Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear. AIM: To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients. METHODS: We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I 2) were estimated using Review Manager version 5.3. RESULTS: From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I 2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I 2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I 2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients. CONCLUSION: Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Point-of-care hepatitis C screening with direct access referral to improve linkage to care among halfway house residents: a pilot randomised study.

INTRODUCTION: Linkage to care among individuals with substance misuse remains a barrier to the elimination of the hepatitis C virus (HCV). We aimed to determine whether point-of-care (PoC) education, screening and staging for liver disease with direct access to hospitals would improve linkage to care among this group. METHODS: All participants were offered PoC education and HCV screening. HCV-positive participants were randomised to standard care (controls) or direct access, which provided a direct pathway to hospitals. Linkage to care was determined by reviewing electronic medical records. Linkage of care cascade was defined as attendance at the specialist clinic, confirmation of viraemia by HCV RNA testing, discussion about HCV treatment and initiation of treatment. RESULTS: 351 halfway house residents were screened. The overall HCV prevalence was 30.5% (n = 107), with 69 residents in the control group and 38 in the direct access group. The direct access group had a significantly higher percentage of cases linked to specialist review for confirmatory RNA testing (63.2% vs. 40.6%, p = 0.025), HCV treatment discussion (p = 0.009) and treatment initiation (p = 0.01) compared to the controls. Overall, only 12.6% (n = 13) had treatment initiation during follow-up. PoC HCV screening with direct access referral had significantly higher linkage to HCV treatment initiation (adjusted odds ratio 9.13, p = 0.005) in multivariate analysis. CONCLUSION: PoC HCV screening with direct access improves linkage to care and simplifies the HCV care cascade, leading to improved treatment uptake. PoC education, screening, diagnosis and treatment may be an effective strategy to achieving HCV micro-elimination in this population.

Clinical implications of prompt ascitic drain removal in cirrhosis with refractory ascites.

INTRODUCTION: Large-volume paracentesis (LVP) is the first-line treatment for decompensated cirrhosis with refractory ascites. While ascitic drain removal (ADR) within 72 hours of the procedure was once considered safe, it was uncertain whether ADR within 24 hours could further reduce the risk of ascitic drain-related bacterial peritonitis (AdBP). This study aimed to investigate the association between the timing of ADR and the presence of AdBP. METHODS: All patients with cirrhosis with refractory ascites who underwent LVP in our institution from 2014 to 2017 were studied. AdBP was diagnosed based on an ascitic fluid neutrophil count ≥ 250 cells/mm3 or positive ascitic fluid culture following recent paracentesis within two weeks. RESULTS: A total of 131 patients who underwent LVP were followed up for 1,806 patient-months. Their mean age was 68.3 ± 11.6 years, and 65.6% were male. Their mean Model for End-Stage Liver Disease score was 15.2. The overall incidence of AdBP was 5.3%. ADR beyond 24 hours was significantly associated with a longer median length of stay (five days vs. three days, p < 0.001), higher risk of AdBP (0% vs. 8.9%, p = 0.042) and acute kidney injury (AKI) following LVP (odds ratio 20.0, 95% confidence interval 2.4-164.2, p = 0.021). The overall survival was similar in patients who underwent ADR within and beyond 24 hours of LVP. CONCLUSION: ADR within 24 hours of LVP is associated with a reduced risk of AdBP and AKI. As AdBP is associated with resistant organisms and AKI, we recommend prompt ADR within 24 hours, especially in patients who have Child-Pugh class C alcoholic cirrhosis.

Novel albumin, bilirubin and platelet criteria for the exclusion of high-risk varices in compensated advanced chronic liver disease: A validation study.

BACKGROUND AND AIMS: Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40 g/l, Bilirubin <22 µmol/l and Platelet >114,000/µl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients. METHODS: Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort. RESULTS: Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60-0.76) and 0.66 (0.60-0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were -0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, p < 0.001), without missing more HRVs. CONCLUSION: We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE.

The impact of unrestricted access to direct-acting antiviral among incarcerated hepatitis C virus-infected patients.

BACKGROUND/AIMS: Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. METHODS: In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. RESULTS: A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). CONCLUSION: In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

What is required for achieving hepatitis C virus elimination in Singapore? A modeling study.

BACKGROUND AND AIM: The vast majority of hepatitis C virus (HCV) infection in Singapore is among those with a history of injecting drug use (IDU), yet harm reduction is not available and what is required to achieve the World Health Organization (WHO) HCV elimination targets (80% incidence reduction and 65% mortality reduction by 2030) is unknown. We model the intervention scale-up required to achieve WHO targets in Singapore. METHODS: A dynamic model of HCV transmission and progression among those with a history of IDU was calibrated to Singapore, a setting with declining IDU and no harm reduction (~11 000 people with IDU history in 2017 and 45% HCV seropositive). We projected HCV treatment scale-up from 2019 required to achieve WHO targets with varying prioritization scenarios, with/without opiate substitution therapy scale-up (to 40% among people who inject drugs [PWID]). RESULTS: We estimated 3855 (95% confidence interval: 2635-5446) chronically HCV-infected individuals with a history of IDU and 148 (87-284) incident HCV cases in Singapore in 2019. Reaching the HCV incidence target requires 272 (187-384) treatments in 2019, totaling 2444 (1683-3452) across 2019-2030. By prioritizing PWID or PWID and cirrhotics, 60% or 30% fewer treatments are required, respectively, whereas the target cannot be achieved with cirrhosis prioritization. Opiate substitution therapy scale-up reduces treatments required by 21-24%. Achieving both WHO targets requires treating 631 (359-1047) in 2019, totaling 3816 (2664-5423) across 2019-2030. CONCLUSIONS: Hepatitis C virus elimination is achievable in Singapore but even with declining IDU requires immediate treatment scale-up among PWID. Harm reduction provision reduces treatments required and provides additional benefits.

Efficacy and safety of sofosbuvir/velpatasvir in a real-world chronic hepatitis C genotype 3 cohort.

BACKGROUND AND AIM: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

The difference in histological yield between 19G EUS-FNA and EUS-fine-needle biopsy needles.

BACKGROUND AND OBJECTIVE: EUS-guided fine-needle biopsy (EUS-FNB) with acquisition of tissue core is possible with the use of 19G fine-needle aspiration (FNA) and dedicated biopsy needles. Published data of direct comparisons between biopsy needles are more limited compared to the abundant data comparing EUS-FNA with EUS-FNB. We performed a retrospective study to determine the difference in histologic yield between 19G FNA needle and EUS-FNB needles in patients with solid masses. MATERIALS AND METHODS: Consecutive patients who underwent EUS-FNB of solid masses from January 2014 to July 2018 were identified from a database. The difference in histologic yield between needles was analyzed. RESULTS: A total of 159 patients underwent 179 EUS-FNB procedures (median of 2 needle passes [range: 1-4]). The use of 19G FNA, 19G, 20G, and 22G FNB needles allowed acquisition of a histologic core in 67.4% (29/43), 72.5% (29/40), 82.1% (46/56), and 75.9% (22/29), respectively (P = 0.368). A significant difference in the yield of histologic core was detected when 19G FNA needle was compared with 22G Acquire™ FNB needle (67.4% [29/43] vs. 94.1% [16/17], P = 0.032). The presence of histologic core was significantly associated with a positive diagnosis (95.6% vs. 30.2%, P < 0.0001). CONCLUSION: EUS-FNB with acquisition of histologic core improved the diagnostic yield. Dedicated FNB needles appeared to achieve a higher yield of histologic core compared to 19G FNA needles.

Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination: A population study of ex-substance users in Singapore.

BACKGROUND: Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population. METHODS: HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score. RESULTS: A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P < 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients. CONCLUSIONS: Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings.

TC-325 versus the conventional combined technique for endoscopic treatment of peptic ulcers with high-risk bleeding stigmata: A randomized pilot study.

OBJECTIVE: Preliminary studies on a new topical hemostatic agent, TC-325, have shown its safety and effectiveness in treating active upper gastrointestinal (GI) bleeding. However, to date there have been no randomized trials comparing TC-325 with the conventional combined technique (CCT). Our pilot study aimed to compare the efficacy and safety of TC-325 with those of CCT in treating peptic ulcers with active bleeding or high-risk stigmata. METHODS: This was a comparative randomized study of patients with upper GI bleeding who had Forrest class I, IIA or IIB ulcers. RESULTS: Altogether 20 patients with a mean age of 70 years (range 23-87 years) were recruited, including 16 men, with a mean hemoglobin of 97 g/L. Initial hemostasis was successful in 19 (95.0%) patients, including 90.0% (9/10) in the TC-325 group and 100% (10/10) in the CCT group. TC-325 monotherapy failed to stop bleeding in a patient with Forrest IB posterior duodenal wall ulcer. Rebleeding was seen in 33.3% (3/9) of the patients in the TC-325 group and 10.0% (1/10) in the CCT group. One patient required angio-embolization therapy while three had successful conventional endotherapy. Two patients from the TC-325 group had serious adverse events that were not procedure- or therapy-related. In patients with Forrest IIA or IIB ulcers, five received TC-325 monotherapy; none had rebleeding. CONCLUSIONS: Our pilot study showed that TC-325 has a tendency towards a higher rebleeding rate than CCT, when treating actively bleeding ulcers. Larger trials are necessary for definitive results.

Comparative study of strategies for preventing post-ERCP pancreatitis after early precut sphincterotomy for biliary access.

OBJECTIVE: Needle knife precut sphincterotomy (PS) during endoscopic retrograde cholangiopancreatography (ERCP) has been associated with a high risk of post-ERCP pancreatitis (PEP). This study aimed to examine the effect of no prophylaxis, somatostatin, rectal diclofenac and pancreatic duct (PD) stenting in reducing rates of PEP in patients who underwent early PS. METHODS: This was a retrospective comparative study and the study period was from January 2006 to December 2015. A standardized approach to early PS was used: (i) inadvertent guidewire cannulation of the PD > thrice; (ii) impacted bile duct stone; (iii) inability to achieve deep cannulation within 10 min. PEP prophylactic measures included: (i) none when there was minimal papilla trauma; (ii) somatostatin infusion; (iii) rectal diclofenac; (iv) PD stent. The difference in rates of PEP between the different strategies was analysed. RESULTS: During the study period, PS was performed in 191 ERCP patients (mean age 66 years; 56.5% males). The ERCP success rate after PS was 93.2% (178/191). Overall the PEP rate was 3.1% (6/191) and the severity in all cases was mild. PEP occurred in 6.1% of patients with PD cannulation but not in those without (P = 0.016). PEP rates were 1.8%, 7.3%, 1.8% and 0% in control, somatostatin, diclofenac and PD stenting groups, respectively (P = 0.209). CONCLUSIONS: There was no significant difference in PEP rates after early PS whether or not prophylactic measures were adopted if there was minimal papilla trauma. A trend towards lower PEP rates was observed in patients who had either rectal diclofenac or PD stenting, compared to somatostatin.

Is narrow band imaging superior to high-definition white light endoscopy in the assessment of diminutive colorectal polyps?

BACKGROUND AND AIM: Diminutive polyps measuring ≤ 5 mm in size constitute 80% of polyps in the colon. We prospectively assessed the performance of high-definition white light endoscopy (hWLE) and narrow band imaging (NBI) in differentiating diminutive colorectal polyps. METHODS: In this prospective, multicenter study, videos of 50 diminutive polyps (31 hyperplastic, 19 adenomatous) in hWLE followed by NBI (total 100 videos) were initially obtained and placed in random order into five separate folders (each folder 20 videos). Eight endoscopists were then invited to predict the histology (each endoscopist 100 videos, 800 video assessments in all). Polyps were classified into types 1-3 (hyperplastic) and type 4 (adenoma). Feedback on individual performance was given after each folder (20 videos) was assessed. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in differentiating hyperplastic from adenomatous polyps by hWLE (400 videos) and NBI (400 videos) were 67.8%, 90.7%, 81.7%, 82.1%, and 82.0%; and 82.2%, 81.5%, 73.1%, 88.2%, and 81.8%, respectively. In the pretest and post-test analysis, the accuracy with NBI improved markedly from 68.8% to 91.3% (P = 0.001) compared with hWLE, 76.3-78.8% (P = 0.850). Overall, the interobserver agreement was 0.46 for hWLE (moderate) and 0.64 for NBI (good). CONCLUSIONS: NBI was as accurate as hWLE in differentiating diminutive colorectal polyps. Once a learning curve was reached, NBI achieved significantly higher accuracies with good interobserver agreement. Using a simplified classification, a didactic learning session and feedback on performance, diminutive colorectal polyps could be predicted with high accuracies with NBI.

Role of narrow band imaging in Barrett's esophagus.

The present recommended strategy for detection of dysplasia and cancer in Barrett's esophagus is by randomly carrying out four quadrant biopsies every 2 cm. This approach is however prone to sampling error. Narrow band imaging has been routinely available for clinical use for more than half a decade now. This review will focus on the available data to date on the role of narrow band imaging in the detection and characterization of specialized intestinal metaplasia, high grade dysplasia and intramucosal cancer in Barrett's esophagus.