Effect of hypoalbuminemia on mortality in cirrhotic patients with spontaneous bacterial peritonitis.

Objectives: The impact of hypoalbuminemia on the short-term and long-term mortality of cirrhotic patients with spontaneous bacterial peritonitis (SBP), both with and without renal function impairment, remains insufficiently elucidated based on population-based data. Materials and Methods: We retrieved data from Taiwan's National Health Insurance Database encompassing 14,583 hospitalized patients diagnosed with both cirrhosis and SBP during the period from January 1, 2010, to December 31, 2013. Prognostic factors influencing 30-day and 3-year survival were computed. Furthermore, the impact of hypoalbuminemia on the mortality rate among SBP patients, with or without concurrent renal function impairment, was also assessed. Results: The 30-day mortality rates for patients with SBP, comparing those with hypoalbuminemia and those without, were 18.3% and 29.4%, respectively (P < 0.001). Similarly, the 3-year mortality rates for SBP patients with hypoalbuminemia and those without were 73.7% and 85.8%, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for patients' gender, age, and comorbid conditions, substantiated that individuals with hypoalbuminemia exhibit an inferior 30-day survival (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.51-1.74, P < 0.001) and reduced 3-year survival (HR: 1.57, 95% CI: 1.50-1.63, P < 0.001) in comparison to those lacking hypoalbuminemia. Among SBP patients with renal function impairment, those presenting hypoalbuminemia also experienced diminished 30-day survival (HR: 1.81, 95% CI 1.57-2.07, P < 0.001) as well as reduced 3-year survival (HR: 1.70, 95% CI 1.54-1.87, P < 0.001). Likewise, in SBP patients without renal function impairment, the presence of hypoalbuminemia was associated with poorer 30-day survival (HR: 1.54, 95% CI 1.42-1.67, P < 0.001) and 3-year survival (HR: 1.53, 95% CI 1.46-1.60, P < 0.001). Conclusion: Among cirrhotic patients with SBP, the presence of hypoalbuminemia predicts inferior short-term and long-term outcomes, regardless of renal function.

Update in diagnosis and management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a lack of structural or biochemical abnormalities. The current diagnosis of IBS is based on the Rome IV criteria, and it is recommended to approach IBS patients using a multidimensional clinical profile (MDCP). The pathophysiology of IBS is multifactorial and involves motility disorders, genetic factors, immune responses, visceral hypersensitivity, brain-gut dysregulation, and altered intestinal microbiota. The management of IBS includes both nonpharmacologic and pharmacologic therapies. Nonpharmacologic therapy options include physical activity, low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet, as well as cognitive behavioral therapy. Pharmacologic therapy options include probiotics, antidepressants, antispasmodics, and new agents. In clinical practice, a multidisciplinary strategy, including nonpharmacologic or/and pharmacologic treatment for IBS, is emphasized. Therefore, clinicians should carefully consider the underlying pathophysiology before selecting an appropriate therapeutic option for the treatment of IBS. In other words, individualized treatment plans are necessary for managing IBS.

Prognostic factors of cirrhotic patients with invasive fungal infections.

Fungal infection (FI) is a life-threatening condition in cirrhotic patients. However, a population-based study is required to determine the short-term mortality of these patients. The Taiwan National Health Insurance Database was used to enroll 1214 cirrhotic patients with FIs who were hospitalized between January 1, 2010 and December 31, 2013. Among them, 165 were diagnosed with invasive FIs. The overall 30-day and 90-day mortality rates for patients with invasive FIs were 25.7% and 49.9%, respectively (P < .001). After adjusting for sex, age, and other comorbidities, the following 90-day mortality prognostic factors were statistically different: renal function impairment (hazard ratio = 1.98, 95% confidence interval = 1.05-3.70, P = .034), concurrent with bacterial infections (hazard ratio = 1.75, 95% CI = 1.07-2.88, P = .027). Half of the cirrhotic patients died within 90-daysdue to invasive FIs, highlighting the importance of renal function impairment and concurrent with bacterial infections as an important prognostic factor.

The role of hepatic reserve in the mortality of cirrhotic patients with small hepatocellular carcinoma receiving radiofrequency ablation.

Although radiofrequency ablation (RFA) is considered a curative treatment for early stage small hepatocellular carcinoma (HCC), the long-term prognosis is suboptimal. The major complications in cirrhotic patients are usually related to poor prognosis and include esophageal variceal bleeding, ascites, and hepatic encephalopathy. This study aimed to evaluate the role of liver reserve on mortality after RFA for early stage HCC among cirrhotic patients, according to the presence of the number of complications. The Taiwan National Health Insurance Database was used to identify 2389 cirrhotic patients with treatment-naïve HCC (<3 cm) undergoing RFA hospitalized between January 1, 2010 and December 31, 2013. Of these, 594 patients had concurrent or a history of cirrhotic-related complications. The 1-year and 3-year survival rates in the cirrhotic patients with complications were 78.5% and 39.8%, respectively, and those in the patients without complications were 92.7% and 65.9% (P < .001), respectively. Age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.02-1.04, P < .001) and cirrhotic-related complications (HR 2.65, 95% CI 2.22-3.16, P < .001) significantly increased 3-year mortality. The HR of mortality in patients with 1, 2, or 3 complications compared to those without complications were 2.35 (95% CI 1.92-2.88), 3.27 (95% CI 2.48-4.30), and 4.63 (95% CI 2.82-7.62), respectively (all P < .001). In cirrhotic patients with early stage HCC undergoing RFA, poor liver reserve correlates with poor outcome. The presence or history of three cirrhotic-related complications increased 3-year mortality 4-fold.

Prognosis of hypoglycemia episode in cirrhotic patients during hospitalization.

BACKGROUND: Studies have shown that hyperglycemia in cirrhotic patients increases mortality. However, no population-based study has evaluated the influence of hypoglycemia upon hospital admission on death in these patients. The aim of this study was to assess the effect of hypoglycemia at admission on the mortality of patients with liver cirrhosis. METHODS: The Taiwan National Health Insurance Database was searched, and 636 cirrhotic patients without baseline diabetes mellitus who presented with hypoglycemia upon hospitalized from 2010 to 2013 were included in the study. A one-to-four propensity score matching was performed to select a comparison group based on age, sex and comorbidities. RESULTS: The overall 30-day mortality rate was 30.2% in the hypoglycemia group and 7.4% in the non-hypoglycemia group (P < 0.001). After Cox regression modeling adjusting for age, sex and comorbid disorders, cirrhotic patients with hypoglycemia had a hazard ratio (HR) of 30-day mortality of 4.96 (95% confidence interval [CI] 4.05-6.08, P < 0.001) as compared to the non-hypoglycemia group. In subgroup analysis, the cirrhotic patients with hypoglycemia and hepatocellular carcinoma (HCC) had a 30-day mortality HR of 6.11 (95% confidence interval [CI] 4.40-8.49, P < 0.001) compared to those with neither hypoglycemia nor HCC. CONCLUSIONS: Hypoglycemia is a very important prognostic factor in the 30-day mortality of cirrhotic patients, especially in those with underlying HCC.

Effects of poor hepatic reserve in cirrhotic patients with bacterial infections: A population-based study.

OBJECTIVE: Ascites, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, and esophageal variceal bleeding are major complications associated with cirrhosis. The presence of these complications indicates poor hepatic reserve. This study aimed to identify the effects of poor hepatic reserve on mortality in cirrhotic patients with bacterial infections. PATIENTS AND METHODS: The Taiwan National Health Insurance Database was used to identify 43,042 cirrhotic patients with bacterial infections hospitalized between January 1, 2010, and December 31, 2013, after propensity score matching analysis. Of these, 21,521 cirrhotic patients had major cirrhotic-related complications and were considered to have poor hepatic reserve. RESULTS: Mortality rates at 30 and 90 days were 24.2% and 39.5% in the poor hepatic reserve group and 12.8% and 21.7% in the good hepatic reserve group, respectively (P < 0.001 for each group). The cirrhotic patients with poor hepatic reserve (hazard ratio [HR], 2.10; 95% confidence interval [CI] = 2.03-2.18; P < 0.001) had significantly increased mortality at 90 days. The mortality HRs in patients with one, two, and three or more complications compared to patients without complications were 1.92 (95% CI = 1.85-1.99, P < 0.001), 2.61 (95% CI = 2.47-2.77, P < 0.001), and 3.81 (95% CI = 3.18-4.57, P < 0.001), respectively. CONCLUSION: In cirrhotic patients with bacterial infections, poor hepatic reserve is associated with a poor prognosis. The presence of three or more cirrhotic-related complications increases mortality almost four folds.

Endoscopic papillary balloon dilation decreases the risk of bleeding in cirrhotic patients compared with endoscopic biliary sphincterotomy: A national population-based study.

Although endoscopic papillary balloon dilation (EPBD) seems to cause fewer instances of bleeding, there are insufficient data to determine the optimal methods for decreasing the risk of bleeding in cirrhotic patients.In this study, we compared the bleeding risks following endoscopic biliary sphincterotomy (EST) vs EPBD in cirrhotic patients and identified clinical factors associated with bleeding and 30-day mortality.Taiwan's National Health Insurance Database was used to identify 3201 cirrhotic patients who underwent EST or EPBD between January 1, 2010, and December 31, 2013.We enrolled 2620 patients receiving EST and 581 patients receiving EPBD. The mean age was 63.1 ±â€Š13.9 years, and 70.4% (2252/3201) were men. The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding was higher among patients treated with EST than those treated with EPBD (EST vs EPBD: 3.5% vs 1.9%). Independent predisposing factors for bleeding included EST, renal function impairment, and antiplatelet or anticoagulant therapy. The overall 30-day mortality was 4.0% (127/3201). Older age, renal function impairment, hepatic encephalopathy, bleeding esophageal varices, ascites, hepatocellular carcinoma, biliary malignancy, and pancreatic malignancy were associated with higher risks for 30-day mortality.To decrease post-ERCP hemorrhage, EPBD is the preferred method in patients with cirrhosis, especially for those who have renal function impairment or are receiving antiplatelet or anticoagulant therapy.

Effect of proton pump inhibitors on mortality of cirrhotic patients with pneumonia.

OBJECTIVE: Pneumonia is life-threatening in patients with liver cirrhosis. Proton pump inhibitors (PPIs) may increase the risk of these patients developing pneumonia. However, whether PPIs increase mortality in patients with cirrhosis and pneumonia remain unknown. METHODS: We used the Taiwan National Health Insurance Database to enroll 1,201 cirrhotic patients with pneumonia without active gastrointestinal bleeding who were receiving PPIs and were hospitalized between January 1, 2010 and December 31, 2013. A one-to-three propensity score match was performed to select a comparison group based on age, gender, and comorbid disorders. RESULTS: The overall 30-day and 90-day all-cause mortality rates were 13.7% and 26.9% in the PPI group, and 14.3% and 25.1% in the non-PPI group, respectively. After Cox regression model adjusting for age, gender, and comorbid disorders, the hazard ratios of the effect of PPIs on 30-day and 30 to 90-day mortality were 0.94 (95% Confidence Interval [CI], 0.79-1.12, P = 0.468) and 1.26 (95% CI, 1.05-1.52; P = 0.013), respectively. CONCLUSIONS: PPIs were not associated with 30-day mortality among cirrhotic patients with pneumonia but not active gastrointestinal bleeding. However, prolonged PPI therapy may be associated with higher mortality.

Statin use in cirrhotic patients with infectious diseases: A population-based study.

BACKGROUND: Recent studies have shown benefits of statins in patients with liver cirrhosis. However, it is still unknown if statins have a beneficial effect on the mortality of cirrhotic patients with bacterial infections. METHODS: The Taiwan National Health Insurance Database was searched, and 816 cirrhotic patients receiving statins with bacterial infections hospitalized between January 1, 2010 and December 31, 2013 were included in the study. A one-to-four propensity score matching was performed to select a comparison group based on age, sex, and comorbid disorders. RESULTS: The overall 30-day mortalities in statin and non-statin group were 5.3% and 9.8%, respectively (P = 0.001). After Cox regression modeling adjusting for age, sex, and comorbid disorders, the hazard ratio (HR) of statin use on 30-day mortality was 0.52 (95% confidence interval [CI]: 0.38-0.72, P<0.001). In subgroup analysis, the 30-day mortality effect of statin use was more pronounced in patients with pneumonia (HR = 0.34; 95% CI: 0.19-0.59; P<0.001) and bacteremia (HR = 0.55; 95% CI: 0.35-0.85; P = 0.008). Atovastatin (HR = 0.59; 95% CI: 0.37-0.93) and rosuvastatin (HR = 0.59; 95% CI: 0.36-0.98) were associated with a decreased 30-day mortality risk compared to patients not taking statins. CONCLUSIONS: Statin use decreases the 30-day mortality of cirrhotic patients with bacteremia and pneumonia.

Population-based study of Entecavir and long-term mortality in chronic hepatitis B-related decompensated liver cirrhosis.

BACKGROUND AND AIMS: We lack population-based studies that identify the role of entecavir (ETV) in extending long-term survival in chronic hepatitis B (CHB)-related decompensated liver cirrhotic patients. Since 2010, National Health Insurance in Taiwan has covered long-term medical payment for antiviral therapy in CHB-related cirrhotic patients whose HBV DNA is ≥ 2000 IU/mL. We studied the effect of ETV on the mortality of CHB-related decompensated cirrhosis patients compared with patients who did not receive antiviral agents at baseline. METHODS: From the Taiwan National Health Insurance Database, we collected 758 CHB-related decompensated cirrhosis patients with elevated viral loads (HBV DNA ≥ 2000 IU/mL) using ETV and discharged between January 1, 2010, and December 31, 2013. The comparison group consisted of 1516 selected CHB-related decompensated cirrhotic patients without antiviral therapy at baseline using propensity score matching analysis. RESULTS: The 1-, 2-, and 3-year mortality probabilities were 34.7%, 42.5%, and 48.5 % in the ETV group and 21.1%, 37.8% and 51.3 % in the non-ETV group, respectively. Based on a Cox proportional hazards regression model adjusted by patients' sex, age, and comorbid disorders, the hazard ratios (HR) in the ETV group for 1-year, 1-2-year, and 2-3-year mortalities were 1.22 (95% confidence interval [CI] 1.05-1.43, P = .010), 1.02 (0.86-1.20, P = .866), and 0.59 (0.38-0.90, P = .016), compared with the non-ETV group. CONCLUSIONS: Even in CHB-related decompensated cirrhotic patients, higher initial viral loads were correlated with poor outcomes. However, the long-term usage of ETV can decrease long-term mortality in these patients.

Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking. Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE. METHODS: The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor. DISCUSSION: SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent. TRIAL REGISTRATION: Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139 ) on Sep. 29, 2016. This study is ongoing.

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.

Chinese herbal medicine therapy and the risk of mortality for chronic hepatitis B patients with concurrent liver cirrhosis: a nationwide population-based cohort study.

Chronic hepatitis B (CHB) is increasingly recognized as a public health problem in Taiwan. After affected patients are diagnosed with contaminant liver cirrhosis (LC), adverse clinical outcomes, especially death, are common. This study aimed to investigate the effect of Chinese herbal medicine (CHM), an essential branch of Traditional Chinese medicine (TCM), on the mortality risk among CHB patients with contaminant LC. This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 1522 patients 20-70 years of age with newly diagnosed CHB with LC during 1998-2007. Among them, 508 (33.37%) had received CHM products after the onset of CHB (CHM users), and the remaining 1014 patients (66.63%) were designated as a control group (non-CHM users). All enrollees were followed until the end of 2012 to determine deaths during the study period. We applied the Cox proportional hazards regression model to compute the hazard ratio for the association of CHM use and the subsequent risk of death. During the follow-up period, 156 CHM users and 493 non-CHM users died. After controlling for potential confounders, CHM users were found to have a significantly reduced risk of death compared with non-CHM users by 56%, and the effect was predominantly observed among those treated with CHM for > 180 days. CHM therapy lowered the risk of death among CHB patients with contaminant LC, which supported CHM might provide further treatment options for those with chronic liver diseases.

Effect of proton pump inhibitors in hospitalization on mortality of patients with hepatic encephalopathy and cirrhosis but no active gastrointestinal bleeding.

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric complication of decompensated cirrhosis. Proton pump inhibitors (PPIs), used as potent acid suppressants, are associated with HE occurrence in cirrhotic patients. However, it is still unknown if PPIs contribute to mortality in cirrhotic patients with HE and no active gastrointestinal bleeding. METHODS: We used the Taiwan National Health Insurance Database to identify 1004 cirrhotic patients with HE and no active gastric bleeding, who received oral PPIs between January 1, 2010 and December 31, 2013. On the basis of comorbid disorder data, we used propensity score matching at a 1:4 ratio to select 4016 cirrhotic patients with HE and no active gastric bleeding who did not receive PPIs as a comparison group. All patients were followed up for one year from the index time. RESULTS: The overall 30-day, 90-day, and 1-year mortalities were 36.1%, 52.6%, and 70.1% in PPI group, and 27.5%, 41.7%, and 62.4% in non-PPI group. Using Cox regression model analysis with adjustment for age, gender, and other comorbid disorders, we obtained hazard ratios of 1.360 (95% CI: 1.208-1.532, P<0.001), 1.563 (95% CI: 1.314-1.859; P<0.001), and 1.187 (95% CI: 1.008-1.398; P=0.040) for, respectively, 30-day, 30-day to 90-day, and 90-day to 1-year mortality in patients taking PPIs. CONCLUSION: PPIs increase short-term and long-term mortality of cirrhotic patients with HE and no active gastrointestinal bleeding.

The long-term outcomes of cirrhotic patients with pleural effusion.

Background/Aim: A pleural effusion is an abnormal collection of fluid in the pleural space and may cause related morbidity or mortality in cirrhotic patients. Currently, there are insufficient data to support the long-term prognosis for cirrhotic patients with pleural effusion. In this study, we investigated the short- and long-term effects of pleural effusion on mortality in cirrhotic patients and evaluated the benefit of liver transplantation in these patients. Patients and Methods: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic patients with pleural effusion requiring drainage between January 1, 2007 and December 31, 2010. The proportional hazards Cox regression model was used to control for possible confounding factors. Results: The 30-day, 90-day, 1-year, and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the cirrhotic patients with pleural effusion. After Cox proportional hazard regression analysis adjusted by patient gender, age, complications of cirrhosis and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and without liver transplantation conferred higher risks for 3-year mortality in the cirrhotic patients with pleura effusion. Liver transplantation is the most important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11- 0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the non-liver transplantation group. Conclusion: In cirrhotic patients, the presence of pleural effusion predicts poor long-term outcomes. Liver transplantation could dramatically improve the survival and should be suggested as soon as possible.

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.

Effect of Proton Pump Inhibitors on Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis.

INTRODUCTION AND AIM: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection in patients with cirrhosis. However, it is unknown whether patients with SBP and cirrhosis who do not have active gastrointestinal bleeding have a poorer prognosis if treated with proton pump inhibitors (PPI). MATERIAL AND METHODS: We used the Taiwan National Health Insurance Database to identify 858 patients with SBP and cirrhosis who were administered PPIs and hospitalized between January 1, 2010, and December 31, 2013. One-to-two propensity score matching was performed to select a comparison group based on age, gender, and comorbidities. All patients obtained follow-up for 1 year. RESULTS: The overall 30-day, 90-day, and 1-year mortality was 27.9%, 49.0%, and 73.7%, respectively, in the PPI group and 25.6%, 43.8%, and 67.2%, respectively, in the non-PPI group. After adjusting the Cox regression model for age, gender, and comorbidities, the hazard ratios for PPIs regarding 30-day, 30- to 90-day, and 90-day to 1-year mortality were 1.074 (95% CI 0.917-1.257, P = 0.377), 1.390 (95% CI 1.154-1.673, P = 0.001), and 1.297 (95% CI 1.099- 1.531, P = 0.002), respectively. CONCLUSIONS: PPIs did not increase the short-term mortality of patients with SBP and cirrosis who did not have active gastrointestinal bleeding, but PPIs increased the long-term mortality risk. For these patients, physicians should discontinue PPIs as early as possible.

Increased occurrence of brain abscesses in cirrhotic patients: A population-based 3-year follow-up study.

BACKGROUND/AIMS: Cirrhotic patients are prone to various infectious diseases. However, it is still unknown if the occurrence of a brain abscess is associated with cirrhosis. The purpose of this study was to identify the relationship between the occurrence of a brain abscess and cirrhosis. MATERIALS AND METHODS: The National Health Insurance Database, which is derived from the Taiwan National Health Insurance program, was used to collect data from 40,878 patients with cirrhosis and from 40,896 randomly selected age- and sex-matched patients. All patients were followed up to identify the occurrence of brain abscesses in 3 years. RESULTS: A total of 143 patients (0.17%) were diagnosed with brain abscesses in the 3-year follow-up period. There were 94 (0.23%) patients with cirrhosis and 49 (0.12%) without cirrhosis (p<0.001). After regression analysis, cirrhotic patients had a higher risk of occurrence of brain abscesses than non-cirrhotic patients (hazard ratio: 1.88, 95% confidence interval: 1.30-2.72; p=0.001). In addition, the risk of occurrence of brain abscesses was higher in complicated cirrhotic patients than in non-complicated cirrhotic patients (adjusted hazard ratio: 2.07, 95% confidence interval: 1.36-3.14; p=0.001). CONCLUSION: Cirrhotic patients, particularly those with complicated cirrhosis, have a higher risk of the occurrence of brain abscesses than non-cirrhotic patients.

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.