Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease

Background  Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS).
Aim  To assess the correlation between LS and HVPG and to investigate the performance of transient elastography for the diagnosis of significant portal hypertension (PHT).
Methods  Liver stiffness was measured by Fibroscan in 150 consecutive patients who underwent a liver biopsy with haemodynamic measurements. Usual clinical and biological data were collected. Significant PHT was defined as a HVPG ≥10 mmHg.
Results  Hepatic venous pressure gradient was found to be ≥10 mmHg in 76 patients. Cirrhosis was diagnosed in 89 patients. HVPG was found to be correlated with: LS ( ρ  = 0.858; P  < 0.001) and inversely correlated with prothrombin index ( ρ  = −0.718; P  < 0.001). Regarding significant PHT, AUROC for LS and prothrombin index were 0.945 [0.904–0.987] and 0.892 [0.837–0.947] respectively. The cut-off value of 21 kPa accurately predicted significant PHT in 92% of the 144 patients for whom LS was successful.
Conclusion  Liver stiffness measurement is correlated with HVPG and transient elastography identifies patients with significant PHT.     

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis

Background  In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM.
Aims  To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis.
Methods  Nondiabetic patients with genotype 1 CHC ( n  = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemical and metabolic features including IR. Furthermore, all subjects underwent LSM by TE.
Results  Severe fibrosis (F3–F4) was associated with LSM (OR 1.291; 95%CI 1.106–1.508). LSM was also independently correlated with low platelets ( P  =   0.03), high γGT ( P  <   0.001) and high HOMA ( P  =   0.004) levels. A stiffness value ≥8 KPa was identified as the best cut-off for predicting severe fibrosis ( AUC 0.870); yet this cut-off still failed to rule out F3–F4 fibrosis in 22.7% of patients (false-negative rate) or rule in F3–F4 in 19.6% (false-positive rate). Platelets <200 × 10³/mmc and a HOMA of >2.7 were the major determinants of these diagnostic errors in predicting severe fibrosis.
Conclusions  In nondiabetic patients with genotype 1 CHC, insulin resistance, γGT and platelet levels contribute to LSM independently of liver fibrosis. The identification of these three factors contributes to a more correct interpretation of LSM.     

瞬时弹性成像联合APRI在慢性乙型肝炎肝纤维化诊断中的应用价值

目的 评价瞬时弹性成像(FibroScan) 联合天冬氨酸转移酶(AST)与血小板指数(PLT)的比值(APRI)在判断慢性乙型肝炎患者肝纤维化程度中的作用。 方法 选择152例临床确诊为慢性乙型肝炎患者,进行常规实验室检查、FibroScan检查和肝脏活组织检查,探究FibroScan及APRI的诊断价值,并绘制FibroScan、APRI以及联合诊断模型的受试者工作特征曲线(ROC曲线),分析三者与肝脏纤维化病理分期的相关性。 结果 FibroScan 与 APRI对显著纤维化(S2~S4期)的曲线下面积(AUROC值)和95% 可信区间(95%CI)分别为0.752(0.672~0.832),0.717(0.630~0.805),对S3~S4期的 AUROC值分别为0.937(0.890~0.985),0.911(0.836~0.986),对S4期的AUROC值分别为0.973(0.947~0.998),0.934(0.862~1.000);两者联合后对S2~S4期的AUROC值为0.811(0.732~0.890)。结论 FibroScan联合APRI诊断模型可以进一步提高对显著期肝纤维化的诊断效能,对临床选择抗病毒治疗,干预肝纤维化进程具有一定的指导意义。     

Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease

Background  Small-intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications.
Aim  To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis.
Methods  Small-intestinal bacterial overgrowth was determined by glucose–hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by ≥12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis.
Results  Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control ( P  = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child–Pugh A 20%, B 52% and C 73%; P  = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut-off of serum bilirubin was ≥2 mg/dL [AUROC 0.77 (95% CI 0.64–0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin ≥2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO.
Conclusions  Small-intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO.     

Transient elastography to assess hepatic fibrosis in primary biliary cirrhosis

Background  Liver stiffness measurements may have potential for detecting and monitoring hepatic fibrosis in chronic liver disease.
Aim  To study the detection, quantification and progression of hepatic fibrosis in primary biliary cirrhosis by liver stiffness measurements.
Methods  Liver stiffness measurements were generated in 80 patients with primary biliary cirrhosis by applying transient elastography; however, as there were 55 with liver biopsy, histological stage (METAVIR) and liver stiffness measurements were compared only in these 55 patients. The efficiency of liver stiffness measurements in predicting stage of fibrosis was determined from the area under receiver operating characteristics curve analysis.
Results  Of the 80 patients included, 91, 4% were women and their mean age was 56 ± 12 (s.d.) years. A significant correlation was found ( P  < 0.05) between histological fibrosis stage (METAVIR) and liver stiffness measurements. The values obtained from area under receiver operating characteristic curve analysis of liver stiffness measurement data were 0.89 for F  > 2 and 0.96 for F  = 4. Liver stiffness measurements were 9.0 ± 5.3 and 7.9 ± 6.0 kPa for patients followed up more than 5 years and less than 5 years, respectively ( P  > 0.05).
Conclusions  In patients with primary biliary cirrhosis, median values of liver stiffness measurements correlated with histological severity of hepatic fibrosis. Liver stiffness measurements appear to be promising for liver fibrosis detection and quantification, as well as monitoring its progression, in patients with primary biliary cirrhosis. The progression rate of hepatic fibrosis in our primary biliary cirrhosis patients appears to be slow.     

Optimized stepwise combination algorithms of non-invasive liver fibrosis scores including Hepascore in hepatitis C virus patients

Background  Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients.
Aim  To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy.
Methods  The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years.
Results  Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%).
Conclusions  Hepascore is an accurate non-invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.     

Histological subclassification of cirrhosis based on histological-haemodynamic correlation

Background  Determining a relationship between specific histological parameters in cirrhosis and hepatic venous pressure gradient can be used to subclassify cirrhosis.
Aim  To determine the relationship between hepatic venous pressure gradient and specific histological parameters in cirrhosis.
Methods  Forty-seven patients (mean age: 46.2 ± 13.6 years; 36 male) with biopsy-proven cirrhosis and hepatic venous pressure gradient measurements within 1 month of biopsy were studied. The following histological parameters were scored semiquantitatively: nodule size, loss of portal tracts and central veins, portal inflammation, periportal inflammation, bile duct proliferation, lobular inflammation, ballooning, fatty change, cholestasis and septal thickness.
Results  On multiple ordinal regression analysis, small nodule size (odds ratio: 21.0; 95% confidence interval: 2.1–208.2, P  = 0.009) and thick septa (OR: 42.6; CI: 2.3–783.7, P  = 0.011) were significantly associated with the presence of clinically significant portal hypertension. A score was assigned to each of the two parameters (nodule size: large = 1, medium = 2, small = 3 and septal thickness: thin = 1, medium = 2, thick = 3). Two subcategories were devised based on the composite score: category A ( n  = 12): score 1–3 and category B ( n  = 35): score 4–6. On ordinal regression, subcategory B (OR: 15.5; CI: 3.3–74.2, P  = 0.001) was significantly associated with clinically significant portal hypertension.
Conclusion  Small nodularity and thick septa are independent predictors of the presence of clinically significant portal hypertension.     

Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patients

Background  Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis.
Aims  To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients.
Methods  A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 μg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively.
Results  Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 ( P  < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0–217.3), 4.2 (95% CI 1.2–15.3) and 9.1 (95% CI 2.2–38.0), respectively.
Conclusion  In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.     

Predictors of serious complications due to Clostridium difficile infection

Background  Identifying individuals with severe Clostridium difficile infection (CDI) at risk for major complications has become an important objective. Presence of clinical variables that predict complications from CDI would have the potential to strongly influence management.
Aim  To determine which clinical variables predict complications from CDI.
Methods  Cross-sectional study of all individuals admitted to Temple University Hospital between 12/1/03 and 7/1/08 with the primary discharge diagnosis of CDI were eligible. Only patients experiencing their first episode of CDI were included. Abstracted data included demographic, physiological, laboratory, radiological, endoscopic, pharmacy and outcome data. Response was categorized as none, partial or complete. Complications attributed to CDI were defined as colon resection or death.
Results  Overall 32 of 200 patients (16%) experienced a complication due to CDI including death ( n  = 20) and colectomy ( n  = 12). White blood cell count above 30,000 cells/mm³ (OR = 4.06; 95% CI, 1.28–12.87) and a rise in the creatinine to over 50% above baseline (OR = 7.13; 95% CI, 3.05–16.68) predicted a complication. AROC for percent rise in serum creatinine was 0.73 (95% CI: 0.64–0.85) and 0.62 (95% CI: 0.58–0.80) for white blood cell count.
Conclusions  Severe white blood cell count elevation and a rise in the creatinine to over 50% above baseline are important independent predictors of serious adverse events due to CDI. These patients likely would benefit from more intensive care and early surgical consultation.     

Epidemiological study of gastro-oesophageal reflux disease: reflux in spouse as a risk factor

Background  Gastro-oesophageal reflux disease (GERD) is a growing health-care problem with variable distribution.
Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population-based study.
Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self-administered questionnaires were used.
Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m² (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first-degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first-degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months ( P  < 0.05).
Conclusions  Gastro-oesophageal reflux disease is common in Tehran. The association of 'infrequent symptoms' with GERD history in first-degree relatives and 'frequent symptoms' with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.     

Clinical trial: interferon alpha-2b continuous long-term therapy vs. repeated 24-week cycles for re-treating chronic hepatitis C

Background  Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy.
Aim  To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy.
Methods  A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase and negative hepatitis C virus -RNA, n  =   244) were then randomized to continuous interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III) and necrosis (IV) scores at baseline vs. year 2 were compared.
Results  Patients receiving continuous low-dose therapy vs. cycled therapy had larger reductions in inflammation (−3.9 vs. −3.1) and fibrosis (−0.49 vs. −0.24). Among both groups, the mean change was −3.4 for inflammation and −0.36 for fibrosis. Overall, 73% (95% CI: 67–79) of patients experienced reduced inflammation and 28% (95% CI: 22–34) had reduced fibrosis.
Conclusions  Our results suggest hepatitis C virus patients experiencing viral suppression during long-term maintenance therapy with interferon demonstrate histological improvement. Further prospective trials testing this hypothesis are in progress.     

The association between coeliac disease and cardiovascular disease

Background  Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear.
Aim  To investigate whether coeliac disease patients have an increased risk of cardiovascular events.
Methods  A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study.
Results  The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4–14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6–10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00–3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22–5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort ( P  = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort ( P  < 0.01).
Conclusion  Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.     

The epidemiology of haemochromatosis: a population-based study

Background  The discovery of the HFE genotype has revolutionized the diagnosis of haemochromatosis, changing the associated mortality and morbidity.
Aim  To investigate the clinical significance of a diagnosis of haemochromatosis.
Methods  In a cohort study, we identified 501 people with haemochromatosis and 4950 age- and gender-matched controls from the UK General Practice Research Database between 1987 and 2002.
Results  The incidence of a diagnosis of haemochromatosis increased approximately 2-fold over the study period and was associated with a 2.2-fold increase in mortality [hazard ratio, 95% confidence interval (95% CI), 1.6–3.0]. There was no increase in extra hepatic malignancy, but an absolute risk excess of liver cancer of 0.89% per year. Diabetes, impotence, osteoarthritis and crystal arthritis were associated with haemochromatosis with odds ratios of 5.4 (95% CI, 4.1–7.0), 2.7(95% CI, 1.8–4.0), 1.9(95% CI, 1.5–2.4) and 2.1(95% CI, 1.4–3.1) respectively.
Conclusion  Increasing numbers of people are being diagnosed with haemochromatosis, and the mortality associated with this disease remains high. However, people are living with considerably lower levels of morbidity than previously reported. This encouragingly suggests earlier diagnoses are being made, prior to the development of complications.     

凸阵探头实时组织弹性成像、声辐射力脉冲弹性成像与瞬时弹性成像诊断慢性乙肝相关肝纤维化程度的比较

目的 比较凸振探头实时组织弹性成像（C-RTE）、声辐射力脉冲弹性成像（ARFI）及瞬时弹性成像（TE）评 估肝纤维化的诊断效能。方法 选取167例慢性乙肝（CHB）患者,分别进行C-RTE、ARFI及TE检查及肝穿刺活检, 以病理学结果为金标准。比较病理纤维化分期之间各弹性成像肝硬度检测指标差异,分析C-RTE、ARFI及TE与病 理纤维化分期的相关性,构建受试者工作特征（ROC）曲线分析3种成像方法的诊断效能,并采用DeLong法比较不同 检测方法的曲线下面积（AUC）。结果 除C-RTE及ARFI诊断S0/S1和S3/S4之间,TE诊断S0/S1和S0/S2之间差异 无统计学意义（P＞0.05）,余各组间比较差异均有统计学意义;C-RTE、ARFI及TE与病理肝纤维化分期的相关系数 分别为 0.72、0.65、0.68（P＜0.001）;C-RTE、ARFI 及 TE 3 者诊断≥S1、≥S2、≥S3 及 S4 期的曲线下面积分别为 0.812、 0.917、0.848及0.785;0.824、0.818、0.858及0.822;0.858、0.833、0.876及0.884,最佳临界值分别为1.3、1.74、2及2.64; 5.3 kPa、7.2 kPa、8.9 kPa及19.4 kPa;1.29 m/s、1.71 m/s、1.89 m/s及2.02 m/s;且在≥S2时,C-RTE的诊断效能优于ARFI 及TE（Z分别为2.56和2.84,P＜0.01）。结论 C-RTE对各级肝纤维化具有较高的诊断价值,值得临床推广。     

The impact of liver disease aetiology and the stages of hepatic fibrosis on the performance of non-invasive fibrosis biomarkers: an international study of 2411 cases

Aliment Pharmacol Ther 2011; 34: 1202–1216

Summary

Background Performance of non‐invasive fibrosis biomarkers may be influenced by aetiology of chronic liver disease (CLD) and the stages of hepatic fibrosis, but large‐scale studies are pending. Aim To investigate the effect of aetiogy and stages of hepatic fibrosis on the performance of fibrosis biomarkers. Methods A total of 2411 patients with compensated CLD (HCV = 75.1%, HBV = 10.5%, NASH = 7.9%, HIV/HCV = 6.5%) were consecutively enrolled in 9 centres. APRI, Forns’index, Lok index, AST‐to‐ALT ratio, Fib‐4, platelets and Fibrotest‐Fibrosure were tested against liver biopsy, considered the gold standard. The effect of the stages of hepatic fibrosis to diagnose significant fibrosis and cirrhosis (≥F2 and F4 respectively) was investigated through difference between advanced and non‐advanced fibrosis stages (DANA). Performance was expressed as observed area under the ROC curve (ObAUROC) and AUROC adjusted for DANA (AdjAUROC). Results Performance of APRI and Fibrotest‐Fibrosure was higher than other biomarkers. In all aetiologies, AdjAUROC was higher than ObAUROC. APRI showed its best performance in HCV monoinfected cases, with an AdjAUROC of 0.77 and 0.83 for ≥F2 and F4 respectively. In HBV and non‐alcoholic steatohepatitis (NASH) patients, its performance was poor (AdjAUROC <0.70). Performance of Fibrotest‐Fibrosure was good in all aetiologies for both ≥F2 and F4 (AdjAUROC >0.73), except for ≥F2 in NASH (AdjAUROC = 0.64). Performance of all biomarkers was reduced in HCV cases with normal ALT. Conclusions Aetiology is a major factor influencing the performance of liver fibrosis biomarkers. Even after correction for DANA, APRI and Fibrotest‐Fibrosure exhibit the best performance. However, liver biopsy is not replaceable, especially to diagnose ≥F2 and in HCV carriers with normal ALT.

     

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C

Aliment Pharmacol Ther 2011; 33: 138–148

Summary

Background Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. Aim To validate and compare the diagnostic performance of non‐invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. Methods The performances of Forns’ score, AST to platelet ratio index (APRI), FIB‐4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. Results Forns’ score, APRI, FIB‐4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB‐4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non‐1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. Conclusions Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.     

Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements

Background  The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory.
Aim  To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers.
Methods  Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses.
Results  We identified 20 randomized trials (211 818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83–1.06, I ²  = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96–1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43–0.80, test of interaction P  < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97–1.07, I ²  = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02–1.07).
Conclusions  We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality.     

Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group ( P  <   0.001). The PPI response rates at 8 weeks were different ( P  =   0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.     

Evidence of allelic heterogeneity for associations between the NOD2/CARD15 gene and ulcerative colitis among North Indians

Background  Three common disease susceptibility variants in the NOD2 gene are associated with inflammatory bowel disease in Caucasians, but not in Asians.
Aim  To screen for NOD2 variants and examine susceptibility for inflammatory bowel disease in North Indians.
Methods  A case–control study was carried out in Punjab, India. Confirmed cases of ulcerative colitis and Crohn's disease and healthy controls matched for age (±10 years) and ethnicity were studied. Besides genotyping the three disease susceptibility variants (SNP8, SNP12 and SNP13), all 12 exons were resequenced to determine other potential single nucleotide polymorphisms.
Results  Two hundred and ninety-eight ulcerative colitis, 25 Crohn's disease and 262 controls were investigated. Median age (range) at diagnosis was 39 (7–78) years for ulcerative colitis and 40 (32–58) years for Crohn's disease. All three disease susceptibility variants were either monomorphic or rare in the population. Sequencing ( n  = 30) revealed two single nucleotide polymorphisms: SNP5 (268 Pro/Ser) and rs2067085 (178 Ser/Ser). The frequency of SNP5 was higher among ulcerative colitis (17% vs. 12% in controls, P  = 0.016) and Crohn's disease cases (20% vs. 12%, P  = 0.28). SNP5 carriers had elevated risks for ulcerative colitis (OR = 1.72, 95% CI = 1.17–2.52, P  = 0.005).
Conclusions  The absence of known inflammatory bowel disease susceptibility variants and potential associations between SNP5 and ulcerative colitis in North Indians suggests the presence of allelic heterogeneity for ulcerative colitis susceptibility.