Seroepidemiology of Hepatitis B Virus Infection in Native and Immigrant Pregnant Women: A 20-Year Retrospective Study in Taiwan.

Universal immunoprophylaxis against hepatitis B virus (HBV) is regarded as a key element to prevent perinatal HBV infection. The aim of the present study was to investigate the changes in the hepatitis B surface antigen (HBsAg)- and hepatitis B envelope antigen (HBeAg)-positive rates in native and immigrant pregnant women, to realize the impact of immigrants, and to identify any weaknesses 30 years after the implementation of hepatitis B vaccination in Taiwan. A total of 20,020 test results of HBsAg and HBeAg in pregnant women-2,915 (14.6%) immigrant women and 17,105 native Taiwanese-from 1996 to 2015 were analyzed for changes during this 20-year retrospective cohort study. Native Taiwanese have a higher HBsAg-positive rate than immigrant women (P < 0.001). However, the HBsAg-positive rates decreased by 0.6% per year among native women, but did not decrease significantly (only by 0.18% per year) among immigrant women. The overall HBsAg-positive rate remained at high levels, 4.8% in the year 2015. The HBeAg-positive rate decreased significantly, by 0.22% per year, in the total women as well as by 0.23% per year in the native women (all P < 0.001); by contrast, the HBeAg-positive rate in immigrants decreased at a slower rate (0.10% per year), without a significant decreasing trend (P = 0.300). Higher HBeAg (+)/HBsAg (+) rate was found for the immigrants than for the native women (P < 0.001). To quickly and effectively lower the risk of vertical transmission, new approaches combined with vaccination may be needed in the post-immunization era.

Treatment and Cost of Hepatocellular Carcinoma: A Population-Based Cohort Study in Taiwan.

Hepatitis B virus vaccination and antiviral therapies reduce the risk of hepatocellular carcinoma (HCC). However, the lifetime healthcare expenditure involved in caring for HCC patients remains unclear. We examined the use and direct costs of healthcare services for a cohort of HCC patients to the healthcare system using Taiwan national health insurance program research database between 1997 and 2012. Total medical cost for all reimbursed patient encounters, including hospitalizations and outpatient care was cumulated from HCC onset to the end of follow-up or death. The mean follow-up time was 2.7 years (standard deviation, SD = 3.3) for the entire HCC cohort. Insurance payments of approximately US$92 million were made to 5522 HCC patients, with a mean cost of US$16,711 per patient (21,350). On average, the total cost per patient per month was US$2143 (5184); it was 50% higher for advanced cirrhosis patients at the baseline but 23% lower for mild-to-moderate cirrhotic patients. In the two-part regression, patients' underlying comorbid conditions, liver transplants, hepatectomy, and transarterial chemoembolization were associated with increased total cost, with liver transplants having the greatest impact over time. Hepatocellular carcinoma imposes substantial burden on the healthcare system. Real-world evidence on treatment and cost outcomes highlighted the needs to expand effective screening strategies and to optimize healthcare delivery to meet HCC patients' clinical needs.

Multiple bacterial infections increase the risk of hepatic encephalopathy in patients with cirrhosis.

OBJECTIVE: Patients with liver cirrhosis (LC) are at increased risk for bacterial infections. It is not fully understood how exposure to infections induces further development of hepatic encephalopathy (HE). This study estimated risks of infection associated with HE among patients with LC. METHODS: A nested case-control study of 14,428 adult patients with LC was performed using the population-based Longitudinal Health Insurance Database 2000 in Taiwan. Cases were cirrhotic patients who developed HE during follow-up. Controls were matched to each case by age at LC diagnosis (±2 years), sex, Charlson Comorbid index score, year of LC, and follow-up time with a 1:1 ratio. A multivariate logistic regression model was used to determine and compare the odds of developing HE based on exposure to various risk factors, including site of infection, cirrhosis-related complications, Helicobacter pylori eradication therapy, and peptic ulcer bleeding. Patient survival was evaluated using the time-dependent Cox regression model. RESULTS: Cirrhotic patients with HE (n = 714) and without HE (n = 714) were matched to compare risks. Infections and more frequent yearly infections were significantly associated with increased risk of HE. Independent predictors of HE included spontaneous bacterial peritonitis (aOR, 5.13; 95% CI, 3.03-8.69), sepsis (aOR, 2.54; 95% CI, 1.82--3.53), and biliary tract infection (aOR, 2.03; 95% CI, 1.2-3.46), controlling for confounders. CONCLUSION: Frequent infections are associated with increased risk of HE in cirrhotic patients. More frequent exposure to infection increases the risk of HE and mortality rates. Appropriate prevention of infection and the use of antibiotics for cirrhotic patients at risk for HE are needed.

Association between Helicobacter pylori eradication and the risk of coronary heart diseases.

The evidences on the association of Helicobacter pylori (H. pylori) to coronary heart diseases (CHD) are conflicting. In order to answer this important but yet unanswered clinical health issue, a large cohort study such as big data from the Taiwan National Health Insurance Research Database should be more convincing. Therefore, we aimed to make use of these big data source to analyze and clarify the relevance of H. pylori eradication and CHD risks. We looked through a total of 208196 patients with peptic ulcer diseases (PUD) from the years of 2000 to 2011. First, 3713 patients who received H. pylori eradication within 365 days of the index date were defined as the group A. We randomly selected the same number of patients as cohort A from 55249 non-eradication patients to be the comparison group B using propensity scores (including age, gender and comorbidity) so that we could control the confounding variables of CHD and mortality. Importantly, we perform sensitivity analysis for the time-dependent association between H. pylori eradication and risk of CHD, interactions between patient demographic characteristics and therapy by age (≥ or < 65 years old). The results showed that a trend of decreased association of CHD in patients with early eradication was observed compared to those without eradication (2.58% vs. 3.35%, p = 0.0905). The mortality rate was lower in early eradication subgroup compared to cohort B (2.86% vs. 4.43%, p = 0.0033). Interestingly, there was also significant difference observed in composite end-points for CHD and death in the early eradication subgroup (0.16% vs.0.57%, p = 0.0133). Further, the cumulative CHD rate was significantly lower in younger patients (< 65 years old) with H. pylori eradication therapy started < 1 year compared to those patients without eradication at all (p = 0.0384); the treatment did not appear to have an effect in older patients (≥ 65 years old) (p = 0.1963). Multivariate analysis showed that hypertension and renal diseases were risk factors for CHD in patients without eradication whilst younger age (< 65 years old) initiated with H. pylori therapy was a protective factor. In conclusion, the trend of decrease in CHD occurrence after early H. pylori eradication in addition to the significant decrease in composite end points for CHD and death, the significantly lower cumulative CHD rate in younger patients < 65 years old with H. pylori treated within 365 days suggested that there was positive association between H. pylori eradication and CHD.

Association between complicated liver cirrhosis and the risk of hepatocellular carcinoma in Taiwan.

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997-2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10-1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01-1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74-0.96, p = 0.009), and patients with alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65-2.26, p<0.001) had a statistically significant difference in the incidence of HCC. In conclusion, complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan compared with cirrhosis without complications.

Risk of Rebleeding and Mortality in Cirrhotic Patients with Peptic Ulcer Bleeding: A 12-Year Nationwide Cohort Study.

Although a few studies have investigated the risks of peptic ulcer bleeding (PUB) in cirrhotic patients, large population-based studies on in-hospital and long-term reports on recurrent PUB in a cohort of cirrhotic patients are lacking. This 12-year nationwide cohort study aimed to investigate the risks of in-hospital and long-term rebleeding and mortality in cirrhotic patients and to identify possible risk factors. Patient data from 1997 to 2008 were extracted from the National Health Insurance Research Database in Taiwan. A total of 15,575 patients who were discharged with a diagnosis of PUB were identified after strict exclusions (n = 2889). Among them, patients with cirrhosis (n = 737) and those with chronic hepatitis (n = 1044) were compared to propensity-score matched normal controls at a ratio of 1:1. Accumulated in-hospital and long-term follow-up PUB-free survival rates were analyzed in patients with cirrhosis, patients with chronic hepatitis, and matched controls. Cox proportional hazards regression was used to identify each independent risk factor. Compared with matched controls, patients with cirrhosis exhibited a 2.62-fold (95% CI: 1.74-3.92) higher risk of developing in-hospital rebleeding, but the risk of long-term rebleeding was comparable between cirrhotic patients and matched controls (hazard ratio: 1.29, 95% CI: 0.8-2.09). On the other hand, no significant difference was observed in in-hospital and long-term rebleeding between chronic hepatitis patients and matched controls. We compared the survival rates of cirrhotic and chronic hepatitis patients to that of matched controls. After propensity score matching, both cirrhotic and chronic hepatitis patients showed significantly lower survival than the matched controls (P < 0.0001 and 0.033, respectively) during the 12-year follow-up period. However, in-hospital and long-term rebleeding rates were not significantly different between chronic hepatitis patients and matched controls (P = 0.251 and 0.474, respectively). In conclusion, liver cirrhosis increased health care expenses in patients with PUB and these patients exhibited higher recurrent bleeding rate than non-cirrhotic patients during hospitalization. Cirrhosis and chronic hepatitis are independently associated with an increased long-term mortality when compared with patients without liver disease.

The Role of Adjuvant Acid Suppression on the Outcomes of Bleeding Esophageal Varices after Endoscopic Variceal Ligation.

The impact of adjuvant acid suppression via proton pump inhibitors or histamine-2 receptor antagonists after endoscopic variceal ligation remains uncertain. We therefore aimed to evaluate the effect of adjuvant acid suppression on the rebleeding and mortality rates in patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices. Data from 1997 to 2011 were extracted from the National Health Insurance Research Database in Taiwan. A total of 1576 cirrhotic patients aged > 18 years with a primary diagnosis of acute esophageal variceal bleeding who received endoscopic variceal ligation therapy were screened. After strict exclusion, 637 patients were recruited. The exclusion criteria included patients with gastric variceal bleeding, failure in the control of bleeding, mortality within 12 hours, and history of hepatocellular carcinoma or gastric cancer. Patients were divided into two groups: the vasoconstrictors group (n = 126) and vasoconstrictors plus acid suppression group (n = 511). We observed that the rebleeding and mortality rates were not significantly different between 2 groups during hospitalization and the 15-year follow-up period after discharge. A Charlson score ≥3 (odds ratio: 2.42, 95% confidence interval: 1.55 ~3.79, P = 0.0001), presence of hepatitis C virus (odds ratio: 1.70, 95% confidence interval: 1.15 ~2.52, P = 0.0085), and cirrhosis (odds ratio: 1.69, 95% confidence interval: 1.08 ~2.66, P = 0.0229) were the independent risk factors of mortality after discharge. In conclusion, the results of the current study suggest that adjuvant acid suppression prescription to patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices may not change the rebleeding and mortality outcomes compared to that for those who received endoscopic variceal ligation and vasoconstrictor agents without acid suppression.

The Association of Helicobacter pylori Eradication with the Occurrences of Chronic Kidney Diseases in Patients with Peptic Ulcer Diseases.

The association of Helicobacter pylori eradication with the occurrence of renal dysfunction in patients with peptic ulcer diseases is still unclear. This study aimed to clarify the relevance of H. pylori eradication to the occurrence of chronic kidney diseases in patients with peptic ulcer diseases. Data that were available from 2000-2011 were extracted from the National Health Insurance Research Database in Taiwan, and all patients with peptic ulcer diseases (n = 208 196) were screened for eligibility. We divided randomly selected patients into an H. pylori eradication cohort (cohort A, n = 3593) and matched them by age and sex to a without H. pylori eradication cohort (cohort B, n = 3593). Subgroup analysis was further performed for H. pylori eradication within ≤ 90 days of the diagnosis date (early eradication, n = 2837) and within 91-365 days (non-early eradication, n = 756). Cox proportional hazards regression analysis was used to estimate the association of H. pylori eradication with the risk of developing chronic kidney diseases and mortality. We observed that there were more patients suffering from chronic kidney disease in cohort B than in the early eradication subgroup of cohort A (8.49% vs. 6.70%, respectively, p = 0.0075); the mortality rate was also higher in cohort B (4.76% vs. 3.70%, respectively, p = 0.0376). Old age, pulmonary disease, connective tissue disorders, and diabetes were risk factors for chronic kidney diseases but early H. pylori eradication was a protective factor against chronic kidney diseases (hazard ratio: 0.68, 95% confidence interval: 0.52-0.88, p = 0.0030), and death (hazard ratio: 0.69, 95% confidence interval: 0.49-0.96, p = 0.0297). In conclusion, our findings have important implications suggesting that early H. pylori eradication is mandatory since it is associated with a protective role against the occurrence of chronic kidney diseases.

Risk factors influencing the outcome of peptic ulcer bleeding in chronic kidney disease after initial endoscopic hemostasis: A nationwide cohort study.

Patients with chronic kidney disease (CKD) who had peptic ulcer bleeding (PUB) may have more adverse outcomes. This population-based cohort study aimed to identify risk factors that may influence the outcomes of patients with CKD and PUB after initial endoscopic hemostasis. Data from 1997 to 2008 were extracted from the National Health Insurance Research Database in Taiwan. We included a cohort dataset of 1 million randomly selected individuals and a dataset of patients with CKD who were alive in 2008. A total of 18,646 patients with PUB were screened, and 1229 patients admitted for PUB after endoscopic hemostasis were recruited. The subjects were divided into non-CKD (n = 1045) and CKD groups (n = 184). We analyzed the risks of peptic ulcer rebleeding, sepsis events, and mortality among in-hospital patients, and after discharge. Results showed that the rebleeding rates associated with repeat endoscopic therapy (11.96% vs 6.32%, P = 0.0062), death rates (8.7%, vs 2.3%, P < 0.0001), hospitalization cost (US$ 5595±7200 vs US$2408 ±â€Š4703, P < 0.0001), and length of hospital stay (19.6 ±â€Š18.3 vs 11.2 ±â€Š13.1, P < 0.0001) in the CKD group were higher than those in the non-CKD group. The death rate in the CKD group was also higher than that in the non-CKD group after discharge. The independent risk factor for rebleeding during hospitalization was age (odds ratio [OR], 1.02; P = 0.0063), whereas risk factors for death were CKD (OR, 2.37; P = 0.0222), shock (OR, 2.99; P = 0.0098), and endotracheal intubation (OR, 5.31; P < 0.0001). The hazard ratio of rebleeding risk for aspirin users after discharge over a 10-year follow-up period was 0.68 (95% confidence interval [CI]: 0.45-0.95, P = 0.0223). On the other hand, old age (P < 0.0001), CKD (P = 0.0090), diabetes (P = 0.0470), and congestive heart failure (P = 0.0013) were the independent risk factors for death after discharge. In-hospital patients with CKD and PUB after endoscopic therapy had higher recurrent bleeding, infection, and mortality rates, and the need for second endoscopic therapy. Age was the independent risk factor for recurrent bleeding during hospitalization. After being discharged with a 10-year follow-up period, nonaspirin user was a significant factor for recurrent bleeding.

Hepatitis B virus infection among pregnant women in Taiwan: comparison between women born in Taiwan and other southeast countries.

BACKGROUND: Taiwan's national vaccination program has successfully decreased the prevalence of hepatitis B infection after twenty years of implementation and might be indirectly beneficial to the second generation. In this study, we compared the hepatitis B infection status of two groups: pregnant Taiwanese women and other Southeast Asian women, who because they had immigrated later in life to Taiwan by marriage to a Taiwanese man, had not been exposed to that vaccination program to evaluate the effect of hepatitis vaccination program on women of child-bearing age and further explored the potential impact of immigration on the hepatitis B public health policy in Taiwan. METHODS: Data was collected from 10,327 women born in Taiwan and 1,418 women born in other Southeast Asian countries, both groups receiving prenatal examinations at Fooyin University Hospital between 1996 and 2005. The results of serum hepatitis B s-Antigen (HBsAg) and hepatitis B e-Antigen (HBeAg) tests and other demographic data were obtained by medical chart review. RESULTS: The pregnant women from Taiwan had a higher HBsAg positive rate (15.5%) but lower HBeAg(+)/HBsAg(+) ratio (32.1%) than the women from other countries (8.9% and 52.4%). For those born before July, 1984, the period of no national vaccination program, Taiwanese women had a higher HBsAg positive rate than other Southeast Asian women (15.7% vs. 8.4%), but for women born after that day and before June 1986, the period of vaccination for high risk newborns, the HBsAg positive rates found to be slightly lower for Taiwanese women than for other Southeast Asian women (11.4% vs. 12.3%) and the difference was more significant (3.1% vs. 28.6%) after June 1986, the period of vaccination for all newborns. While the HBeAg(+)/HBsAg(+) ratios decreased with age in both groups, they were consistently higher in women from other Southeast Asian countries than in women born in Taiwan after age 20. CONCLUSION: In Taiwan, the neonatal vaccination program that was implemented in 1984 has successfully reduced hepatitis B infection among pregnant women in present day, and is likely to indirectly prevent hepatitis B infection in the next generation. However, the increasing number of pregnant women from other Southeast Asian countries without a national neonatal vaccination program or with a program that was introduced later than the one in Taiwan will likely lessen the positive impact of this program and should be further assessed.