A prevalence study of chronic hepatitis B infection among Filipino seafarers at Seamens’ Hospital Manila

Background@#Chronic hepatitis B infection is endemic in the Philippines, where there is a large population of seafarers, a group considered high risk for HBV infection. As such, epidemiological data on this population group is vital for the targeted approach on health- related policies.@*Objective@#To establish the prevalence of chronic hepatitis B infection among seafarers who underwent pre-employment medical examination (PEME) at Association of Maritime Officers and Seafarers’ Union of the Philippines-Seamen’s Hospital (AMOSUP-SH) from 2013-2017.@*Methods@#3696 charts were included for review. Charts with positive HbsAg results were sorted, counted, and analyzed. Subsequent data extraction was done on age, sex, marital status, religion, position on board, history of STD and prior surgeries, presence of tattoos, and the result of HIV and syphilis serology test. These were then described using frequency and percentage.@*Results@#4.17% (n=154) were HbsAg positive. All were male with a mean age of 44 years old. Majority were married (134, 87%), catholic (149, 96.7%) and on deck position (84, 54.5%). 29.8% had identifiable risk factors and these were surgical history (37, 24.03%) and body tattoos (11, 7.14%) while none had a history of STD and a positive test for HIV and syphilis.@*Conclusions@#The level of HBsAg seroprevalence among Filipino seafarer is at the low intermediate level of endemicity.

Studies of Efficacy of tenofoviralafenamide in the treatment of chronic hepatitis B infection / Монголын Анагаах Ухаан

@#Worldwide, an estimated two billion people have evidence of HBV infection, and approximately 240 million have CHB. In April 2017, EASL added a drug newly approved for treatment of CHB, tenofoviralafenamide (TAF) to their list of recommended first-line therapies. Treatment with these therapies can achieve sustained suppression of HBV DNA replication, decreases in inflammation, and histological activity that decrease the risk of cirrhosis and hepatocellular carcinoma in both cirrhotic and noncirrhotic patients and, ultimately, of CHB-associated mortality [1, 2]. However, recent advances in understanding the HBV life cycle have enabled multiple, novel therapeutic targets to be identified and new therapies of direct-acting antiviral (DAAs) and host-targeting agents (HTAs) are indevelopment.</br> In most clinical trials, TAF was non-inferior to TDF in achieving HBV DNA levels below 29 IU/ml.No amino-acid substitutions associated with viral breakthrough were detected by deep sequencing, and no resistance to TAF.With clear evidence from major studies showing that TAF is safe, tolerable, and non-inferior to TDF, its recommendation as a first-line therapy is appropriate.</br> Long-term safety is an important consideration in the therapeutic management of patients with CHB because treatment is often life-long.</br> The efficacy of TAF in patients with resistance mutations associated with older nucleos(t)ide analogues is unclear. Although no evidence of TAF or TDF resistance was detected in the phase III studies through 96 weeks of treatment, very small numbers of patients had baseline mutations indicating resistance to lamivudine, adefovir or entecavir and efficacy data specifically for this group is not available.

Efficacy of tenofovir alafenamide in the treatment of chronic hepatitis B infection / Монголын Анагаах Ухаан

Introduction@#Worldwide, an estimated two billion people have evidence of HBV infection, and approximately 240 million have CHB. In this study, a representative group of Mongolian adults was tested for hepatitis B virus (HBV) in 2017. The prevalence estimates of HBV the general Mongolian adult population were found to be 11.1%, respectively.</br> In April 2017, EASL added a drug newly approved for treatment of CHB, tenofovir alafenamide (TAF) to their list of recommended first-line therapies. The requirement for long-term therapy in chronic HBV highlights the importance of these efficacy and safety trends, however their true clinical relevance is yet to be established and further studies with long-term follow up and real-world clinical data are needed.@*Goal@#Evaluate for result of tenofovir alafenamide in the treatment of chronic hepatitis B infection.@*Materials and Methods@#The clinical trials have evaluated TAF in HBeAg-positive and HBeAg-negative chronic HBV patients. The trials have similar designs and are randomized, double blind, non-inferiority studies. The primary efficacy endpoint was the proportion of patients with HBV DNA<29 IU/ml at week 24 and 48. Other prespecified efficacy endpoints were the proportion of patients with HBsAg seroncoversion to anti-HBs at week 24 and 48. Key secondary safety end- points at week 24 and 48 included the percentage change in T-score, and Z-score bone mineral density (BMD), percentage change in BMD and change from baseline serum creatinine.@*Results@#The primary efficacy endpoint, an HBV DNA level <29 IU/ml at week 24, was achieved by 120 (59.1%) of 203 patients receiving TAF, which was non-inferior to the 63 (55.2%) of 114 patients receiving TDF who had an HBV DNA<29 IU/ml. After 24 weeks of treatment, patients receiving TAF had significantly smaller reductions in bone mineral density (BMD) compared with patients receiving TDF.@*Conclusion@#The development of TAF, specifically designed to deliver potent antiviral activity but with an improved safety profile compared with TDF, is therefore timely.

Serum regucalcin is a useful indicator of liver injury severity in patients with hepatitis B virus-related liver diseases

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.

Association between TGFß1 polymorphisms and chronic hepatitis B infection in an Iranian population

Abstract INTRODUCTION: Transforming growth factor-beta 1 (TGFβ1) is a potent suppressive cytokine that contributes to chronic hepatitis B (CHB) infection. Disparities in TGFβ1 production among individuals have been attributed to TGFβ1 genetic polymorphisms. We examined whether three putative polymorphisms in TGFβ1[-509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T (rs1800472)]are associated with CHB infection in a South-Eastern Iranian population. METHODS: In total, 341 subjects were recruited, including 178 patients with CHB and 163 healthy individuals as controls. Genotyping of the three TGFβ1 SNPs was performed by tetra amplification refractory mutation system-PCR. RESULTS: TheTGFβ1 +869 TT vs.CC genotype in codominant (OR=0.445, p=0.012) and TT vs. TC+CC in the recessive (OR=0.439, p=0.003) model as well as the variant allele T vs. C(OR=0.714, p=0.038) were associated with lower CHB infection risk. However, the +11929 C/T polymorphism was associated with increased CHB risk, and the CT vs. CC genotype (OR=2.77, P=0.001) and T variant allele (OR=2.53, P=0.002) were risk factors for CHB. Furthermore, TTT (+869/-509/+11929) and CCC haplotypes were risk and protective factors for CHB, respectively. We found no significant association between viral DNA load and TGFβ1 genotype or hepatic enzyme levels (p >0.05). CONCLUSIONS: Results indicated that the TGFβ1+869TT genotype and T allele were protective factors, whereas the +11929 CT genotype and T allele were risk factors for CHB infection.

A Survey for Understanding of Breastfeeding among Mothers with Chronic Hepatitis B Infection / 소아감염

PURPOSE: Breastfeeding should be recommended for infants born to mothers with chronic hepatitis B Infection after postexposure prophylaxis. However, high proportion of these mothers are reluctant to engage in breastfeeding in Korea. This survey was taken to identify the cause of that reluctance. Method:Questionnaires were given to mothers with chronic hepatitis B infection who were registered at the 'Hepatitis B Perinatal Transmission Prevention Program' operated by Korea Center for Disease Control and Prevention. They visited a community health center for blood sample collection and signed a consent paper. The questionnaires were sent to the mothers. Result:Among 839 mailed questionnaires, 114 were returned marked 'address unknown'. The overall reply rate was 17% (n=125). Among responders, 52% (n=62) were breastfeeding and 48% (n=60) were formula-feeding. The most influential factor for breastfeeding was the mother's own decision (75%) and the obstetrician's recommendation (17%). For formula- feeding mothers, their decisions were influenced by obstetricians (57%), and by their own thinking (28%). The relationship between breastfeeding and perinatal prophylaxis failure was recognized as 45% 'related' and 50% 'not-related'. A total of 91% of breastfeeding mothers replied that they will breast-feed again. Among formula-feeding mothers, 78% answered that they will breast-feed if they were known that 'there is no direct relationship between breastfeeding and perinatal prophylaxis failure'. Conclusion:Despite the fact that there is no direct relationship between breastfeeding and perinatal prophylaxis failure, many were reluctant to breast-feed. Healthcare professionals have influence over the mothers for decision making. It will be necessary to educate healthcare personnel so that they can make a conceptual change as well as to promote the fact to the general public.

Hepatitis B Virus Precore and Core Promotor Mutations in Children with Chronic Hepatitis B Infection

PURPOSE: The aims of this study were to investigate the frequencies and role of hepatitis B virus(HBV) precore and core promotor mutations in children with chronic hepatitis B infection. METHODS: Sera from 31 children with chronic HBV infection were analyzed by direct sequencing of polymerase chain reaction amplification of HBV DNA. RESULTS: Twenty-nine adr type were analyzed. The mutations in HBV precore region were observed in 8(27.6%) of 29 cases. The G->A mutation of nucleotide 1896(A1896; stop codon) were observed in 4 cases(13.8%). The mutations in HBV core promotor region were observed in 27 (93.1%) of 29 cases. The G(1764)->A mutation(A1764) was observed in 14 cases(48.3%), and among these 12 cases combined with a A to T change at nucleotide 1762(T1762). The mutations in HBV precore region were obsereved in 4(21%) of 19 cases of HBeAg positive group and 9(90%) of 10 cases of HBeAg negative group. A1896 mutation was observed in 2 cases in both HBeAg positive and negative group, respectively. The mutations in HBV core promotor region were observed in 18(94.7%) of 19 cases of HBeAg positive group and 9(90%) of 10 cases of HBeAg negative group. T1762 mutation were observed in 6(31.6%) of 19 cases of HBeAg positive group and 6(60%) of 10 cases of HBeAg negative group(P=0.14). A1764 mutation was obsereved in 7 (36.8%) of 19 cases of HBeAg positive group and 7(70%) of 10 cases of HBeAg negative group (P=0.089). A1896 mutation was observed in 2(18.2%) of 11 cases in increased AST/ALT group and 2(11.1%) of 18 cases in normal AST/ALT group. A1764 and T1762 mutations were higher (61.1%) in AST/ALT increased group than those(27.3%) in AST/ALT normal group, but there was no statistical significance(P=0.077). CONCLUSION: Mutations in the precore and core promotor regions can be frequently detected in children with chronic HBV infection. T1762 and A1764 mutations were observed more frequently in HBeAg negative group and in AST/ALT increased group but there was no statistical significance.

A Study of Serum Cytokines in the Patients with Chronic Hepatitis B Virus Infection / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to clarify the serum cytokine pattern in patients with chronic HBV infection in terms of their clinical state. METHODS: Intravenous blood samples were taken from 35 patients who were seropositive for HBsAg for at least 6 months and 7 healthy controls. Samples were initially tested for serum aminotransferases and serologic markers for hepatitis B virus by EIA. Serum levels of interleukin(IL)-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-4, and IL-10 were measured by ELISA. RESULTS: Among 35 patients, seropositive for HBeAg was 20 and for anti-HBe was 15. The histologic diagnosis of 19 patients underwent liver biopsy were chronic persistent hepatitis (CPH) in 10 and chronic active hepatitis (CAH) in 9. Serum IL-10 level in patients seropositive for HBeAg was significantly higher than that in patients seropositive for anti-HBe (p 100 U/L. High level of IL-4 was seen in patients with normal aminotransferase levels. Conclusion: These results were thought to indicate that anti-inflammatory Th2-like cytokine (IL-10) production in chronic HBV infection is related to circulating HBeAg rather than activity of hepatitis and that Th1 cytokines seem to be associated with the increasing activity of hepatitis.