Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients.

BACKGROUND: Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. AIM: To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS: We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed. RESULTS: The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2 , 95% confidence interval [CI]: 13.76-17.70 vs 5.96 mL/min/1.73 m2 , 95% CI: 4.72-7.19; P < 0.001). The cumulative incidence of renal function deterioration was significantly higher in the TDF group (TDF vs ETV: 11.1%, 95% CI: 7.4-14.8 vs 1.7%, 95% CI: 1.0-2.4; P < 0.001). After adjusting for age, pre-existing CKD and diabetes, TDF was independently associated with an increased risk of renal function deterioration (HR 5.36, 95% CI: 2.16-13.35; P < 0.001). Pre-existing CKD (HR 6.71, 95% CI: 2.25-17.65), proteinuria (HR 3.39, 95% CI: 1.23-9.39), and haematuria (HR 4.25, 95% CI: 1.32-13.68) were also independent factors of renal dysfunction. CONCLUSION: By following the KDIGO guidelines, we confirmed that TDF was associated with a higher risk of renal dysfunction as compared to ETV.

Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study.

Objective We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy. Methods We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation. Results During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis. Conclusions The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

The risk of colorectal cancer is related to frequent hospitalization of IBD in an Asian population: results from a nationwide study.

BACKGROUND: The occurrence of inflammatory bowel disease (IBD) is higher in Western countries and is increasing worldwide. The incidence of IBDs is about nearly 20-fold in Western countries than Asia and has risen in Taiwan over the past few decades. Epidemiological studies have demonstrated an increased risk of colorectal cancer (CRC) in patients with IBD. The prevalence of IBD as well as IBD-associated CRC is changing and the risk of CRC in patients with IBD appears to be greater in Western countries, but CRC risk in IBD patients is less well understood in low endemic areas, such as Asia. METHODS: This population-based cohort study collected data from the Taiwan Health Insurance Research Database (from January 1998 to December 2011). In total, 10 650 patients with confirmed diagnosis of IBD served as the IBD cohort and 42 600 non-IBD subjects were enrolled. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the risk of CRC. RESULTS: The incidence of CRC was slightly lower in the IBD cohort compared with that in the non-IBD cohort (0.94 vs. 1.13 per 1000 person-years), with an adjusted HR of 0.99 (95% CI: 0.71-1.37). More than four hospitalizations were associated with a significantly higher risk of CRC in IBD patients in the Cox model (adjusted HR = 3.48, 95% CI: 1.59-7.63). CONCLUSIONS: The risk for CRC was not increased among IBD patients overall, but appeared to be increased with cumulative frequency of hospitalizations for IBD.

IL-10 promoter gene polymorphisms and sustained response to combination therapy in Taiwanese chronic hepatitis C patients.

BACKGROUND AND AIMS: Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. The role of immunopathogenesis in chronic hepatitis C leads to extensive exploration of host immunity including inflammatory cytokines. METHODS: We examined interleukin 10 (IL-10) promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site and studied their association with response to 24 weeks of pegylated interferon plus ribavirin treatment in 143 chronic hepatitis C patients, of whom 97 (67.8%) achieved a sustained virologic response (SVR). In addition, 134 healthy adults were used as controls. RESULTS: Of chronic hepatitis C patients, 111 (77.6%) were genotype 1 infection, 32 (22.4%) were genotype 2 infection. Patients with sustained virologic response were younger and had higher pretreatment ALT levels than those without. No statistical difference was found between chronic hepatitis C patients who achieved SVR or not in terms of gender, HCV genotype, pretreatment HCV RNA levels, and severity of liver disease. The serum IL-10 levels were comparable between healthy controls and chronic hepatitis C patients as well as between HCV patients with and without SVR. The distribution of IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site was comparable between HCV patients and healthy controls as well as HCV patients with and without SVR. A high frequency of ATA haplotype of common IL-10 promoter gene SNPs was found in both chronic hepatitis C patients (70.3%) and healthy controls (69.8%). However, ATA haplotype was not associated with SVR in chronic hepatitis C patients. CONCLUSIONS: Our data fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Taiwanese chronic hepatitis C patients. The impact of genetic variations in IL-10 haplotype on the response to anti-HCV treatment among different ethnic populations deserves further examination.

Improvement of tissue-adhesive obliteration of bleeding gastric varices using adjuvant hypertonic glucose injection: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Rebleeding can occur after endoscopic injection of gastric varices with tissue adhesive. The aim of this study was to evaluate whether adjuvant hypertonic glucose solution injections enhance the effects of Histoacryl after successful initial variceal obliteration. PATIENTS AND METHODS: A total of 67 patients (37 men, 30 women; mean age +/- standard deviation [SD] 60 +/- 17 years) with initially successful Histoacryl obliteration of bleeding gastric varices were included in the study and randomly divided into two groups: a "combined" group of patients who had adjuvant injection of hypertonic glucose solutions in cases of residual gastric varices (F1 or less) and a "control" group of patients who did not receive such therapy. End points were either variceal recurrence/progression (F2 or more) requiring Histoacryl reinjection or rebleeding. RESULTS: Residual small varices were found in 56% of patients in the combined group and in 60% of patients in the control group. Adjuvant therapy was only performed in the combined group. During the follow-up period (mean duration +/- SD 37.9 +/- 18.5 months, range 19-56 months), two patients in the combined group showed gastric variceal progression, compared with nine patients showing progression in the control group, with two cases of rebleeding, both occurring in the control group. Two years after the first Histoacryl injection, the cumulative proportion of patients who did not have gastric variceal progression was significantly higher in the combined group than it was in the control group (92.8% vs. 71.4%, P = 0.029). There was no significant difference between the two groups with respect to their survival curves (P = 0.12). No marked immediate or delayed symptoms or complications were observed in the patients given hypertonic glucose injections. CONCLUSIONS: Adjuvant treatment with hypertonic glucose solution for residual small gastric varices is a safe and simple method. It helps reduce the recurrence or progression of gastric varices after tissue adhesive injections and can therefore reduce the risk of rebleeding.

Predictive factors of the long-term outcome in reflux esophagitis in a low-prevalence gastroesophageal reflux disease region.

BACKGROUND: There are no data concerning the long-term outcome of patients with reflux esophagitis in Taiwan. In this study the outcome and the specific prognostic indicators associated with outcome in patients were assessed retrospectively, 7 years after diagnosis of esophagitis. METHODS: The study comprised a total of 128 patients with endoscopic esophagitis, diagnosed between January and June 1995, at Taichung Veterans' General Hospital. The outcome at 7 years after diagnosis was assessed by outpatient or telephone interview. Factors associated with requiring long-term acid suppression therapy were analyzed. RESULTS: In all, 105 patients were eligible for analysis: 61 patients (58.1%) with LA (Los Angeles classification) grade A, 29 patients (27.6%) with grade B, 11 patients (10.5%) with grade C and 4 patients (3.5%) with grade D esophagitis. Seven years after diagnosis, there were 52 patients (49.5%) with no or occasional reflux symptoms, 8 patients (7.6%) with occasional symptoms requiring treatment with histamine-2 receptor antagonists (H2RAs), 12 patients (11.4%) with occasional symptoms requiring treatment with proton pump inhibitors (PPIs), as needed, and 33 patients (31.3%) with sustained symptoms needing daily maintenance with PPIs. CONCLUSION: Nearly 50% of patients in Taiwan with endoscopic esophagitis still required treatment 7 years after diagnosis. Approximately 31% of patients still required daily acid suppression therapy. Presence of hiatal hernia and the severity of esophagitis at initial endoscopy independently were predictive of those who would require long-term acid suppression therapy.

Role of Helicobacter pylori in cirrhotic patients with dyspepsia: a 13C-urea breath test study.

The role of Helicobacter pylori in dyspeptic, cirrhotic patients remains unclear. This prospective outpatient study, conducted to assess the relationship of gastroduodenal disease and H. pylori as determined by the (13C) urea breath test, enrolled 109 consecutive cirrhotic patients with dyspepsia. All patients underwent upper-gastrointestinal endoscopy, which revealed respective prevalences of peptic ulcer, gastric ulcer, and duodenal ulcer of 41.3%, 23.9%, and 22.9%; H. pylori infection was found in 52.3%. The rate of peptic ulcer disease in the H. pylori-positive (45.6%) and -negative (36.5%) groups was not significantly different; neither was the prevalence of H. pylori in patients with or without portal hypertensive gastropathy and with or without esophageal varices. The relationship between peptic ulcer disease and H. pylori in dyspeptic patients with cirrhosis appears to be weak. Likewise, no significant relationship was evident between H. pylori and portal hypertensive gastropathy or esophageal varices. This organism may not be a major pathogenetic factor in gastroduodenal diseases in dyspeptic patients with cirrhosis.

The effect of jejunal meal feeding on gastroesophageal reflux.

BACKGROUND: Postprandial gastric distention is frequently associated with transient lower esophageal sphincter relaxation and gastroesophageal reflux (GER). Since the role of nutrient perfusion into the jejunum in inducing GER is not well understood, we studied the effect of jejunal feeding on GER through a percutaneous gastrojejunal tube in patients with and without reflux esophagitis. METHODS: Nine stroke patients with reflux esophagitis were fed through a percutaneous gastrojejunal tube with either a liquid meal (2 kcal/2 ml/min) or saline for 2 h randomly on 2 separate days. An esophageal pH probe was placed 5 cm above the gastroesophageal junction to detect acid reflux. Six stroke patients without esophagitis were enrolled as controls. RESULTS: In both the patients with esophagitis and the controls, esophageal acid exposure (15.3% (4.9%-28.2%) versus 2.7% (0.0%-10.8%), P=0.003; 5.9% (0.5%-6.7%) versus 0.0% (0.0%-1.5%), P = 0.01) and events of acid reflux (5 (1-16) versus 2 (0-8), P = 0.02; 12 (3-17) versus 1 (0-4), P = 0.02) were significantly greater during jejunal meal feeding than during saline infusion. Furthermore, in the reflux patients, but not in the controls, acid clearance time was also greater during jejunal meal feeding than during saline infusion (2.9 min (0.5-9.6 min) versus 0.7 min (0.0-4.3 min), P = 0.04). CONCLUSIONS: We therefore conclude that jejunal nutrient infusion without gastric distention can induce GER in both patients with reflux esophagitis and controls. This implies that GER induced by jejununal nutrients may in part explain the incapability of jejunal tube feeding to prevent gastropulmonary aspiration in patients at risk.

Small intestinal bacterial overgrowth versus antimicrobial capacity in patients with spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic patients with ascites. Both defects in the host defense mechanisms and the enhancement of the offensive factor (small intestinal bacterial overgrowth (SIBO)) may contribute to the development of SBP. Therefore, the aim of this study was to evaluate the role of SIBO versus various antimicrobial capacities in the pathogenesis of SBP in cirrhotic patients. METHODS: Forty-five cirrhotic patients were enrolled in this study. Bacterial overgrowth was evaluated by breath hydrogen test (BH2T). The hepatic reticuloendothelial system phagocytic index (HRESPI) was measured by intravenously injected colloid suspensions. RESULTS: The Child-Pugh scores in the SBP group were higher than in the non-SBP group (10.5 +/- 2.0 versus 8.0 +/- 1.8, P < 0.01). The ascitic protein concentration was significantly lower in the SBP group than in the non-SBP group (897 +/- 425 mg/l versus 1,325 +/- 453 mg/l, P < 0.01). Furthermore, the serum C3 concentration was lower in the SBP group than in the non-SBP group (43.1 +/- 13.6 ng/dl versus 73.2 +/- 26.4 ng/dl, P < 0.01). The serum C4 concentration was also lower in the SBP group than in the non-SBP group (12.4 +/- 4.0 ng/dl versus 16.9 +/- 6.6 ng/dl, P < 0.05). The incidence of SIBO was higher in the SBP group than in the non-SBP group (68.2% versus 17.4%, P < 0.01). HRESPI values were significantly higher in the two groups of cirrhotic patients than in the normal reference. However, there were no statistical differences in HRESPI between the two groups (8.4 +/- 2.8 min in the SBP group versus 7.9 +/- 2.8 min in the non-SBP group). CONCLUSIONS: The results of this study showed that the hepatic reticuloendothelial function is impaired in cirrhotic patients, but the degree of impairment does not differ between patients with and without previous history of SBP. Lower ascitic total protein, lower serum C3 and C4 concentrations, and presence of SIBO are all risk factors for SBP. Based on the results of our study, defects in the host defense mechanisms and the enhancement of the offensive factor (SIBO) may act in concert for the development of SBP.

Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: long-term efficacy and safety.

BACKGROUND: The long-term efficacy and safety of the endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) were evaluated to define its role as the initial treatment for bleeding gastric varices. METHODS: Ninety patients with bleeding gastric varices underwent endoscopic injections of Histoacryl for hemostasis within a 6-year period. Histoacryl was injected intravariceally as a 1:1 mixture with Lipiodol. Among the 90 patients, 5 had active bleeding and 85 had recent bleeding. Most of the varices were large (F2 or F3, 85 cases). The most common locations were the fundus and the posterior wall of the proximal body (94.4%). After Histoacryl injection, patients were followed endoscopically with retreatment as necessary. RESULTS: The rate of hemostasis at 1 week was 94.4%. Recurrent bleeding occurred in 23.3% of the patients from 3 days to 16 months after the initial injection. Recurrent bleeding was stopped with reinjections of Histoacryl in 16.7% of the patients. The rate of definitive hemostasis was 93.3% (84 of 90). The treatment failure-related mortality rate was 2.2% (2 of 90). To date, 35 patients have died, mostly as a result of malignancy or liver failure, and 55 are still alive. The determining factor for long-term survival was the underlying disease leading to portal hypertension. There were few long-term complications except for Histoacryl cast extrusion-related mucosal defects. CONCLUSIONS: Endoscopic injection of Histoacryl is highly effective for the treatment of bleeding gastric varices, with rare complications both acutely and long term. This treatment modality is appropriate as the first choice for bleeding gastric varices.

Nasogastric lansoprazole is effective in suppressing gastric acid secretion in critically ill patients.

AIM: To evaluate the effect of nasogastric lansoprazole on acid suppression in critically ill patients. METHODS: Patients were eligible for the study if they had a nasogastric tube in place and had not received acid-suppressive agents for 3 days prior to enrolment into the study. Patients with active gastrointestinal bleeding or a baseline gastric pH > 4.0 were excluded. Patients served as their own controls during a 24 h lead-in period. Lansoprazole 30 mg was administered once daily with water through a nasogastric tube for 2 days. Intragastric pH was measured by continuous 24 h pH-metry for 3 days. RESULTS: Fifteen patients were enrolled into the study. The baseline median 24 h intragastric pH was 2.25 +/- 1.01, and increased to 6.70 +/- 0.82 (P= 0.001) after 2 days of lansoprazole. Mean percentage of time intragastric pH was > or = 4.0 was 25 +/- 13% at baseline, and increased to 84 +/- 14% (P=0. 001) after 2 days of lansoprazole. CONCLUSIONS: Nasogastric lansoprazole 30 mg daily is effective in suppressing gastric acid secretion in critically ill patients.

The effect of intragastric acidity on Helicobacter pylori eradication with bismuth-metronidazole-amoxicillin.

BACKGROUND/AIMS: Adding an acid secretion inhibitor to anti-H. pylori regimens may be potentially valuable for enhancing the effectiveness of antimicrobials that exhibit markedly reduced activity at low pH. This study was conducted to evaluate intragastric acidity as a factor in H. pylori eradication with bismuth-based triple therapy. METHODOLOGY: Forty patients with duodenal ulcer and H. pylori infection were included. The patients were divided into 2 groups--normacid (n = 20) and hyperacid (n = 20)--based on the amount of time that 24-hour intragastric pH took to reach the level pH > or = 3. All patients received bismuth subsalicylate (600 mg 3 times daily), metronidazole (500 mg 3 times daily) and amoxicillin (500 mg 3 times daily) for 2 weeks. Then, all patients continued treatment with ranitidine (150 mg twice daily) for 8 weeks prior to the follow-up examination. Blood samples were collected before treatment for measurement of fasting gastrin and pepsinogen-I. RESULTS: Nine patients (45%) in the normacid group and 8 patients (40%) in the hyperacid group reported side effects. However, there were only 2 patients (10%) in each group who withdrew from the study due to intolerance of side-effects. There was no difference in the H. pylori eradication rate between the normacid and hyperacid groups (16/18, 88.9% vs. 15/18, 83.3%). CONCLUSIONS: Without co-administration of anti-secretary agents, intragastric acid is not a significant factor in the effectiveness of H. pylori eradication with bismuth-based triple therapy.

Interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs in peptic ulcer bleeding.

BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the two primary causes of peptic ulcer disease. How H. pylori and NSAIDs interact and influence the development of ulcer bleeding is still not clear. METHODS: A hospital-based, age- and sex-matched case-control study was conducted. Multivariate and stratified analyses were performed for further evaluation of the interaction between H. pylori and NSAIDs. RESULTS: Ninety-seven patients (52 gastric ulcers, 45 duodenal ulcers) and 97 non-ulcer controls were enrolled in the study. H. pylori and NSAIDs were both found to be independent risk factors for ulcer bleeding (H. pylori odds ratio, 2.22; 95% confidence interval (CI), 1.23-4.01; NSAIDs odds ratio, 4.57; 95% CI, 2.50-8.35). There was no synergistic effect. In contrast, a negative interaction was observed in the logistic regression and stratified analysis, although the difference was not significant (H. pylori adjusted odds ratio, 3.47; 95% CI, 1.73-6.95; NSAID adjusted odds ratio, 6.16; 95% CI, 3.14-12.09). CONCLUSION: H. pylori increases the risk of peptic ulcer bleeding but may play a protective role in NSAID users.

Helicobacter pylori infection and gastric emptying in cirrhotic patients with symptoms of dyspepsia.

BACKGROUND/AIMS: Chronic gastric Helicobacter pylori infection is common in patients with dyspeptic symptoms. The effect of H. pylori infection on gastric emptying, in cirrhotic patients with dyspeptic symptoms, has never been studied. Therefore, we investigated the incidence of H. pylori infection and its relationship with gastric emptying in cirrhotic patients with dyspepsia. METHODOLOGY: A solid-phase gastric emptying study and 14C urea breath test were performed in 80 cirrhotic patients with dyspepsia. The severity of cirrhosis was assessed according to Child-Pugh's classification. RESULTS: The overall incidence of delayed gastric emptying was 75%. Delayed gastric emptying incidences according to severity of cirrhosis were 71.4% for Child-A, 73.1% for Child-B, and 80.8% for Child-C. The differences were not significant. The incidence of H. pylori infection was 52.5% overall. H. pylori infection rates were 46.4% for Child-A, 42.3% for Child-B, and 69.2% for Child-C. Although there was a tendency for the infection rate to increase with the severity of liver cirrhosis, the difference was not significant. In addition, there were no significant differences in the incidences of H. pylori infection among patients with normal and delayed gastric emptying. CONCLUSIONS: Delayed gastric emptying is common in cirrhotic patients with dyspepsia. However, the status of H. pylori infection does not seem to play a role in delayed gastric emptying in these patients.

Electrogastrographic study of the effect of transcatheter arterial chemoembolization on gastric myoelectric activity.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) of the hepatic artery is frequently used in the treatment of inoperable hepatocellular carcinoma (HCC). TACE causes not only effective tumor tissue necrosis in patients with hepatoma but also adverse effects on extrahepatic abdominal organs. There are no published reports on the effect of TACE on the gastric myoelectric activity. In this study, using cutaneous electrogastrography (EGG), we evaluated the effect of TACE on gastric myoelectric activity in patients with HCC. METHODS: A total of 27 patients (24 men and 3 women, aged 22 to 78 years) with hepatoma, admitted for TACE, were included in this study. Furthermore, 28 patients (24 men and 4 women, aged 26 to 75 years), admitted for diagnostic angiography of the liver, served as the control group. Cutaneous EGG was performed before and after TACE or angiography. RESULTS: In the TACE group there were significant changes in dominant frequency (DF) and percentages of DF in the defined normal range, bradygastric range, and tachygastric range on post-meal EGG. On fasting EGG, only the dominant frequency and percentages of DF in the bradygastric range changed significantly. However, there was no correlation between the occurrence of nausea/vomiting and the degree of change in the EGG variables, during both fasting and postprandial states. In the control group there were no significant differences in EGG variables before and after angiography. CONCLUSIONS: TACE can affect gastric myoelectric activity in HCC patients. Nevertheless, the relationship between changes in myoelectric activity and the occurrence of gastrointestinal symptoms needs further investigation.