Primary biliary cholangitis (PBC) is a progressive liver disease affecting the small intrahepatic bile ducts, specifically the interlobular and septal bile ducts, associated with an elevated alkaline phosphatase and positive anti-mitochondrial antibody on laboratory testing, which can lead to cirrhosis and the need for liver transplant. The goal of this review paper is to critically evaluate the current treatment algorithms for primary biliary cholangitis and propose future modifications. The first-line treatment option for PBC is ursodeoxycholic acid. FDA-approved second-line therapies are elafibranor and seladelpar. Off-label use of fenofibrate can also be considered. Traditionally, second-line therapies have been added after 12 months of treatment with ursodeoxycholic acid if the alkaline phosphatase and bilirubin levels are above desired goals. Evolving algorithms should consider earlier addition of second-line therapies at 6 months, especially in younger patients with increased liver stiffness, a goal of normalization of the alkaline phosphatase, and assessment of fatigue and pruritus in the decision about treatment options.
This review highlights the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), assesses comparability of the former definition of non-alcoholic fatty liver disease (NAFLD)-era estimates with the 2023 steatotic liver disease (SLD) framework, and identifies emerging regional hotspots. High concordance between NAFLD-era definitions and SLD subclassification supports continuity of established cohorts for trend analyses. Globally, imaging-based steatosis prevalence was 38
This narrative review summarizes recent evidence supporting sarcopenia as a modifiable therapeutic target rather than merely a prognostic marker in hepatocellular carcinoma (HCC). Sarcopenia is one of the most consistent predictors of adverse outcomes across treatment modalities, including resection, locoregional therapy, systemic therapy, and transplantation. Muscle loss in HCC stems from converging mechanisms such as cirrhosis-related hyperammonemia, tumor-associated cachexia, and immune dysfunction linked to myokine depletion. The rise of MASLD-associated HCC has increased the prevalence of myosteatosis and the sarcopenic obesity phenotype. Sarcopenia can be assessed with imaging or bedside markers such as phase angle. After detection, nutritional therapy including branched-chain amino acids, resistance exercise, and selected pharmacological interventions can preserve muscle mass and functional reserve, ideally incorporated into a prehabilitation program. Incorporating sarcopenia assessment into routine care and pairing nutritional therapy and exercise with all HCC treatment modalities, including transplantation, may improve outcomes.
Long-term nucleos (t)ide analogue (NAs) treatment is usually required to maintain viral suppression in patients with chronic hepatitis B (CHB), with raising concerns on the long-term safety of NA therapy. In this review, we comprehensively summarized the current evidence on the long-term safety of NA therapy, with a particular focus on the first-line NAs (entecavir [ETV], tenofovir disoproxil fumarate [TDF], and tenofovir alafenamide [TAF]). The first-line NAs have no (TDF, TAF) or very low (ETV) viral resistance rates in treatment-naïve patients. ETV is associated with birth defects in animal studies. TDF is associated with a small risk renal and bone toxicity, primarily in older and higher risk patients. TAF has favorable renal and bone safety as compared to TDF, while its impact on lipid metabolism warrants attention. Although extremely rare, severe lactic acidosis can occur during NA treatment. Long-term therapy with NAs is generally very safe, with potential risk of birth defects with ETV based on animal studies, potential viral resistance with ETV (rare if treatment-naïve and significant if prior lamivudine exposure/resistance), potential renal and bone mineral density adverse effects with TDF, lipid metabolism dysfunction with TAF, and rare but potentially severe lactic acidosis.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is rapidly being recognized as a world health crisis, touching nearly a third of the world’s population. A key step in the progression of MASLD from simple steatosis to full-blown fibrosis is the unregulated lipid metabolism of the liver, especially the overexpression of de novo lipogenesis (DNL). This article aims to explore the relationship between m6A remodeling pathways and DNL in MASLD pathogenesis. It also addresses the therapeutic implications including both synthetic and natural products of these regulators towards managing MASLD by means of epitranscriptomic profiling. Studies have identified RNA methylation in the form of N-6 Methyladenosine (m6A) as the master regulator of this unregulated lipid metabolism. It incorporates different regulators, termed writers, erasers, and readers, which determine the fate of lipid metabolism regulator transcripts. In MASLD, these regulators have been found to be compromised, especially in instances where the regulators expression are altered which results in the stabilization of lipid regulators such as SREBP-1c, FASN etc. However, of specific interest is the fact that m6A regulators are connected not only to lipid synthesis but also integrate signals of insulin resistance, oxidative stress, and mitochondrial dysfunction. The recent emergence of epitranscriptomics has revolutionized our understanding of MASLD by revealing m6A methylation as a master regulator of DNL. The complex interplay between writers, erasers, and readers has established a highly complex post-transcriptional regulatory circuit that modulates the stability, export, and translation of primary lipogenic enzymes and transcription factors. The integration of epitranscriptomic profiling with current clinical diagnostic tools may, in the future, provide the means for personalized medicine strategies to be employed for the accurate treatment of MASLD according to the individual’s specific molecular profile. In the end, the connection between epitranscriptomic principles and clinical translation has the potential to turn MASLD from a global health crisis into a manageable disease.
This review synthesizes the current knowledge of hepatocellular carcinoma (HCC) epidemiology across Northern and sub-Saharan Africa. We examine how causes of HCC differ by region, highlight prevention and early detection strategies, and identify gaps in treatment and palliative care to improve outcomes. The causes of HCC vary markedly across the continent. HCV predominates in Northern Africa, whereas HBV infection and dietary aflatoxin exposure prevail in sub-Saharan Africa. Rising obesity, diabetes, harmful alcohol use, and hepatitis D co-infection are important but under-researched contributors. Most patients still present with advanced disease, fewer than 6
This narrative examines how palliative care can be effectively integrated into routine management of advanced liver disease (ALD). It evaluates the gap between evidence supporting palliative care and its limited adoption in hepatology practice, focusing on implementation needs. The multisite cluster randomized PAL-LIVER trial demonstrated that integrated palliative care improves quality of life, symptom burden, and patient satisfaction in ALD. However, uptake in routine practice remains inconsistent because of challenges involving patient identification, workforce capacity, workflow integration, reimbursement, and inequities in access. Evidence supports the benefits of palliative care integration in ALD, but translation into clinical practice remains limited. Key priorities for future research include developing scalable care models, improving workforce training, redesigning workflows, establishing quality metrics, integration into transplant and addressing reimbursement barriers. An implementation-focused research agenda is needed to support sustainable and equitable integration of palliative care into hepatology practice.
Alcoholic liver disease (ALD) is a clinically significant and progressive condition encompassing hepatic steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma, This review examines the interactions between serum trace elements (zinc, selenium, copper, manganese, and iron) and vitamins (A, C, E, D, and the B-complex group) in relation to hepatic enzyme activities including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase in patients with ALD. Global evidence consistently demonstrates that serum zinc and selenium depletion correlate inversely with transaminase and gamma-glutamyl transferase (GGT) activities, while iron overload and copper dysmetabolism contribute to Fenton-mediated free radical generation and worsening hepatic damage. Vitamins C and E are significantly depleted in ALD, amplifying oxidative injury. Vitamin D deficiency, now documented in Nigerian cirrhosis cohorts, compounds immune dysregulation, while pyridoxine (B6) deficiency mechanistically explains the elevated aspartate aminotransaminase/ alanine transaminase (AST/ALT) or the De Ritis ratio characteristic of ALD. Hospital-based studies confirm alcohol as a leading cause of chronic liver disease, accounting for 35–52
This review examines the challenges of care coordination in patients with cirrhosis, with a particular focus on transitions of care as a critical period driving hospital readmissions. We aim to identify key drivers of failed transitions and evaluate evidence-based and emerging strategies to improve care. Cirrhosis readmissions are driven by disease severity, comorbidities, social barriers, and breakdowns in the transition of care. Evidence supports early post-discharge follow-up, pharmacist-led medication reconciliation, and multidisciplinary care models in reducing readmissions. Telehealth and remote monitoring have emerged as promising tools. Additionally, advanced practice provider-led models and integrated care pathways further improve care delivery. Improving outcomes in cirrhosis requires a coordinated, multidisciplinary approach with attention to safer transitions, close monitoring, and early recognition of decompensations. Telehealth and protocol-driven care led by advanced providers are key. Longitudinal models of care, supported by new digital tools, should be further studied to reduce readmissions and improve overall patient care.
The purpose of the review is to integrate existing information about the immune pathogenesis and potential targets for therapy of primary biliary cholangitis (PBC). Recent advancements in immunology have shed light on the roles of various factors (like CXCL10, CCR2/CCR5, and IL-12/23), the generation of autoantibodies (such as AMA), and the immune dysregulation involving various cell types, including B-cells, CD4+, CD8+, Th17, Treg, NK cells, and macrophages. Clinical trials involving biologics such as rituximab, belimumab, ustekinumab, abatacept, NI-0801, Cenicriviroc, Secukinumab, Ruxolitinib, Baricitinib, PD 1/PD L1 Pathway Blockade, CNP-104, and Mesenchymal stem cells (MSCs) have demonstrated a modest or short-term immunological and biochemical impact in early-stage or pilot studies, but no consistent and long-lasting clinical advantages have been shown, highlighting the intricate nature of immune modulation in PBC. PBC is a complex autoimmune liver disease influenced by a mix of genetic, environmental, and immune factors. While traditional immunosuppressants haven’t shown much promise, researchers are exploring precision therapies that focus on B-cells, T-cells, cytokines, and co-stimulatory pathways. Early trials have shown that they are safe and can modulate the immune response, but the research needs larger, more detailed studies to really understand their effectiveness and tackle pressing clinical issues.
This review aims to summarize the available literature on malignancy screening in patients with primary sclerosing cholangitis (PSC). Primary sclerosing cholangitis (PSC) is a chronic, slowly progressive inflammatory disease of both the large and small bile ducts that ultimately leads to biliary fibrosis, cholestatic liver injury, and cirrhosis. Given its chronic inflammatory nature, PSC is associated with malignancy. PSC is associated with an 160-400 fold risk of cholangiocarcinoma and 9-78 fold risk of gallbladder cancer. If associated with inflammatory bowel disease, as is true in 80
Here is reviewed the epidemiology, pathophysiology, clinical impact and management strategies for hyponatremia in patients with cirrhosis. Hyponatremia in cirrhosis has many etiologies but is predominantly hypervolemic. The foundations of management include free water restriction and albumin infusion. Attempts should be made to increase solute intake, predominantly via increased protein. Vasopressor receptor antagonists (“vaptans”) are safe to use when clinically indicated. Hypertonic saline should be reserved for symptomatic patients or those requiring urgent correction of sodium prior to liver transplant. Other agents, including sodium-glucose co-transporter inhibitors, hold promise but require further study. Hyponatremia is common in patients with cirrhosis and associated with significant morbidity and mortality. Treatment strategies are dictated by etiology, severity and acuity. This review covers the complex pathophysiology that precipitates hyponatremia in this setting and the multifaceted treatment approach that is required due to this complexity.
We aim to evaluate the efficacy of risk-based surveillance strategies for hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) patients, addressing key questions: How can risk stratification enhance early detection? What are cost-effective approaches across diverse settings? How may novel diagnostic tools enhance surveillance? Recent studies highlight a persistent risk of HCC despite antiviral therapy, with reported annual incidences of 0.01–5.4
To evaluate the critical role of international registries in understanding idiosyncratic drug-induced liver injury (DILI) by comparing clinical and epidemiological data from the Spanish DILI Registry, the Pro-Euro DILI registry, and the US DILIN. Although amoxicillin-clavulanic acid remains the leading global DILI trigger, DILI cases in the US show higher severity and more herbal supplement involvement. Immune checkpoint inhibitors present new toxicity phenotypes. Registry collaborations have yielded advanced prognostic tools like the nR criteria for predicting liver failure, and RECAM, a novel electronic causality assessment scale offering greater diagnostic precision than RUCAM. Registries are crucial for identifying rare DILI events that are missed by clinical trials, as well as for highlighting regional differences in triggers and outcomes. These networks are essential for identifying diagnostic biomarkers, and their findings benefit not only clinicians, but also regulators. Future research should prioritize the global validation of RECAM and utilize multinational biobanks to identify genetic risk factors, ultimately improving drug safety.
This review aims to synthesize current evidence on metabolic dysfunction-associated steatotic liver disease (MASLD) as a systemic driver of extrahepatic complications beyond its hepatic manifestations. We sought to answer two key questions: (1) Which multisystemic diseases show independent associations with MASLD after adjustment for traditional cardiometabolic risk factors? (2) What shared pathophysiological mechanisms link hepatic steatosis to distant organ dysfunction? Large cohort studies and meta-analyses demonstrate MASLD independently increases cardiovascular, renal, gastrointestinal, and oncologic risks, independently from traditional cardiometabolic risk factors. Key mechanisms include systemic inflammation, insulin resistance with hyperinsulinemia, endothelial dysfunction, visceral adipose tissue dysregulation, gut dysbiosis with metabolic endotoxemia, atherogenic dyslipidemia, PNPLA3 genetic variants, and oxidative stress. Hepatic fibrosis consistently amplifies multisystemic risk across organ systems. MASLD represents a multisystem metabolic disorder requiring integrated risk assessment. Systematic fibrosis staging emerges as the strongest disease-specific prognostic factor. Future research must develop risk prediction models and liver-directed interventions targeting the gut-liver axis to mitigate MASLD's growing population-level burden
Purpose of Review:Chronic pain affects 40-80% of patients with chronic liver disease, yet management remains challenging due to impaired drug metabolism, limited evidence, and the absence of disease-specific guidelines. This review summarizes the evidence for pharmacologic and non-pharmacologic pain management strategies in patients with cirrhosis. Recent Findings:Nearly every analgesic class carries risk in patients with cirrhosis, and most prescribing recommendations are based on pharmacokinetic data and expert opinion rather than clinical trials. Opioid prescribing has declined in recent years, but nonopioid alternatives have not increased proportionally. Non-pharmacologic modalities have been scarcely studied in this population. Shared comorbidities and risk factors, including alcohol use, metabolic disease, sleep disturbances, and psychiatric conditions, represent modifiable therapeutic targets that may improve pain while altering liver disease trajectory. Summary:Pain management in patients with cirrhosis requires an individualized, multimodal approach integrating pharmacologic therapy, non-pharmacologic interventions, and comorbidity management. Further research, including both well-designed observational studies and prospective trials, is needed to generate evidence-based guidance for this underserved population.
This systematic review and meta-analysis aimed to evaluate the safety and efficacy of permanent peritoneal catheters (PPC) and peritoneal ports (PP) in patients with refractory ascites of malignant and non-malignant etiology, irrespective of etiology, and to compare these devices to large-volume paracentesis (LVP). Twenty-nine studies were included, with the majority being case series. Meta-analysis found no significant difference in peritonitis risk between PPC/PP and LVP. Cellulitis, occlusion, and ascites leakage were variably reported across studies. Average catheter patency was approximately 72 days. Quality of life improvements were reported in only a subset of studies, with considerable heterogeneity in assessment tools and limited standardization of definitions and prophylaxis protocols. Despite substantial heterogeneity and risk of bias across included studies, no significant differences in safety were observed between PPC/PP and LVP. Available evidence suggests these devices may offer practical advantages in symptom control and could reduce the need for repeated paracentesis in selected patients. However, further randomized studies are needed to standardize protocols and better guide clinical implementation. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. This protocol was register with PROSPERO (CRD42024622692).
Telehealth is emerging as an integral part of care along the Hepatocellular Carcinoma (HCC) care continuum. In this review, we highlight the innovative ways telehealth is used to facilitate HCC care delivery and novel opportunities to leverage telehealth tools toward improved patient outcomes in HCC. Telehealth tools demonstrate effectiveness in key aspects of HCC care. Televisits maintain HCC surveillance adherence and improve patient access to HCC specialty care. Furthermore, teleconsultations provide unique pathways for the multidisciplinary evaluation and management of patients with HCC without the need for direct patient contact. Lastly, mobile application-based and remote patient monitoring tools show increasing promise in identifying and addressing patient symptoms and complications related to HCC and cirrhosis. Telehealth has revolutionized the delivery of HCC care. As telehealth adoption and use cases increase, the field will move closer to ensuring specialty HCC care is more accessible regardless of geography.
This review aims to synthesize current evidence on the role of microRNAs (miRNAs) as key epigenetic regulators in metabolic dysfunction-associated steatotic liver disease (MASLD) and to evaluate their emerging potential as non-invasive biomarkers and therapeutic targets. Dysregulated miRNAs—including miR-122, miR-34a, and miR-21—have been shown to modulate central pathways in MASLD, such as lipid metabolism, insulin signaling, inflammation, and fibrogenesis. Circulating miRNAs, particularly those encapsulated within extracellular vesicles like exosomes, show promise as non-invasive biomarkers for diagnosis and staging, although discordance between hepatic and serum expression remains a challenge. Combinatorial miRNA panels improve diagnostic accuracy and prognostic stratification. Therapeutically, strategies using antagomirs and mimics have demonstrated potential in preclinical models, yet issues of delivery efficiency and off-target effects hinder clinical translation. miRNAs play a multifaceted role in MASLD pathogenesis and represent promising tools for biomarker development and targeted therapy. Future efforts should focus on standardizing detection methods, validating miRNA panels in large cohorts, and advancing delivery systems to realize the clinical potential of miRNA-based interventions in MASLD.
This review explores the challenges of accurately assessing obesity in patients with liver cirrhosis complicated by ascites. It aims to clarify the limitations of traditional anthropometric methods and evaluate emerging tools that account for fluid overload and altered body composition. Recent studies emphasize that conventional indices such as BMI, waist circumference, and bioelectrical impedance are unreliable in this setting. Advanced imaging modalities, including CT, and MRI, as well as newer techniques like multifrequency BIA and muscle and fat ultrasound, added to the simple bedside skinfold thickness might improve accuracy in evaluating fat and muscle compartments despite ascitic interference. Obesity assessment in cirrhosis with ascites requires multimodal evaluation rather than reliance on BMI. Combining ultrasound with skinfold or impedance measures provides a practical, low-cost, and reproducible approach. This integrated framework enhances diagnostic precision and offers a foundation for personalized management and future research in metabolic and nutritional assessment in liver disease.
