Gastroenterology Elsewhere

ELAFIBRANOR FOR PRIMARY BILIARY CIRRHOSIS - ELATIVE TRIAL Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med 2024;390:795-805. Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by damage of interlobular biliary ducts causing bile stasis and fibrosis. The recommended drug of choice is ursodeoxycholic acid (UDCA). However, up to 40% of patients on UDCA have inadequate response. Newer drugs, for example, obeticholic acid have a partial biochemical response and may worsen pruritus. Elafibranor, a dual peroxisome proliferator-activated receptor that has been studied previously in diabetes and dyslipidemia, is evaluated for PBC in this study. Patients with PBC who had an inadequate response to UDCA were randomized to receive elafibranor, n = 108 (80 mg/day), or placebo, n = 53 for 52 weeks. The primary response was a reduction in alkaline phosphatase <1.67 of the upper limit of normal and a reduction of <15% from baseline and normal total bilirubin levels. 51% of the elafibranor group achieved primary response as compared to 4% in the placebo group (95% confidence interval [CI], 32–57, P < 0.0001). This response was rapid, occurring within a month, and was seen to be sustained for up to a year. 15% had normalization of alkaline phosphatase levels in the elafibranor while none did in the placebo group (95% CI, 6–23, P = 0.002). Pruritus results varied among different scores. In the Worst Itch Numeric Rating Scale score, no significant differences were seen. The results are encouraging and head-to-head comparison trials with other drugs are needed. Elafibranor could be considered the second-line drug in UDCA refractory PBC patients. However, it should be borne in mind that pruritus response may vary. DOES OPIOID USAGE IN ACUTE PANCREATITIS IMPACT OUTCOME? PAINAP TRIAL Pandanaboyana S, Knoph CS, Olesen SS, Jones M, Lucocq J, Samanta J, et al. Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis. United European Gastroenterol J. 2024 Mar 4. doi: 10.1002/ueg2.12542. Epub ahead of print. Pain management is an important aspect of the treatment of acute pancreatitis (AP). Analgesia options include simple analgesics such as paracetamol to opioids and epidural analgesia. Opioids offer effective pain relief, but there have been concerns about their safety as suggested by past experimental and retrospective studies. In this multicentric prospective observational study, researchers aim to seek the effect of opioid usage on the severity outcomes of AP. Of 1768 patients, approximately two-thirds received opioid analgesia and one-third received nonopioid analgesics. In the 1-month follow-up, 13% developed moderately severe AP and 6% developed severe AP. Multivariate analysis showed alcohol etiology, higher Charlson Comorbidity Index, high pain score at admission, and opioid usage were independently associated with the severity of AP. Opioid initiation after admission day and prolonged administration (>6 days) were significantly associated with the severity of AP. The study questions the use of opioids in AP, a condition where pain indicates ongoing inflammation reflecting severity and thereby makes it difficult to eliminate the confounding elements. Randomized control trials comparing opioids and nonopioids are needed to confirm the results. For clinical practice, one could infer that prolonged opioid use may not be beneficial and may cause more harm. RECTAL INDOMETHACIN PLUS PANCREATIC STENTS VERSUS RECTAL INDOMETHACIN ALONE Elmunzer BJ, Foster LD, Serrano J, Coté GA, Edmundowicz SA, Wani S, et al. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: A randomized non-inferiority trial. Lancet 2024;403:450-8. Societal guidelines recommend periprocedural rectal indomethacin in all patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) unless contraindicated. In high-risk patients for PEP (post-ERCP pancreatitis), placing a pancreatic stent is recommended. The authors suggest from hypothetical studies that indomethacin may obviate the need for pancreatic stents in practice. 1950 patients undergoing ERCP and are high-risk candidates for PEP were randomized equally to receive rectal indomethacin alone or rectal indomethacin plus pancreatic duct stenting in this noninferiority trial. 15% in the indomethacin group and 11% in the combo group developed PEP (risk difference 3.6%, P = 0.18). Post hoc analysis showed indomethacin alone was inferior to the combo in preventing PEP (P = 0.11), especially in those who had a history of PEP and underwent pancreatic sphincterotomy. This study echoes the existing recommendations by various societies and can be considered as a reminder to stent the pancreatic duct in addition to rectal indomethacin in high-risk patients undergoing ERCP. LIVER STIFFNESS COULD PREDICT HEPATOCELLULAR CARCINOMA RISK POSTSUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH HEPATITIS C John BV, Dang Y, Kaplan DE, Jou JH, Taddei TH, Spector SA, et al. Liver stiffness measurement and risk prediction of hepatocellular carcinoma after HCV eradication in veterans with cirrhosis. 2023 Dec 5:S1542-3565(23)00958-8. doi: 10.1016/j.cgh.2023.11.020. Epub ahead of print. Patients with hepatitis C need follow-up for the development of portal hypertension and hepatocellular carcinoma (HCC). However, postsustained virological response (SVR) fibrosis regresses. Recent guidelines, like the Baveno VII consensus, suggest measuring liver stiffness by transient elastography (TE) as a guide to screen for varices. As portal hypertension is associated with increased risk for HCC, the authors in this retrospective study aim to look if liver stiffness measured using FibroScan can risk stratify patients who need HCC surveillance. 1850 patients treated for hepatitis C and had TE measurements/FIB-4 (Fibrosis) values were analyzed. 102 patients developed HCC. The adjusted hazard ratio (aHR) increased as liver stiffness increased, highest for values >25 kPa 3.03 (95% CI, 1.74–5.26; P < 0.0001). A similar trend was found in those with FIB-4 scores >3.25 - aHR of 3.16 (95% CI, 1.68–5.97). The authors recommend stopping surveillance for nondiabetic patients with lower liver stiffness <5 kPa as the risk for HCC is lowest (annual aHR <0.4 per 100 person-years). This study adds additional value to TE which is widely used to assess fibrosis stage and thereby portal hypertension. Serial measurements may be needed as fibrosis regresses after SVR and prospective studies could answer if liver stiffness can single-handedly predict HCC. CONSERVATIVE MANAGEMENT OF UNCOMPLICATED SYMPTOMATIC GALLSTONE DISEASE Ahmed I, Hudson J, Innes K, Hernández R, Gillies K, Bruce R, et al. Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): Pragmatic, multicenter randomized controlled trial. BMJ 2023;383:e075383. Gallstone disease is a common cause of abdominal pain and surgery for the same is being increasingly performed due to better imaging and prompt diagnosis. Even with the advancement of laparoscopy and robotics, cholecystectomies are not free of complications. In addition, postcholecystectomy syndrome can occur in up to 40% of operated patients. Authors in this paper randomize 434 patients equally to receive either conservative management or laparoscopic cholecystectomy. Demographics and Short Form (SF)-36 scores were comparable in both groups. A quarter of the patients in the conservative management group ended up having surgery in the next 1.5 years, whereas, in the surgery group, 146 patients were operated on over the same time. The bodily pain domain of the SF-36 score remained similar in both groups (mean difference 0.0, 95% CI, 1.7–1.7; P = 1.00). Complications were also comparable between both groups. Authors not only find the outcomes of conservative management similar to surgical measures but also cost-effective for the National Health Service. Similar to appendicitis without high-risk imaging findings, uncomplicated gallstone disease may be managed conservatively after carefully explaining the risks for recurrence and complications. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.