乙肝病毒相关肝病肝脏移植术后乙肝复发的预防和治疗

在我国施行肝移植的患者中,绝大多数是乙肝病毒相关性终末性肝病患者,术前病毒复制程度、个体免疫状态和病毒类型与移植术后易感复发密切相关。联合应用乙肝免疫球蛋白与核苷类似物可用于肝脏移植术后抗病毒治疗,近年来报道乙肝疫苗也可有效预防移植术后乙肝复发。本文重点介绍肝脏移植术后乙肝复发的机制及影响因素,探讨预防乙肝复发的各种方案的优劣。     

RECK gene polymorphisms in hepatitis B-related hepatocellular carcinoma: A case-control study

Background and study aimsChronic hepatitis B (CHB) infection is a major risk factor for hepatocellular carcinoma (HCC). The RECK gene is a critical tumor suppressor gene. This study aimed to assess the association between RECK gene single nucleotide polymorphisms (SNPs) and the development of HCC in Egyptian patients with chronic hepatitis B.Patients and methodIn this case-control study, we enrolled patients with CHB from the Gastroenterology Department, Benha University, from June 2016 to February 2018. The RECK gene SNP rs10814325 was identified using real-time PCR allelic discrimination via TaqMan SNP genotyping assays (Applied Biosystems, USA).ResultsWe enrolled 140 participants in this study. The participants were divided into Group I, which comprised 50 participants with CHB only, Group II, which comprised 50 participants with CHB and HCC, and Group III, which comprised 40 healthy participants. A significantly higher hepatitis B virus DNA viremia level was found in patients with HCC. The predominant RECK genotype was the T/T allele, followed by the T/C allele; however, no significant difference in the distribution of RECK gene SNPs was found between the study groups. No statistically significant difference in RECK gene SNPs was reported among patients with HCC of different Child classes or based on the number, site, size of HCC, and lymph node involvement. Receiver operating characteristic curves showed that a serum alpha-fetoprotein level of 92 ng/ml was 96 % sensitive and 100 % specific for the detection of HCC, with an area under the operating characteristic curve of 0.98.ConclusionRECK gene SNPs have no significant association with the development and characteristics of hepatitis B-related HCC in Egyptian patients.     

Significance of viral status on occurrence of hepatitis B-related hepatocellular carcinoma

Hepatitis B virus (HBV) infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of developing hepatocellular carcinoma (HCC). Interactions that occur among host, environmental, and viral factors determine the natural course and predict the prognosis of patients with chronic HBV infection. In the past decades, several important viral factors of predictive of HCC have been identified, such as high hepatitis B surface antigen level, seropositivity of hepatitis B e antigen, high viral load, viral genotype, and specific viral sequence mutations. Identification of certain viral risk factors for HCC development and stratification of patient risk are very important to perform future surveillance programs. In this article, we thus reviewed the risk of viral factors involved in hepatocarcinogenesis.     

Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma

Approximately 350 million people worldwide are chronically infected by hepatitis B virus (HBV). HBV causes severe liver diseases including cirrhosis and hepatocellular carcinoma (HCC). In about 25% of affected patients, HBV infection proceeds to HCC. Therefore, the mechanisms by which HBV affects the host cell to promote viral replication and its pathogenesis have been the subject of intensive research efforts. Emerging evidence indicates that both autophagy and microRNAs (miRNAs) are involved in HBV replication and HBV-related hepatocarcinogenesis. In this review, we summarize how HBV induces autophagy, the role of autophagy in HBV infection, and HBV-related tumorigenesis. We further discuss the emerging roles of miRNAs in HBV infection and how HBV affects miRNAs biogenesis. The accumulating knowledge pertaining to autophagy and miRNAs in HBV replication and its pathogenesis may lead to the development of novel strategies against HBV infection and HBV-related HCC tumorigenesis.     

Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

ObjectiveThe clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB.MethodsIn this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan–Meier analysis.ResultsThe serological pattern of coexistence of HBsAg/anti-HBs, with high levels of (“High”) HBsAg/low levels of (“Low”) anti-HBs, were considered as independent risk factors for HCC. In particular, patients with “High” HBsAg/“High” anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104–16.699; p = 0.035] and “Low” HBsAg/ “High” anti-HBs (OR, 3.207; 95%CI, 1.299–7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only “Low” HBsAg /“High” anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study.ConclusionThe coexistence of “Low” HBsAg /“High” anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.     

人微小病毒B19与乙肝病毒相关肝病的临床关系

目的 探讨人微小病毒B19在乙肝病毒相关肝病患者中的感染情况及其对这些疾病的影响.方法 应用ELISA技术检测原发性肝癌、肝硬化、慢性乙型肝炎三组患者(各50例)和健康对照组(50例)血清中HPV B19特异性抗体IgM(B19-IgM),同时检测其丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肝功能Child-Pugh评分,分析HPV B19感染对肝脏功能的影响.结果 乙肝病毒相关肝病组人微小病毒B19感染率(16.7%)远高于正常对照组(2%),差别有显著性(P<0.05);原发性肝癌人微小病毒B19-IgM阳性率(28%)远高于慢性乙型肝炎组(10%)、肝硬化组(12%)及正常对照组(2%)(P<0.05);肝硬化组人微小病毒B19-IgM抗体阳性率明显高于正常对照组(P<0.05);原发性肝癌组中人微小病毒B19-IgM阳性患者转氨酶(ALT、AST)水平、肝功能Child-Pugh评分及肝癌分期较阴性者高,差异有统计学意义(P<0.05).结论 乙肝病毒相关肝病患者合并人微小病毒B19的感染常见,其中原发性肝癌组感染率最高;且转氨酶的水平及肝功能Child-Pugh评分高于未感染者,提示受人微小病毒B19感染的原发性肝癌患者肝功能受损将更严重.     

Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

INTRODUCTIONHepatocellular carcinoma (HCC) ranks fifth of the most common cancers worldwide and its incidence is rising in the Western world[1]. Due to the high mortality associated with HCC it is the third leading cause of cancer death worldwide[1]. The …     

Geographic variations of predominantly hepatitis C virus associated male hepatocellular carcinoma townships in Taiwan: identification of potential high HCV endemic areas

Purpose

The proportion of B-HCC cases in Taiwan has progressively decreased over the last 20 years. It was not really due to an overall decrease in B-HCC but due to an increase in HCV-related HCC. The identification of potential HCV endemic areas in Taiwan has consequently become important.

Methods

Data were collected retrospectively from eight Taiwan medical centers from 1981 to 2001, the geographical variations of male C-HCC townships in Taiwan were illustrated on maps. Goodness of fit was used to compare the anti-HCV prevalence in townships and cities, with the mean anti-HCV prevalence for Taiwan as a whole. Township-, city-, and county-specific prevalence of anti-HCV was presented as the median, ranges, and SMRs.

Results

Geographic variation can be analyzed in only 263 townships and cities. The maps were designed on the basis of different SMRs. The mean anti-HCV prevalence for male HCC patients in Taiwan was 31.9% (95% confidence interval: 30.7–33.0). Twenty-five townships distributed throughout central-western and south-western Taiwan have significantly higher prevalence (P < 0.05) (12 townships SMR ≥ 2; 13 townships 1.5 ≤ SMR < 2). Twenty-two townships have significantly lower prevalence (P < 0.05) (6 townships 0.5 ≤ SMR<1; 16 townships SMR < 0.5). Four different patterns of geographic variation in different counties were also noted and demonstrated.

Conclusion

We successfully highlighted some potential high HCV endemic townships in Taiwan.     

非酒精性脂肪性肝病与乙型肝炎病毒既往感染者肝癌发生关系的研究

目的:乙型肝炎表面抗原（HBsAg）清除并不能消除乙型肝炎病毒（HBV）感染患者的肝细胞癌（HCC）风险,本研究旨在探讨非酒精性脂肪性肝病（NAFLD）在HBV既往感染者（HBsAg阴性、抗-HBc阳性）HCC发生中的作用。方法:本研究是回顾性调查研究,纳入2015年至2017年在南方医院住院并首次诊断为HCC的患者共...     

Latent hepatitis B is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C

AIM:To study the potential association between hepatocellular carcinoma(HCC)in patients with chronic hepatitis C(CHC),cirrhosis and latent hepatitis B(LHB)infection,defined as the absence of detectable serum hepatitis B surface antigen(HBsAg)and the presence of hepatitis B core antibody(HBcAb).METHODS:This retrospective analysis is comprised of 185 cirrhotic patients with HCC who were hepatitis C virus antibody(HCV Ab)(+)and HBsAg(-)at Wayne State University between 1999 and 2008.From these,108 patients had HCV polymerase chain reaction confirmation of viremia while the remaining(77)were considered to have CHC on the basis of a positive HCV Ab and the absence of any other cause of liver disease.Controls were drawn from our institutional database from the same time period and consisted of 356 HBsAg(-)age,race and gender matched patients with HCV RNA-confirmed CHC and without evidence of HCC.A subgroup of controls included 118matched patients with liver cirrhosis.χ2test and t test were used for data analysis.RESULTS:Seventy-seven percent of patients in all3 groups were African Americans.Patients with HCC had a significantly higher body mass index(P=0.03),a higher rate of co-infection with human immunodeficiency virus(HIV)(P=0.05)and a higher prevalence of alcohol abuse(P=0.03)than the controls.More patients with HCC had LHB than controls(78%vs39%,P=0.01).Sixty three percent of patients with HCC were both hepatitis B surface antigen(HBsAb)(-)and HBcAb(+)compared to 23%of controls(P<0.01).When compared to cirrhotic controls,the frequency of HBcAb(+)remained higher in patients with HCC(78%vs 45%,P=0.02).Patients with HCC were more likely to be both HBsAb(-)and HBcAb(+)than the cirrhotic controls(63%vs 28%,P=0.01).Although not statistically significant,100%of CHC and HIV coinfected patients with HCC(n=11)were HBcAb(+)when compared to controls(44%;n=9).CONCLUSION:These data suggest that LHB occurs at a significantly increased frequency in patients with CHC and HCC than in patients with CHC without HCC.     

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis

BACKGROUNDHepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. AIMTo determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). METHODSThis was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. RESULTSThe APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). CONCLUSIONOur results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.     

Clinical features of hepatitis B virus-related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of cancer death,and chronic hepatitis B is a serious worldwide problem.The epidemiology of HCC is distinctive.Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis.Prevention of HBV-related HCC is a key issue in current hepatology.This paper describes the prevention and clinical features of HBVrelated HCC,along with a short review of the disease.     

Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis

Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating miRNA s during different stages of HBV infection. Circulating miRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating miRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis,and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.     

Current impact of viral hepatitis on liver cancer development: The challenge remains

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.     

Dermatomyositis associated with hepatocellular carcinoma in an elderly female patient with hepatitis C virus-related liver cirrhosis

A 79-year-old female patient with hepatitis C virus-related liver cirrhosis was diagnosed as having hepatocellular carcinoma (HCC) with a diameter of 2.0 cm. She refused therapy for HCC. Nine months after the diagnosis, she developed dermatomyositis when the HCC enlarged to a diameter of 6.0 cm. She underwent therapy for dermatomyositis, and then transcatheter arterial chemoembolization for HCC. Although the manifestations of dermatomyositis improved and entire tumor necrosis was achieved, she died of pneumonia 2 mo after the treatment of HCC. HCC and/or chronic hepatitis C virus infection might be involved in the pathogenesis of dermatomyositis.     

The STAT4 and not the IFNL3 variant is associated with hepatitis B virus clearance in a population from the Khyber Pakhtunkhwa region of Pakistan

Background and study aimsHost genetic modifiers of the risk and persistence of hepatitis B virus (HBV) infection in the Pakistani population have not been clearly elucidated. Recently, two genome-wide association studies described that STAT4 and IFNL3 variants are associated with different aspects of the course of HBV infection. However, the roles of these variants in the persistence of HBV infection have not been investigated in the HBV-infected population of Pakistan. Therefore, we examined the roles of the STAT4 and IFNL3 variants in a chronic HBV-infected population from the Khyber Pakhtunkhwa (KPK) region of Pakistan.Patients and methodsSTAT4 rs7574865 and IFNL3 rs12979860 genotyping were performed in 297 subjects (240 infected with HBV and 57 controls). Statistical analyses were performed using the chi-squared test, Student’s t-test, Hardy–Weinberg equilibrium tests and logistic regression models.ResultsAmong the 297 subjects, compared with the IFNL3 rs12979860 genotype [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.39–1.29, p = 0.2), the STAT4 rs7574865 genotype was independently associated with the risk of developing chronic HBV infection [OR = 1.9, 95% CI = 1.09–3.50, p = 0.02].ConclusionThe STAT4 rs7574865 and not the IFNL3 rs12979860 variant is associated with persistence of HBV infection in a Pakistani population from the KPK region.