Adverse events with endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction-A systematic review and meta-analysis.

BACKGROUND: The technical and clinical effectiveness of endoscopic ultrasonography (EUS)-guided gastroenterostomy (GE) has been reported by several meta-analyses, but few of them have addressed the adverse events (AE). The goal of the current meta-analysis was to analyze the AEs associated with various types of EUS-GE. METHODS: All relevant studies reporting the AEs with EUS-GE were searched from 2000 to 31st March 2023 in MEDLINE, Embase, and Scopus. The event rates were pooled using a random effects model. RESULTS: A total of 36 studies (n = 1846) were included in the meta-analysis. The present meta-analysis reports a pooled technical success rate of 96.9% (95.9-98.0; I2 = 29.3%) with a pooled clinical success rate of 90.6% (88.5-92.7; I2 = 60.9%). The pooled incidence of overall AEs with EUS-GE was 13.0% (10.3-15.7; I2 = 69.7%), with the commonest being maldeployment of the stent, seen in 4.6% (3.2-6.0; I2 = 50.6%). The pooled incidences of serious AE and procedure-related mortality were 1.2% (0.7-1.8; I2 = 1.9%) and 0.3% (0.0-0.7; I2 = 0.0%), respectively. Subgroup analysis of studies using only the free-hand technique showed a significantly lower overall AE and maldeployment but not serious AE and other individual AEs. The pooled incidences of delayed stent migration and stent occlusion were 0.5% (0.0-1.1; I2 = 0.0%) and 0.8% (0.2-1.3; I2 = 0.0%), respectively. CONCLUSION: Despite a technical and clinical success rate of >90%, AEs are seen in around one-seventh of the cases of EUS-GE, maldeployment being the commonest. However, the pooled incidence of serious AE and mortality remains low, which is reassuring.

Lumen-apposing metal stents: A primer on indications and technical tips.

Lumen-apposing metal stents have ushered a new frontier for interventional endoscopic ultrasound. Initial use for the drainage of pancreatic fluid collections has rapidly expanded to the bile duct, gallbladder and small bowel. Intra-luminal applications for short strictures have also emerged. Electrocautery enhancement has made the stent delivery speedy. While the advent of lumen-apposing metal stents (LAMS) has brought a paradigm shift in the practice of interventional endoscopic ultrasound, their use is associated with certain technicalities that any advanced endosonologist should know. Understanding indications for LAMS is critical and their use in appropriate settings. Troubleshooting in tricky situations is always a challenge and the background considerations for their use include knowing the target organ, cautery and puncture technique, managing partially opened LAMS and also managing maldeployment. In this review, we discuss the intricacies and technical tips for the use of lumen-apposing metal stents.

Changing Etiological Spectrum of Hepatocellular Carcinoma in India-A Systematic Review and Meta-analysis.

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Outcome of individuals with alcoholic cirrhosis hospitalized with first decompensation and their predictors.

BACKGROUND OBJECTIVES: Alcohol is one of most common aetiologies of cirrhosis and decompensated cirrhosis is linked to higher morbidity and death rates. This study looked at the outcomes and mortality associated risk variables of individuals with alcoholic cirrhosis who had hospitalization with their first episode of decompensation. METHODS: Individuals with alcoholic cirrhosis who were hospitalized with the first episode of decompensation [acute decompensation (AD) or acute-on-chronic liver failure (ACLF)] were included in the study and were prospectively followed up until death or 90 days, whichever was earlier. RESULTS: Of the 227 study participants analyzed, 167 (73.56%) and 60 (26.43%) participants presented as AD and ACLF, respectively. In the ACLF group, the mortality rate at 90 days was higher than in the AD group (48.3 vs 32.3%, P=0.02). In the AD group, participants who initially presented with ascites as opposed to variceal haemorrhage had a greater mortality rate at 90 days (36.4 vs 17.1%, P=0.041). The chronic liver failure-consortium AD score and the lactate-free Asian Pacific Association for the study of the Liver-ACLF research consortium score best-predicted mortality in individuals with AD and ACLF. INTERPRETATION CONCLUSIONS: There is significant heterogeneity in the type of decompensation in individuals with alcoholic cirrhosis. We observed significantly high mortality rate among alcoholic participants hospitalized with initial decompensation; deaths occurring in more than one-third of study participants within 90 days.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS: We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS: Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION: This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.

Dengue-related acute liver failure-A scoping review.

Infection by dengue virus is common in tropical countries. Hepatic involvement in dengue can range from asymptomatic elevation of transaminases to life-threatening acute liver failure (ALF). Dengue-related ALF (DALF) is responsible for significant morbidity and mortality, especially in Southeast Asia. However, there is a scarcity of literature on DALF, necessitating a thorough examination of its clinical determinants and management strategies. All relevant studies related to DALF were reviewed until December 2023. Case reports, case series and studies reporting ALF in dengue infection were included. Demographics, clinical profiles, management and outcomes of DALF cases were analyzed, which revealed a predominance of DALF incidence in pediatric patients (1.1% to 15.8%) and an upward trend over the years, particularly in India. The proportion of ALF cases attributable to dengue was also higher among pediatric ALF patients (6.7% to 34.3%). Age ≤ 40 years, persistent nausea, vomiting and elevated serum bilirubin and alkaline phosphatase (ALP) with aspartate aminotransferase (AST) > 1000 IU/mL within the first five days of illness, more than 10% of atypical lymphocytes in peripheral blood, platelet count of < 50,000/cu·mm, severe hepatitis at presentation and baseline model for end-stage liver disease (MELD) > 15 were the risk factors for the development of DALF. Histopathological features of DALF included multi-lobular hepatic necrosis, steatosis and occasional cholestasis. Mortality in DALF ranged from 0% to 80%; admission pH and lactate strongly predicted mortality, while mortality was found to be significantly higher in patients with cirrhosis. N-Acetyl cysteine (NAC) has been used as a treatment modality with varying results. There is limited evidence regarding the use of extra-corporeal support systems, while candidate selection for liver transplantation (LT) in DALF remains poorly defined.

Role of contrast-enhanced ultrasound for differentiation of benign vs. malignant portal vein thrombosis in hepatocellular carcinoma - A systematic review a meta-analysis.

Introduction/Purpose: Patients with cirrhosis and hepatocellular carcinoma (HCC) can develop both benign and malignant portal vein thrombosis (PVT). Characterising the nature of PVT is important for planning an optimal therapeutic strategy. In the absence of typical findings or contraindications to computed tomography (CT) or magnetic resonance imaging (MRI), contrast-enhanced ultrasound (CEUS) could help in this differentiation. The present meta-analysis aimed to evaluate the performance of CEUS for characterising PVT in patients with HCC. Methods: Electronic databases of PubMed, Embase and Scopus were searched from inception to 31 December 2022 for studies analysing the role of CEUS in the differentiation of benign and malignant PVT in HCC. Using the bivariate random effect model, pooled sensitivity and specificity were calculated, and the summary receiver operating characteristic (sROC) curve was plotted. Results: A total of 12 studies with data from 712 patients were included in the meta-analysis. The pooled sensitivity and specificity of CEUS for the diagnosis of tumour in vein were 97.0% (95% CI: 93.0-98.7) and 96.8% (95% CI: 92.1-98.7), respectively, without significant heterogeneity. A sROC curve was plotted, and the area under the receiver operating characteristic was 0.99 (95% CI: 0.98-1.00). Despite the presence of publication bias, sensitivity analysis did not show any change in sensitivity and specificity. Discussion: Our meta-analysis summarises the accuracy data from 12 studies, including >700 subjects. Contrast-enhanced ultrasound had excellent diagnostic accuracy with pooled sensitivity and specificity of 97.5% (95% CI: 93.5-99.1) and 98.2% (95% CI: 91.5-99.6), respectively, without any significant heterogeneity. Additionally, the pooled positive LR, negative LR and DOR were 54.6 (95% CI: 11.1-25.6), 0.02 (0.01-0.07) and 2186.8 (318.3-15022.2), respectively. A positive result increases the pretest probability of malignant PVT from 50% to 98%, whereas a negative result decreases it from 50% to 2%. Most of the studies included in our meta-analysis used identical techniques and 6-12-month follow-up scans to check for thrombus progression or regression. Our analysis showed no significant heterogeneity in the studies, and area under receiver operating characteristic curve (AUROC) with 95% CI was 1.00 (95% CI: 0.99-1.00). This critical meta-analysis thus propels CEUS to the forefront for differentiating benign from tumoural PVT and suggests routinely using CEUS in patients presenting with HCC and evidence of thrombus on greyscale ultrasound. Conclusion: Contrast-enhanced ultrasound is an effective diagnostic modality differentiation of benign and malignant PVT in patients with HCC and can be an alternative modality to CT or MRI. Further studies are required to study the role of CEUS as initial diagnostic modality for the characterisation of PVT in HCC.

PREDICTORS OF FAILURE OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN CLEARING BILE DUCT STONES DURING INDEX PROCEDURE - A PROSPECTIVE STUDY.

BACKGROUND: Common bile duct (CBD) stones are known to complicate 10-15% of gallstone diseases. Endoscopic retrograde cholangiopancreatography (ERCP) is the therapeutic modality of choice for bile duct clearance in CBD stones but may fail to achieve stone clearance. This prospective study was done to identify the predictors of failure of CBD clearance with ERCP. OBJECTIVE: This prospective study was done to identify the predictors of failure of CBD clearance with ERCP. METHODS: All consecutive patients with bile duct stones undergoing ERCP at a tertiary care center were prospectively included from October 2020 to October 2021. The study's primary outcome was to identify and analyze factors that could predict the failure of complete CBD clearance. RESULTS: A total of 120 patients (50.8% males, median age: 53.5 years) were included in the final analysis. Successful clearance of CBD stones during the index procedure was achieved in 70% of patients. At a cut-off stone diameter of >10.5 mm and CBD diameter of >12.5 mm, the AUC was 0.890 and 0.884, respectively, to predict failed clearance of CBD. On multivariate analysis, stone diameter ≥15 mm [odds ratio (OR) 16.97, 95% confidence interval (CI): 1.629-176.785], location of stones in hepatic ducts (OR 7.74, 95%CI: 2.041-29.332), presence of stricture distal to stone (OR 6.99, 95%CI: 1.402-34.726) and impacted stone (OR 21.61, 95%CI: 1.84-253.058) were independent predictors of failed bile duct clearance. CONCLUSION: Stone size and location are independent predictors of failed bile duct clearance. The endoscopist should consider these factors while subjecting a patient to biliary ductal clearance to plan additional intervention. BACKGROUND: • Failure to clear bile duct stones in the index ERCP can be seen in 15-20% of cases, and identifying the factors associated with failure is important. BACKGROUND: • A prospective analysis was conducted to identify and analyze the factors that could predict the failure of complete CBD clearance. BACKGROUND: • The present study reported a successful clearance of CBD stones during the index procedure in only 70% of patients. BACKGROUND: • A stone diameter ≥15 mm, location of stones in hepatic ducts, presence of stricture distal to stone, and impacted stone were independent predictors of failed bile duct clearance.

Liver Transplantation in Chronic Liver Disease and Acute on Chronic Liver Failure- Indication, Timing and Practices.

Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.

Risk of tuberculosis with anti-TNF therapy in Indian patients with inflammatory bowel disease despite negative screening.

BACKGROUND AND STUDY AIMS: Tuberculosis (TB) is a well-recognized adverse effect associated with using biological therapy to manage various autoimmune conditions. There is a dearth of information about the development of TB after using anti-TNF agents in patients with inflammatory bowel disease (IBD) from TB-endemic countries like India. This study aimed to estimate the risk of TB and its predictors after treatment with anti-TNF agents in patients with IBD. PATIENTS AND METHODS: The present study is a retrospective analysis of data of patients with IBD from two tertiary care centers in India receiving anti-TNF therapy. Patients who had undergone chest X-ray, high-resolution computed tomography of the chest, and tuberculin skin test, with a follow-up duration of at least 6 months, were included in the analysis. RESULTS: In this multi-center study, 95 patients on anti-TNF agents for IBD (Median age of onset: 27 years, 62.1 % males) were followed up for a median duration of 9 (6-142) months. Among patients with IBD, 79 (83.2 %) had Crohn's disease, and 16 (16.8 %) had ulcerative colitis. Infliximab was the commonest biological, used in 82.1 % of cases, followed by adalimumab (17.9 %). On follow-up, 8.4 % (8/95) of the patients developed TB, among which the majority had extrapulmonary tuberculosis (5/8). On multivariate analysis, the duration of biological (Odds ratio: 1.047, 95 % confidence interval 1.020-1.075; p = 0.001) use was the only independent predictor of the development of TB with biologicals. CONCLUSION: Among Indian patients with IBD, there is a high risk of TB with anti-TNF agents, which increases with the duration of therapy. The current methods for latent TB screening in Indians are ineffective, and predicting TB after initiating biological therapy is difficult.

Impact of nutritional status on the outcome of transjugular intrahepatic portosystemic shunt in patients with cirrhosis: a systematic review.

OBJECTIVES: Malnutrition and sarcopenia have been reported to adversely affect the outcome of patients with cirrhosis of the liver. There is an emerging body of evidence suggesting malnutrition and sarcopenia increase the risk of hepatic encephalopathy (HE) and mortality after transjugular intrahepatic portosystemic shunt (TIPS). The current systematic review aims to determine whether the body of evidence supports an association between nutritional status and post-TIPS outcomes in patients with cirrhosis. METHODS: Electronic databases of PubMed, Embase, and Scopus were searched from inception to June 3, 2023, for studies analysing the effect of nutritional status on post-TIPS outcomes in patients with cirrhosis. RESULTS: A total of 22 studies were included in the systemic review. Assessment of sarcopenia was done by skeletal muscle index (SMI) at the L3 level, transversal psoas muscle thickness, psoas muscle density, malnutrition as per ICD, relative sarcopenia with excess adiposity, lipid profile, controlling nutritional status score, body composition analysis, hospital frailty risk score, and visceral and subcutaneous fat area index. Ten out of 12 studies in this systematic review showed a significant association with the incidence of post-TIPS HE. Thirteen out of 14 studies reported that the presence of malnutrition was associated with increased odds of mortality following TIPS. One study reported sarcopenia as an independent predictor of liver failure, and another study reported that Pre-TIPS SMI was an independent predictor of substantial improvement in post-TIPS SMI. CONCLUSIONS: The current systematic review shows that the presence of pre-TIPS malnutrition or sarcopenia is an independent predictor of adverse outcomes after TIPS. Incorporating these parameters into present prediction models can provide additional prognostic information. ADVANCES IN KNOWLEDGE: Nutritional assessment should be part of the evaluation of patients planned for TIPS for prediction of adverse events after the procedure.

Upfront tofacitinib in patients with biological-naïve ulcerative colitis - An Indian multicentric experience.

OBJECTIVES: Tofacitinib is a Janus Kinase inhibitor used for treating moderate to severe ulcerative colitis (UC), mainly after the failure of biological therapy. There is a paucity of data on the outcome of tofacitinib in biological-naïve UC patients. The present study was aimed at analyzing the safety and efficacy of tofacitinib in biological-naïve Indian patients with UC. METHODS: The present study retrospectively evaluated consecutive patients with biological-naïve moderate-to-severe active UC from six tertiary care centers in India receiving tofacitinib from September 2020 to September 2022. Clinical remission or response assessment was based on partial Mayo score (PMS) calculated at baseline and weeks eight, 16 and 24. RESULTS: Total 47 cases (57.4% male, median age: 32 years) were included. After eight weeks of therapy, 33 (70.2%) achieved clinical remission and eight (17.0%) had a primary failure. The baseline serum albumin at treatment initiation was the only independent predictor of remission at eight weeks (Odds ratio: 11.560, 95% CI: 1.478 - 90.404), but not at 16 weeks. By 24 weeks, 59.6% (28/47) of the patients were in remission and 29.8% (14/47) had stopped tofacitinib either due to failure (27.6%) or adverse events (AEs) (2.1%). Among the 47 patients, 10 (21.2%) cases developed AEs during follow-up, including two tuberculosis (4.2%), one cytomegalovirus (CMV) colitis (2.1%) and one herpes zoster (2.1%). Four patients with infection required temporary drug discontinuations. One required permanent discontinuation (mania). CONCLUSION: Upfront tofacitinib is effective in biologic-naïve Indian patients with moderate-severe UC. Further randomized studies are required to validate the study findings.

Previsores de falha da colangiopancreatografia retrógrada endoscópica na limpeza de cálculos do ducto biliar durante o procedimento inicial - Um estudo prospectivo / Predictors of failure of endoscopic retrograde cholangiopancreatography in clearing bile duct stones during index procedure - a prospective study

ABSTRACT Background: Common bile duct (CBD) stones are known to complicate 10-15% of gallstone diseases. Endoscopic retrograde cholangiopancreatography (ERCP) is the therapeutic modality of choice for bile duct clearance in CBD stones but may fail to achieve stone clearance. This prospective study was done to identify the predictors of failure of CBD clearance with ERCP. Objective: This prospective study was done to identify the predictors of failure of CBD clearance with ERCP. Methods: All consecutive patients with bile duct stones undergoing ERCP at a tertiary care center were prospectively included from October 2020 to October 2021. The study's primary outcome was to identify and analyze factors that could predict the failure of complete CBD clearance. Results: A total of 120 patients (50.8% males, median age: 53.5 years) were included in the final analysis. Successful clearance of CBD stones during the index procedure was achieved in 70% of patients. At a cut-off stone diameter of >10.5 mm and CBD diameter of >12.5 mm, the AUC was 0.890 and 0.884, respectively, to predict failed clearance of CBD. On multivariate analysis, stone diameter ≥15 mm [odds ratio (OR) 16.97, 95% confidence interval (CI): 1.629-176.785], location of stones in hepatic ducts (OR 7.74, 95%CI: 2.041-29.332), presence of stricture distal to stone (OR 6.99, 95%CI: 1.402-34.726) and impacted stone (OR 21.61, 95%CI: 1.84-253.058) were independent predictors of failed bile duct clearance. Conclusion: Stone size and location are independent predictors of failed bile duct clearance. The endoscopist should consider these factors while subjecting a patient to biliary ductal clearance to plan additional intervention.

RESUMO Contexto: Cálculos do ducto biliar comum (CDC) são conhecidos por complicar 10-15% das doenças de cálculos biliares. A colangiopancreatografia retrógrada endoscópica (CPRE) é a modalidade terapêutica de escolha para a limpeza do CDC, mas pode falhar na sua remoção. Objetivo: Este estudo prospectivo foi realizado para identificar os previsores de falha na limpeza do CDC com CPRE. Métodos: Pacientes consecutivos com cálculos no ducto biliar submetidos a CPRE em um centro de atendimento terciário foram incluídos prospectivamente de outubro de 2020 a outubro de 2021. O principal resultado do estudo foi identificar e analisar fatores que poderiam prever a falha na limpeza completa do CDC. Resultados: Um total de 120 pacientes (50,8% homens, idade média: 53,5 anos) foram incluídos na análise final. A limpeza bem-sucedida dos cálculos de CDC durante o procedimento inicial foi alcançada em 70% dos pacientes. Com um diâmetro de corte de cálculos >10,5 mm e de diâmetro de CDC de >12,5 mm, a AUC foi de 0,890 e 0,884, respectivamente, para prever a falha na limpeza do CDC. Na análise multivariada, diâmetro da cálculos ≥15 mm [razão de chances (OR) 16,97, intervalo de confiança de 95% (IC): 1,629-176,785], localização dos cálculos nos ductos hepáticos (OR 7,74, IC95%: 2,041-29,332), presença de estreitamento distal ao cálculo (OR 6,99, IC95%: 1,402-34,726) e cálculo impactado (OR 21,61, IC95%: 1,84-253,058) foram previsores independentes de falha na limpeza do ducto biliar. Conclusão: O tamanho e a localização dos cálculos são previsores independentes de falha na limpeza do ducto biliar. O endoscopista deve considerar esses fatores ao submeter um paciente à limpeza ductal biliar para planejar intervenção adicional.

Prophylactic Lactulose Therapy in Patients with Cirrhosis and Upper Gastrointestinal Bleeding: A Meta-analysis of Randomized Trials.

BACKGROUND AND AIMS: Lactulose is the first-line drug for both treatment and secondary prophylaxis for overt hepatic encephalopathy (HE). The use of lactulose for the primary prophylaxis of HE in patients with cirrhosis and acute upper gastrointestinal bleeding (AUGIB) has been debated. Hence, we conducted this meta-analysis to assess the role of lactulose in HE prophylaxis in patients with cirrhosis and AUGIB. METHODS: A comprehensive search of literature from inception to December 2022 was performed of three databases for randomized studies comparing lactulose and placebo in patients with cirrhosis and AUGIB. Risk ratios (RR) with 95% confidence intervals were calculated for all the dichotomous outcomes. RESULTS: A total of five studies were included in the final analysis, out of which three studies had a low risk of bias, and two had a moderate risk of bias. Lactulose therapy was associated with a significantly lower risk of OHE compared to placebo, with a RR of 0.38 (0.23-0.62) and a number needed to treat of 6. There was no difference in the risk of mortality between the groups, with a RR of 0.71 (0.29-1.76). The pooled incidence rates of overall adverse events (AEs) and diarrhea with the use of lactulose therapy were 53.2% (42.2- 64.2) and 34.7% (17.7-51.7), but a majority did not require drug discontinuation. The certainty of the evidence was moderate to low. CONCLUSIONS: Prophylactic lactulose reduces the incidence of HE after AUGIB but has no effect on mortality. Diarrhea and abdominal discomfort are common AEs but do not need drug discontinuation.