Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Circulating Biomarkers for the Early Diagnosis and Management of Hepatocellular Carcinoma with Potential Application in Resource-Limited Settings.

Hepatocellular carcinoma (HCC) is among the world's third most lethal cancers. In resource-limited settings (RLS), up to 70% of HCCs are diagnosed with limited curative treatments at an advanced symptomatic stage. Even when HCC is detected early and resection surgery is offered, the post-operative recurrence rate after resection exceeds 70% in five years, of which about 50% occur within two years of surgery. There are no specific biomarkers addressing the surveillance of HCC recurrence due to the limited sensitivity of the available methods. The primary goal in the early diagnosis and management of HCC is to cure disease and improve survival, respectively. Circulating biomarkers can be used as screening, diagnostic, prognostic, and predictive biomarkers to achieve the primary goal of HCC. In this review, we highlighted key circulating blood- or urine-based HCC biomarkers and considered their potential applications in resource-limited settings, where the unmet medical needs of HCC are disproportionately highly significant.

Significant gaps in hepatitis B vaccination in adults in Viet Nam: Important targets toward hepatitis B elimination by 2030.

BACKGROUND: Gaps in adult hepatitis B vaccination were undefined in Vietnam, a lower-middle-income country. To address these gaps, this study defined hepatitis B vaccine coverage in adults and its associated factors in Ho Chi Minh City (HCMC), Viet Nam. We also proposed interventional strategies, prioritizing gap identification to facilitate hepatitis B elimination by 2030 and beyond. METHOD: During 2019-2020, a multi-stage cluster serosurvey with probability proportional to size was conducted to representatively invite 20,000 adults (18 years or older) throughout HCMC for hepatitis B screening (HBsAg, anti-HBs, and anti-HBc). Serologic results defined two dependent variables: vaccine-induced immunity (i.e., isolated anti-HBs) and susceptibility (i.e., HBV naive). Associations of dependent variables with surveyed demographics, socioeconomic statuses, behaviors, and medical history at risk for hepatitis B were evaluated using weighted Poisson regression. RESULTS: The prevalence was 18.5% (95%CI, 17.3-20.0%) for vaccine-induced immunity and 37.7% (35.6-39.8%) for susceptibility. Even though analyses in the general population revealed a falling trend in vaccine-induced immunity prevalence from younger to older age groups, sensitivity analyses in the non-infected population (i.e., those who were both negative for HBsAg and anti-HBc) showed that younger age groups, especially those aged 30 to 50 years, had the lowest prevalence. Social inequalities existed in different ethnicities, residence areas, education levels, house ownership, and health insurance statuses. There was no significant association between vaccine-induced immunity or susceptibility and risky behaviors and medical histories. CONCLUSION: This study depicts a significant unmet need for hepatitis B vaccination in the general adult population in HCMC, Viet Nam. Indeed, the lack of vaccination was unevenly distributed regarding age groups, geographical areas, and socioeconomic statuses, which reveals profound social disparities. Therefore, to achieve hepatitis B elimination goals, besides the current recommendations for infants and risk-based strategies, hepatitis B vaccination should be recommended for the broader population.

Establishing baseline framework for hepatitis B virus micro-elimination in Ho Chi Minh City, Vietnam - A community-based seroprevalence study.

Background: We conducted a community-based seroprevalence study using three HBV seromarkers (HBsAg, anti-HBs, anti-HBc) in Ho Chi Minh City (HCMC), Vietnam, to (1) determine the prevalence of HBV serologic profiles; (2) document factors associated with HBV infection or susceptibility; and (3) propose strategies toward HBV elimination by 2030. Methods: During 2019-2020, we deployed a multistage cluster design with probability proportionate to size, to recruit 20,000 adults for an HBV screening and linkage to care program citywide. Screening results with interpretation, recommendations, and health education materials were returned to participants. Post-study surveys were conducted within three months to identify gaps in linkage to care. Findings: Of the 17,600 adults invited, 15,275 (86.7%) participated in the study, 14,674 (96.1%) completing all data for final analyses. The prevalence of HBsAg (+) and HBV-naïve were 7.5% and 37.7%, respectively. HBV vaccination rates were 18.7% and about 50% of HCMC population had been exposed to HBV. Of the persons with HBsAg (+), 27.1% linked to care (76% used health insurance). There were wide variations in HBsAg (+) and HBV vaccination rates between districts, risk factors, and socio-economic statuses. Interpretation: The significant disease burden of and gaps in the continuum of care highlight the need and urgency to address the HBV public health problem in Vietnam. Using three screening seromarkers that tailor interventions to the needs of HBV micro-populations could be an effective strategy to pursue HBV elimination goals. Funding: Gilead Sciences Inc; Roche Diagnostic International Ltd; Roche Diagnostics-Vietnam; Abbott Diagnostics-Vietnam; Hepatitis B Foundation; Medic MedicalCenter, Vietnam; Center of Excellence for Liver Disease in Vietnam, Johns Hopkins University School of Medicine.

Demonstration of a population-based HCV serosurvey in Ho Chi Minh City, Viet Nam: Establishing baseline prevalence of and continuum of care for HCV micro-elimination by 2030.

Background: A baseline of hepatitis C virus (HCV) burden and other HCV epidemiological profiles is necessary for HCV micro-elimination in Ho Chi Minh City (HCMC), Viet Nam. This study aimed to determine HCV exposure and prevalence of HCV viremia as well as the proportion of HCV testing and treatment uptake among participants. Methods: From 2019 to 2020, the probability proportionate to size sampling method was deployed to representatively invite approximately 20,000 adults (18 or older) throughout HCMC to free screening and linkage to care for HCV. Findings: In HCMC, the weighted prevalence of anti-HCV was 1·3% (95% CI, 1·1%-1·6%). Individuals born from 1945 to 1964 had the anti-HCV prevalence of 3·6% (95% CI, 3·0%-4·2%) and represented 40·4% of all HCV cases. There were wide variations in anti-HCV prevalence in HCMC, including variations between districts, risk factors, and socioeconomic statuses. A baseline HCV continuum of care for the city demonstrated that only 28·5% (85/298, 95%CI 23·4-33·7%) of persons with anti-HCV (+) were aware of their HCV status, with 77.6% (66/85, 95%CI 68·8-86·5%) diagnosing HCV incidentally, 82·7% (62/75, 95%CI 74·1-91·2%) initiating anti-HCV therapy, and 53.6% (30/56, 95%CI 40·5-66·6%) achieving HCV cures. Interpretation: There remains a considerable disease burden of HCV in HCMC of which a significant proportion was in the age group born between 1945 to 1964. Additionally, there were significant gaps in HCV awareness, screening, and access to care in the community in Viet Nam. Thus, future interventions must have pragmatic targets, be tailored to the local needs, and emphasise screening. Funding: This work was supported by investigator-sponsored research grants from Gilead Sciences Inc. (Grant No: IN-US-987-5382); Roche Diagnostic International Ltd. (Grant No. SUB-000196); and in-kind donations from Abbott Diagnostic Viet Nam; Hepatitis B Foundation; Medic Medical Center, Viet Nam; Johns Hopkins University School of Medicine's Center of Excellence for Liver Disease in Viet Nam; and the Board of Directors, Viet Nam Viral Hepatitis Alliance (V-VHA).

Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal causes of cancer-related death worldwide. The treatment of HCC remains challenging and is largely predicated on early diagnosis. Surveillance of high-risk groups using abdominal ultrasonography, with or without serum analysis of α-fetoprotein (AFP), can permit detection of early, potentially curable tumours, but is limited by its insensitivity. Reviewed here are two current approaches that aim to address this limitation. The first is to use old re-emerged empirically derived biomarkers such as AFP, now applied within statistical models. The second is to use circulating nucleic acid biomarkers, which include cell-free DNA (for example, circulating tumour DNA, cell-free mitochondrial DNA and cell-free viral DNA) and cell-free RNA, applying modern molecular biology-based technologies and machine learning techniques closely allied to the underlying biology of cancer. Taken together, these approaches are likely to be complementary. Both hold considerable promise for achieving earlier diagnosis as well as offering additional functionalities including improved monitoring of therapy and prediction of response thereto.

Unmet needs in occupational health: prevention and management of viral hepatitis in healthcare workers in Ho Chi Minh City, Vietnam: a mixed-methods study.

OBJECTIVES: Vietnam is an endemic area for hepatitis B virus and hepatitis C virus infection (HBV-HCV), yet its largest city, Ho Chi Minh City (HCMC), has no comprehensive policy to educate, screen, treat and protect healthcare workers (HCWs) from viral hepatitis. We conducted a mixed-methods study to document HBV-HCV infection rates, risk factors, local barriers and opportunities for providing education, screening and medical care for HCWs. DESIGN: This mixed-methods study involved an HBV and HCV serological evaluation, knowledge, attitude and practice survey about viral hepatitis and many in-depth interviews. Descriptive statistics and thematic content analysis using inductive and deductive approaches were used. SETTING: HCMC, Vietnam. PARTICIPANTS: HCWs at risk of viral hepatitis exposure at three hospitals in HCMC. RESULTS: Of the 210 invited HCWs, 203 were enrolled. Of the 203 HCWs enrolled, 20 were hepatitis B surface antigen-positive, 1 was anti-hepatitis C antibody (anti-HCV Ab)-positive, 57 were anti-hepatitis B core Ab-positive and 152 had adequate anti-hepatitis B surface Ab (anti-HBs Ab) titre (≥10IU/mL). Only 50% of the infected HCWs reported always using gloves during a clinical activity involving handling of blood or bodily fluid. Approximately 50% of HCWs were still not vaccinated against HBV following 1 year of employment. In-depth interviews revealed two major concerns for most interviewees: the need for financial support for HBV-HCV screening and treatment in HCWs and the need for specific HBV-HCV guidelines to be independently developed. CONCLUSIONS: The high HBV infection rate in HCWs coupled with inadequate preventive occupational practices among the population in HCMC highlight the urgent needs to establish formal policy and rigorous education, screening, vaccination and treatment programmes to protect HCWs from HBV acquisition or to manage those living with chronic HBV in Vietnam.

Progressive Scale-up of HBV AND HCV Testing for Hepatitis Elimination in Vietnam.

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High frequency of the PNPLA3 rs738409 [G] single-nucleotide polymorphism in Hmong individuals as a potential basis for a predisposition to chronic liver disease.

BACKGROUND: An exploratory study was performed to determine the prevalence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs78409 [G] allele among the Hmong as a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic liver disease and is expected to replace viral hepatitis as the leading cause of cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all populations in California, the Hmong experience the highest risk of death from HCC and the highest prevalence of metabolic syndrome risk factors among Asians that predispose them to NAFLD. Here a genetic explanation was sought for the high rates of chronic liver disease among the Hmong. The literature pointed to the PNPLA3 rs738409 [G] allele as a potential genetic culprit. METHODS: Cell-free DNA was isolated from 26 serum samples previously collected in community settings. Quantitative polymerase chain reaction-based single-nucleotide polymorphism (SNP) genotyping was performed with a validated TaqMan SNP genotyping assay, and results were analyzed with TaqMan Genotyper software. RESULTS: The PNPLA3 rs738409 [C>G] variant occurred at a frequency of 0.46 (12 of 26; 95% confidence interval, 0.27-0.67). This carrier rate would rank the Hmong as the third highest population in the 1000 Genomes Project. CONCLUSIONS: Although this small sample size limits the generalizability, the high frequency rates of this allele along with the presence of metabolic syndrome risk factors warrant further studies into the etiology of NAFLD among the Hmong. Cancer 2018;124:1583-9. © 2018 American Cancer Society.

High burden of hepatocellular carcinoma and viral hepatitis in Southern and Central Vietnam: Experience of a large tertiary referral center, 2010 to 2016.

AIM: To examine the largest tertiary referral center in southern and central Vietnam from 2010 to 2016, evaluating epidemiological trends of hepatocellular carcinoma (HCC) and viral hepatitis B-C in this resource-limited setting. METHODS: We extracted data of patients receiving care from Cho Ray Hospital (Ho Chi Minh City), the largest oncology referral center in southern and central Vietnam, from 2010 to 2016. We collected information on patient age, gender, geographic distribution, and disease characteristics including disease stage, tumor biomarker levels [serum alpha-fetoprotein (AFP), AFP-L3 isoform percentage, and prothrombin induced by induced by vitamin K absence-II], and serological testing for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. RESULTS: Data from 24091 HCC patients were extracted, with sample demographics comprising mostly male (81.8%) and older age (however with 8.5% younger than 40 years old). This patient sample included a geographic catchment population of 56 million people (60% of the country's total population of 92.7 million), derived from 38 provinces and municipalities in Vietnam. Chronic HBV infection was found in 62.3% of cases, and chronic HCV infection in 26.0%. HBV and HCV co-infection was seen in 2.7%. Cirrhosis was found in an estimated 30% to 40% of cases. Nine percent of patients were not found to have chronic viral hepatitis. Twenty three point two percent of the patients had a normal AFP level. A total of 2199 patients were tested with AFP-L3 and PIVKA II over two years, with 57.7% having elevated AFP-L3%, and 88.5% with elevated PIVKA II levels. Over this 7-year period, the incidence of HCC increased, with a large proportion of cases (overall 40.8%) presenting initially an advanced stage, not amendable to surgical or locoregional therapy. CONCLUSION: HCC contributes significant health care burden in southern and central Vietnam, with increasing case volume over this seven-year period. Viral hepatitis likely explains this high HCC prevalence.

Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels.

UNLABELLED: Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0.030). CONCLUSIONS: AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis.

Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure.

BACKGROUND AND AIMS: The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. METHODS: The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. RESULTS: The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1-21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P = 0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P = 0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, P = 0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, P < 0.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, P = 0.012] were predictors of improved transplant-free survival. CONCLUSIONS: Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Hepatitis B virus genotype G: prevalence and impact in patients co-infected with human immunodeficiency virus.

Relatively little is known about the role of hepatitis B virus (HBV) genotype G (HBV/G) in patients co-infected with human immunodeficiency virus (HIV) and HBV. This study examined the prevalence and association of HBV/G to liver fibrosis in co-infected patients. HBV genotypes were determined by direct sequencing of the HBV surface gene or Trugene® HBV 1.0 assay in 133 patients infected with HIV/HBV. Quantitative testing of HBV-DNA, HBeAg, and anti-HBe were performed using the Versant® HBV 3.0 (for DNA) and the ADVIA®Centaur assay. The non-invasive biomarkers Fib-4 and APRI were used to assess fibrosis stage. Genotype A was present in 103/133 (77%) of the cohort, genotype G in 18/133 (14%) with genotypes D in 8/133, (6%), F 2/133 (1.5%), and H 2/133 (1.5%). Genotype G was associated with hepatitis B e antigen-positivity and high HBV-DNA levels. Additionally, HBV/G (OR 8.25, 95% CI 2.3-29.6, P = 0.0012) was associated with advanced fibrosis score using Fib-4, whereas, being black was not (OR 0.19, 95% CI 0.05-0.07, P = 0.01). HBV/G in this population exhibited a different phenotype than expected for pure G genotypes raising the question of recombination or mixed infections. The frequent finding of HBV/G in co-infected patients and its association with more advanced fibrosis, suggests that this genotype leads to more rapid liver disease progression. Further studies are needed to understand why this genotype occurs more frequently and what impact it has on liver disease progression in patients with HBV/HIV.