Dual strategy involving hospital-based study and community-based screening to eliminate hepatitis C in remote areas.

BACKGROUND: /Purpose: To achieve the World Health Organization goal of eliminating viral hepatitis by 2030, a key strategy in resource-limited areas is to identify the areas with high prevalence and to prioritize screening and treatment intervention. We hypothesized that a hospital-based laboratory database could be used to estimate the township- and village-specific anti-hepatitis C virus (HCV) prevalence. METHODS: Yunlin County Public Health Bureau has been collecting anti-HCV test data from eight major hospitals. Township- and village-specific screening testing rates and anti-HCV prevalence were calculated for residents 40 years or older. A township with a wide range of anti-HCV prevalence rates was selected for outreach universal screening and for validating the village-specific prevalence of anti-HCV in the analysis of the data from the hospitals. RESULTS: The overall anti-HCV screening testing rate in Yunlin County was 30.4 %, whereas the anti-HCV prevalence rate for persons 40 years or older was 15.4 %. The village-specific anti-HCV prevalence rates ranged from 3.8 % to 85.8 %. Community-based screening was conducted in Kouhu Township. The village-specific anti-HCV prevalence rates ranged from 0 % to 18.8 %. Three of the four villages had the highest village-specific anti-HCV prevalence in the community-based study and the hospital-based study. Additionally, 95.8 % of the new HCV cases detected by universal screening received anti-HCV therapy. CONCLUSION: The hospital-based database provided a framework for identifying the villages with high anti-HCV prevalence. Additionally, community-based universal screening should be prioritized for villages with high prevalence in hospital-based databases.

Above-Standard Survival of Hepatocellular Carcinoma as the Final Outcome of Comprehensive Hepatology Care Programs in a Remote HCV-Endemic Area.

Early detection and prompt linkage to care are critical for hepatocellular carcinoma (HCC) care. Chang Gung Memorial Hospital (CGMH) Yunlin branch, a local hospital in a rural area, undertakes health checkup programs in addition to its routine clinical service. Patients with HCC are referred to CGMH Chiayi branch, a tertiary referral hospital, for treatment. This study enrolled 77 consecutive patients with newly diagnosed HCCs between 2017 and 2022, with a mean age of 65.7 ± 11.1 years. The screening group included HCC patients detected through health checkups, and those detected by routine clinical service served as the control group. Compared to the 24 patients in the control group, the 53 patients in the screening group had more cases with early stage cancer (Barcelona Clinic Liver Cancer or BCLC stage 0 + A 86.8% vs. 62.5%, p = 0.028), better liver reserve (albumin-bilirubin or ALBI grade I 77.3% vs. 50%, p = 0.031) and more prolonged survival (p = 0.036). The median survival rates of the 77 patients were >5 years, 3.3 years, and 0.5 years in the BCLC stages 0 + A, B, and C, respectively, which were above the expectations of the BCLC guideline 2022 for stages 0, A, and B. This study provides a model of HCC screening and referral to high-quality care in remote viral-hepatitis-endemic areas.

Non-B, Non-C Hepatocellular Carcinoma in an HBV- and HCV-Endemic Area: A Community-Based Prospective Longitudinal Study.

A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019−1.098, p = 0.003); male sex (2.446, 1.200−4.985, p = 0.014); high aspartate aminotransferase levels (6.816, 2.945−15.779, p < 0.001); fibrosis index based on four factor score (1.262, 1.154−1.381, p < 0.001); blood sugar (1.009, 1.002−1.015, p = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094−480.760, p < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074−0.625, p = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening.

Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information.

BACKGROUND/PURPOSE: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

Community-based screening by Anti-HCV reflex HCV Ag test and accessible post-screening care toward elimination of hepatitis C in two hyperendemic townships.

BACKGROUND: Hyperendemic townships of hepatitis C virus (HCV) infection should devote extra efforts to eliminate HCV. We aimed to evaluate efficacy of the screening and linkage to care in two HCV hyperendemic townships. METHODS: Village-to-village HCV screening using anti-HCV reflex HCV Ag test was conducted in two HCV hyperendemic rural townships (Lioujiao and Yijhu). All residents aged 30 years or older were invited. Those patients detected as infected were referred to nearby hospitals or clinics in Lioujiao and to an accessible outreach hepatology clinic in Yijhu. RESULTS: The populations of Lioujiao and Yijhu townships at time of survey were 18,389 and 14,787 with 6086 (33.1%) and 4604 (31.1%) having ever been previously screened, and 1517 and 1071 responded to this screening respectively. Their crude screening coverage rates were 41.5% and 38.5%, and adjusted screening coverage rates were 54.3% and 94.6% respectively. The prevalence rates of anti-HCV and HCV Ag were 17.9% and 11.9% in Lioujiao, and 9.2% and 5.6% in Yijhu respectively, with their rates of antigenemia (HCV Ag/anti-HCV) being 62.1% and 60.6% respectively. Numbers needed to test (NNT) to find a candidate for anti-viral treatment were 9 and 18. For linkage to care, treatment rate by referral (Lioujiao) was slightly lower than by accessible outreach hepatology clinic (Yijhu) (84.9% vs. 93.3%, p = 0.093). Overall successful sustained virological response rate at week 12 was 98.2% (161/164) in outreach hepatology clinic. CONCLUSION: Since NNT was low, it was worthwhile conducting intensive screening in these hyperendemic townships. For high treatment rate, accessible outreach hepatology clinic is feasible especially in areas without adequate medical resources.

Liver Disease Screening and Hepatitis C Virus Elimination in Taiwan Rural Indigenous Townships: Village-By-Village Screening and Linking to Outreach Hepatology Care.

Medical resources are limited for hepatitis C virus (HCV) elimination in rural indigenous areas of Taiwan. This study aimed to investigate liver disease risk and conduct a HCV elimination program in two rural indigenous townships. A program of village-by-village screening tests was conducted including hepatitis B virus surface antigen (HBsAg), antibody to HCV (anti-HCV) and gamma-glutamyl transferase (GGT), linking to outreach hepatology care at two indigenous townships (Laiyi and Mudan). Adult residents were invited to join this program. One hepatology specialist assessed liver disease risk, provided HCV treatment counselling and initiated direct acting antivirals (DAA) at an outreach hepatology clinic in primary health centers. A total of 3503 residents attended this program with a screening coverage of 73.5%. The prevalence of HBsAg, anti-HCV, and high GGT level was 8.2%, 10.0% and 19.5%, respectively. Laiyi had significantly higher prevalence of anti-HCV than Mudan. While males had significantly higher prevalence of HBsAg and high GGT in both townships, females in Laiyi had higher anti-HCV prevalence. HBsAg and high GGT prevalence peaked at 40-59 years of age and anti-HCV prevalence increased significantly with age. Two hundred and sixty-three residents visited the outreach hepatology clinic for HCV treatment evaluation, with 121 (46%) residents having active HCV, while 116 received DAA, with 111 (95.7%) achieving HCV elimination. For rural indigenous townships in southern Taiwan, HCV infection and alcohol consumption were two major liver disease risks. While HCV infection was predominant in old females, chronic hepatitis B virus infection and habitual alcohol consumptions predominated in middle-aged males. HCV elimination was achieved by the village-by-village screening model and linked to outreach hepatology care.

Community-Based Screening for Hepatitis B and C Infectivity Using Two Quantitative Antigens to Identify Endemic Townships.

Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection. This screening was conducted in Chiayi County from 2018-2019. All residents aged 30 years or older were invited to participate in quantitative HBsAg (qHBsAg) and HCV Ag screening. Among the 4010 participants (male:female = 1630:2380), the prevalence of qHBsAg and HCV Ag was 9.9% (396/4010) and 4.1% (163/4010), respectively. High-prevalence townships were identified, three for qHBsAg > 15% and two for HCV Ag > 10%. The age-specific prevalence of qHBsAg was distributed in an inverse U-shape with a peak (16.0%, 68/424) for subjects in their 40 s; for HCV, prevalence increased with age. Concentrations of qHBsAg < 200 IU/mL were found in 54% (214/396) of carriers. The rate of oral antiviral treatment for HCV was 75.5% (114/151), with subjects younger than 75 years tending to undergo treatment (85.6% vs. 57.4%, p < 0.001). QHBsAg and HCV Ag core antigens can reflect the concentration of the viral load, which serves as a feasible screening tool. Using quantitative antigen screening for hepatitis B and C in community-based screening, two hyperendemic townships were identified from an endemic county.

Village-to-village screening for hepatitis B and C using quantitative HBsAg and anti-HCV testing with reflex HCV core antigen tests in the remote communities of a resource-rich setting: a population-based prospective cohort study.

OBJECTIVES: Community-based screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for hepatitis elimination. This study attempted to increase screening accessibility and efficacy by using alternative tools. DESIGN: Population-based prospective cohort study. SETTING: Hepatitis elimination program at Yunlin County, Taiwan. PARTICIPANTS: All 4552 individuals participated in 60 screening sessions of a community-based HBV and HCV screening project in five rural townships with approximately 95 000 inhabitants in central-western Taiwan. INTERVENTIONS: To increase accessibility, 60 outreach screening sessions were conducted in 41 disseminative sites. Quantitative HBV surface antigen (qHBsAg) and anti-HCV testing with reflex HCV core antigen (HCV Ag) tests were employed as alternative screening tools. MAIN OUTCOME MEASURES: Calculate village-specific prevalence of HBsAg, anti-HCV and HCV Ag and establish patient allocation strategies according to levels of qHBsAg HCV Ag and alanine aminotransferase (ALT). RESULTS: Of 4552 participants, 553, 697 and 290 were positive for HBsAg, anti-HCV and HCV Ag, respectively; 75 of them had both HBsAg and anti-HCV positivity. The average (range) number of participants in each screening session was 98 (31-150). The prevalence rates (range) of HBsAg, anti-HCV and HCV Ag were 12.1% (4.3%-19.4%), 15.3% (2.6%-52.3%) and 6.4% (0%-30.2%), respectively. The HCV Ag positivity rate among anti-HCV-positive participants was 42% (0%-100%). Using cut-off values of >200 IU/mL for qHBsAg, >3 fmol/L for HCV Ag and >40 IU/mL for ALT as criteria for patient referral, we noted an 80.2% reduction in referral burden. Three villages had high anti-HCV prevalences of 52.3%, 53.8% and 63.4% with corresponding viraemic prevalences of 23.2%, 30.1% and 22% and thus constituted newly identified HCV-hyperendemic villages. CONCLUSION: Outreach hepatitis screening increases accessibility for residents in rural communities. Screening HBV and HCV through qHBsAg and HCV Ag tests provides information concerning viral activities, which might be conducive to precise patient allocation in remote communities.

Usefulness of quantitative hepatitis B surface antigen testing in hepatitis B community-based screening.

BACKGROUND/PURPOSE: Low viral load (LVL) of hepatitis B virus (HBV) is a predictor of chronic HBV infection. However, the usefulness of quantitative hepatitis B surface antigen (qHBsAg) in predicting LVL in community-based screening has not been well studied. We aimed to measure the prevalence of LVL in HBV carriers and validate the efficacy of qHBsAg in predicting LVL. METHODS: This community-based screening study was conducted in Taiwan. HBV DNA was assayed in HBsAg carriers. Participants were randomized to training and validation sets to determine the ability of qHBsAg to predict LVL. Receiver operating characteristic curves were used to identify the best cutoff values in the training set. RESULTS: Among the 2919 participants, 359 (12.2%) were HBsAg carriers. There were 132 and 137 carriers in the training and validation sets, respectively. Significant correlations were found between qHBsAg and HBV DNA in both training and validation sets. Thirty and 29 participants with qHBsAg <8 IU/mL in the training and validation sets, respectively, had LVL. Using 8 IU/mL as the cutoff, negative predictive value (NPV) of qHBsAg for HBV DNA levels >2000 IU/mL was 100%. The best cutoff level of qHBsAg to predict HBV LVL was 200 IU/mL, with a sensitivity, specificity, and accuracy of 75.0%, 76.1%, and 75.8%, respectively, in the training set. The positive predictive value and NPV were 70.0% and 77.9%, respectively, in the validation set. CONCLUSION: Approximately 60% of HBsAg carriers had HBV LVL, and qHBsAg <8 IU/mL accurately predicts LVL. This quantitative test provides additional information for community-based screening.

Feasibility of anti-HCV reflex HCV Ag screening strategy in an HCV endemic community.

BACKGROUND/PURPOSE: The HCV core antigen (HCV Ag) assay displays high sensitivity and strong correlation with HCV RNA. However, the feasibility of anti-HCV reflex HCV Ag screening in a community-wide setting is rarely discussed. METHODS: We performed a two-phase community-based hepatitis C screen in an HCV-prone area of central Taiwan. During the training phase, all participants were test for anti-HCV, HCV Ag and HCV RNA to validate sensitivity, specificity, and accuracy of HCV Ag. During the validation phase, an anti-HCV reflex HCV Ag screen was conducted based on the results of training phase. Outcomes of the study were presented as positive and negative predictive values (PPV and NPV). RESULTS: Of 935 training phase participants, the rate of positive anti-HCV and HCV Ag were 175 (18.7%) and 78 (8.3%), respectively. Test sensitivity, specificity, and accuracy of HCV Ag were 97.1%, 98.6%, and 97.8%, respectively. During validation phase, only anti-HCV-positive serum samples were tested for HCV Ag. Of 1932 participant, 285 (14.8%) were anti-HCV-positive. 133 (46.7%) of the 285 anti-HCV-positive samples were HCV Ag-positive. PPV and NPV were 98.4% and 99.3%, respectively. Across the entire participant sample, a significant linear correlation between HCV Ag and HCV RNA concentration was noted (r2 = 0.93, p-value<0.001) following log-log transformation. CONCLUSION: Anti-HCV reflex HCV Ag screening is a feasible strategy for aiding HCV-prone communities.

Secular Trends and Geographic Maps of Hepatitis C Virus Infection among 4 Million Blood Donors in Taiwan from 1999 to 2017.

The prevalence of hepatitis C virus (HCV) infection in Taiwan was approximately 4% a decade ago, much higher than the worldwide average. This study aimed to assess the HCV burden among 4 million voluntary blood donors after 2 decades of prevention and treatment policies. We retrieved screening results for anti-HCV and HCV RNA from the Database for Evaluating Voluntary Taiwanese Eligible Donors. First-time blood donors who donated blood after 1999 and repeat donors who donated blood more than once between 2013 and 2017 were included to estimate HCV prevalence and incidence, respectively. The Cox proportional hazards model was used to estimate hazard ratios. Geographic variation in HCV prevalence and incidence in 364 townships was also analyzed. The prevalence study included 3,656,598 first-time donors. The overall crude prevalence of anti-HCV decreased from 15.5 to 4.5 per 1,000 donors between 1999 and 2017. Younger birth cohorts had a significantly lower prevalence of anti-HCV. The majority of townships (64.3%) in Taiwan showed a significantly decreased prevalence. The incidence study included 1,393,014 repeat donors followed for 3,436,607 person-years. Ninety-eight donors seroconverted to HCV RNA positivity, resulting in an HCV incidence of 2.9 per 100,000 person-years. Donors living in townships where HCV RNA prevalence was greater than 2 per 1,000 had at least 2.5-fold greater risk of new HCV infection. Conclusion: HCV prevalence in Taiwanese first-time blood donors decreased by 71% in the last 2 decades. However, townships with higher HCV prevalence also showed higher HCV incidence and require more active intervention.

Using AST-platelet ratio index and fibrosis 4 index for detecting chronic hepatitis C in a large-scale community screening.

BACKGROUND: Aspartate transaminase-platelet ratio index (APRI) and fibrosis 4 (FIB-4) are two non-invasive indexes to predict liver fibrosis in liver disease. This study was to use APRI and FIB-4 to detect chronic virus hepatitis in community screenings. METHODS: From 2004 to 2013, a series of community-based health screenings for residents aged 40 and older were held in Tainan city. APRI and FIB-4 of each participant were calculated and their association further analyzed with hepatitis status. RESULTS: We enrolled 180359 participants including 18726 (10.4%) hepatitis B virus (HBV), 13428 (7.4%) hepatitis C virus (HCV), 1337 (0.7%) HBV plus HCV and 146868 (81.5%) Non-HBV Non-HCV. The prevalence of chronic HCV increased with the elevation of APRI cut-offs or FIB-4 cut-offs (13.9%, 28.1%, 38.8%, 45.2%, to 49.9% in APRI≥0.3, 0.5, 0.7, 0.9,1.1, p<0.001 for the linear trend; or 15.8%, 26.4%, 34.4% to 39.7% in FIB-4≥1.75, 2.75, 3.5, 4.25, p<0.001). At the township level, APRI≥ 0.7 and FIB-4≥ 3.5 were highly correlated with HCV infection (r = 0.95, p<0.001 in APRI and r = 0.809, p<0.001 in FIB-4) and hepatocellular carcinoma (HCC) development (r = 0.894, p<0.001 in APRI and r = 0.804, p<0.001 in FIB-4), but not correlated with HBV infection. CONCLUSIONS: Community screenings derived APRI or FIB-4 can identify patient subsets with increased of underlying HCV infection and risk of incident HCC.

Association between chronic viral hepatitis and metabolic syndrome in southern Taiwan: a large population-based study.

BACKGROUND: The impact of metabolic syndrome (MetS) on hepatitis is an interesting issue. AIM: To evaluate the association of MetS and chronic viral hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in southern Taiwan. METHODS: From 2004 to 2013, a series of community-based health screenings for residents aged 40 and older were held in Tainan city. MetS was defined according to the Joint Scientific Statement. Cut-offs of body-mass index measures of 24 kg/m2 and 27 kg/m2 were used to stratify lean, overweight and obese subjects. RESULTS: We enrolled 180 359 participants; the prevalence of MetS was 30.1%, which was significantly associated with advanced age and female sex. There were 18 726 (10.4%) HBV, 13 428 (7.4%) HCV, 1337 (0.7%) HBV plus HCV (B+C) and 146 868 (81.5%) non-HBV non-HCV participants (NBNC). Prevalence rates of MetS in subjects with HBV, HCV, B+C and NBNC were 25.2%, 31.5%, 28.9% and 30.7% respectively (P < 0.001). There were 18.8% lean body, 35.4% overweight and 45.8% obese participants among 54 361 MetS subjects. Lean MetS subjects were older, had more diabetes, and had higher metabolic component levels, but lower alanine transaminase and aspartate transaminase-platelet ratio index levels compared with obese MetS subjects. HCV infection was positively associated with MetS (P < 0.001). However, HBV infection was inversely associated with MetS only among lean subjects (P = 0.002), but not among the general population. CONCLUSIONS: This large population-based study indicated that HCV infection was positively associated with MetS. However, HBV infection was inversely associated with MetS only among lean subjects.