Long-term use of oral nucleos(t)ide analogues for chronic hepatitis B does not increase cancer risk - a cohort study of 44 494 subjects.

BACKGROUND: Patients with chronic hepatitis B (CHB) need long-term antiviral treatment with nucleos(t)ide analogues (NA). Animal studies suggest that some NA may increase cancer risk, but human data are lacking. AIM: To investigate cancer risks in patients with or without NA treatment. METHODS: We conducted a territory-wide cohort study using the database from Hospital Authority in Hong Kong. The diagnosis of CHB and various malignancies was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes between 2000 and 2012. Patients exposed to any of the oral NA for CHB were included. The primary outcome was incident cancers. A 3-year landmark analysis, with follow-up up to 7 years, was used to evaluate the relative risk of cancers in treated and untreated patients. RESULTS: A total of 44 494 patients (39 712 untreated and 4782 treated) were included in the analysis. During 194 890 patient-years of follow-up, hepatocellular carcinoma developed in 402 (1.0%) untreated patients and 179 (3.7%) treated patients, while other cancers developed in 528 (1.3%) and 128 (2.7%) patients respectively. After propensity score weighting, treated patients had similar risks of all malignancies [weighted hazard ratio (wHR): 1.01, 95% CI: 0.82-1.25, P = 0.899], lung/pleural cancers (wHR: 0.82, 95% CI: 0.52-1.31, P = 0.409) and urinary/renal malignancies (wHR: 1.04, 95% CI: 0.38-2.81, P = 0.944) when compared with untreated patients. CONCLUSIONS: Oral nucleos(t)ide analogue treatment does not appear to increase cancer risk in patients with chronic hepatitis B. Given the beneficial effect on liver outcomes, our data support the current practice of long-term anti-viral therapy.

Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity.

BACKGROUND: Many strategies are used to prevent nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal toxicity, but the comparative effectiveness remains unclear. AIM: To evaluate the comparative effectiveness of clinical strategies for preventing gastrointestinal toxicity induced by NSAIDs. METHODS: MEDLINE, EMBASE and the Cochrane Library (from their inception to May 2015) were searched for randomised controlled trials comparing the risk of gastrointestinal adverse events in patients taking nonselective NSAIDs, selective cyclooxygenase(COX)-2 inhibitors or nonselective NSAIDs/COX-2 inhibitors plus gastroprotective agents [proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol]. Both pairwise meta-analysis and Bayesian network meta-analysis were performed. RESULTS: Analyses were based on 82 trials including 125 053 participants. Network meta-analysis demonstrated that selective COX-2 inhibitors + PPIs [Risk ratio (RR), 95% Credible Interval (CrI): ulcer complications 0.07, 0.02-0.18], selective COX-2 inhibitors (RR, 95% CrI: ulcer complications 0.25, 0.15- 0.38; symptomatic ulcer 0.12, 0.04-0.30), nonselective NSAIDs + PPIs (RR, 95% CrI: ulcer complications 0.28, 0.18-0.41; symptomatic ulcer 0.11, 0.04-0.23), nonselective NSAIDs + misoprostol (RR, 95% CrI: ulcer complications 0.47, 0.24-0.81; symptomatic ulcer 0.41, 0.13-1.00) were associated with significantly lower risk of clinical gastrointestinal events compared with nonselective NSAIDs. For all effectiveness endpoints, selective COX-2 inhibitors + PPIs was associated with the lowest absolute event probability and the highest rank, followed by selective COX-2 inhibitors and thirdly by nonselective NSAIDs + PPIs. CONCLUSION: The combination of selective COX-2 inhibitors plus PPIs provides the best gastrointestinal protection, followed by selective COX-2 inhibitors, and thirdly by nonselective NSAIDs plus PPIs.

Systematic review with meta-analysis: faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies.

BACKGROUND: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. AIM: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. METHODS: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). RESULTS: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8-15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7-95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. CONCLUSION: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.

Oral nucleos(t)ide analogues reduce recurrence and death in chronic hepatitis B-related hepatocellular carcinoma.

BACKGROUND: In patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC), high viral load was associated with tumour recurrence and deaths. AIMS: To investigate the effect of nucleos(t)ide analogues (NA) on the clinical outcomes after different HCC treatments. METHODS: A territory-wide cohort study was conducted using the database from Hospital Authority. We identified CHB patients with HCC by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in 2000-2012. HCC treatments, NA use and laboratory parameters were retrieved. The primary endpoint was HCC recurrence and death. A 3-month landmark analysis was used to evaluate the primary outcome in patients with or without NA treatment. RESULTS: A total of 2198 CHB patients (1230 NA-untreated and 968 NA-treated) with HCC, receiving at least one type of HCC treatment were included in the analysis. At a median follow-up of 2.8 (IQR 1.4-4.9) years, tumour recurrence and death occurred in 451 (36.7%) and 578 (47.0%) untreated patients; and in 216 (22.3%) and 301 (31.1%) NA-treated patients respectively. NA therapy reduced the risk of overall HCC recurrence [adjusted sub-hazard ratio (SHR) 0.63, 95% confidence interval (CI) 0.49-0.80; P < 0.001]. The effect was most obvious in patients undergoing resection (SHR = 0.58, 95% CI = 0.37-0.91, P = 0.018). The possibility of NA therapy reducing the risk of death (HR = 0.82, 95% CI = 0.64-1.03, P = 0.092), is most obvious in resection subgroup (HR = 0.64, 95% CI = 0.41-0.99, P = 0.050) but insignificant in the other treatment groups. CONCLUSION: Our findings show that nucleos(t)ide analogues treatment reduces the risk of HCC recurrence in patients with chronic hepatitis B treated by surgical resection.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

Systematic review: the efficacy of herbal therapy in inflammatory bowel disease.

BACKGROUND: Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited. AIM: To systematically review the literature on the efficacy of herbal therapy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Publications in English and non-English literatures (MEDLINE, EMBASE, EBM Reviews, AMED, Global Health) were searched from 1947 to 2013 for controlled clinical studies of herbal therapy in IBD. Outcome measures included response and remission rates. RESULTS: Twenty-one randomised controlled trials (14 UC; 7 CD) including a total of 1484 subjects (mean age 41, 50% female) were analysed. In UC, aloe vera gel, Triticum aestivum (wheat grass juice), Andrographis paniculata extract (HMPL-004) and topical Xilei-san were superior to placebo in inducing remission or response, and curcumin was superior to placebo in maintaining remission; Boswellia serrata gum resin and Plantago ovata seeds were as effective as mesalazine, whereas Oenothera biennis (evening primrose oil) had similar relapse rates as omega-3 fatty acids in the treatment of UC. In CD, Artemisia absinthium (wormwood) and Tripterygium wilfordii were superior to placebo in inducing remission, and preventing clinical recurrence of post-operative CD respectively. CONCLUSIONS: Randomised controlled trials of herbal therapy for the treatment of IBD show encouraging results but studies remain limited and heterogenous. Larger controlled studies with stricter endpoints and better-defined patient groups are required to obtain more conclusive results on the use of CAM therapies in IBD.

Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding.

BACKGROUND: The efficacy of adjuvant use of intravenous proton pump inhibitors (PPIs) after endoscopic therapy has been proved in peptic ulcer bleeding patients, but the efficacy of oral PPIs is uncertain. AIM: To compare the clinical outcomes of oral PPIs vs. intravenous PPIs in patients with peptic ulcer bleeding. METHODS: Prospective randomised controlled trials were systematically searched from OVID databases until June 2012. Trials comparing oral and intravenous PPIs among patients with peptic ulcer bleeding were included. Recurrent bleeding, length of hospitalisation, blood transfusion, requirement of surgery and mortality were measured. The risk of bias, study quality and heterogeneity were also evaluated. RESULTS: Six randomised trials from 2006 to 2011 were included. A total of 615 patients were randomly assigned to receive oral PPIs (n = 302) or intravenous PPIs (n = 313). The mean age was 60 years and 71.1% was male. No significant difference between oral and intravenous PPIs was observed regarding recurrent bleeding (RR: 0.92, 95% CI: 0.56-1.50), mean volume of blood transfused (-0.02 unit, 95% CI: -0.29-0.24 unit), requirement of surgery (RR: 0.82, 95% CI: 0.19-3.61) and all-cause mortality (RR: 0.88, 95% CI: 0.29-2.71). The duration of hospital stay in days was significantly shortened in those using oral PPIs (-0.74 day, 95% CI: -1.10 day to -0.39 day). CONCLUSION: Oral PPIs demonstrate a similar effectiveness to intravenous PPIs among patients with peptic ulcer bleeding, but the results were combined from open-labelled trials with limited sample size. A large double-blind non-inferiority trial is required to better assess the role of oral PPIs.

Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma.

BACKGROUND: The role of anti-viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined. AIM: To investigate the role of anti-viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)-related HCC. METHODS: A systematic electronic search on keywords including HCC and different anti-viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV-related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality. RESULTS: Nine cohort studies were included with a total number of 551 patients: 204 patients with anti-viral treatment group and 347 patients without anti-viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti-viral treatment group (55% vs. 58%; odds risk (OR)=0.59, 95% CI 0.35-0.97, P=0.04). The risk of HCC was reduced by 41% in the anti-viral treatment group. There were also significant differences in favour of anti-viral treatment group in terms of liver-related mortality (0% vs. 8%; OR=0.13, 95% CI 0.02-0.69, P=0.02) and overall mortality (38% vs. 42%; OR=0.27, 95% CI 0.14-0.50, P<0.001). CONCLUSIONS: Anti-viral therapy has potential beneficial effects after the curative treatment of HBV-related hepatocellular carcinoma in terms of tumour recurrence, liver-related mortality and overall survival. Anti-viral therapy should be considered after curative treatment of hepatocellular carcinoma.

Meta-analysis: reduction in hepatic events following interferon-alfa therapy of chronic hepatitis B.

BACKGROUND: The long-term benefit of interferon-alfa (IFN-α) treatment in preventing various hepatic complications is not certain. AIM: To study the effects of IFN-α on reducing the risk of developing overall hepatic events (hepatocellular carcinoma, cirrhotic complications and liver-related mortality) in chronic hepatitis B patients. METHODS: Randomized controlled trials, case-control studies and cohort studies were retrieved from electronic databases and conference abstracts. Relative risks (RRs) of different hepatic complications among patients treated by IFN-α vs. no treatment or placebo were studied. RESULTS: Eleven studies were identified totalling 975 patients treated by IFN-α vs. 1147 untreated controls for analysis. Patients were treated by IFN-α for 1-24 months with a post-treatment follow-up of 1-13 years. Treatment by IFN-α reduced the risk of overall hepatic events (RR 0.55, 95% confident interval or CI 0.43-0.70, P < 0.001) and cirrhotic complications (RR 0.46, 95% CI 0.32-0.67, P < 0.001) by 45% and 54% respectively. Patients who responded to IFN-α had more profound reduction in overall hepatic events (RR 0.20, 95% CI 0.05-0.87, P = 0.03) and cirrhotic complications (RR 0.19, 95% CI 0.09-0.38, P < 0.001) vs. the untreated controls. CONCLUSION: Interferon-alfa treatment reduces the risk of hepatic events particularly among responders to treatment.

A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: a prospective study among Chinese.

BACKGROUND: Preferences to choose immunochemical faecal occult blood test (FIT) and colonoscopy as colorectal cancer (CRC) screening modalities among asymptomatic Chinese subjects remain unknown. AIM: To evaluate the preference of choosing colonoscopy vs. FIT among CRC screening participants. METHODS: From a community-based CRC screening programme for asymptomatic Hong Kong Chinese aged 50-70 years, participants attended standardized educational sessions and chose the options of annual FIT for 5 years or direct colonoscopy once. Factors associated with choosing colonoscopy were evaluated by multivariate regression analysis. RESULTS: Among 3430 participants [mean age 56.8 years (s.d. 5.0); female 55.1%, male 44.9%], 51.3% chose colonoscopy and 48.7% chose FIT. Older participants (65-70 years) were less likely to choose colonoscopy [adjusted odds ratio (aOR) 0.731, P = 0.041]. Subjects who chose colonoscopy were those disagreed screening would lead to discomfort (aOR 1.356, P < 0.001), had relatives or friends who had CRC (first degree relatives aOR 1.679, P < 0.001; second degree relatives aOR 1.304, P = 0.019; friends or others aOR 1.252, P = 0.026) and those who self-perceived their health as poor (aOR 1.529, P = 0.025). CONCLUSIONS: Faecal occult blood test and direct colonoscopy were equally preferable to Chinese. Colonoscopy was preferred among the younger subjects, those with positive family history of CRC and self-perceived poor health status.

Development and validation of a disease-specific quality of life questionnaire for gastro-oesophageal reflux disease: the GERD-QOL questionnaire.

BACKGROUND: A simple and meaningful health-related quality of life (HRQoL) questionnaire for gastro-oesophageal reflux disease (GERD) patients is lacking. AIM: To develop and validate a disease-specific HRQoL instrument (GERD-QOL) for GERD patients. METHODS: An 18-item questionnaire was generated to measure the impact of GERD on sleep, exercise, diet, need for medication, sex life, work, social activity and psychological well-being. GERD patients were invited to complete the GERD-QOL, a visual analogue scale (VAS) and a validated Chinese generic QoL (SF-36) questionnaire before and after esomeprazole treatment. Factor analysis was performed for item selection and psychometric properties were measured. An English version was developed by a forward-backward translation process. RESULTS: A final 16-item GERD-QOL questionnaire was developed. The items were grouped into four subscales (Daily activity, Treatment effect, Diet, and Psychological well-being) after factor analysis. GERD-QOL had good item-internal consistency (Cronbach's alpha: 0.64-0.88), high test-retest reliability (intraclass correlation coefficient: 0.73-0.94, P < 0.001). Its subscale scores were correlated with SF-36 and VAS, which demonstrated high construct validity (P < 0.001). Discriminant validity was verified by correlating GERD-QOL scores with symptom severity (P < 0.001). Responsiveness after esomeprazole treatment was significant (paired-t-test P < 0.001). An English version of GERD-QOL was developed. CONCLUSION: The instrument, GERD-QOL, is valid and reliable.

Predictors of corticosteroid-dependent and corticosteroid-refractory inflammatory bowel disease: analysis of a Chinese cohort study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) who are corticosteroid-dependent or -refractory are at higher risk of developing disease- and treatment-related complications. AIMS: To identify retrospectively clinical factors present at diagnosis that predict the occurrence of corticosteroid dependency and refractoriness in Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: A total of 310 IBD patients (134 CD, 176 UC) were observed for 2140 person years and their use of systemic corticosteroids was determined. Outcomes of corticosteroid dependency and refractoriness were recorded. Univariate and multivariate analyses were performed to determine the clinical factors associated with outcomes. RESULTS: Seventy-seven (57.5%) CD and 95 (54.0%) UC patients had received corticosteroids during study period. In CD, thrombocytosis [Hazard ratio (HR):3.0] predicted, whereas colonic CD (HR:0.3) negatively predicted corticosteroid dependency. Stricturing phenotype (HR:4.5) predicted corticosteroid-refractory CD. For UC, thrombocytosis (HR:3.9) and extensive colitis (HR:1.7) predicted corticosteroid dependency. Presence of anaemia (HR:10.8) at diagnosis and initial requirement of total parenteral nutrition (TPN) (HR:18.8) predicted corticosteroid-refractory UC. The cumulative risks of surgery were 17.8% and 5.4% for CD and UC patients respectively at 1 year after starting corticosteroids. CONCLUSIONS: Thrombocytosis at diagnosis predicted corticosteroid-dependency in IBD. Stricturing phenotype of CD and the presence of anaemia in UC predicted subsequent course of corticosteroid refractoriness.

Cost-effectiveness analysis on screening for colorectal neoplasm and management of colorectal cancer in Asia.

BACKGROUND: Faecal occult blood testing (FOBT), flexible sigmoidoscopy (FS) and colonoscopy are recommended for subjects above 50 years of age for screening for colorectal cancer (CRC). AIM: To evaluate the cost-effectiveness of FOBT, FS and colonoscopy on the basis of disease prevalence, compliance rate and cost of screening procedures in Asian countries. METHODS: A hypothetical population of 100 000 persons aged 50 undergoes either FOBT annually, FS every 5 years or colonoscopy every 10 years until the age of 80 years. Patients with positive FOBT or polyp in FS are offered colonoscopy. Surveillance colonoscopy is repeated every 3 years. The treatment cost of CRC, including surgery and chemotherapy, was evaluated. A Markov model was used to compare the cost-effectiveness of different screening strategies. RESULTS: Assuming a compliance rate of 90%, colonoscopy, FS and FOBT can reduce CRC incidence by 54.1%, 37.1% and 29.3% respectively. The incremental cost-effectiveness ratio (ICER) for FOBT (US$6222 per life-year saved) is lower than FS (US$8044 per life-year saved) and colonoscopy (US$7211 per life-year saved). When the compliance rate drops to 50% and 30%, FOBT still has the lowest ICER. CONCLUSION: FOBT is cost-effective compared to FS or colonoscopy for CRC screening in average-risk individuals aged from 50 to 80 years.

Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma.

BACKGROUND: Chronic hepatitis B (CHB) infection leads to development of hepatocellular carcinoma (HCC), but the effects of treatment in preventing HCC are not clear. AIM: To study the effects of interferon (IFN) or nucleoside/tide analogue (NA) on the risk of developing HCC in CHB patients. METHODS: Randomized trials, case-control and cohort studies were retrieved from five electronic databases and international conferences over the past 10 years. Relative risks (RRs) of HCC with or without treatment were studied. RESULTS: Twelve studies (n = 2742) enrolling patients treated by IFN vs. control showed that the risk of HCC after treatment was reduced by 34% (RR: 0.66, 95% CI: 0.48-0.89). Benefit is more significant among patients with early cirrhosis than among those without cirrhosis. Five studies (n = 2289) compared patients treated by NA with control. The risk of HCC after treatment was reduced by 78% (RR: 0.22, 95% CI: 0.10-0.50). HBeAg-positive patients showed more significantly reduced HCC risk with treatment. Patients without cirrhosis benefited more from NA than those with cirrhosis. Resistance to NA has obviated the benefit of the treatment. CONCLUSIONS: IFN or NA treatment significantly reduces risk of HCC. While IFN benefited patients with cirrhosis, NA benefited patients with no cirrhosis and HBeAg-positive CHB infection.