Hepatitis B-related Liver Disease Research Articles

Chronic Viral Hepatitis B and Intestinal Microecology

Hepatitis B is one of the leading causes of chronic liver disease worldwide. After HBV infection, some patients develop chronic hepatitis, and long-term inflammation and fibrosis may lead to cirrhosis and hepatocellular carcinoma. In recent years, the role of gut microecology in liver disease has received widespread attention. The balance of the gut microbial community is essential for maintaining the health of the host immune system, and HBV infection may affect this balance. Based on this, this article investigates hepatitis B-related chronic liver disease and gut microecology for reference.

Imaging Changes and Clinical Complications After Drug-Eluting Bead Versus Conventional Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Multicenter Study.

BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selection between the approaches remains controversial. OBJECTIVE. The purpose of this study was to compare DEB-TACE and cTACE in the treatment of patients with unresectable HCC in terms of hepatobiliary changes on imaging and clinical complications. METHODS. This retrospective study included 1002 patients (871 men, 131 women; mean age, 59 ± 12 years) from three centers who had previously untreated unresectable HCC and underwent DEB-TACE with epirubicin (780 procedures in 394 patients) or cTACE with ethiodized oil mixed with doxorubicin and oxaliplatin (1187 procedures in 608 patients) between May 2016 and November 2018. Among these patients 83.4% had hepatitis B-related liver disease, 57.6% had Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC, and 42.4% had three or more nodules. Mean tumor size was 6.3 ± 4.2 cm. Hepatobiliary changes and tumor response were evaluated with CT or MRI 1 month after TACE. Clinical records were reviewed for adverse events. RESULTS. Bile duct dilatation (p < .001) and portal vein narrowing (p = .006) on imaging and liver failure (p = .03) and grade 3 abdominal pain (p < .001) in clinical follow-up occurred at higher frequency in the DEB-TACE group (15.5%, 4.6%, 2.3%, and 6.1%) than in the cTACE (7.4%, 1.6%, 0.7%, and 2.1%) group. Higher frequency of bile duct dilation in patients who underwent DEB-TACE was observed in subgroup analyses that included patients with BCLC stage A or B HCC (p = .001), with cirrhosis (p < .001), without cirrhosis (p = .04), and without main portal vein tumor thrombus (p = .002). Total bilirubin level 1 month after treatment was 1.5 ± 2.4 mg/dL (95% CI, 1.2-1.8 mg/dL) for DEB-TACE versus 1.3 ± 2.0 mg/dL (95% CI, 1.1-1.5 mg/dL) for cTACE (p = .02). The cTACE and DEB-TACE groups did not differ in other manifestations of postembolization syndrome or systemic toxicity (p > .05). Local tumor disease control rates did not differ between the cTACE and DEB-TACE groups (1 month, 96.7% vs 98.5%, p = .06; 3 months, 81.8% vs 82.4%, p = .87), but overall DCR was significantly higher in the cTACE than in the DEB-TACE group (1 month, 87.5% vs 80.0%, p = .001; 3 months, 78.5% vs 72.1%, p = .02). CONCLUSION. Compared with cTACE, DEB-TACE was associated with greater frequency of hepatobiliary injury and severe abdominal pain. CLINICAL IMPACT. Greater caution and closer follow-up are warranted for patients who undergo DEB-TACE for unresectable HCC than for those who undergo cTACE.

Efficacy and safety of YinQiSanHuang-antiviral decoction in chronic hepatitis B: study protocol for a randomized, placebo-controlled, double-blinded trial

IntroductionChronic hepatitis B (CHB) is a global public health problem. Antiviral therapy is the primary treatment. Studies have shown that a combined therapy of traditional Chinese medicine (TCM) and conventional antiviral drugs has better efficacy than conventional antiviral for treatment of CHB. YinQiSanHuang-antiviral decoction (YQSH) is a TCM compound preparation that has shown an effect on anti-hepatitis B virus and on slowing progression of hepatitis B-related liver diseases. To evaluate the efficacy and safety of YQSH combined with entecavir and its preventive effect on hepatitis B cirrhosis, we designed this randomized, double-blind and placebo-controlled trial. The objective is that the combination of YinQiSanHuang-antiviral decoction with entecavir will reduce the annual incidence of liver fibrosis/cirrhosis to 1%.MethodsThis is a multicenter, randomized, placebo-controlled, double-blinded trial involving five hospitals. A total of 802 patients are randomly allocated to two groups: the YQSH group (n = 401) or the placebo group (n = 401). The YQSH group receives YQSH with entecavir; the placebo group receives granules of placebo with entecavir. Patients receive treatment for 52 weeks and then are followed up for 52 ± 2 weeks. The primary outcome measure is the annual incidence of cirrhosis. The secondary outcome measures are hepatitis B virus DNA negative rate, hepatitis B surface antigen negative rate, hepatitis B e antigen seroconversion rate, liver function (alanine aminotransferase, aspartate aminotransferase , gamma-glutamyl transferase , alkaline phosphatase , serum albumin, and total bilirubin), spleen thickness, evaluation scores of patients’ clinical symptoms, and safety assessment. Outcomes will be assessed at baseline and after treatment.DiscussionCombination therapy could become a trend for treatment of CHB, and this trial expects to provide credible clinical evidence for the future combination of TCM and conventional antiviral drugs for the treatment of CHB.Trial registrationChinese Clinical Trial Registry: ChiCTR1900021521. Registered on 25 February 2019.

Diagnostic Value of Abnormal Prothrombin in HBV-related AFP-negative Hepatocellular Carcinoma

To evaluate the diagnostic value of abnormal prothrombin (DCP) in Alpha-fetoproteins (AFP)-negative (AFP≤20 ng/mL) hepatocellular carcinoma and the relationship between DCP level and Child-Pugh grade, tumor size, TNM stage as well as differentiation. The inpatients diagnosed with hepatitis B-related liver disease were collected from June 2016 to December 2017, The diagnostic efficacy of DCP for AFP-negative HCC was analyzed by ROC. Area under the curve ( AUC), the best cut point, sensitivity, specificity, positive predictive value and negative predictive value were calculated. The relationship between DCP levels and the clinical characteristic of HCC was analyzed. A total of 459 hepatitis B markers positive patients were included, including 136 cases of hepatocellular carcinoma, 173 cases of hepatitis B cirrhosis and 150 cases of chronic hepatitis B. DCP in AFP-negative hepatocellular carcinoma group was significantly higher than that in non-HCC group (CHB and LC) ( P<0.05). The AUC of DCP was 0.858, P<0.05. The optimal cut-off point for the diagnosis of hepatocellular carcinoma was 61 mAU/mL. The corresponding sensitivity, specificity, positive predictive value and negative predictive value were 72.8%, 88.2%, 61.1% and 89.7%, respectively. In different size of hepatocellular carcinoma, DCP level of those with diameter>3 cm was significantly higher than those with diameter≤3 cm ( P<0.05). In different TNM stages, DCP level in stage Ⅱ and Ⅲ was significantly higher than that in stage Ⅰ ( P<0.05). There was no significant difference of DCP level among different Child-Pugh grades and differentiation ( P>0.05). DCP has diagnostic value for AFP-negative hepatocellular carcinoma, its level may reflects the degree of tumor progression.

PP-12 - The role of hepatitis B-related chronic liver disease on the changes of iron parameters, B12 and folic acid levels

PP-12 - The role of hepatitis B-related chronic liver disease on the changes of iron parameters, B12 and folic acid levels

Expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases

Objective To investigate the expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases. Methods 159 cases of hepatitis B related liver disease (case group) and 64 cases of health examinees (control group) in our hospital were selected. The case group was further divided into three subgroups according to the disease type, namely, chronic hepatitis B (CHB) group (n=40), hepatitis B virus associated liver cirrhosis (HBV-LC) group (n=65) and HBV associated hepatocellular carcinoma (HBV-HCC) group (n=54). Then the levels of miR-125b-5p, albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), HBV-DNA, total bilirubin (TBIL), total cholesterol (TC), alpha fetoprotein (AFP), triglyceride (TG) and prothrombin time (PT) were measured in each group. Results The levels of ALT, AST, HBV-DNA, TBIL, PT, AFP, TC and TG in the case group were higher than those in the control group (P 0.05); The expression level of serum miR-125b-5p was positively correlated with the pathological grade, tumor node metastasis (TNM) stage, lymphatic vascular infiltration, lymph node metastasis and recurrence (P 0.01), which were all smaller than miR-125b-5p combined with AFP (χ2=12.657, 13.052, P<0.01). Conclusions Serum miR-125b-5p is elevated in hepatitis B related liver diseases, such as CHB, HBV-LC, HBV-HCC, and is associated with disease progression; High levels of miR-125b-5p, HBV-DNA, and AFP are risk factors for adverse prognosis outcomes in patients with hepatitis B-related liver disease; The sensitivity and specificity of combined detection of miR-125b-5p and AFP in the diagnosis of HBV-HCC are relatively high, so the combined detection of the two indicators can be widely applied in clinical practice. Key words: MicroRNAs; Hepatitis B, chronic; Liver cirrhosis; Liver neoplasms

The epidemiology of hepatitis B virus infection in Korea.

The global burden of hepatitis B virus (HBV) infection is profound, and represents a public health threat as chronic infection can lead to liver cirrhosis, hepatocellular carcinoma, and death. The risk factors for chronic hepatitis B-related liver disease differ according to HBV endemicity, hepatitis B e-antigen seropositivity, and viral load. It is important to identify these risk factors and start antiviral treatment at an appropriate time according to current guidelines. The most crucial step in reducing HBV infection is prevention in infancy or early childhood, as infection at an early stage may lead to chronicity. South Korea was formerly an HBV-endemic area, but the epidemiology of HBV infection was changed by the introduction of vaccination in 1983 and nationwide immunization in 1995. The government and the private sector made efforts to reduce the prevalence of HBV infection, and Korea is on target to meet the World Health Organization goal of eliminating viral hepatitis by 2030. To eliminate hepatitis worldwide, the costs of antiviral treatment to prevent perinatal HBV transmission in pregnant women with high viremia should be covered by a national program, and strategies to reduce the prevalence of HBV infection in immigrant populations are needed.

Iron metabolism disorders in patients with hepatitis B-related liver diseases.

AIMTo investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases.METHODSThis case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls’ staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTSSignificantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis).CONCLUSIONIron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

Reverse stress cardiomyopathy post-liver transplant needing mechanical circulatory support.

A 39-year-old female patient with hepatitis B-related decompensated chronic liver disease underwent living donor liver transplantation. Preoperatively, she had a normal electrocardiogram (ECG) and echocardiography, and also a negative dobutamine stress echocardiography test. Intraoperative course went uneventful. Two hours postoperatively, she developed hypotension. Initially, hypotension was treated with fluids and blood products after confirming normal echocardiography, but with time, patient's haemodynamics worsened. Repeat echocardiography showed postero-inferior regional wall motion abnormality. Troponin I was significantly elevated, but ECG was normal. Suspecting myocardial infarction coronary angiography was done which was normal. Based on Mayo's criteria, patient was diagnosed with reverse Takotsubo cardiomyopathy since postero-inferior wall was involved. Inotropic support failed to maintain haemodynamics and intra-aortic balloon pump (IABP) was placed. Inotropes were gradually tapered and IABP was removed at day 4. Twenty days later, repeat echocardiography was normal and patient was subsequently discharged.

Role of Glutathione S Transferase M1 and T1 Gene Polymorphism in Hepatitis B-Related Liver Diseases and Cryptogenic Cirrhosis

Introduction: Progression of hepatitis B virus infection (HBV) might be affected by host genetic factors. The present study was undertaken to study the role of glutathione S-transferases (GST)-M1 and T1 gene polymorphisms in different stages of HBV infection: HBV inactive carrier, chronic hepatitis B and cirrhosis, and cryptogenic cirrhosis. Methods: The study population comprised of 170 subjects; 120 cases (HBV inactive carrier, n = 30; HBV related chronic hepatitis, n = 30; HBV related cirrhosis, n = 30; cryptogenic cirrhosis, n = 30 and 50 unrelated healthy adults without liver disease as controls. Analysis of GSTM1 and GSTT1 gene polymorphisms was done by multiplex polymerase chain reaction (PCR). Results: The GSTM1 null genotype was seen more commonly in hepatitis B cirrhosis (n = 21; 70%), chronic hepatitis B (n = 19; 63.33%) and cryptogenic cirrhosis (n = 17; 56.67%) as compared with inactive carrier (n = 9; 30%) and controls (n = 13; 26%). The GSTT1 null genotype was seen less frequently in all the groups, the observed frequencies were controls (n = 7; 14%), inactive carrier (n = 5; 16.67%), chronic hepatitis B (n = 8; 26.67%) and hepatitis B cirrhosis (n = 7; 23.33%). The difference of GSTM1 null genotype frequencies was statistically significant for hepatitis B cirrhosis versus controls (P = 0.0002), chronic hepatitis B versus controls (P = 0.002) and cryptogenic cirrhosis versus controls (P = 0.01). The GSTT1 null genotype was not found to vary significantly between the groups. Conclusion: The patients with GSTM1 null genotype are at risk of progression of liver disease as the frequency of GSTM1 null genotype was found to be significantly higher in chronic hepatitis B, hepatitis B cirrhosis and cryptogenic cirrhosis as compared with controls. Abbreviations: GST, Glutathione S-transferase; HBV, Hepatitis B virus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

Trends in mortality burden of hepatocellular carcinoma, cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: An analysis of death certificate data

The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960–1990) and after (1991–2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28–10.48%; P<0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20–16.10%; P<0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70–50.30%; P<0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P<0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P<0.026) decreased in 5–14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15years, following implementation of the vaccination program against hepatitis B.

Serum ischemic modified albumin (IMA) concentration and IMA/albumin ratio in patients with hepatitis B-related chronic liver diseases.

Albumin is the most important protein synthesized by the liver. Posttranscriptional changes occur in the molecular structure of albumin due to various factors and isoforms arise. Ischemic modified albumin (IMA) is one such isoform. This study was conducted to evaluate serum IMA concentrations in patients with hepatitis B virus (HBV)-related chronic liver diseases. This study included 74 treatment-naive chronic hepatitis B patients, 25 patients with HBV-related cirrhosis, and 49 healthy controls. Serum IMA concentration was measured spectrophotometrically using the albumin cobalt binding test. The mean IMA concentrations in the chronic hepatitis B group and healthy controls were 0.33 ± 0.11 ABSU and 0.27 ± 0.70 ABSU, respectively, and the difference was statistically significant (P < 0.001). Mean IMA/albumin ratios (IMAR) in the chronic hepatitis B and control groups were 0.08 ± 0.04 and 0.06 ± 0.17, respectively, and the difference was also statistically significant (P < 0.001). Higher serum IMA concentrations and IMAR were detected in patients with advanced fibrosis. Serum IMA concentration and IMAR are increased in patients with HBV-related chronic liver diseases and IMA and IMAR are associated with the degree of liver fibrosis. IMA and IMAR may have potential use as noninvasive markers of fibrosis in chronic hepatitis B patients.

Impact of hepatitis B-related chronic liver disease and its therapy on bone health

Impact of hepatitis B-related chronic liver disease and its therapy on bone health

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.

Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10-14 yr on background hepatitis B-related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six-yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6-15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B-related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow-up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever-increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.

DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease.

BackgroundChronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B.ResultsTo identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium BeadArrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies.ConclusionsOur findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. CpG methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0218-1) contains supplementary material, which is available to authorized users.

Differential timing of oxidative DNA damage and telomere shortening in hepatitis C and B virus-related liver carcinogenesis.

In viral hepatitis, inflammation is correlated with chronic oxidative stress, one of the biological events leading to DNA damage and hepatocellular carcinoma (HCC) development. Aim of this study was to investigate the complex molecular network linking oxidative damage to telomere length and telomerase activity and regulation in hepatitis C and B virus-related liver carcinogenesis. We investigated 142 patients: 21 with HCC (in both tumor and peritumor tissues) and 121 with chronic viral hepatitis in different stages. We evaluated 8-hydroxydeoxyguanosine (8-OHdG), marker of oxidative DNA damage, OGG1 gene polymorphism, telomere length, telomerase activity, TERT promoter methylation, and mitochondrial TERT localization. In hepatitis C-related damage, 8-OHdG levels increased since the early disease stages, whereas hepatitis B-related liver disease was characterized by a later and sharper 8-OHdG accumulation (P=0.005). In C virus-infected patients, telomeres were shorter (P=0.03), whereas telomerase activity was higher in tumors than that in the less advanced stages of disease in both groups (P=0.0001, P=0.05), with an earlier increase in hepatitis C. Similarly, TERT promoter methylation was higher in tumor and peritumor tissues in both groups (P=0.02, P=0.0001). Finally, TERT was localized in mitochondria in tumor and peritumor samples, with 8-OHdG levels significantly lower in mitochondrial than those in genomic DNA (P=0.0003). These data describe a pathway in which oxidative DNA damage accumulates in correspondence with telomere shortening, telomerase activation, and TERT promoter methylation with a different time course in hepatitis B and C virus-related liver carcinogenesis. Finally, TERT localizes in mitochondria in HCC, where it lacks a canonical function.

One-year extended, monthly vaccination prophylaxis combined with hepatitis B immune globulin for hepatitis B after liver transplantation.

The feasibility of vaccination in liver transplant recipients is highly controversial, and the present study aimed to investigate the efficacy of a 1-year extended, monthly vaccine prophylaxis protocol of a second-generation recombinant vaccine for transplant recipients. The recombinant hepatitis B vaccine (10 µg) was administrated s.c. every month for 12 months as the vaccination protocol to 39 liver transplant recipients in stable condition, including those with hepatitis B-related chronic liver disease (n = 30), those with acute hepatitis B liver failure (hepatitis B surface antibody [HBsAb], n = 4), and those with hepatitis B core antibody positive grafts (n = 5). A fixed dose of hepatitis B immune globulin (HBIG) was administrated during the study based on the monoprophylaxis approach, and the increase in the hepatitis B surface antibody titer was measured to evaluate the efficacy of the vaccination. The vaccination protocol was initiated a mean of 54 months (range, 13-124) after liver transplantation, and all patients tolerated the vaccination well without adverse effects. The overall hepatitis B virus (HBV) recurrence rate was 5% (2/39) based on hepatitis B surface antigen positivity, and 2% (1/39) based on HBV DNA detectability. Six (15%) patients showed a good response to vaccination with an increase in the HBsAb titer greater than 100 IU/L at the end of vaccination, but only three (8%) maintained an adequate HBsAb level to spare HBIG during the 2-year observation period. While a few patients demonstrated an adequate response to vaccination, the clinical indication for the HBV vaccination for liver transplant recipients is currently minimal.

The plasma S-adenosylmethionine level is associated with the severity of hepatitis B-related liver disease.

Alterations in methionine metabolism that involve changes in the plasma S-adenosylmethionine (SAMe) level occur in chronic liver diseases. However, no evidence is available on whether circulating SAMe is involved in the development of liver cirrhosis and liver cancer.Cross-sectional data on clinical characteristics and plasma SAMe were collected for 130 cases of chronic hepatitis B (CHB) and HCC as well as for normal volunteers. Univariate and multivariate linear regression and receiver operating characteristic curves were introduced to determine their correlations.Serum ALB and PT levels were independent clinical factors that were correlated with the plasma SAMe levels in CHB and HCC patients. A higher SAMe concentration was observed in the HCC than in the normal and CHB. By exploring the association of the Child–Pugh score with the plasma SAMe level, we found a higher SAMe level at advanced Stage C than at stage A in CHB and HCC patients. We further assessed the diagnostic performance of SAMe with respect to the stages of liver fibrosis and Child–Pugh stage. The AUROC of SAMe for the prediction of cirrhosis was 0.721, and the sensitivity and specificity was 0.707 and 0.769, respectively. The AUROC of plasma SAMe to predict Child–Pugh stage C was 0.706 in patients with CHB and 0.825 in HCC patients. The sensitivity was 0.467 and 0.800, respectively; the specificity was 0.904 and 0.781, respectively.The plasma SAMe level was positively correlated with the severity of liver disease and might be a potential noninvasive biomarker.

Individualized management of pregnant women with high hepatitis B virus DNA levels

Hepatitis B is a major health concern in the Asia-Pacific region, and is endemic in China, Southeast Asia, and Africa. Chronic hepatitis B virus (HBV) infection may cause hepatic cirrhosis and liver cancer. It is estimated that there are more than 350 million chronic HBV carriers worldwide, of whom approximately one quarter will die of chronic hepatitis B-related liver diseases. HBV is transmitted horizontally through blood and blood products or by sexual transmission, and vertically from mother to infant. Perinatal infection is the predominant mode of transmission in countries with a high prevalence of hepatitis B surface antigen (HBsAg) carriage, and perinatal transmission leads to high rates of chronic infection. Therefore, it is important to prevent the mother-to-child transmission (MTCT) of HBV. Research has shown that pregnant women with high HBV DNA levels have an increased risk of MTCT. However, most of the obstetrics guidelines do not make a distinction between pregnant women with high HBV DNA levels and those who are HBsAg positive only. This review addresses the management of pregnant women with high levels of HBV viremia, in terms of antiviral therapy, use of hepatitis B immunoglobulin (HBIG), the combined application of hepatitis B vaccine and HBIG, choice of delivery mode and feeding practices.