Sulfamethoxazole-trimethoprim-induced liver injury and genetic polymorphisms of NAT2 and CYP2C9 in Taiwan.

OBJECTIVES: Sulfamethoxazole-trimethoprim (SMX-TMP) is one of the most frequently used antibiotics. SMX is metabolized by N-acetyltransferase (NAT) and cytochrome P450 2C9 (CYP2C9) to nontoxic or toxic intermediates. Little is known about the association between genetic variations of these enzymes and SMX-TMP-induced liver injury (SILI). The aim of this study was to explore the genetic polymorphisms of NAT2 and CYP2C9 and the susceptibility to SILI in a Han Chinese population. METHODS: A total of 158 patients with SILI and 145 controls were recruited in this study. PCR-based genotyping with matrix-assisted laser desorption ionization-time of flight was used to assay the major NAT2 and CYP2C9 genotypes including NAT2 rs1495741, rs1041983, rs1801280, CYP2C9 rs1799853, rs1057910 and rs4918758. RESULTS: The SILI group had a higher frequency of the NAT2 rs1495741 variant AA genotype and rs1041983 variant TT genotype than the controls (42.4 vs. 25.5%; P = 0.008, and 40.5 vs. 25.5%; P = 0.022, respectively). The SILI group had more slow acetylators than the controls (43.7 vs. 25.5%; P = 0.001). There were no significant differences in the genetic variations of CYP2C9 between the SILI and control groups. After adjusting for confounding factors, the NAT2 slow acetylators still had an increased risk of SILI (adjusted OR: 2.49; 95% confidence interval: 1.46-4.24; P = 0.001), especially in those with hepatocellular and mixed type SILI. CONCLUSIONS: NAT2 slow acetylators are associated with a higher risk of SILI in the Han Chinese population. However, CYP2C9 genetic polymorphisms are not associated with the susceptibility to SILI.

Statin-induced liver injury in an area endemic for hepatitis B virus infection: risk factors and outcome analysis.

AIMS: Statin-induced liver injury (SILI) is quite rare, but may be severe. Little is known about the impact of chronic hepatitis B infection (CHBI) on SILI. We aimed to investigate the risk factors and outcome of SILI, with special reference to its interaction with CHBI. METHODS: Patients with SILI were recruited from our hospital, and three-to-one drug-matched controls were randomly selected. The clinical data of the patients were then compared. RESULTS: A total of 108 patients with SILI and 324 controls were enrolled. The patients with SILI were both older and had a higher statin dose than the controls. There was no predilection of liver injury associated with the seven available statins. Among the SILI patients, there was no statistical difference between the baseline and peak liver enzyme tests, and latency and severity between hepatitis B carriers (n = 16) and non-carriers (n = 92). High dose of statin and age were the two independent risk factors of SILI (OR and 95% CI: 1.93, 1.08-3.35, P = 0.025, and 1.73, 1.07-2.80, P = 0.027, respectively). Permanent discontinuation of statin was noted in 50 (46.3%) patients with SILI due to severe SILI or recurrent hepatotoxicity after rechallenge of other statins. CONCLUSION: High dose of statin and old age may increase patient susceptibility to SILI; however, CHBI and abnormal baseline liver tests are not risk factors of SILI. Nonetheless, SILI is still worthy of notice, because nearly half of the overt cases discontinued statin treatment due to severe hepatotoxicity in this study.

Superoxide Dismutase 2 Genetic Variation as a Susceptibility Risk Factor for Alcoholic Cirrhosis.

AIMS: Superoxide dismutase 2 (SOD2) is an important antioxidant phase 2 enzyme. The associations of SOD2 genetic variation and the risk of advanced alcoholic liver diseases are still debatable. We aimed to investigate the association of the main SOD2 genetic variant (47T>C) and the susceptibility to alcoholic cirrhosis. METHODS: A total of 80 patients with alcoholic cirrhosis (AC), 80 patients with alcoholic non-cirrhosis (ANC), 80 with viral hepatitis B-related cirrhosis (VC), and 165 healthy controls (HC) were enrolled into this study. A polymerase chain reaction was used to genotype their SOD2 47T>C (rs4880). RESULTS: There was no statistical difference in the frequency distribution of the three SOD2 47T>C genotypes among groups. However, if individuals with C variant were grouped together, the AC group had higher frequency of SOD2 C/C or C/T genotype than ANC, VC and HC groups had (38.7% vs. 21.3%, 26.3% and 21.8%, respectively, P = 0.010). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of AC (adjusted OR: 2.79 and 3.50, respectively, P < 0.03, compared with ANC and HC groups). In contrast, there was no significant difference of SOD2 genetic variation between VC and HC groups. CONCLUSIONS: Anti-oxidative enzyme SOD2 47T>C genetic variant may increase the susceptibility to AC. This suggests that oxidative stress plays a role in the development of AC.

Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease is the most prevalent liver disease in the world. However, the exact mechanisms that lead to development of advanced non-alcoholic steatohepatitis (NASH) are unknown. Oxidative stress may be an important pathogenic factor in NASH. Manganese superoxide dismutase (SOD2) is an important antioxidant phase 2 enzyme that can reduce reactive oxidative substances and protect hepatocytes. In contrast, cytochrome P450 2E1 (CYP2E1) has pro-oxidant activity and may enhance oxidative stress and counteract the effect of SOD2. Little is known regarding the associations of genetic variants of these enzymes with the risk of NASH. We aimed to investigate the association of genetic variants of SOD2 and CYP2E1 with susceptibility to NASH. METHODS: Data from 100 patients with NASH, 31 patients with non-alcoholic steatosis (NAS) and 90 healthy controls were analysed. Their DNA was retrieved for genotyping SOD2 47T>C and CYP2E1 -1053C>T variation by polymerase chain reaction. RESULTS: There was no statistical difference in the frequency distributions of SOD2 and CYP2E1 genotypes among the NASH, NAS and control groups. However, the frequency of the SOD2 C variant was significantly higher in the NASH group than in the NAS and control groups (22% vs. 14.5% and 11.1%, respectively; P = 0.015). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of NASH (odds ratio, 2.81; 95% confidence interval, 1.37-5.76; P = 0.005). CONCLUSIONS: The anti-oxidative SOD2 47T>C genetic variant might increase susceptibility to NASH in Chinese. Individuals with the SOD2 C variant may have a higher risk for NASH.

Polymorphism of N-acetyltransferase 2 gene and the susceptibility to alcoholic liver cirrhosis: interaction with smoking.

BACKGROUND: Polymorphism of N-acetyltransferase 2 gene was reported to be associated with the susceptibility of various cancers and liver diseases. However, its relationship to alcoholic liver disease is controversial and open to debate. The aim of this study was to evaluate the relationship of NAT2 genetic polymorphisms and the susceptibility to alcoholic liver cirrhosis (ALC) in Chinese, with special emphasis on the interaction of smoking. METHODS: Peripheral white blood cell DNA from 148 patients with ALC, 104 patients with long-term alcoholic drinking but without cirrhosis (ANC) and 209 healthy controls were genotyped for NAT2 using a polymerase chain reaction-restriction fragment length polymorphism method. The possible confounding factors were included for analysis. RESULTS: There was no statistical difference in the frequency of NAT2 genotype or NAT2 acetylator status among the 3 groups. However, among the chronic alcoholic drinkers, the rapid acetylators with smoking habits had higher percentage of ALC than those without smoking habit (18.9% vs. 9.5%, p=0.002). The adjusted odds ratio for rapid acetylator smoker to have ALC was 3.45 (95% CI=1.53 to 7.76, p=0.003). CONCLUSIONS: The genetic factor, NAT2 polymorphism, may interact with environmental factor, smoking, to confer different susceptibilities to ALC. NAT2 rapid acetylators with smoking habit may increase the risk of ALC in Chinese.

Genetic variations of three important antioxidative enzymes SOD2, CAT, and GPX1 in nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is closely related to reactive oxygen species (ROS). Superoxide anion radicals, the main product of ROS, can be reduced by manganese superoxide dismutase (SOD2) to hydrogen peroxide, which is further reduced by catalase (CAT) and glutathione peroxidase (GPX) to water. We aimed to investigate the association between the most important genetic variants of SOD2, CAT, and GPX1 and susceptibility to NASH. METHODS: A total of 126 adults with liver tissue-verified NASH, 56 patients with liver tissue-verified nonalcoholic fatty liver (NAFL), and 153 healthy controls were enrolled. Their DNA profiles were retrieved for genotype assessment of SOD2 47T>C (rs4880), CAT -262C>T (rs1001179), and GPX1 593C>T (rs1050450) variation. RESULTS: There were statistical differences between the SOD2 and CAT genotypes across the NASH, NAFL, and control groups, but not GPX1. The NASH group had a significantly higher frequency of subjects with SOD2 C allele (38.8%) compared with the NASL group (25.0%) and the controls (22.9%, p = 0.010). Similarly, the NASH group had a significantly higher percentage of subjects with CAT T allele (23.0%) compared with the NAFL group (10.7%) and the controls (7.2%, p = 0.001). For subjects with both the SOD2 C allele and CAT T allele, 88.2% were in the NASH group. After adjusting for confounders, the CAT mutant T allele and SOD2 mutant C allele were still the highest independent risk factors for NASH (odds ratio [OR] 3.10 and 2.36, respectively). In addition, there was a synergistic effect for those two alleles and the occurrence of NASH with an adjusted OR of 8.57 (p = 0.030). CONCLUSION: The genetic variations of CAT and SOD2 may increase the risk of NASH, which may aid in the screening of patients who are at high risk of NASH, and offer a potential anti-oxidant targeting route for the treatment of NASH.

Hepatotoxicity, efficacy and completion rate between 3 months of isoniazid plus rifapentine and 9 months of isoniazid in treating latent tuberculosis infection: A systematic review and meta-analysis.

BACKGROUND: The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens. METHODS: We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis. RESULTS: A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001). CONCLUSION: The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.

The association of transporter ABCC2 (MRP2) genetic variation and drug-induced hyperbilirubinemia.

BACKGROUND: Hyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATP-binding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin; however, little is known about these transporters and the risk of DILI. The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia. METHODS: A total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays. RESULTS: There were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs 27.9%, p = 0.048). CONCLUSION: Carriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.

A randomized controlled trial comparing two different dosages of infusional pantoprazole in peptic ulcer bleeding.

AIM: The optimal dosage of proton pump inhibitor in bleeding peptic ulcers remains controversial. The aim was to compare the clinical effectiveness of two doses of infusional pantoprazole in peptic ulcer bleeding. METHODS: Peptic ulcer patients (n= 120) with bleeding stigmata were enrolled after successful endoscopic therapy. After an initial bolus injection of 80 mg pantoprazole, patients were randomized to receive continuously infused pantoprazole at either 192 mg day(-1) or 40 mg every 6 h (i.e. 160 mg day(-1)) for 3 days. Clinical outcomes between the two groups within 14 days were compared, with 14-day recurrent bleeding regarded as the primary end-point. RESULTS: Both groups (n= 60 each) were well matched in demographic and clinical factors upon entry. Bleeding totally recurred in 11 (9.2%) patients, with six (10%) in the 192 mg day(-1) group and five (8.3%) in the 160 mg day(-1) group (relative risk of bleeding recurrence between two treatments 1.2; 95% CI 0.39, 3.72). All secondary outcomes between the two groups were similar, including the amount of blood transfusion (mean 1179 ml vs. 1203 ml, P > 0.1), hospital stay (mean 9.5 days vs. 9.9 days, P > 0.1), need for surgery (n= 1 vs. n= 0, P > 0.1), and mortality (n= 1 vs. n= 0, P > 0.1). CONCLUSIONS: Following endoscopic haemostasis, infusional pantoprazole at either 192 mg day(-1) or 40 mg every 6 h appear similar.

Endoscopic papillary balloon dilatation less than three minutes for biliary stone removal increases the risk of post-ERCP pancreatitis.

OBJECTIVES: The adequate duration for EPBD was unclear. Therefore, we aimed to investigate the effect of balloon dilatation duration of EPBD on the occurrence of PEP. METHODS: One hundred and ninety-eight patients with common bile duct (CBD) stone treated by EPBD were retrospectively recruited. The dilatation duration was determined according to adequate opening of the biliary orifice without bleeding. The clinical outcomes and complications of EPBD were recorded. RESULTS: We stratified the patients according to dilatation duration (Group A, <3 minutes; Group B, 3-5 minutes; Group C, ≥5 minutes). The group C patients had a higher proportion of large CBD stones (stones ≥10 mm) (33.3% vs. 26.8% vs. 53.5%, p = 0.01). Patients in group A had a significantly higher PEP rate than patients in group B (13.3 vs. 3.1, p = 0.032). There were no significant differences in perforation and bleeding rate among the three groups. Univariate and multivariate analyses showed that a dilatation duration of <3 minutes, CBD diameter < 10 mm and age ≤ 75 years were independent risk factors of PEP in post-EPBD patients. CONCLUSIONS: In patients receiving EPBD, dilatation duration <3 minutes, lower CBD diameter, and younger age were independent risk factors of PEP.

Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection.

AIMS: We aimed to assess the clinical effectiveness of oral vs. intravenous (i.v.) regular-dose proton pump inhibitor (PPI) after endoscopic injection of epinephrine in patients with peptic ulcer bleeding. METHODS: Peptic ulcer patients with active bleeding, nonbleeding visible vessels, or adherent clots were enrolled after successful endoscopic haemostasis achieved by epinephrine injection. They were randomized to receive either oral rabeprazole (RAB group, 20 mg twice daily for 3 days) or i.v. omeprazole (OME group, 40 mg i.v. infusion every 12 h for 3 days). Subsequently, the enrolled patients receive oral PPI for 2 months (rabeprazole 20 mg or esomeprazole 40 mg once daily). The primary end-point was recurrent bleeding up to 14 days. The hospital stay, blood transfusion, surgery and mortality within 14 days were compared as well. RESULTS: A total of 156 patients were enrolled, with 78 patients randomly allocated in each group. The two groups were well matched for factors affecting the clinical outcomes. Primary end-points (recurrent bleeding up to 14 days) were reached in 12 patients (15.4%) in the OME group and 13 patients (16.7%) in the RAB group [95% confidence interval (CI) of difference -12.82, 10.22]. All the rebleeding events occurred within 3 days of enrolment. The two groups were not different in hospital stay, volume of blood transfusion, surgery or mortality rate (1.3% of the OME group and 2.6% of the RAB group died, 95% CI of difference -5.6, 3.0). CONCLUSIONS: Oral rabeprazole and i.v. regular-dose omeprazole are equally effective in preventing rebleeding in patients with high-risk bleeding peptic ulcers after successful endoscopic injection with epinephrine.

The role of regular liver function monitoring in antituberculosis drug-induced liver injury.

BACKGROUND: Antituberculosis (TB) drug-induced liver injury (ATLI) is a common adverse effect of anti-TB drugs. Whether regular monitoring of liver function can ameliorate ATLI has been widely debated. The current study aimed to investigate the liver test monitoring status of patients receiving anti-TB treatment in Taiwan, as well as the impact of scheduled liver function monitoring on the risk of ATLI. METHODS: Patients who received anti-TB treatment at our hospital between 2009 and 2017 were enrolled for retrospective analysis. RESULTS: A total of 1062 patients were included, and of them 469 (44.2%) received regular liver function monitoring (good monitoring group). ATLI was recognized in 100 (9.4%) patients. The good monitoring group detected more ATLI cases early compared with the poor monitoring group (14.7% vs 5.2%, and 21.4 vs 61.6 days, p < 0.01), with a lower peak serum alanine aminotransferase (276.1 vs 507.1 IU/L, p = 0.05). CONCLUSION: In the current study, less than half of all patients who received anti-TB drugs had their liver function monitored regularly. Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury. The implementation of periodic liver function monitoring tests in patients receiving anti-TB treatment should be re-emphasized and encouraged.

Use of proton pump inhibitors and the risk of hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Worldwide, proton pump inhibitors (PPIs) are commonly used for the treatment of peptic ulcer and gastro-esophageal reflux disease. Recently, concern has arisen over the potential association between PPIs and hepatocellular carcinoma (HCC). The aim of the current study was to evaluate the influence of PPI use on the risk of HCC, through a systematic review and meta-analysis. METHODS: A review of all English-language literature was conducted, using the subject search terms: "hepatocellular carcinoma", "liver cancer", "hepatic tumor", and "proton pump inhibitor" in the major medical databases. A meta-analysis of the qualifying publications was then performed. RESULTS: A total of five studies, which had shown that PPIs were associated with HCC (crude risk ratio [RR] = 2.27, 95% confidence interval [CI]: 1.44-3.57; p < 0.01) when an unadjusted RR were adopted, were eligible for meta-analysis. It was observed that the cumulative dose of PPIs may increase the risk of HCC in a linear model (p < 0.01). However, when using data that were adjusted by comorbidities and concurrent medications, the association between PPIs and HCC became insignificant (adjusted RR = 1.62, 95% CI: 0.89-2.93; p = 0.11) and this result was consistent in the sensitivity analysis. CONCLUSION: The current meta-analysis has shown that PPI use does not significantly increase the risk of HCC after adjusting for confounding factors. However, further studies are warranted to verify the association between PPIs and HCC in special populations, such as viral or alcoholic liver diseases.

OLGA gastritis staging in young adults and country-specific gastric cancer risk.

Geographical differences have been shown in the clinical outcomes of Helicobacter pylori-associated gastritis phenotypes and in gastric cancer risk. This study tested whether the Operative Link on Gastritis Assessment (OLGA) staging correlated with gastric cancer risk in populations from 3 continents. Mapped gastric biopsies were obtained from 316 dyspeptic adults aged less than 41 years from 8 geographic areas that differed in gastric cancer risk. Gastric atrophy was assessed according to internationally validated criteria. Gastritis stage was established according to the OLGA staging system. The most prevalent gastritis stages were 0 to II, which included all subjects entered from Chile, Germany, India, Italy, and Thailand. Gastritis Stages III and IV were limited to the Chinese and Korean populations. Indians had a high prevalence of H pylori infection without high-stage gastritis. In populations at different cancer risk, the gastritis OLGA stage mirrored the gastric cancer incidence. Gastritis staging identifies a subgroup of higher-risk patients.

The susceptibility of anti-tuberculosis drug-induced liver injury and chronic hepatitis C infection: A systematic review and meta-analysis.

BACKGROUND: Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. METHODS: We systemically reviewed all English-language literature in the major medical databases with the subject search terms "anti-tuberculosis drug-induced liver injury" and "anti-tuberculosis drug-induced hepatotoxicity". We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications. RESULTS: A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30-4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79-4.90) and Caucasians (OR = 4.07, 95% CI: 2.70-6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95-4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36-7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58-4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96-6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93-5.90) and case-control studies (OR = 2.43, 95% CI: 1.29-4.58). CONCLUSION: This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy.

The factors associated with negative colonoscopy in screening subjects with positive immunochemical stool occult blood test outcomes.

BACKGROUND: The immunochemical fecal occult blood test (iFOBT) is an alternative method to colonoscopy that can be used for colorectal cancer (CRC) screening. If the iFOBT result is positive, a colonoscopy is recommended. In this retrospective study, we identify factors associated with negative colonoscopy and positive iFOBT results obtained during CRC screening. METHODS: We collected data for subjects who received a colonoscopy at Taipei Veterans General Hospital after receiving a positive iFOBT result during CRC screening from January 2015 to December 2015. Subjects' baseline data, medications, and co-morbidities as well as colonoscopy and histological findings were recorded. A negative colonoscopy result was defined as no detection of any colorectal neoplasia including non-advanced adenoma, advanced adenoma, and adenocarciona. Multivariate logistic regression analysis was conducted to identify the associated factors in screening subjects with positive iFOBT but negative colonoscopy results. RESULTS: 559 (46.3%) out of 1207 eligible study subjects received a colonoscopy with a negative result. Multivariate logistic regression analysis revealed that the use of antiplatelets [odds ratio (OR) = 0.654; 95% confidence interval (CI), 0.434-0.986], occurrence of hemorrhoid (OR = 0.595; 95% CI, 0.460-0.768), and the existence of colitis/ulcer (OR = 0.358; 95% CI, 0.162-0.789) were independent factors associated with negative colonoscopy but positive iFOBT results during CRC screening. The colon clean level, underlying diseases of gastrointestinal bleeding tendency (e.g., chronic kidney disease, cirrhosis), and the use of anticoagulant or nonsteroidal anti-inflammatory agents were not associated with negative colonoscopy and positive iFOBT results. CONCLUSION: The use of antiplatelet agents and the presence of hemorrhoids and colitis/ulcers were factors associated with negative colonoscopy and positive iFOBT results.

Effects of 3-day IV pantoprazole versus omeprazole on 24-hour intragastric acidity at 3 days in Chinese patients with duodenal ulcer: A single-center, prospective, randomized, comparative, pilot trial.

BACKGROUND: Pantoprazole and omeprazole are irreversible proton pump inhibitors that have been found to significantly reduce intragastric acidity in patients with peptic ulcer and/or esophagitis. It has been reported that gastric acid secretion is lower in the Chinese patients compared with the Western population. Based on a MEDLINE search, no studies of the treatment of intragastric acidity with IV pantoprazole have been conducted in the Chinese population to date. OBJECTIVE: This trial was performed to compare the effects of IV pantoprazole versus omeprazole on 24-hour intragastric acidity in Chinese patients with endoscopically confirmed duodenal ulcer. METHODS: This single-center, randomized, pilot study was conducted at the Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan. Chinese patients aged 18 to 80 years with endoscopically confirmed duodenal ulcer were randomly assigned to receive a continuous IV infusion of pantoprazole or omeprazole 160 mg/d for 3 days. On days 4 to 14, patients received pantoprazole 40 mg/d or omeprazole 20 mg/d orally. During endoscopic examination at enrollment, an antral biopsy specimen was obtained for rapid urease test, with each patient's agreement, by a blinded investigator. The primary end point was 24-hour intragastric pH on day 3. Secondary end points were percentage of the total time during the 24-hour period (%t) pH <3 and <4 and proportions of patients with healed ulcers on day-14 endoscopy. Endoscopic examination for monitoring of adverse effects of both drugs was repeated 8 weeks after study completion. RESULTS: A total of 40 patients were enrolled (35 men, 5 women; mean age, 63.3 years; 20 per treatment group). Twenty-four-hour intragastric pH was not significantly different between the omeprazole and pantoprazole groups (mean [SD], 6.61 [1.27] vs 6.84 [0.78]). The %t pH <3 (mean [SD], 8.01% [19.60%] vs 2.70% [7.18%]) and pH <4 (mean [SD], 9.28% [21.41%] vs 3.87% [9.79%]) were not significantly different between the omeprazole and pantoprazole groups. On day-14 endoscopy, ulcers were found to be healed in 3 (15%) patients in each group. In the omeprazole group, 1 (5%) patient experienced mild diarrhea, and 1 (5%) experienced mild abdominal fullness. These adverse effects were considered treatment related. No adverse effects were reported in either treatment group at 8 weeks after the study. CONCLUSIONS: The results of this pilot study of 3-day treatment with a continuous IV infusion of pantoprazole or omeprazole 160 mg/d found that these 2 treatments had similar effects on 24-hour intragastric pH in this small population of Chinese patients with duodenal ulcer. Both treatments were well tolerated.

N-Acetyltransferase 2 (NAT2) genetic variation and the susceptibility to noncardiac gastric adenocarcinoma in Taiwan.

BACKGROUND: N-Acetyltransferase (NAT) is an important enzyme with the capacity to metabolize carcinogenic aromatic amines. However, it remains controversial whether the encoded functional NAT2 genetic polymorphism is related to the risk of gastric adenocarcinoma (GA). The aim of this study was to evaluate the association between NAT2 genetic variation and gastric adenocarcinoma (GA), with special reference to the gastric noncardiac adenocarcinoma (GNA). METHODS: Peripheral white blood cell DNA from 368 GA patients and 368 age- and sex-matched controls were genotyped for NAT2 by a polymerase chain reaction method. The lifestyle habits of the participants were assessed using a semiquantitative food-frequency questionnaire. NAT2 genotype, interaction with lifestyle habits, and the risk of GA and GNA were analyzed by logistic regression. RESULTS: GA patients were more likely to have a smoking habit, ate more salted foods, and consumed more well-done meat than the controls. There was no association between the NAT2 genotypes and susceptibility to GA. However, if patients with gastric cardiac adenocarcinoma (GCA; n = 42) were excluded, the NAT2 slow acetylators (without rapid acetylator allele) had a higher risk of GA than intermediate and rapid acetylators (odds ratio = 1.53; 95% confidence interval, 1.05-2.23, p = 0.027). In addition, there was a synergic effect of NAT2 slow acetylator and well-done meat intake to the development of GNA (odds ratio = 3.83; 95% confidence interval, 1.68-8.76, p = 0.001). CONCLUSION: NAT2 slow acetylators have a higher risk of GNA than intermediate and rapid acetylators have in a Taiwanese population. The intake of well-done meat, an additive to the acetylator status, may contribute to the incidence of gastric carcinogenesis.

Chronic hepatitis B infection and risk of antituberculosis drug-induced liver injury: Systematic review and meta-analysis.

BACKGROUND: Antituberculosis drug-induced liver injury (ATDILI) is a major safety concern for the treatment of tuberculosis (TB). The impact of chronic hepatitis B infection (CHBI) on the risk of ATDILI is still controversial. In this study, we aimed to assess systematically the influence of CHBI on the susceptibility to ATDILI. METHODS: We reviewed all English-language medical literature with the medical subject search headings hepatitis B and antitubercular agents from the major medical databases. Thereafter, a systematic review and meta-analysis was performed on those publications that qualified. RESULTS: A total of 938 citations were retrieved on the initial major database search, from which 15 studies were determined to be eligible for analysis. While undergoing anti-TB treatment, 575 cases with drug-induced liver injury (DILI) and 4128 controls without DILI were enrolled into this analysis. The pooled odds ratio of all studies for the CHBI to ATDILI was 2.18 (95% confidence interval, 1.41-3.37). Among the studies with a strict definition of DILI (alanine aminotransferase > 5 × upper limit of normal value) and combination anti-TB regimen, the impact of CHBI on ATDILI was significant only in the prospective studies (odds ratio, 3.41; 95% confidence interval, 1.77-6.59), but not in the case-control studies. However, in the studies with a strict definition of DILI and isoniazid only treatment, the association between CHBI and ATDILI was not statistically significant. CONCLUSION: This meta-analysis suggests that CHBI may increase the risk of ATDILI in the standard combination therapy for active TB. Close follow-up and regular liver test monitoring are mandatory to treat TB in chronic hepatitis B carriers.

Fragmentation of CagA Reduces Hummingbird Phenotype Induction by Helicobactor pylori.

Infection with Helicobacter pylori (H. pylori) has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.