HBV-infected Individuals Research Articles

Hepatitis B/D-Related Hepatocellular Carcinoma. A Clinical Literature Review.

Given the current literature data, this article aims to shed light on the epidemiological and clinical effects of HBV, as well as its impact on the development of hepatocellular carcinoma (HCC). A review of the English language literature based on a MEDLINE (PubMed) database was searched. The keywords were cirrhosis, hepatocellular carcinoma, epidemiology, hepatitis delta virus, hepatitis B virus, and co-infection. All references from retrieved papers were reviewed systematically to find additional collection of reports. The study has broadly confirmed the contribution of HDV viremia to liver disease and cirrhosis. However, uncertainty over the mechanism of action on HCC development remains. As the recent data has demonstrated, the HCC-HDV has a unique molecular profile which is distinct from that of HBV-HCC. Owing to the dependence of HDV on HBV, it is not clear whether HCC is a consequence of the cumulative effect of both HBV and HDV, an effect of the underlying cirrhosis, or a direct oncogenic effect of HDV. Many questions concerning the oncogenic role of HDV remain unanswered. To better understand the role of HDV in carcinogenesis, studies at the molecular level that consider genotype differences should be increased. Multicenter, high-volume, and prospective studies that compare HBV/HDV co-infected and HBV-infected individuals will be pivotal in determining the oncogenic role of HDV.

Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

Applicability of oral fluid samples for tracking hepatitis B virus mutations, genotyping, and phylogenetic analysis.

Little is known about the usefulness of saliva samples for hepatitis B virus (HBV) genotyping and mutation analysis. The aim of this study was to evaluate the usefulness of oral fluid samples to determine HBV genotype distribution, S/polymerase mutations, and HBV subpopulation diversity among chronically HBV-infected individuals. Serum and oral fluid samples were obtained from 18 individuals for PCR and nucleotide sequencing of the HBV surface antigen gene. Biochemical analysis of liver enzymes (ALT, AST, GGT) and HBV, HCV, and HIV serological tests were also performed. All serum samples were HBsAg (+), anti-HBc (+), and anti-HBs (-); 55.6% were HBeAg (+)/anti-HBe (-), and 11.1% were anti-HIV (+). The mean HBV DNA viral load was 6.1 ± 2.3 log IU/mL. The HBV genotype distribution was as follows: A, 72.2%; D, 11.1%; E, 5.6%; F, 11.1%. A concordance of 100% in genotype classification and 99.8% in sequence similarity between paired oral fluid and serum samples was observed. HBsAg mutations were detected in all samples, but no resistance mutations were found in the polymerase gene. This study demonstrates that oral fluid samples can be used reliably for tracking HBV mutations, genotyping, and phylogenetic analysis. This could be important for molecular epidemiology studies with hard-to-reach populations.

Effect of oxidative stress and calcium deregulation on FAM26F (CALHM6) expression during hepatitis B virus infection

BackgroundFamily with sequence similarity 26, member F (FAM26F) is an important innate immunity modulator playing a significant role in diverse immune responses, however, the association of FAM26F expression with HBV infection is not yet known. Thus, the current study aims to explore the differential expression of FAM26F in vitro in HepAD38 and HepG2 cell lines upon HBV infection, and in vivo in HBV infected individuals. The effects of antioxidant and calcium inhibitors on the regulation of FAM26F expression were also evaluated. The expression of FAM26F was simultaneously determined with well-established HBV infection markers: IRF3, and IFN-β.MethodsThe expression of FAM26F and marker genes was analyzed through Real-time qPCR and western blot.ResultsOur results indicate that the differential expression of FAM26F followed the same trend as that of IRF3 and IFN-β. The in vitro study revealed that, in both HBV infected cell lines, FAM26F expression was significantly down-regulated as compared to uninfected control cells. Treatment of cells with N-acetyl-L-cysteine (NAC), EGTA-AM, BAPTA-AM, and Ru360 significantly upregulated the expression of FAM26F in both the cell lines. Moreover, in in vivo study, FAM26F expression was significantly downregulated in all HBV infected groups as compared to controls (p = 0.0007). The expression was higher in the HBV recovered cases, probably due to the decrease in infection and increase in the immunity of these individuals.ConclusionOur study is the first to show the association of FAM26F with HBV infection. It is proposed that FAM26F expression could be an early predictive marker for HBV infection, and thus is worthy of further investigation.

Anti-HDV seroprevalence in patients with decompensated liver cirrhosis due to hepatitis B

Aim: Hepatitis B (HBV) and Hepatitis D (HDV) viruses are among the two important causes of end-stage liver disease today. In this study, we aimed to increase HDV awareness in people infected with HBV by examining the prevalence of HDV in patients with end-stage liver disease due to HBV and who were evaluated for liver transplantation.Materials and Methods: The study was designed as a retrospective single-center and cross-sectional. Patients with HBV decompensated liver cirrhosis were divided into two groups as anti-HDV positive and negative. Child-turcott pugh (CTP), Model for End-Stage Liver Disease (MELD) score, complications of liver cirrhosis, viral hepatitis serology, and platelet count variables were statistically compared between the groups.Results: A total of 147 patients with decompensated liver cirrhosis due to HBV were included in the study. Anti-HDV positivity was detected in 46 (31.3%) patients, and anti-HDV negative in 101 (68.7%) patients. The mean age of HDV positive patients (48.39±9.20) was statistically significantly lower than HDV negative (54.37±7.80) patients (p<0.001). Although MELD and CTP scores were slightly higher in the anti-HDV negative group, there was no statistically significant difference between the groups in terms of both scores (p=0.401; p=0.782, respectively). The platelet count was found to be significantly lower in the anti-HDV positive group than in the anti-HDV negative group (p=0.008).Conclusion: The rate of encountering HDV in end-stage liver disease due to HBV was found to be quite high. HDV is an important factor in the development of end-stage liver disease in HBV-infected individuals, especially at an early age, and taking precautions for this is of great importance.

Prevalence of liver cirrhosis in individuals with hepatitis B virus infection in sub-Saharan Africa: Systematic review and meta-analysis.

Background & AimsChronic hepatitis B virus (HBV) infection accounts for 30%‐50% of cirrhosis related deaths in sub‐Saharan Africa (SSA). Since HBV‐related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment‐naïve patients with chronic HBV infection in SSA.MethodsWe performed a systematic review of published articles which evaluated liver fibrosis stage among treatment‐naïve HBV‐infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg‐positive persons, which was estimated using random‐effects meta‐analysis. Risk factors for cirrhosis were explored using subgroup‐analyses and multivariable meta‐regression.ResultsOf 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono‐infection and nine cohorts (688 patients) with HIV/HBV‐coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6‐6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6‐18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15‐0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV‐coinfection.ConclusionsDepending on the setting, between 4% and 13% of HBV‐infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients.

BACKGROUNDThe presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals.AIMTo examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODSTwo hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models.RESULTSSerum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn’s score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSIONCPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

NTCP gene polymorphisms and hepatitis B virus infection status in a Ghanaian population

BackgroundSLC10A1 gene codes NTCP, a receptor through which the hepatitis B virus (HBV) gets access into hepatocytes - a stage of the viral cycle necessary for replication. Polymorphism variants of SLC10A1 play roles in HBV infection, viral clearance, treatment outcome, and complications, in diverse ethnic groups and countries. However, no such study has been conducted in the Ghanaian population, a country with HBV endemicity. Therefore, an exploratory study was conducted to investigate the presence of three (3) single nucleotide polymorphisms (SNPs) in the SLC10A1 gene (rs2296651, rs61745930, and rs4646287) and assessed the risk of HBV infection among the Ghanaian population.MethodPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the presence of the SNPs among 292 participants comprising 146 HBV infected persons as case-subjects and 146 HBV non-infected persons as control-subjects.ResultsThe minor allele frequency (T) of rs2296651 was present in a significantly high proportion of cases compared with the control group (11.6% vs. 3.1%, p < 0.0001). The homozygote recessive variant of rs61745930 was present in 2.7% of the control group and 5.5% of the case group. Moreover, the minor allele frequencies of rs4646287 were 9.3 and 8.2% among the control and the case group, respectively (p = 0.767). Under the dominant (CC) genetic model of inheritance, rs2296651 was found to be protective of HBV infection [OR = 0.18 (0.07–0.44)], whereas under the co-dominant and additive model, rs2296651 was a potential risk factor for HBV infection [OR = 5.2 (95%CI: 2.1–12.8); 3.5 (95%CI: 1.6–7.6], respectively. Variants of rs61745930 and rs4646287 were not associated with HBV infection (p > 0.05). Polymorphisms in SLC10A1, however, did not show any significant association with HBV infectivity (p > 0.05).ConclusionThe study highlights some polymorphism proof that variants rs2296651, rs61745930, and rs4646287 exist in HBV-infected individuals in Ghana. Although variant rs2296651 was found to be associated with HBV infection, this association warrants more studies. Polymorphisms in SLC10A1 were not associated with HBV infectivity among the Ghanaian population. Further investigation is warranted to assess the offensive role of the relationship between rs2296651 and HBV infectivity.

The autophagy gene ATG16L1 (T300A) variant is associated with the risk and progression of HBV infection

Autophagy pathway genes variants that play crucial roles in immune responses are involved in many diseases but their role in viral diseases is ill-defined. ATG16L1 gene plays a crucial role in the autophagy process. In this study, we have investigated the role of ATG16L1 variant T300A in the risk of HBV infection. rs2241880 (T300A) variant in 551 HBV infected patients (at various stages of infection) and 247 healthy controls were genotyped applying PCR-RFLP. Data analysis revealed that mutant allele G contributes to the risk of hepatitis B infection. Mutant alleles were significantly associated the HBV risk in allelic (OR = 1.31; 95%CI = 1.06–1.63, p = .01) and homozygous (OR = 1.87; 95%CI = 1.17–2.99, p = .009) models. On stratifying HBV infected individuals according to the stage of infection, a significant association was observed in asymptomatic (allelic; OR = 1.52; 95%CI = 1.10–2.09, p = .01 and homozygous; OR = 2.30; 95%CI = 1.22–4.36, p = .01) and chronic (allelic; OR = 1.36; 95%CI = 1.07–1.73, p = .01 and homozygous; OR = 2.07; 95%CI = 1.22–3.53, p = .008) stages of infection. High HBV DNA levels were associated with mutant genotype GG in asymptomatic and chronic carriers. Significantly higher ALT levels were observed in the liver cirrhosis patients with mutant genotypes. In conclusion, our data suggest that rs2241880 mutant allele carriers (allelic and homozygous models) were associated with increased risk of hepatitis B virus infection in North Indian population.

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV.

Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection.Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study.We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56neg NK cell population. The proportion of NK cells in CD56dim and CD56bri NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C+ and NKG2C+NKG2A− NK cells, while positively correlated with the proportion of NKG2A+ and NKG2C-NKG2A+ NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels.These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.

Efficacy of a Mobile Texting App (HepTalk) in Encouraging Patient Participation in Viral Hepatitis B Care: Development and Cohort Study.

BackgroundChronic hepatitis B virus (HBV) infection is a major cause of liver-related morbidity and mortality among Asian Americans in the United States. Despite the available resources, a majority of HBV-infected individuals are not able to access adequate health care owing to numerous barriers.ObjectiveThis study aimed to assess the efficacy of a newly developed mobile texting app (HepTalk) in overcoming these barriers and improving patient engagement and health care access among HBV-infected and nonimmune individuals.MethodsHepTalk was employed for two-way communication between participants and patient navigators. A total of 82 Korean American participants who were either HBV infected or nonimmune to HBV, identified from a community hepatitis B campaign in New York, were enrolled in the study. After informed consent was obtained, both the frequency and themes of the text messages were evaluated. The effects of this communication on linkage to care at the end of the 6-month intervention period were analyzed and discussed.ResultsOn average, patient navigators sent and received 14 and 8 messages per participant, respectively, during the 6-month period. The themes of the messages were similar to the following 4 categories: finding providers, scheduling appointments with providers, health education, and financial issues. Of the 82 participants, 78 were linked to care within 6 months (a 95% linkage rate).ConclusionsHepTalk may be employed as an effective and strategic tool to facilitate communicative interaction between patients and patient navigators or health care providers, thereby improving patient engagement and health care access.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n=713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio=0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

New epidemiology of hepatitis delta.

Hepatitis D virus (HDV) is a defective pathogen that needs hepatitis B virus (HBV) for infection. Co-infection of HBsAg-positive individuals with HDV is commonly associated with a more rapid progression to cirrhosis, a higher incidence of hepatocellular carcinoma (HCC) and increased mortality. Initial studies have shown that about 5% of chronic HBV carriers worldwide (15-20millions) were also infected with HDV. However, recent studies suggest that the prevalence of HDV is at least two- to three-fold higher than previous estimations. Improved diagnostic techniques have shown that HDV infection remains endemic in certain areas of the world. Injection drug users, individuals with high-risk sexual behaviour and patients co-infected with human immunodeficiency virus (HIV) represent the major reservoir of the disease in the Western world. Although the burden of HDV infection significantly decreased in Europe in the nineties, there has been no further decrease in the last decade, probably because of migration from HDV endemic countries. Until new and more effective therapies are available, public health measures should be reinforced by increasing prophylactic HBV vaccination programs, preventing transmission of the virus among parenteral drug users and implementing universal HDV screening of all HBV-infected individuals.

Surveillance of human retroviruses in blood samples from patients with hepatitis B and C in São Paulo, Brazil.

INTRODUCTION Human retroviruses and the hepatitis B and C viruses (HBV and HCV, respectively) share routes of transmission; thus, coinfections occur and could alter subsequent disease outcomes. A preliminary study on human T-lymphotropic virus types 1 and 2 (HTLV-1/2) in serum samples from HBV- and HCV-infected individuals in São Paulo revealed 1.3% and 5.3% rates of coinfection, respectively. These percentages were of concern since they were detected in HTLV-endemic regions and in high-risk individuals in Brazil. The present study was conducted to extend and confirm these data. METHODS HTLV-1/2 and human immunodeficiency virus (HIV) infection status were identified in 1,984 sera for HBV and HCV viral load quantification - 1,290 samples from HBV-infected individuals (53.3% men, mean age: 47.1 years) and 694 samples from HCV-infected individuals (56.3% men, mean age: 50.1 years). HTLV-1/2 antibodies were detected by enzyme immunoassay, followed by western blotting and line immunoassay; HIV infection was detected by enzyme immunoassay. RESULTS HTLV-1/-2 infection was detected in 1.9% HBV-infected individuals (0.7% HTLV-1 and 1.2% HTLV-2) and in 4.0% (2.4% HTLV-1 and 1.6% HTLV-2) HCV-infected individuals; HIV infection was detected in 9.2% and 14.5%, respectively. Strong associations with HTLV and HIV, male sex, and older age were found in HBV/HTLV and HCV/HTLV-coinfected individuals (p<0.05). CONCLUSIONS HTLV-1 and HTLV-2 were confirmed to be prevalent in individuals with HBV and HCV in São Paulo; coinfected individuals deserve further clinical and laboratory investigation.

Role of microRNA 4717, its effects on programmed cell death protein-1 in hepatitis B infection, and interaction between PDCD1 and miR-4717

It is suggested that programmed cell death protein-1 (PD-1) is involved in hepatitis B virus (HBV) infection, the leading cause of hepatocellular carcinoma globally. This study was multi-aimed, that is, to investigate the role of microRNA (miR) 4717 and its target, PD-1 and to determine how the rs10204525 polymorphism in the 3′ untranslated region (3′UTR) of PD-1 affects its interaction with miR-4717. The expression levels of miR-4717 with various single-nucleotide polymorphisms were measured by reverse transcription–quantitative polymerase chain reaction (RT-qPCR). A total of 54 tissue samples from HBV-infected individuals were collected, genotyped, and categorized into three groups; AA (n = 32), AG (n = 18), and GG (n = 4). The expression levels of gene PDCD1 and its corresponding PD-1 protein were significantly declined in the AA group as compared to AG and GG groups. There was a negative linear association between PDCD1 and miR-4717 in the tissue samples. HEPG2 cells transfected with an miR-4717 mimic or PD-1 small interfering (si)RNA exhibited significantly reduced expression levels of PDCD1 and PD-1, whereas cells transfected with an inhibitor of miR-4717 demonstrated greater expression levels of PDCD1 and PD-1 compared with the scramble control. In addition, cell viability and apoptosis were assessed in cells transfected with an miR-4717 mimic, PD-1 siRNA, or an miR-4717 inhibitor. Results revealed that treatment with the miR-4717 mimic or PD-1 siRNA enhanced viability of cells and reduced apoptosis. The results of this study suggest that rs10204525 polymorphism interferes with the interaction between PD-1 and miR-4717 and therefore induces apoptosis in liver cancer cells.

Low Level of Hepatitis B Surface Antigen Screening in a Tertiary Health Facility in Nigeria 2000-2014: Imperative for Provider Initiated Testing and Counselling for Hepatitis B Virus?

Introduction: Viral hepatitis is a major public health challenge that requires an urgent response. Reducing mortality requires major scale-up in prevention, testing and treatment access; coverage in HBV vaccination, testing and treatment is low and must accelerate massively to achieve the 2030 targets. Less than 1% of HBV-infected individuals are diagnosed in Sub-Sahara Africa, despite the availability of rapid tests with good diagnostic accuracy. Materials and Methods: This was retrospective cross sectional study conducted in Federal Teaching Hospital Gombe, in North East Nigeria. All children and adults who presented to the out-patient departments, and those that were admitted irrespective of their HIV and or Hepatitis C virus status and had Hepatitis B and/or Hepatitis B envelope antigen test were conducted between 2000 to 2015. All children and adults were tested using the Hospital standard for Hepatitis B surface antigen test strip. Results: Between 2000 and 2014, 739,456 children and adults were admitted and reviewed in the outpatient units of the Federal Teaching Hospital Gombe; there were 685,552 adults and 53,904 children. Children constituted 7.3% (53,904/739,456) of admissions and outpatient consultations. 2.8% (210/7570), 3.3% (773/23,783), 3.6% (1145/32,142), 5.2% (1694/33,043), 3.3% (986/29,216), 1.9% (661/3321), 0.1% (53/41,626), 0.2% (113/46,634), 2.6% (1418/54,423), 5.4% (3717/69,696), 3.7% (2332/62,086), 3.5% (3241/90,623), 3.2% (2881/89,398), 3.8% (2428/62,687), 2.8% (1835/63,208) of children and adults were tested for HBsAg in 2000, 2001, 20002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013 and 2014 respectively. 23,487 children and adults were tested for HBsAg with a cumulative testing rate of 3%. Overall 4465/23,487 children and adults were seropositive for HBsAg giving a cumulative prevalence of 19%. Conclusion: HBV screening in our health facility is very low. Massive scale up in awareness and HBV vaccination are required. Provider initiated testing and counseling for HBV in health facilities needs support for implementation in Health Facilities in Sub Saharan Africa.

Nailfold capillaroscopic changes in patients with chronic viral hepatitis

BackgroundNailfold capillaroscopy is a highly sensitive, inexpensive, simple, safe, and noninvasive technique used in the investigation of the microcirculation. However, the diseases having a vasculitic component can cause changes in the nailfold capillaries like viral hepatitis, the microvascular characteristics of the nailfold area in HBV and HCV infected individuals have not been systematically investigated. In this study, we investigated possible dermoscopic differences in the vascular appearance of the nailfold capillaries and their association with the disease's clinical status. MethodA hundred and forty-seven patients and 147 healthy controls were enrolled in this study. The patients' group consisted of chronic viral hepatitis B (CHB: 54 cases), chronic hepatitis C (CHC: 36 cases) and carrier of hepatitis B virus infection (CRHB: 57 cases). Nailfold capillaroscopy was performed using a digital dermoscope (Molemax II, X30). All capillaroscopy images were evaluated for capillary density, capillary loop enlargement, capillary tortuosities, branching vessels, micro hemorrhages, avascular areas and splinter hemorrhages, and routine laboratory examinations of all patients were performed. ResultsStatistical differences in all of the categories of capillary morphology were prominent between the capillary abnormalities of Hepatitis B and the control group, also the capillary abnormality was significant between hepatitis C and the control group (p < 0.01). None of the 147 healthy control had any nailfold capillary changes. There was a significant difference between the CHB-Control and CRHB-Control groups in all of the capillaroscopic changes (p < 0.01). The avascular area was also the most common finding in Hepatitis C and Hepatitis B infected individuals, and capillary dilatation (CD), capillary tortuosity (CT) and capillary enlargement (CE) were the major nailfold capillary changes in both of two diseases. ConclusionNailfold capillary abnormalities are one of the extrahepatic dermatologic finding which could be a sign of the endothelial tissue damage in chronic viral hepatitis, we do not have any data about the effects of these two usual infections on the nailfold capillary morphology. This is the first study evaluating the microvasculature abnormalities of the nailfold capillaries in hepatitis B and hepatitis C infected individuals by capillaroscopic examination.

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

Influence of PON1 gene polymorphisms (rs662 and rs854560) on the chronicity of HBV infection

Hepatitis B is a major health problem in Turkey as it is all over the world. Therefore, it is noteworthy to understand the genetic background of hepatitis B virus (HBV)-infection. In order to investigate the effect of the PON1 gene in different clinical conditions of HBV infection, we analyzed common Q192R (rs662) and L55 M (rs854560) polymorphisms in HBV-infected individuals through PCR and RFLP technics. The present study involved 59 HBV carriers (chronic inactive hepatitis B patients) and 60 chronic active hepatitis B patients. The chi-square test was used to compare allele and genotype frequencies of chronic active hepatitis patients and HBV carriers. Any statistically significant diversity was not observed between HBV carriers and chronic active hepatitis B patients according to genotype and allele frequencies of PON1 gene polymorphisms. However, chronic active hepatitis patients and HBV carriers showed statistically significant diversities in terms of combined genotypes of Q192R and L55 M polymorphisms. According to results of our study, a possible relationship could be suggested between combined genotypes of Q192R and L55 M polymorphisms of PON1 gene and chronicity of HBV infection in Turkish population.

Distribution and difference of APOBEC-induced mutations in the TpCpW context of HBV DNA between HCC and non-HCC.

Hepatitis B virus (HBV) DNA is vulnerable to editing by human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases. However, the distribution of APOBEC-induced mutations on HBV DNA is not well characterized. To this end, we obtained the HBV DNA sequence of HBV-infected individuals with and without hepatocellular carcinoma (HCC and non-HCC groups, respectively) from NCBI database and calculated the rapo values of APOBEC-induced TpCpW→TpKpW mutation prevalence in HBV DNA. The results showed that the APOBEC-induced mutations were mainly distributed in the minus strand of non-HCC-derived HBV DNA (rapo = 2.04), while the mutation on the plus-strand was weaker (rapo = 0.99). There were high APOBEC-induced mutation regions in the minus strand of HBV DNA 1 to 1000 nucleotides (nts) region and in the plus-strand of HBV DNA 1000 to 1500 nts region; the mutations in the 1 to 1000 nts region were mainly TpCpW→TpTpW mutation types (total T/G: 111/18) and a number of these were missense mutations (missense/synonymous: 35/94 in P gene, 17/15 in S gene, and 5/10 in X gene). The difference between minus to plus-strand rapo of HCC-derived HBV DNA (1.96) was greater than that of the non-HCC group (1.05). The minus-strand rapo of HCC-derived HBV DNA regions 1000 to1500nts and 1500 to 2000 nts (rapo = 4.2 and 4.2) was also higher than that of the same regions of non-HCC-derived HBV DNA (rapo = 1.2 and 1.1). Finally, the ratio of minus to plus-strand rapo was used to distinguish HCC-derived HBV DNA from non-HCC-derived HBV DNA. This study unraveled the distribution characteristics of APOBEC-induced mutations on double strands of HBV DNA from HCC and non-HCC samples. Our findings would help understand the mechanism of APOBECs on HBV DNA and may provide important insights for the screening of HCC.