The association between hepatic viral infections and cancers: a cross-sectional study in the Taiwan adult population.

BACKGROUND: Hepatitis B (HBV) and hepatitis C (HCV) viruses are diseases of global public health concern and are associated with liver cancer. Recent studies have revealed associations between hepatic viral infections and extrahepatic cancers. This study aimed to explore the associations between hepatitis B and C viruses and cancer at baseline in the Taiwan Biobank database while controlling for a wide range of confounding variables. METHODS: In a cross-sectional study of adults aged > 20 years, we compared the distribution of demographic factors, lifestyle, and comorbidities between viral and nonviral hepatic groups using the chi-square test. Univariate and multivariate logistic regressions were performed to observe the associations between hepatitis B and C viral infections and cancers by estimating the odds ratio (OR) and 95% confidence interval (CI). Multivariate regression analysis was adjusted for sociodemographic factors, lifestyle, and comorbidities. RESULTS: From the database, 2955 participants were identified as having HCV infection, 15,305 as having HBV infection, and 140,108 as the nonviral group. HBV infection was associated with an increased likelihood of liver cancer (adjusted OR (aOR) = 6.60, 95% CI = 3.21-13.57, P < 0.001) and ovarian cancer (aOR = 4.63, 95% CI = 1.98-10.83, P = 0.001). HCV infection was observed to increase the likelihood of liver cancer (aOR = 4.90, 95% CI = 1.37-17.53, P = 0.015), ovarian cancer (aOR = 8.50, 95% CI = 1.78-40.69, P = 0.007), and kidney cancer (aOR = 12.89, 95% CI = 2.41-69.01, P = 0.003). CONCLUSION: Our findings suggest that hepatic viral infections are associated with intra- and extrahepatic cancers. However, being cross-sectional, causal inferences cannot be made. A recall-by-genotype study is recommended to further investigate the causality of these associations.

Association of Cognitive Impairment With Chronic Viral Hepatitis Among Older Adults in Taiwan.

OBJECTIVE: To evaluate the risk of cognitive impairment among patients with chronic viral hepatitis. DESIGN: A cross-sectional study. SETTING: Population-based. PARTICIPANTS: Individuals 60 years or older were enrolled from the Taiwan Biobank database from 2012. EXPOSURE: Hepatitis B virus and hepatitis C virus infections. MEASUREMENT: Cognitive impairment was evaluated using the mini-mental state examination (MMSE). Logistic regression models were used to calculate odds ratios and 95% confidence intervals (CIs). The effects of APOE ε4 polymorphisms on the association between viral hepatitis and the risk of cognitive impairment were also investigated. RESULTS: We recruited 912 participants with cognitive impairment and 22 869 participants without cognitive impairment. The adjusted odds ratio (aOR) for cognitive impairment was 1.38 (95% CI: 1.03-1.85, p = 0.033) among participants with hepatitis C virus infection and 1.14 (95% CI: 0.91-1.43, p = 0.257) among participants with hepatitis B virus infection. Participants with hepatitis C virus infection and without hepatitis B virus infection had a higher risk of cognitive impairment (aOR: 1.52, 95% CI: 1.13-2.04, p = 0.006). The MMSE subcategories most associated with hepatitis C virus infection were orientation and design copying. The association between hepatitis C virus infection and cognitive impairment was higher among participants with ε4 alleles of the APOE gene than among those without alleles (aOR: 2.18, 95% CI: 1.21-3.91, p = 0.009). CONCLUSIONS: Our findings suggest that individuals 60 years or older with chronic hepatitis C virus infection are at increased risk of cognitive impairment.

Association of HLA-DPA1, HLA-DPB1, and HLA-DQB1 Alleles With the Long-Term and Booster Immune Responses of Young Adults Vaccinated Against the Hepatitis B Virus as Neonates.

The neonatal hepatitis B vaccination (HBVac) was implemented 35 years ago in Taiwan, but many vaccinees exhibit inadequate long-term vaccine-induced seroprotective hepatitis B surface antibody (anti-HBs) levels. We investigated the association of the human leukocyte antigen (HLA) alleles (DPA1, DPB1, DQA1, and DQB1) with the long-term immunological response to the neonatal HBVac and adolescent booster HBVac in a Taiwanese cohort. We divided 281 Han students (median age 22, age range 17-29 years) into the following groups: (1) Group A (n = 61): anti-HBs titer ≥ 10 mIU/mL at the beginning of the study; (2) Group B (n = 75): anti-HBs level > 1000 mIU/mL after the first booster; (3) Group C (n = 37): anti-HBs level < 10 mIU/mL after the first booster; and (4) Group D (n = 5): anti-HBs level < 10 mIU/mL after three boosters. DQA1, DQB1, DPA1, and DPB1 typing of the participants was performed using sequence-specific oligonucleotides. Associations of HLA alleles and haplotypes with effects on neonatal HBVac and booster HBVac were examined through logistic regression analysis and Fisher's exact test. A false discovery rate-based measure of significance, the q-value, was used for multiple comparisons, and an association was considered significant if the corresponding q-value was < 0.1. DPA1 alleles were associated with the long-term immunological response to the neonatal HBVac. The estimated odds ratio (OR) of the lack of HBV protective immunity when carrying an additional DPA1*01 and DPA1*02 was 0.36 [95% confidence interval (CI) = 0.17-0.76, p = 0.0076] and 2.39 (95% CI = 1.17-4.87, p = 0.016), respectively. DPB1 and DQB1 alleles were associated with a response to the adolescent booster vaccination. The estimated ORs of being nonresponsive to the first booster when carrying an additional DPB1*05 and DQB1*02 were 2.11 (95% CI = 1.13-3.93, p = 0.019) and 3.73 (95% CI = 1.43-9.71, p = 0.0070), respectively. All DPB1*03 carriers responded to the first booster (p of Fisher's exact test = 0.0045). In our study, we discovered that HLA-DPA1 was primarily associated with the long-term response of primary infantile HBVac, and HLA-DPB1 and HLA-DQB1 exhibited associations with the HBV booster vaccination.

Analysis of Different Types of Interferon-Associated Retinopathy in Patients with Chronic Hepatitis C Virus Infection Treated with Pegylated Interferon Plus Ribavirin.

This retrospective cohort study aims to investigate interferon (IFN)-associated retinopathy incidence in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon (PegIFN) plus ribavirin (RBV). We selected 1688 patients undergoing PegIFN/RBV therapy for HCV (HCV-treated cohort), 3376 patients not receiving HCV treatment (HCV-untreated cohort) and 16,880 controls without HCV (non-HCV cohort) from the Taiwan Longitudinal Health Insurance Database. The patients were frequency-matched by age, sex, and index date at a 1:2:10 ratio, and followed up until the end of 2013. Cox proportional hazard regression models were used to compare the incidences of any retinal vascular events, including subtypes, among the three cohorts. Compared with the non-HCV cohort, the HCV-treated cohort had a significantly increased risk of retinopathy (hazard ratio (HR) = 4.98, 95% confidence interval (CI): 2.02-12.3). The risk was particularly prominent for retinal hemorrhage (HR = 12.7, 95% CI: 3.78-42.9). When the HCV-untreated cohort was used as the reference, the aforementioned HRs increased to 9.02 (95% CI: 3.04-26.8) and 32.3 (95% CI: 3.94-265), respectively. This study suggested that PegIFN/RBV therapy significantly increased the risk of retinal hemorrhage but not retinal vascular occlusions in the HCV-treated cohort.

Increased Risk of Age-Related Macular Degeneration with Chronic Hepatitis C Virus Infection: A Nationwide Population-Based Propensity Score-Matched Cohort Study in Taiwan.

Studies evaluating the association between age-related macular degeneration (AMD) risk and HCV infection are scant. In this population-based cohort study, 13,300 patients newly diagnosed as having HCV (HCV cohort) and 26,600 propensity score-matched patients without HCV (non-HCV cohort) were identified from the Taiwan National Health Insurance Research Database between 2000 and 2013. Furthermore, 1,983 patients with HCV who received pegylated interferon and ribavirin treatment (HCV-treated cohort) and propensity score-matched patients with HCV (matched at a ratio of 1:2) who did not receive this treatment (HCV-untreated cohort) were selected from the HCV cohort. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the risk of AMD in the HCV and non-HCV cohorts. The adjusted HR (aHR) for AMD in the HCV cohort was 1.22 (95% CI = 1.09-1.35). This significant association was observed only for nonexudative AMD (aHR = 1.22, 95% CI = 1.09-1.37). Compared with the HCV-untreated cohort, the HCV-treated cohort showed no significant association with any type of AMD (aHR = 1.07, 95% CI = 0.81-1.43). Age and sex did not modify AMD development after the exposure and treatment of chronic HCV infection. Our findings revealed that patients with chronic HCV infection had an increased risk of AMD.

Chronic Hepatitis B Virus Infection Associated with Increased Colorectal Cancer Risk in Taiwanese Population.

Chronic hepatitis B virus (HBV) infections and colorectal cancer (CRC) are prevalent in Taiwan. We carried out a population-based case-control study to assess the association between HBV infection and CRC risk. Using the National Health Insurance Research Database of Taiwan, we identified 69,478 newly diagnosed patients with CRC from 2005 to 2011. We further randomly selected 69,478 age- and gender-matched controls without CRC from the same database. Odds ratios (ORs) were calculated to evaluate the association between chronic HBV infection and CRC using a logistic regression analysis. HBV infection was found to be associated with the risk of CRC (OR = 1.27, 95% confidence interval (CI) = 1.20-1.33). This relationship was similar in men and women. Age-specific analysis revealed that the CRC risk associated with HBV decreased with age. The adjusted ORs for patients aged <55, 55-64, and 65-74 years were 1.63 (95% CI = 1.48-1.79), 1.24 (95% CI = 1.13-1.37), and 1.02 (95% = 0.92-1.13), respectively. In conclusion, this study suggests that chronic HBV infection is significantly associated with an increased risk of CRC. Monitoring the risk of CRC development in young patients with HBV infection is crucial.

Patients With Chronic Hepatitis C Virus Infection Are at an Increased Risk of Colorectal Cancer: A Nationwide Population-Based Case-Control Study in Taiwan.

AIM: Studies evaluating colorectal cancer (CRC) risk associated with chronic hepatitis C virus (HCV) infection are limited. METHODS: In this case-control study, we identify 67,670 CRC cases newly diagnosed from 2005 to 2011 and randomly selected 67,670 controls without HCV and CRC from the same database, frequency matched by age and sex of cases. RESULTS: Results of logistic regression analysis revealed that the adjusted odds ratio (aOR) of CRC was 1.16 (95% confidence interval [CI] = 1.08-1.24, p < 0.001) in association with chronic HCV. The CRC risk was slightly greater for women than for men. The risk decreased with age, with the aOR decreased from 2.26 (95% CI = 1.32-3.87, p = 0.003) in patients under 45 years old to 1.31 (95% CI = 1.10-1.55, p = 0.03) in patients aged 50-59, and 1.10 (95% CI = 1.00-1.22, p = 0.061) in patients aged over 70. CONCLUSIONS: Our findings suggested that patients with chronic HCV infection are at an elevated risk of developing CRC. Our data also imply that the CRC prevention programs are needed to target younger HCV patients.

Association of chronic hepatitis B virus infection with age-related macular degeneration.

PURPOSE: To study the association between chronic hepatitis B virus (HBV) and age-related macular degeneration (AMD). METHODS: Data used in this retrospective, frequency-matched cohort study were acquired from the Longitudinal Health Insurance Database 2000, which includes medical claims and registration files for 1 000 000 enrolees in the Taiwan National Health Insurance programme. The HBV cohort contained 17 796 patients who received a diagnosis of chronic HBV infection between January 1, 2000 and December 31, 2012. The non-HBV cohort contained 71 184 participants who were frequency-matched by age, sex and year of index date for comparison. Participants were followed until the end of 2013, and those who developed AMD during the study period were identified. A Cox proportional hazards regression model was used to compare the risk of AMD between cohorts. RESULTS: The incidence of any type of AMD in all participants was 3.88 per 1000 person-years (PY; 2.27 per 1000 PY in the HBV cohort; 1.61 per 1000 PY in the non-HBV cohort). Compared with the non-HBV cohort, the adjusted hazard ratio (HR) for any type of AMD in the HBV cohort was 1.41 [95% confidence interval (CI) 1.23-1.63; p < 0.001]. This significant positive association was stronger among patients who exhibited disease progression from nonexudative to exudative AMD (adjusted HR = 1.74, 95% CI: 1.01-2.99). CONCLUSION: Our results suggest that patients with chronic HBV infection in Taiwan have a significantly elevated risk of developing any type of AMD and that HBV infection may accelerate the progression of AMD.

Aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer: A population-based analysis.

As reported by the Taiwan Cancer Registry in 2013 squamous cell carcinoma of head and neck cancer (HNSCC) was the sixth most frequently diagnosed cancer and the 5th most common cause of cancer related death and its incidence and mortality rate is still rising. The co-occurrence of HNSCC and secondary primary cancer (SPC) and the chemopreventive effect of aspirin on certain malignancies had been reported. Therefore we conducted this national study to investigate the use of aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer in Taiwan. We searched the Registry for Catastrophic Illness in the National Health Insurance Research Database (NHIRD) for 18,234 patients (3,576 aspirin users and 14,667 non-aspirin users) diagnosed with HNSCC during 2000-2005. The SPC incidence density during follow-up in 2000-2011 was compared between the groups. For HNSCC patients, aspirin use after diagnosis was significantly associated with SPC risk reduction by 25% (adjusted HR, 0.75; 95% CI, 0.63-0.89; p = 0.001) after multivariate analysis. In the subgroup analysis, we found that esophageal cancer and stomach cancer incidence were significantly reduced after aspirin use (adjusted HR, 0.60; 95% CI, 0.41-0.90; p = 0.01 for esophageal cancer; adjusted HR, 0.27; 95% CI, 0.08-0.87; p = 0.03 for stomach cancer). Aspirin use for 1-3 years was associated with SPC risk reduction by 35% (adjusted HR, 0.65; 95% CI, 0.49-0.87; p = 0.003). SPC risk reduction extended continuously for more than 3 years of follow up (adjusted HR, 0.72; 95% CI, 0.53-0.98; p = 0.030). Our data shows aspirin use was associated with reduced SPC incidence for HNSCC patients, attributed mainly to reduced risk of esophageal and stomach cancer.

Women with adenomyosis are at higher risks of endometrial and thyroid cancers: A population-based historical cohort study.

OBJECTIVE: Both adenomyosis and endometriosis are characterized by the presence of ectopic endometrial glands and stroma and have been suggested to share some characteristics with malignant tumors. Although accumulating evidence indicates that endometriosis is associated with some cancer types, the cancer risks in patients with adenomyosis have been rarely examined. In this study, we investigated the relationship between adenomyosis and risks of common cancers. METHODS: This study included a cohort of 12,447 women with adenomyosis but not endometriosis, born in 1951-1984, and a cohort of 124,470 adenomyosis-free women matched by birth year. Their medical records (collected between 1996 and 2011) were obtained from the National Health Insurance Research Database of Taiwan. We first compared the distribution of cancer-free survival (CFS) between cohorts with and without adenomyosis. Subsequently, within the adenomyosis cohort, we examined whether time-to-onset of the identified cancer type was correlated with time-to-onset of adenomyosis. The Cox proportional hazards model was used to compare the distribution of CFS between the adenomyosis and adenomyosis-free cohorts and between the early- and late-diagnosed adenomyosis groups. For comparison, we further evaluated the cancer risks for a cohort of 10,962 women with endometriosis but not adenomyosis and a birth-year matched cohort of 109,620 endometriosis-free women. RESULTS: Compared with adenomyosis-free women, patients with adenomyosis had higher risks of endometrial and thyroid cancers, with estimated hazard ratios (HRs) (95% confidence interval) of 2.19 (1.51-3.16) and 1.70 (1.29-2.24), respectively. For both cancers, distributions of CFS were not significantly different between the early- and late-diagnosed adenomyosis groups. Furthermore, compared with endometriosis-free women, patients with endometriosis had higher risks of endometrial and ovarian cancers, with HRs of 1.89 (1.07-3.35) and 2.01 (1.27-3.16), respectively. CONCLUSIONS: Women with adenomyosis are at higher risks of endometrial and thyroid cancers, while women with endometriosis are at higher risks of endometrial and ovarian cancers.

Seroprevalence of hepatitis B virus in Taiwan 30 years after the commencement of the national vaccination program.

BACKGROUND: In this study, the long-term efficacy of hepatitis B virus (HBV) vaccination was assessed using seroprevalence and an age-period-cohort (APC) model of HBV seromarkers among university entrants 30 years after the introduction of the national neonatal HBV vaccination program in Taiwan. METHODS: In total, data of 17,611 university entrants who underwent university entrance health examinations between 2005 and 2016 were included. The seroprevalence of the HBV surface antigen (HBsAg) and the levels of the antibody against the HBV surface antigen (anti-HBs) in each year group and sex were calculated. The levels of the antibody against the HBV core antigen were examined only for 2012 and 2016. The APC model was used to analyze the HBV carrier rates. RESULTS: The chronic HBV infection (HBsAg positivity) rate decreased from 9.7% in university students born before June 1974 to <1.0% in students born after 1992. The prevalence of anti-HBs positivity declined, particularly between the 1984-1988 cohort (78.2%-53.2%) and the 1990-1994 cohort (60.6%-44.4%). Our APC model revealed that the chronic HBV carrier rate among the student population was affected significantly by age, period, and cohort (P < 0.001). CONCLUSIONS: HBV vaccination is one of the most effective strategies for preventing HBV infection. However, for complete eradication of HBV infection, the development of strategies that detect vaccination failure more effectively than current strategies do and early implementation of appropriate treatments are both necessary.

Kidney Cancer Linked to Chronic Hepatitis in the Asia-Pacific: A Population-Based Analysis.

BACKGROUND: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis. RESULTS: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55≤ age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55 years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64 years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer compared with their counterparts. CONCLUSIONS: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men.

Correction: Chronic Hepatitis C Virus Infection Is Associated with the Development of Rheumatoid Arthritis: A Nationwide Population-Based Study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0113579.].

Chronic hepatitis infection is associated with extrahepatic cancer development: a nationwide population-based study in Taiwan.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major causes of chronic hepatitis infection (CHI). This longitudinal cohort study investigated the association of CHI with hepatic and extrahepatic cancer development in Taiwan. METHODS: Patients with HBV infection and HCV infection were identified from the Taiwan National Health Insurance Research Database. A Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for determining the association between CHI and cancer development. RESULTS: The patients with HBV infection exhibited an increased risk of colorectal cancer (HR: 1.36, 95 % CI: 1.09-1.70), liver cancer (HR: 21.47, 95 % CI: 18.0-25.6), gallbladder and extrahepatic bile duct cancer (HR: 2.05, 95 % CI: 1.07-3.91), pancreatic cancer (HR: 2.61, 95 % CI: 1.47-4.61), kidney cancer (HR: 1.72, 95 % CI: 1.10-2.68), ovarian cancer (HR: 2.31, 95 % CI: 1.21-4.39), and non-Hodgkin's lymphoma (HR: 2.10, 95 % CI: 1.25-3.52). The patients with HCV infection exhibited an increased risk of liver cancer (HR: 25.10, 95 % CI: 20.9-30.2), gallbladder and extrahepatic bile duct cancer (HR: 2.60, 95 % CI: 1.42-4.73), ovarian cancer (HR: 5.15, 95 % CI: 1.98-13.4), and non-Hodgkin's lymphoma (HR: 2.30, 95 % CI: 1.34-3.96). CONCLUSION: The present population-based study revealed that in addition to its association with primary liver cancer, CHI is associated with an increased risk of extrahepatic cancer.

Correction: Association of Sjögren's Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0161958.].

Association of Sjögrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis.

OBJECTIVE: The association between Sjögren's syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections. MATERIALS AND METHODS: We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and ≥55 years) risks of SS were evaluated. RESULTS: The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16-2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98-1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62-4.35; ≥55 years: OR = 2.20, 95% CI = 1.84-2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94-2.63; men: OR = 4.22, 95% CI = 2.90-6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21-2.14). CONCLUSION: HCV infection was associated with SS; however, HBV only associated with SS in men.

Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis.

BACKGROUND: This study evaluated hospitalization and mortality in patients with chronic hepatitis B virus infection (HBV (+)) and matched comparison patients after stratifying the patients according to annual influenza vaccination (Vaccine (+)). METHODS: Data from Taiwan's National Health Insurance program from 2000 to 2009 were used to identify HBV(+)/vaccine(+) (n=4434), HBV(+)/Vaccine(-) (n=3646), HBV(-)/Vaccine(+) (n=8868), and HBV(-)/Vaccine(-) (n=8868) cohorts. The risk of pneumonia/influenza, respiratory failure, intensive care, hospitalization, and mortality in the four cohorts was evaluated. RESULTS: The total hospitalization rate was significantly lower in patients with chronic HBV infection who received an annual influenza vaccination than in chronic HBV-infected patients who did not receive an influenza vaccination (16.29 vs. 24.02 per 100 person-years), contributing to an adjusted hazard ratio (HR) of 0.56 (95% confidence interval (CI)=0.50-0.62). The HBV(+)/Vaccine(+) cohort also had lower risks than the HBV(+)/Vaccine(-) cohort for pneumonia and influenza (adjusted HR=0.79, 95% CI=0.67-0.92), intensive care unit admission (adjusted HR=0.33, 95% CI=0.25-0.43), and mortality (adjusted HR=0.19, 95% CI=0.15-0.24). CONCLUSIONS: Our results suggest that annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.

Hepatitis B virus infection and the risk of male infertility: a population-based analysis.

OBJECTIVE: To evaluate the risk of male infertility among patients with hepatitis B virus (HBV) infection. DESIGN: A nationwide, population-based cohort study. SETTING: Not applicable. PATIENT(S): Men infected with HBV (n = 5,138) and men without HBV infection (n = 25,690). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Male infertility, as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULT(S): The incidence of infertility was 1.59 times higher in patients with HBV infection than in those without HBV infection (2.21 vs. 1.39 per 1,000 person-years). The risk of developing infertility remained significant among patients with HBV infection (hazard ratio 1.52, 95% confidence interval 1.20-1.92) after adjusting for covariates in a multivariate Cox proportional hazards model. CONCLUSION(S): The data show an increased incidence and risk of infertility among men with HBV infection compared with men without HBV.

Chronic hepatitis C virus infection is associated with the development of rheumatoid arthritis: a nationwide population-based study in taiwan.

OBJECTIVE: The association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus. MATERIALS AND METHODS: We used data extracted from the claims of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance program. Among the 49,892 persons identified in 2000-2010 with chronic hepatitis virus infection, 35,652 had chronic HBV infection alone, 10,253 had chronic HCV infection alone, and 3,987 had chronic HBV/HCV dual infections. The comparison cohort comprised 199,568 persons matched on sex, age and calendar year without chronic hepatitis virus infection. All study participants were free of RA at baseline and traced through 2011 with new RA cases identified. RESULTS: After adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR)  = 2.03, 95% confidence interval (CI)  = 1.27-3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI  = 1.15-3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA. CONCLUSION: Our data imply that chronic HCV infection is associated with RA development.

Efficacy of hepatitis B vaccine boosters among neonatally vaccinated university freshmen in Taiwan.

BACKGROUND & AIMS: Long-term protection against hepatitis B virus (HBV) after vaccination remains widely debated. We evaluated the efficacy of a modified 3-dose booster protocol in neonatally vaccinated university students in Taiwan. METHODS: Changes in the levels of antibodies to the hepatitis B surface antigen (anti-HBs) were examined in 250 university students over a 3-year period. Group A (n=39) lacked seroprotective levels of anti-HBs, and declined to receive a booster dose of the HBV vaccine. Group B (n=128) lacked seroprotective levels of anti-HBs, and received booster doses of the HBV vaccine according to a modified 3-dose booster protocol. Group C (n=83) possessed seroprotective levels of anti-HBs, and did not receive a booster dose. RESULTS: The levels of seroprotective anti-HBs increased in 12.8% of Group A and 14.5% of Group C, suggesting that our entire cohort had experienced booster effects from natural HBV exposure. However, no new HBV infections were observed, and 53.9% of Group B maintained protective levels of anti-HBs during the follow-up period. CONCLUSIONS: The use of the modified 3-dose booster protocol induced significant long-term increases in the titer of anti-HBs in over 50% of the neonatally vaccinated participants with previously non-protective titers. However, in the absence of a vaccine booster, some neonatally vaccinated people with low anti-HBs titers may nonetheless produce anamnestic responses to HBV upon exposure, suggesting that protection from neonatal vaccination may persist, despite low titers of anti-HBs.