meta-analysis

AIM:To compare the effects of entecavir(ETV)and lamivudine(LAM)for the treatment of hepatitis B decompensated cirrhosis using a meta-analysis.METHODS:We conducted a literature search for all eligible studies published prior to May 30,2013 using PUBMED,MEDLINE,EMBASE,the China National Knowledge Infrastructure(CNKI),the VIP database,the Wanfang database and the Cochrane Controlled Trial Register.Randomized controlled trials(RCTs)comparing ETV with LAM for the treatment of hepatitis B decompensated cirrhosis were included.The data were analyzed with Review Manager Software 5.0.2.We used RR as an effect measure,and reported its95%CI.The meta-analysis was performed using either a fixed-effect or random-effect model,based on the absence or presence of significant heterogeneity.Two reviewers assessed the risk of bias and extracted data independently and in duplicate.The analysis was executed using the main outcome parameters including hepatitis B virus(HBV)DNA undetectability,HBV DNA level,hepatitis B e antigen(HBeAg)seroconversion,alanine aminotransferase(ALT)level,albumin level,total bilirubin(TBIL)level,prothrombin time activity(PTA)level,Child-Turcotte-Pugh(CTP)score,mortality,drugresistance,and adverse reactions.Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics and the therapeutic effects of the two agents.RESULTS:Thirteen eligible trials(873 patients in total)were included and evaluated for methodological quality and heterogeneity.Of these studies,all had baseline comparability,12 of them reported baseline values of the two treatment groups in detail.Following various treatment durations(12,24,36,48 and>48 wk),both ETV and LAM significantly reduced HBV DNA level,however,reductions were greater in the ETV group(MD=-0.66,95%CI:-0.83-0.50,P<0.00001),(MD=-0.93,95%CI:-1.36-0.51,P<0.0001),(MD=-1.4,95%CI:-1.78-1.01,P<0.00001),(MD=-1.18,95%CI:-1.90-0.46,P=0.001),(MD=-0.14,95%CI:-0.17-0.11,P<0.00001,respectively).At 12