BACKGROUND:A clinically relevant subset of patients with inflammatory bowel disease (IBD) remain partial responders despite multiple advanced therapies. In this setting, reflexive class switching risks forfeiting incremental mechanistic gains, whereas a deliberate "build-on-partial-response" strategy - through dose optimization, extended induction, and, in selected cases, advanced combination therapy (ACT) [an oral Janus kinase inhibitor (iJAK) plus a biologic] - may consolidate disease control. However, real-world data supporting ACT remain limited, particularly regarding phenotype-driven selection, objective reassessment, and safety considerations. CASE SUMMARY:We report nine multi-refractory IBD patients [ulcerative colitis (UC), n = 5; Crohn's disease, n = 4] managed with ACT after incomplete response to an initial advanced therapy. UC strategies included infliximab plus tofacitinib, ustekinumab plus tofacitinib, and vedolizumab combined with iJAK. Crohn's disease cases illustrate three patterns: Add-on anti-tumor necrosis factor therapy after partial iJAK response (e.g., upadacitinib plus adalimumab in two patients with stenosing or perianal phenotypes), interleukin-23 pathway intensification combined with iJAK (guselkumab plus tofacitinib), and phenotype discordance between extraintestinal and luminal disease control. Overall, 8/9 patients (89%) achieved clinical response with improvement in biochemical markers and/or endoscopic findings; among these, 6/9 (67%) achieved documented deep remission (clinical and biochemical, with endoscopic confirmation in 5/6). One patient with severe refractory UC failed ustekinumab plus tofacitinib and infliximab rescue and proceeded to colectomy with ileal pouch construction (11%). Patients did not present any adverse event associated with therapy, only secondary to uncontrolled disease. CONCLUSION:In multi-refractory IBD, add-on ACT may convert partial response into deep remission, averting surgery in selected patients.

BackgroundVanishing bile duct syndrome (VBDS) is an uncommon but clinically important form of cholestatic liver injury, defined by progressive loss of intrahepatic bile ducts and persistent cholestasis. Drug-induced liver injury is one of its recognized causes, and antibiotics are among the most frequently implicated agents. Cephalosporin-associated VBDS remains rare, and cefadroxil has been only exceptionally considered in this context.Case presentationA 72-year-old man developed jaundice and pruritus after completing a 21-day course of cefadroxil for a mild skin infection. Initial liver tests showed a predominantly cholestatic pattern, with marked elevation of gamma-glutamyl transferase and conjugated hyperbilirubinaemia. Viral, autoimmune, and IgG4-related causes were excluded, and magnetic resonance imaging showed no biliary obstruction. As cholestasis persisted despite withdrawal of the suspected drug, liver biopsy was performed and showed intrahepatic cholestasis with bile duct injury and ductopenic features, consistent with VBDS. The patient was treated with ursodeoxycholic acid, with gradual biochemical recovery and subsequent normalization of liver tests.DiscussionThis case illustrates a rare but relevant presentation of antibiotic-associated VBDS after cefadroxil exposure. Although cephalosporins are widely used and generally safe, they can exceptionally be associated with clinically significant cholestatic drug-induced liver injury. The diagnosis of VBDS requires careful exclusion of mechanical obstruction, viral hepatitis, autoimmune cholangiopathies, and other systemic causes, and liver biopsy remains central when cholestasis is prolonged or unexplained. Treatment is mainly supportive, centered on withdrawal of the suspected agent and management of cholestasis; ursodeoxycholic acid is frequently used, although responses are variable across reported cases.ConclusionCefadroxil-associated VBDS appears to be a rare manifestation of cholestatic drug-induced liver injury. Clinicians should consider this diagnosis in patients who develop persistent jaundice and pruritus after antibiotic exposure, particularly when imaging is normal and competing causes have been excluded. Early recognition, drug withdrawal, close biochemical follow-up, and timely biopsy in persistent cases are essential to avoid delayed diagnosis of this potentially severe condition.

BACKGROUND Acute esophageal variceal bleeding (AEVB) is a critical complication in patients with cirrhosis, associated with high mortality despite advancements in management. Traditional prognostic scores often lack predictive accuracy in this context. AIM To develop, internally validate, and prospectively validate a machine learning (ML) model to predict 1-year mortality in patients with cirrhosis presenting with AEVB. METHODS A retrospective cohort of 94 patients treated between 2010 and 2016 was used to train ML models, incorporating 36 clinical, laboratory, and imaging variables. Four algorithms (generalized linear models, boosted generalized linear models, naive Bayes, random forests) were evaluated, and the best-performing model was prospectively validated in a cohort of 24 patients treated between 2017 and 2018. Performance metrics included the area under the curve (AUC), sensitivity, specificity, and calibration via Brier scores. Data preprocessing involved k-nearest neighbor imputation, one-hot encoding, and scaling. RESULTS The random forest model achieved the highest AUC (0.91, 95% confidence interval [CI]: 0.85-0.96) during internal validation and demonstrated robust performance in the prospective cohort (AUC 0.88, 95%CI: 0.80-0.94). Calibration was excellent, with a low Brier score (0.12). The model was deployed as an online prediction tool. CONCLUSION This ML model shows promise in improving mortality prediction for AEVB, potentially aiding timely clinical interventions and decision-making. Prospective validation underscores its generalizability and clinical utility. Future research should explore external validation in diverse settings.

Acute-on-chronic liver failure (ACLF) is the point at which cirrhosis stops behaving as a chronic liver disease and becomes a rapidly destabilising systemic illness. It is the real tipping point in advanced liver disease: the moment when limited hepatic reserve is no longer the only issue, and the clinical picture is instead defined by systemic inflammation, extrahepatic organ dysfunction, and a high risk of short-term death. This has changed how we understand the natural history of cirrhosis. Rather than a simple linear progression toward liver failure, advanced chronic liver disease is now better seen as a dynamic continuum that may lead to first decompensation, recurrent decompensation, ACLF, end-stage disease, or, in selected cases, recompensation if the underlying driver is effectively controlled. This shift matters because patients with ACLF are not simply “sicker cirrhotics”. They are in a distinct pathophysiological state, marked by inflammation, circulatory dysfunction, immune dysregulation, and organ cross-talk that extends beyond the liver. In this setting, the boundaries between liver failure, sepsis, renal dysfunction, and critical illness become blurred, which is why ACLF remains such a difficult syndrome to manage. At the same time, recent guidance has improved the approach to decompensated cirrhosis, HRS-AKI, infection, transplantation, and palliative care, while newer consensus efforts have tried to reduce differences between ACLF definitions. In practice, management still depends on simple but disciplined principles: early recognition, rapid identification of precipitants, parallel organ support, prompt treatment of infection and HRS-AKI, repeated reassessment, and urgent transplant evaluation when appropriate. This review examines ACLF and end-stage liver disease as interconnected stages of advanced cirrhosis and discusses how care can be both aggressive when recovery is possible and humane when recovery is not.

BACKGROUND Non-invasive clinical scores are widely used to detect hepatic steatosis and steatohepatitis, but their accuracy in individuals with obesity is limited. Most of these tools were developed for non-obese populations and do not account for metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum. Moreover, the potential modifying effect of metabolic syndrome (MetS) on the diagnostic performance of these scores remains unclear. Given the global burden of obesity and MASLD, there is a pressing need to refine diagnostic strategies for early detection. We hypothesized that diagnostic performance may vary by MetS status and can be improved with adjusted thresholds. AIM To evaluate and optimize three clinical scores for steatosis and metabolic dysfunction-associated steatohepatitis (MASH), including assessment by MetS status. METHODS This cross-sectional study included 95 individuals undergoing bariatric surgery at a hospital in Brazil. Clinical scores [non-alcoholic fatty liver disease liver fat score (NLFS), hepatic steatosis index (HSI), and fatty liver index (FLI)] were calculated from preoperative data. Liver biopsy was used as the reference standard to assess steatosis and MASH. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve, and optimal cut-offs were determined by Youden's index. Logistic regression with interaction terms assessed whether MetS modified the diagnostic performance of each score across histological outcomes. RESULTS Sixty-six individuals (69.5%) had steatosis, and fifteen (15.8%) had moderate-to-severe steatosis and MASH. The area under the receiver operating characteristic curves for any steatosis was 0.676 (NLFS), 0.540 (HSI), and 0.468 (FLI); for moderate-to-severe steatosis, 0.671 (NLFS), 0.659 (HSI), and 0.700 (FLI); and for MASH, 0.671 (NLFS), 0.625 (HSI), and 0.639 (FLI). Standard cut-offs performed poorly; optimized thresholds improved both sensitivity and specificity. NLFS outperformed FLI for any steatosis (P = 0.021). No significant interactions were found between MetS and any score (all P > 0.05), indicating that diagnostic accuracy did not significantly differ by MetS status. CONCLUSION NLFS, HSI, and FLI show limited accuracy in obese individuals. Adjusting thresholds improves performance. Diagnostic utility remains consistent regardless of MetS, supporting their use across the MASLD spectrum.

Background: Sarcopenia, defined as the progressive loss of skeletal muscle mass and strength, is a critical predictor of morbidity and mortality in patients with cirrhosis. In chronic liver disease, sarcopenia exacerbates adverse clinical outcomes and deteriorates quality of life. Physical activity, particularly resistance training, has demonstrated beneficial effects in reversing muscle depletion in various chronic conditions. Aim: This systematic review aimed to evaluate the impact of resistance training on sarcopenia among cirrhotic patients, with a focus on both pre-liver transplant and post-liver transplant populations, to improve clinical outcomes and enhance quality of life. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE databases were searched for randomized controlled trials (RCTs) using a standardized search command combining MESH terms and Boolean operators. Studies meeting eligibility criteria and reporting improvements in sarcopenia following resistance training were selected for data extraction. Results: Out of 109 references identified, 12 RCTs were included—10 in pre-transplant and 2 in post-transplant populations. Across studies, resistance training led to measurable improvements in key outcomes: peak VO2 increased by up to 5.3 mL/kg/min, 6 min walk distance improved by 18–97 m, quadriceps muscle thickness increased by up to 1.05 cm, and grip strength gains ranged from 0.4 to 3.8 kg. Postoperative studies reported reductions in fatigue severity scores and length of hospital stay, along with improvements in respiratory pressures and peripheral muscle strength. Conclusions: Resistance training is effective in ameliorating sarcopenia in cirrhotic patients, thereby enhancing pre-transplant status and postoperative quality of life. Clinically, structured exercise programs should be routinely implemented.

BACKGROUND:Macrophages play a crucial role in the tumor microenvironment, displaying remarkable plasticity that allows them to either suppress or promote tumor progression. Their polarization into M1 or M2 phenotypes could have significant prognostic implications, and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms. AIM:To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia, specifically comparing cases with and without metalloproteinase mutations. Additionally, it sought to explore potential prognostic factors associated with the disease. METHODS:The study involved two cohorts of patients diagnosed with colorectal neoplasia: 33 patients with metalloproteinase mutations and 33 without. Macrophage quantity and polarization were assessed using markers indicative of M1 (iNOS) and M2 (CD163, CD206) macrophages. Prognostic factors and survival outcomes related to colorectal cancer (CRC) were also analyzed. RESULTS:Among the 61 patients, 28 (45.9%) exhibited metalloproteinase mutations, while 33 (54.1%) did not. Tumor staging revealed that 16.9% were in stage I, 34.2% in stage II, 42.4% in stage III, and 8.5% in stage IV. The study recorded 12 patient deaths (19.7%), with 21.2% from the control group and 17.9% from the mutation group. M2 macrophages, identified by CD163 and CD206 markers, had mean counts of 23 and 17, respectively, with standard deviations of 21 and 17. In contrast, M1 macrophages, identified by iNOS, had a mean count of five per site, with a standard deviation of 11. CONCLUSION:The study found no statistically significant differences in macrophage density between groups, irrespective of metalloproteinase mutation status, age, gender, tumor region, staging, TILS, tumor recurrence, or clinical outcomes. No association was observed between macrophage polarization and CRC prognosis or survival. However, patients with metalloproteinase mutations demonstrated a better survival rate, suggesting a potential protective role of this mutation in colorectal neoplasia.

BACKGROUND Oral 5-aminosalicylic acid (5-ASA) has been a cornerstone treatment for mild to moderate ulcerative colitis (UC), traditionally used to maintain remission. With the rise of advanced therapies (biologics and small molecules), the role of 5-ASA has come under renewed scrutiny. While earlier systematic reviews affirmed its efficacy compared to placebo, these did not account for the advent of advanced therapies. AIM To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC, compared to placebo, alternative 5-ASA formulations, and advanced therapies, in the era of biologics and small molecules. METHODS It was systematically searched MEDLINE, EMBASE, and the Cochrane Library, alongside conference proceedings (European Crohn’s and Colitis Organisation, British Society of Gastroenterology), for randomized controlled trials published between 2003 and 2024 in English. Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months. Outcomes included failure to maintain remission, adverse events, and serious adverse events (SAEs). Data were analyzed using Cochrane methods, with GRADE assessing evidence certainty. RESULTS From 44 studies (9967 participants), 5-ASA was superior to placebo in maintaining remission, with 37% of 5-ASA users relapsing at 6-12 months compared to 55% of placebo users [risk ratios (RR): 0.68; 95%CI: 0.61-0.76; high-certainty evidence]. SAEs were rare and comparable between groups (RR: 0.60; 95%CI: 0.19-1.84; low-certainty evidence). Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies, with notable differences in cost and safety profiles. CONCLUSION 5-ASA remains effective and safe for maintaining remission in quiescent UC, even in the advanced therapy era. However, tailored approaches are needed to balance efficacy, safety, and cost in clinical practice. This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.

BACKGROUND:The natural history of cirrhosis is characterized by an asymptomatic phase (compensated cirrhosis) followed by a rapidly progressive phase (decompensated cirrhosis). The ability to predict the survival of patients with cirrhosis is crucial for decision-making, some as complex as the indication for a liver transplant. Several models have been developed and validated. OBJECTIVE:To analyze and compare the performance of models in predicting 90-day mortality among patients hospitalized with decompensated cirrhosis. METHODS:A sample of 481 hospitalized patients, with a mean age of 59.04 years 73% male, diagnosed with decompensated cirrhosis and a mean Child-Pugh score of 9. The prognostic models were calculated based on tests performed on admission: MELD-Na, MELD-Plus, MELD 3.0, ReMELD, Refit MELD, and Refit MELD-Na. The accuracy of the models was assessed by calculating the area under the receiver operating characteristic (AUROC) curve, and their respective 95% confidence intervals. Comparisons between the areas were conducted using the DeLong test. A comparison was conducted among all scores, with a primary focus on MELD 3.0 and MELD-Plus. These specific scores were the focal points of interest. RESULTS:The scores presented AUROC curve values of 0.703-0.758, indicating a moderate capacity to discriminate between survivors and deceased patients during the considered period. The comparison between the models did not unequivocally establish the superiority of one model over the other. CONCLUSION:The scores have a limited predictive ability for death within 90 days in patients with decompensated cirrhosis. Our study is unable to establish the prognostic superiority of a specific scoring system. BACKGROUND:• This retrospective, multicenter study evaluated the accuracy of six predictive models of death within 90 days in 461 patients hospitalized for decompensated cirrhosis. BACKGROUND:• The scores presented an area under the receiver operating characteristic curve of 0.703-0.758, indicating a good ability to discriminate between survivors and deceased patients during the considered period. BACKGROUND:• The comparison between the models did not unequivocally establish the superiority of one model over the other.

Delving into the immunological crossroads of liver diseases, this editorial explores the dynamic interplay between hepatitis C virus (HCV) and autoimmune hepatitis (AIH). While HCV primarily manifests as a viral infection impacting the liver, previous studies unveil a captivating connection between HCV and the emergence of AIH. The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon—an aberrant autoimmune response leading to the onset of AIH. Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection, hinting at a potential overlap between viral and autoimmune liver diseases. Navigating the intricate terrain of viral replication, immune response dynamics, and genetic predisposition, this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH. In this immunological crossroads, we aim to unearth insights into the complex interplay, using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.

BACKGROUND Blastocystis hominis (B. hominis ), an anaerobic unicellular protist parasite, is known for its diverse clinical manifestations upon infecting the human gastrointestinal tract. Although globally distributed, it is particularly prevalent in developing nations. Examining the symptoms and treatment outcomes of B. hominis infection in low-resource settings holds immense significance, providing healthcare practitioners with valuable insights to enhance patient care. AIM To synthesize existing evidence on the symptomatology and treatment outcomes of B. hominis infection in low-resource settings. METHODS Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, a systematic review was conducted. The search spanned electronic databases including PubMed, Scopus, and Google Scholar. After a comprehensive screening process, a thorough examination of the papers, adhering to inclusion and exclusion criteria, and data extraction from eligible studies was conducted. The findings underwent summarization through simple descriptive analysis. RESULTS The search yielded 1200 papers, with 17 meeting inclusion criteria. Chronic diarrhea due to B. hominis infection was reported in only two studies, while abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting emerged as the most commonly documented symptoms. Recovery rates after one week of treatment ranged from 71.8% to 100%, and after two weeks, from 60% to 100%. CONCLUSION In low-resource settings, chronic diarrhea resulting from B. hominis infection is infrequent. Common symptoms include abdominal pain, diarrhea, flatulence, constipation, and nausea/vomiting. Post-treatment, clinical outcomes are notably favorable, supporting the recommendation for treatment. Metronidazole is advocated as the first-line agent, with consideration for switching to a second-line option in cases of treatment failure or poor response.

BACKGROUNDLiver transplant (LT) patients have become older and sicker. The rate of post-LT major adverse cardiovascular events (MACE) has increased, and this in turn raises 30-d post-LT mortality. Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIMTo assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODSThis retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center. We developed a predictive model for post-LT MACE (defined as a composite outcome of stroke, new-onset heart failure, severe arrhythmia, and myocardial infarction) using the extreme gradient boosting (XGBoost) machine learning model. We addressed missing data (below 20%) for relevant variables using the k-nearest neighbor imputation method, calculating the mean from the ten nearest neighbors for each case. The modeling dataset included 83 features, encompassing patient and laboratory data, cirrhosis complications, and pre-LT cardiac assessments. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC). We also employed Shapley additive explanations (SHAP) to interpret feature impacts. The dataset was split into training (75%) and testing (25%) sets. Calibration was evaluated using the Brier score. We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting. Scikit-learn and SHAP in Python 3 were used for all analyses. The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTSOf the 537 included patients, 23 (4.46%) developed in-hospital MACE, with a mean age at transplantation of 52.9 years. The majority, 66.1%, were male. The XGBoost model achieved an impressive AUROC of 0.89 during the training stage. This model exhibited accuracy, precision, recall, and F1-score values of 0.84, 0.85, 0.80, and 0.79, respectively. Calibration, as assessed by the Brier score, indicated excellent model calibration with a score of 0.07. Furthermore, SHAP values highlighted the significance of certain variables in predicting postoperative MACE, with negative noninvasive cardiac stress testing, use of nonselective beta-blockers, direct bilirubin levels, blood type O, and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level. These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE, making it a valuable tool for clinical practice.CONCLUSIONOur study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE, using both cardiovascular and hepatic variables. The model demonstrated impressive performance, aligning with literature findings, and exhibited excellent calibration. Notably, our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data, reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

This editorial addresses the growing concern of herb-induced liver injury (HILI), focusing on a unique case of Skullcap-induced HILI report. This editorial underscore the significant mortality rate linked to Skullcap-induced HILI, emphasizing the importance of vigilant monitoring and intervention. As herbal supplement usage rises, collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI, particularly those involving Skullcap.

BACKGROUND Liver transplantation (LT) is a life-saving intervention for patients with end-stage liver disease. However, the equitable allocation of scarce donor organs remains a formidable challenge. Prognostic tools are pivotal in identifying the most suitable transplant candidates. Traditionally, scoring systems like the model for end-stage liver disease have been instrumental in this process. Nevertheless, the landscape of prognostication is undergoing a transformation with the integration of machine learning (ML) and artificial intelligence models. AIM To assess the utility of ML models in prognostication for LT, comparing their performance and reliability to established traditional scoring systems. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a thorough and standardized literature search using the PubMed/MEDLINE database. Our search imposed no restrictions on publication year, age, or gender. Exclusion criteria encompassed non-English studies, review articles, case reports, conference papers, studies with missing data, or those exhibiting evident methodological flaws. RESULTS Our search yielded a total of 64 articles, with 23 meeting the inclusion criteria. Among the selected studies, 60.8% originated from the United States and China combined. Only one pediatric study met the criteria. Notably, 91% of the studies were published within the past five years. ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values (ranging from 0.6 to 1) across all studies, surpassing the performance of traditional scoring systems. Random forest exhibited superior predictive capabilities for 90-d mortality following LT, sepsis, and acute kidney injury (AKI). In contrast, gradient boosting excelled in predicting the risk of graft-versus-host disease, pneumonia, and AKI. CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT, marking a significant evolution in the field of prognostication.

The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al , which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.

BACKGROUND End stage liver disease (ESLD) represents a growing health concern characterized by elevated morbidity and mortality, particularly among individual ineligible for liver transplantation. The demand for palliative care (PC) is pronounced in patients grappling with ESLD and acute on chronic liver failure (ACLF). Unfortunately, the historical underutilization of PC in ESLD patients, despite their substantial needs and those of their family caregivers, underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum. AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF. METHODS A systematic search in the Medline (PubMed) database was performed using a predetermined search command, encompassing studies published in English without any restrictions on the publication date. Subsequently, the retrieved studies were manually examined. Simple descriptive analyses were employed to summarize the results. RESULTS The search strategies yielded 721 references. Following the final analysis, 32 full-length references met the inclusion criteria and were consequently incorporated into the study. Meticulous data extraction from these 32 studies was undertaken, leading to the execution of a comprehensive narrative systematic review. The review found that PC provides significant benefits, reducing symptom burden, depressive symptoms, readmission rates, and hospital stays. Yet, barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization. Integrating PC early, upon the diagnosis of ESLD and ACLF, regardless of transplant eligibility and availability, improves the quality of life for these patients. CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF, where liver transplantation stands as the only curative treatment, albeit largely inaccessible, PC services have been overtly provided too late in the course of the illness. A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers, involving healthcare providers, patients, and caregivers.