Economic evaluation of direct-acting antivirals for the treatment of genotype 3 hepatitis C infection in Singapore.

BACKGROUND AND AIM: The prohibitively high cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection remains a barrier to treatment access in Singapore. We aimed to evaluate whether DAA as first-line therapy would be cost-effective for genotype 3 (GT3) HCV patients compared with pegylated interferon and ribavirin (PR). METHODS: A decision tree analysis was used to compare the costs and outcomes of DAA and PR as first-line therapy. Treatment effectiveness, defined as sustained virological response, was assessed using a retrospective cohort of treated GT3 HCV patients. Direct medical costs were estimated from the payer's perspective using billing information. We obtained health utilities from published literature. We performed extensive one-way sensitivity analyses and probabilistic sensitivity analyses to account for uncertainties regarding the model parameters. RESULTS: In base case analysis, first-line therapy with DAA and PR yielded quality-adjusted life years (QALYs) of 0.69 and 0.62 at a cost of USD 54 634 and USD 23 857, respectively. The resultant incremental cost-effectiveness ratio (ICER) (USD 449 232/QALY) exceeded the willingness-to-pay threshold (USD 53 302/QALY). The ICER was robust for uncertainties regarding the model parameters. The cost of DAA is the key factor influencing the cost-effectiveness of HCV treatment. At current price, DAA as first-line therapy is not cost-effective compared with PR, with or without consideration of retreatment. Threshold analysis suggested that DAA can be cost-effective if it costs less than USD 17 002 for a 12-week treatment course. CONCLUSION: At current price, DAA as first-line therapy is not cost-effective compared with PR in GT3 HCV patients in Singapore.

Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: We compared the effects of weight loss induced with the glucagon-like peptide-1 agonist liraglutide, with that of lifestyle modification, followed by weight maintenance after discontinuing intervention, in obese adults with non-alcoholic fatty liver disease (NAFLD). METHODS: Thirty obese (mean age 40.7 ± 9.1 years, BMI 33.2 ± 3.6 kg/m2 , 90% male) adults with NAFLD defined as liver fat fraction (LFF) > 5% on magnetic resonance imaging without other causes of hepatic steatosis were randomized to a supervised programme of energy restriction plus moderate-intensity exercise to induce ≥ 5% weight loss (DE group, n = 15), or liraglutide 3 mg daily (LI group, n = 15) for 26 weeks, followed by 26 weeks with only advice to prevent weight regain. RESULTS: Diet and exercise and LI groups had significant (P < 0.01) and similar reductions in weight (-3.5 ± 3.3 vs -3.0 ± 2.2 kg), LFF (-8.1 ± 13.2 vs -7.0 ± 7.1%), serum alanine aminotransferase (-39 ± 35 vs -26 ± 33 U/L) and caspase-cleaved cytokeratin-18 (cCK-18) (-206 ± 252 vs -130 ± 158 U/L) at 26 weeks. At 52 weeks, the LI group significantly (P < 0.05) regained weight (1.8 ± 2.1 kg), LFF (4.0 ± 5.3%) and cCK-18 (72 ± 126 U/L), whereas these were unchanged in the DE group. CONCLUSIONS: Liraglutide was effective for decreasing weight, hepatic steatosis and hepatocellular apoptosis in obese adults with NAFLD, but benefits were not sustained after discontinuation, in contrast with lifestyle modification. Continuing the exercise learned in the structured programme contributed to the maintenance of liver fat reduction.

Risk of Postpolypectomy Bleeding With Uninterrupted Clopidogrel Therapy in an Industry-Independent, Double-Blind, Randomized Trial.

BACKGROUND & AIMS: Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy. METHODS: We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee. RESULTS: In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4-9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4-9.4) in the placebo group (P = .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P = .380) and cardio-thrombotic events (1.5% vs 2%; P = .713). CONCLUSIONS: In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov, number NCT01806090.

Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients.

BACKGROUND AND AIM: The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. METHODS: A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). RESULTS: Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14-4.85], P = 0.02), hepatic complications (HR 2.04, [1.16-3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05-4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96-4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). CONCLUSION: The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.

Symptom presentations and other characteristics of colorectal cancer patients and the diagnostic performance of the Auckland Regional Grading Criteria for Suspected Colorectal Cancer in the South Auckland population.

AIM: This study reviews the presenting symptoms of colorectal cancer in the ethnically diverse Middlemore Hospital referral population of South Auckland, New Zealand. The performance of the newly introduced Auckland Regional Grading Criteria as prediction tool for selecting colorectal cancer cases referred from primary care was evaluated in this group. METHOD: Retrospective review of all colorectal cancer (CRC) cases diagnosed between January 2006 and January 2011. Information extracted from case note review was used to grade patients using the Auckland Regional Grading Criteria. RESULTS: A total of 799 patients were included. The commonest symptoms were: rectal bleeding (25.5-42.3%) and change in bowel habit (20.6-26.8%). Low-risk symptoms including abdominal pain (16.3-46.8%) and weight loss (18.4-26.1%) were not uncommon. 64.4% of Maori and 64.9% of Pacific patients had stage III or IV cancers. Pacific patients had more stage IV disease, 37.7% (p<0.001) and were less likely to undergo tumour resection, 26.0% (p<0.001). The Auckland Regional Grading Criteria would miss 24.7% of the patients with CRC in the referral population. CONCLUSION: While rectal bleeding and change in bowel habit are frequent presenting symptoms, low-risk atypical symptoms including constipation, weight loss and abdominal pain were not uncommon. Significant proportion of Pacific patients present with late-stage disease. The current Auckland Regional grading criteria would miss significant proportion of our study population with colorectal cancer.

Regional correlation of structure and function in glaucoma, using the Disc Damage Likelihood Scale, Heidelberg Retina Tomograph, and visual fields.

PURPOSE: To evaluate relationships between the Disc Damage Likelihood Scale (DDLS), global and sectoral structural parameters provided by the Heidelberg Retina Tomograph (HRT), and global and regional functional loss in visual field (VF) testing. DESIGN: Consecutive observational case series. PARTICIPANTS: One hundred ten eyes from 110 patients categorized as glaucoma, glaucoma suspect, or normal. METHODS: Participants were examined clinically to grade the DDLS score and were tested with HRT and Swedish Interactive Threshold Algorithm standard 24-2 VF tests. All tests were performed within 6 months of each other by examiners masked to the other findings. For each patient, the eye with the worse mean deviation (MD) of the VF test was enrolled in the study. Each field was divided into 6 sectors based on a published scheme, and the MD for each sector was calculated. The relationships among clinical DDLS score, HRT parameters, and VF indexes were analyzed by correlation coefficients and linear regression analysis. MAIN OUTCOME MEASURES: The relationship between the DDLS score, global and sectoral optic disc (HRT) parameters, and global and sectoral VF MDs was evaluated. RESULTS: The DDLS showed significant correlation with all global and sectoral VF indexes (r = -0.39 to -0.62, all Ps < 0.0001) and with sectoral rim area HRT measurements (r = -0.27 to -0.51, all Ps < 0.006). The DDLS correlated most strongly with superior and inferior regional data from HRT and VF, and less well with temporal and nasal data. Heidelberg Retina Tomograph rim area and rim volume were the only HRT parameters to correlate moderately with global VF MD (r = 0.30, P = 0.0018, and r = 0.28, P = 0.0030, respectively). Sectoral HRT rim area correlated moderately strongly with the corresponding sectoral VF MDs in the superior and inferior sectors (r = 0.35-0.46, P = <0.0001-0.04). CONCLUSION: Clinical disc assessment and laser tomographic data that determine the state of the neuroretinal rim are associated with sensitivity loss in VF testing in corresponding regions.