大剂量胸腺肽联合干扰素治疗慢性乙型肝炎的临床疗效观察

本文选择慢性乙型肝炎90例,分大剂量胸腺肽联合干扰素组,大剂量胸腺肽组和干扰素组。结果表明,大剂量胸腺肽联合干扰素治疗可以促进ALT复常,促使HBeAg、HBcAg、HBV－DNA阴转率与对照大剂量的胸腺肽治疗及干扰素治疗组比较,疗效显著（P＜0．05）。故认为大剂量胸腺肽联合干扰素治疗慢性乙型肝炎（CHB）是阻断或抑制HBV复制且疗效显著的一种新疗法。     

Hemodynamic study about cortical hyperintensity belt sign after direct bypass surgery for moyamoya disease

Transient neurological events (TNEs) are observed after direct bypass surgery in patients with moyamoya disease (MMD). Although a correlation between cortical hyperintensity belt signs (CHBs) and TNEs has been reported, the pathophysiology of CHBs is still unknown. The purpose of this study was to reveal the pathophysiology of CHBs by using dynamic susceptibility contrast-magnetic resonance imaging. Thirty patients with MMD were included in this study. We provided scores (0–2) for the existence of CHBs on postoperative FLAIR images. We placed the ROI for the presented area of CHBs in the images of cerebral blood flow, CBV, and MTT. We calculated the change of the hemodynamic parameters (increase ratio, IR) and analyzed the relationship between IRs, CHB scores, and TNEs. TNEs were observed in 15 cases (50%) and CHBs were detected in 28 cases (93%). TNEs showed significantly higher CHB scores than those without (p < 0.05). The group of CHB score 2 showed a significantly higher CBV IR than the group with of score 0 (p < 0.05). Patients with TNEs showed a significantly higher CBV IR than those without (p < 0.05). As for the cut-off level to predict an appearance of TNEs, the CBV IR was 1.36 by the Receiver Operating Characteristic analysis, and the sensitivity and specificity were 80% respectively. We hypothesize that the pathophysiology of the CHBs are vasogenic edemas because the postoperative CBV increase correlated with the CHBs.     

慢加急性肝功能衰竭患者心理合并症的配对病例-对照研究

目的：探讨慢加急性肝功能衰竭（ACLF）患者心理状况及与其他慢性肝脏疾病患者心理症状差异。方法采用病例对照研究,纳入40例 HBV相关ACLF患者,以年龄、性别因素分别匹配40例 HBV相关肝硬化患者、40例慢性乙型肝炎（CHB）患者及40例健康对照,采用描述性分析方法分析不同组间患者心理症状差异。结果汉密顿抑郁量表评分结果提示,HBV 相关 ACLF 组、HBV 相关肝硬化组评分均高于 CHB 组与健康对照组。症状自评量表（SCL-90）评分显示除敌对和偏执2个维度评分无差异,其他8个维度差异均具有统计学意义。结论 HBV相关ACLF患者抑郁程度和精神神经状况较CHB和健康对照组更严重。     

Natural history of chronic hepatitis B: what exactly has REVEAL Revealed?

Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer‐Hepatitis B Virus (REVEAL‐HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL‐HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver‐related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver‐related mortality compared with HBsAg ‐seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non‐invasive clinical parameters to predict long‐term HCC risk. These will hopefully contribute to evidence‐based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL‐HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL‐HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward.     

慢肝患者HBeAg不同状态HBsAg水平与HBV-DNA载量相关性

目的探讨慢肝患者HBe Ag不同状态下HBs Ag水平与HBV-DNA载量关系。方法选择2013年7月至2014年5月在我院肝病门诊就诊的239例CHB患者,运用化学发光法、FQ-PCR法对患者HBs Ag水平及HBV-DNA载量进行监测分析,并将各指标进行有效性讨论。结果 239例患者中,HBe Ag阳性患者的HBs Ag含量和HBV DNA载量均数分别为38089.34 IU/m L和2.88×107 Copy/m L,HBe Ag阴性患者的HBs Ag含量和HBV DNA载量均数分别为4122.51 IU/m L和3.93×106 Copy/m L,统计学分析表明,两组差异具有统计学意义(P<0.001)。高复制水平(HBV-DNA≥105)组的HBV-DNA及HBs Ag定量均值高于低复制水平(HBV-DNA<105)组,两组差异具有统计学意义(P<0.001),从相关性表明,高复制组的HBV-DNA载量与HBs Ag含量具有显著相关性。结论 HBe Ag阳性患者HBV-DNA载量及HBs Ag水平明显高于HBe Ag阴性患者,HBV-DNA载量越高,HBs Ag水平亦高。HBe Ag阴性患者乙型肝炎病毒虽然处于一个相对较低水平,但仍然存在病毒在体内复制的可能,因此,CHB患者应定期进行相关标志物及HBV-DNA检测,以了解患者个体治疗情况,对患者病情、疗效、预后有良好的判断作用。     

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B

Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.     

Intrahepatic Expression of C-C Motif ligand 5 in Patients with Chronic Hepatitis B

Background: C-C motif ligand 5 (CCL5) is reported to play a key role in acute and chronic liver diseases. However, the association between CCL5 and chronic hepatitis B (CHB) remains to be explored. We aimed to investigate the CCL5 expression in the liver tissues of CHB patients and compared the CCL5 expression among CHB patients with different stages of liver inflammation and fibrosis. Methods: Liver tissue specimens from 51 CHB patients who underwent liver biopsy and twelve healthy liver donors were included in the present study. CCL5 expression in the liver tissues was analyzed using immunohistochemistry. The hepatic inflammation grades and fibrotic stages of CHB patients were assessed by the Scheuer classification system. Results: Livers of CHB patients exhibited significantly accumulated CCL5+ cells when compared to those of healthy controls (42.80 ± 4.37 vs. 7.25 ± 0.99/HPF, P < .001). CHB patients with higher hepatic inflammation grades had more CCL5+ cells in their livers than those with lower grades (P < .05). However, the numbers of CCL5+ cells were not correlated with the fibrotic stages in CHB patients (r = .073, P = .61). The number of CCL5+ cells in the liver tissues of CHB patients was positively correlated with alanine transaminase levels (r = .278, P = .041) and aspartate aminotransferase levels (r = .328, P = .009). Conclusions: CHB patients have a significant accumulation of CCL5+ cells in the liver, and CCL5 may play a pathological role in hepatic inflammation of CHB.