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14 pages, 686 KB

Open AccessArticle

Evaluation of the Potential Benefits of Trimetazidine in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized Controlled Trial

by Maha Youssif, Ragaey Ahmad Eid, Hoda Rabea, Yasmin M. Madney, Arwa Khaled, Khalid Orayj, Dina Attia and Engy A. Wahsh

Pharmaceuticals 2025, 18(9), 1279; https://doi.org/10.3390/ph18091279 - 27 Aug 2025

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Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global public health issue, affecting approximately 25% of the population and currently offering limited treatment options. Trimetazidine (TMZ) serves as a metabolic modulator that shifts cellular energy metabolism from fatty acid oxidation to [...] Read more.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global public health issue, affecting approximately 25% of the population and currently offering limited treatment options. Trimetazidine (TMZ) serves as a metabolic modulator that shifts cellular energy metabolism from fatty acid oxidation to glucose oxidation, thereby providing a novel therapeutic strategy aimed at addressing the underlying metabolic dysfunctions that contribute to the pathogenesis of MASLD. Our study aims to assess the efficacy of trimetazidine in improving hepatic steatosis, inflammation, and various metabolic parameters. Methods: In this double-masked, randomized controlled trial, 60 patients with confirmed MASLD diagnoses were randomly assigned in a 1:1 ratio to receive either trimetazidine 20 mg three times daily or a placebo, alongside lifestyle modifications, for 24 weeks. The trial was conducted in accordance with the Declaration of Helsinki and approved by the ethics committees of both participating institutions. We measured changes in hepatic steatosis, non-invasive fibrosis scores, inflammatory markers (including interleukin-6, tumor necrosis factor-alpha, and highly sensitive C-reactive protein), liver enzymes, and lipid profiles at baseline and at the end of the 24 weeks. Results: Hepatic steatosis decreased significantly, with controlled attenuation parameter scores from 352.5 to 302 dB/m in the TMZ group compared to the control (p < 0.001). TNF-α was reduced significantly in the TMZ group compared to the control group (p = 0.001). Fibrosis to AST score decreased from 0.49 to 0.25 in the TMZ group (p < 0.001). Aspartate aminotransferase decreased significantly compared to the control group (p 0.032). Notably, TMZ also imparted cardioprotective benefits, reducing total cholesterol by 14%, LDL by 17% (both p < 0.05), and triglycerides by 16% (p = 0.176). Conclusions: This groundbreaking trial supports the potential of trimetazidine as a promising therapeutic agent for MASLD, indicating substantial improvements in hepatic steatosis, inflammation, and metabolic disturbances. These findings underscore the urgency and importance of further multicenter trials to validate trimetazidine’s efficacy as a disease-modifying therapy for MASLD. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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14 pages, 1160 KB

Open AccessArticle

The Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study

by Hiroya Kitsunai, Yuka Shinozaki, Sho Furusawa, Naoyuki Kitao, Miki Ito, Hiroyoshi Kurihara, Chiho Oba-Yamamoto, Jun Takeuchi, Akinobu Nakamura, Yumi Takiyama and Hiroshi Nomoto

Pharmaceuticals 2025, 18(1), 129; https://doi.org/10.3390/ph18010129 - 19 Jan 2025

Cited by 3 | Viewed by 2683

Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of [...] Read more.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. Methods: A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. Results: Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. Conclusions: The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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17 pages, 1012 KB

Open AccessArticle

The Effect of Biologic Agents on Steatotic Liver Disease in Patients with Inflammatory Bowel Disease: A Prospective, Open-Label Comparative Trial

by Apostolis Papaefthymiou, Styliani Sarrou, Konstantinos Pateras, Ilias D. Vachliotis, Georgios Agrotis, Ioanna-Konstantina Sgantzou, Georgios Perifanos, Andreas Kapsoritakis, Matthaios Speletas, Marianna Vlychou, George N. Dalekos, Spyros Potamianos, Antonis Goulas, Jannis Kountouras and Stergios A. Polyzos

Pharmaceuticals 2024, 17(11), 1432; https://doi.org/10.3390/ph17111432 - 25 Oct 2024

Cited by 4 | Viewed by 1924

Abstract

Background: Biologic agents used in patients with inflammatory bowel diseases (IBD) may influence the pathophysiology of coexistent metabolic-dysfunction associated steatotic liver disease (MASLD). This study primarily aimed to evaluate the six-month effect of infliximab or vedolizumab vs. no biologics on presumed hepatic steatosis [...] Read more.

Background: Biologic agents used in patients with inflammatory bowel diseases (IBD) may influence the pathophysiology of coexistent metabolic-dysfunction associated steatotic liver disease (MASLD). This study primarily aimed to evaluate the six-month effect of infliximab or vedolizumab vs. no biologics on presumed hepatic steatosis in patients with IBD. Secondary endpoints were their effect on hepatic fibrosis and parameters related to hepatic metabolism. Methods: This prospective, non-randomized, controlled trial assigned adult bio-naïve patients with IBD into three groups: infliximab, vedolizumab, or controls (receiving no biologic). The baseline was the time of the initiation of biologic agents and the endpoint six months later. Hepatic steatosis was evaluated with transabdominal ultrasonography (Hamaguchi score), whereas controlled attenuation parameter (CAP), fatty liver index (FLI), and hepatic steatosis index (HSI) were used as surrogates. Hepatic fibrosis was evaluated with liver stiffness (LS), fibrosis-4 index (FIB-4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score. Results: Sixty-six patients were assigned to infliximab (n = 26), vedolizumab (n = 14), or control (n = 26); At the endpoint, the Hamaguchi score, CAP, FLI, and HSI were not different between groups. LS was not different between groups; however, FIB-4 was increased within all groups, and NAFLD fibrosis score was increased within infliximab and control groups, without significant biologic × time interactions. Conclusions: No positive or adverse effect of infliximab or vedolizumab vs. no biologic agents was shown on presumed hepatic steatosis in patients with IBD, who have not been previously exposed to biologic agents. Although no effect of both biologic agent on LS, a slight but significant increase in FIB-4 and NAFLD fibrosis score warrants further studying. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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14 pages, 1028 KB

Open AccessArticle

Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients

by Matheus De Lucca Thomaz, Carolina Pinto Vieira, Juciene Aparecida Caris, Maria Paula Marques, Adriana Rocha, Tiago Antunes Paz, Rosamar Eulira Fontes Rezende and Vera Lucia Lanchote

Pharmaceuticals 2024, 17(7), 865; https://doi.org/10.3390/ph17070865 - 1 Jul 2024

Cited by 4 | Viewed by 1499

Abstract

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in [...] Read more.

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC_0–24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61–0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66–0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97–1.24), p > 0.05) and 2 (ratio 1.03 (0.94–1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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Review

Jump to: Research

31 pages, 2784 KB

Open AccessReview

Obeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders

by Stefano Fiorucci, Ginevra Urbani, Eleonora Distrutti and Michele Biagioli

Pharmaceuticals 2025, 18(9), 1424; https://doi.org/10.3390/ph18091424 - 22 Sep 2025

Cited by 1 | Viewed by 2766

Abstract

The Farnesoid-X-receptor (FXR) is a bile sensor involved in the regulation of bile acid homeostasis, fibrosis, inflammation, and metabolism. Obeticholic acid (OCA), a semisynthetic derivative of chenodeoxycholic acid (CDCA), initially named 6-ethyl-CDCA or INT-747, is the first in a class of FXR ligands [...] Read more.

The Farnesoid-X-receptor (FXR) is a bile sensor involved in the regulation of bile acid homeostasis, fibrosis, inflammation, and metabolism. Obeticholic acid (OCA), a semisynthetic derivative of chenodeoxycholic acid (CDCA), initially named 6-ethyl-CDCA or INT-747, is the first in a class of FXR ligands that have been approved for clinical use for the treatment of patients with primary biliary cholangitis (PBC) who are unresponsive or intolerant to ursodeoxycholic acid. In this narrative review, we will examine the current status and future perspective of clinical use of OCA. Based on results from phase 2 and 3 clinical trials, OCA received a conditional market approval for its use as a second-line treatment for the management of PBC in 2016. However, concerns over drug (OCA)-induced liver injury (DILI), including hepatic decompensation in cirrhotic and non-cirrhotic PBC patients, have led to discontinuation of OCA commercialization in the EU, but not in North America and the UK, in 2024. Based on positive results from preclinical models, OCA has been investigated also for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Results from phase 2 and 3 trials, however, have shown that while OCA reduces liver fibrosis, the beneficial effects on steatosis are marginal, thus preventing its clinical approval under the current regulatory guidelines. Here, we review potential applications of OCA in PBC patients in the context of a highly competitive therapeutic landscape, generated by the approval for clinical use of safer and effective second-line therapies, including PPARs agonists such as elafibranor and seladelapar and increased off-label use of fibrates. The current status of development of second-generation FXR agonists such as cilofexor, tropifexor, and vonafexor and their potential in the treatment of liver fibrosis in MASH will be discussed and compared to recently approved therapies, resmetirom, and semaglutide, a GLP-1 agonist. Finally, since some of the novel candidates for treating MASH, have shown limited efficacy on liver fibrosis, we suggest that development of combinatorial therapies based on FXR ligands and agents acting on different molecular targets might offer the opportunity for the repositioning of drug candidates whose development has been abandoned for insufficient efficacy, minimizing/recovering costs linked to drug development. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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33 pages, 1036 KB

Open AccessReview

Present and Future Perspectives in the Treatment of Liver Fibrosis

by Lucia Cerrito, Linda Galasso, Jacopo Iaccarino, Alessandro Pizzi, Fabrizio Termite, Giorgio Esposto, Raffaele Borriello, Maria Elena Ainora, Antonio Gasbarrini and Maria Assunta Zocco

Pharmaceuticals 2025, 18(9), 1321; https://doi.org/10.3390/ph18091321 - 3 Sep 2025

Viewed by 2548

Abstract

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption [...] Read more.

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions. Methods: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity. Results: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin–angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut–liver axis. Microbiota-directed interventions—probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation—are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations. Conclusions: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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17 pages, 1642 KB

Open AccessReview

Defenestration of Liver Sinusoidal Endothelial Cells: The Trigger of Liver Fibrosis

by Juntao Zhou, Jianqiao Wang, Lijuan Zhang, Chengliang Zhang and Cheng Tian

Pharmaceuticals 2025, 18(6), 893; https://doi.org/10.3390/ph18060893 - 14 Jun 2025

Viewed by 2094

Abstract

Liver fibrosis is a common pathological manifestation of various chronic liver diseases, distinguished by the excessive accumulation of the extracellular matrix. If unresolved, liver fibrosis can progress to cirrhosis or hepatocellular carcinoma. Fenestrae are important structures of liver sinusoidal endothelial cells (LSECs) regulating [...] Read more.

Liver fibrosis is a common pathological manifestation of various chronic liver diseases, distinguished by the excessive accumulation of the extracellular matrix. If unresolved, liver fibrosis can progress to cirrhosis or hepatocellular carcinoma. Fenestrae are important structures of liver sinusoidal endothelial cells (LSECs) regulating hepatic substance exchange, immune response and hemodynamics. The loss of this structure is usually accompanied by dysfunction of LSECs, which disrupts normal liver physiology by impairing hepatic substance exchange, compromising liver microcirculation, and activating hepatic stellate cells (HSCs). This cascade of events ultimately contributes to the onset and development of liver fibrosis. Oxidative stress, impairment of the NO signaling pathway, actin–myosin complex remodeling and pathological angiogenesis are considered to be the main mechanisms underlying LSEC defenestration. Recently, research on the treatment of LSEC defenestration has made notable progress, and findings suggest a potential value in the application of anti-fibrotic therapies. This article expounds the important correlation between defenestration of LSECs and liver fibrosis, while also reviews therapeutic agents and approaches targeting this pathological process. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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15 pages, 1506 KB

Open AccessReview

Efficacy and Safety of Novel Oral Anti-Cholestatic Agents for Primary Biliary Cholangitis: Meta-Analyses and Systematic Review

by Eyad Gadour, Bogdan Miutescu, Hiba Bashir, Abubaker Ali, Salem Alanzi, Abdullah A. Al-Shahrani, Aymen Almuhaidb, Shahed Mohamed, Faisal Abaalkhail, Hadi Kuriry and Mohammed Saad AlQahtani

Pharmaceuticals 2025, 18(5), 697; https://doi.org/10.3390/ph18050697 - 8 May 2025

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Abstract

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate [...] Read more.

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate the efficacy and safety of novel oral anti-cholestatic agents for PBC. Methods: A systematic literature search was conducted in electronic databases up to September 2024. Randomized controlled trials, cohort studies, and case-control studies evaluating novel oral anti-cholestatic agents in adult PBC patients were included. The primary outcome was a change in alkaline phosphatase (ALP) levels. Safety was assessed by the incidence of serious adverse events. Random-effect meta-analyses were performed. Results: Ten studies involving 878 patients were analyzed. Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. The meta-analysis showed significant reductions in ALP levels with novel agents compared to the controls (SMD −2.80; 95% CI −3.56, −2.03; p < 0.00001), with high heterogeneity (I² = 93%). Saroglitazar achieved the largest effect size. There was no significant difference in serious adverse events between novel agents and controls (OR 1.21; 95% CI 0.81, 1.83; p = 0.35). Conclusions: Novel oral anti-cholestatic agents show promise in improving biochemical markers in PBC patients with suboptimal UDCA responses, with a safety profile comparable to controls. However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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26 pages, 1373 KB

Open AccessReview

Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

by Hao Xiong and Jinsheng Guo

Pharmaceuticals 2025, 18(4), 507; https://doi.org/10.3390/ph18040507 - 31 Mar 2025

Cited by 1 | Viewed by 4454

Abstract

Hepatic stellate cells (HSC) are the major source of myofibroblasts (MFB) in fibrosis and cancer- associated fibroblasts (CAF) in both primary and metastatic liver cancer. Over the past few decades, there has been significant progress in understanding the cellular and molecular mechanisms by [...] Read more.

Hepatic stellate cells (HSC) are the major source of myofibroblasts (MFB) in fibrosis and cancer- associated fibroblasts (CAF) in both primary and metastatic liver cancer. Over the past few decades, there has been significant progress in understanding the cellular and molecular mechanisms by which liver fibrosis and HCC occur, as well as the key roles of HSC in their pathogenesis. HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects. Recent advances in omics, particularly single-cell sequencing and spatial transcriptomics, hold promise for identifying new HSC targets for diagnosing and treating liver fibrosis/cirrhosis and liver cancer. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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31 pages, 1092 KB

Open AccessReview

Side Effects of Immunosuppressant Drugs After Liver Transplant

by Filippo Gabrielli, Elisa Bernasconi, Arianna Toscano, Alessandra Avossa, Alessia Cavicchioli, Pietro Andreone and Stefano Gitto

Pharmaceuticals 2025, 18(3), 342; https://doi.org/10.3390/ph18030342 - 27 Feb 2025

Cited by 3 | Viewed by 4196

Abstract

Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal [...] Read more.

Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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19 pages, 2355 KB

Open AccessReview

Pharmacological Treatment of Ascites: Challenges and Controversies

by Jimmy Che-To Lai, Junlong Dai, Lilian Yan Liang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong and Terry Cheuk-Fung Yip

Pharmaceuticals 2025, 18(3), 339; https://doi.org/10.3390/ph18030339 - 27 Feb 2025

Viewed by 5320

Abstract

Ascites is the most common complication from cirrhosis related to portal hypertension and depicts the onset of hepatic decompensation. Ranging from uncomplicated to refractory ascites, the progression carries prognostic value by reflecting the deterioration of underlying cirrhosis and portal hypertension. Diuretics have been [...] Read more.

Ascites is the most common complication from cirrhosis related to portal hypertension and depicts the onset of hepatic decompensation. Ranging from uncomplicated to refractory ascites, the progression carries prognostic value by reflecting the deterioration of underlying cirrhosis and portal hypertension. Diuretics have been the mainstay of treatment to control ascites, but the side effects heighten when the dosage is escalated. Non-selective beta-blockers (NSBBs) are widely used nowadays to prevent hepatic decompensation and variceal hemorrhage. However, with worsening systemic vasodilation and inflammation when ascites progresses, patients on NSBBs are at risk of hemodynamic collapse leading to renal hypoperfusion and thus hepatorenal syndrome. Long-term albumin infusion was studied to prevent the progression of ascites. However, the results were conflicting. Sodium-glucose cotransporter-2 inhibitors are under investigation to control refractory ascites. With that, patients with refractory ascites may require regular large-volume paracentesis. With an aging population, more patients are put on anti-thrombotic agents and their risks in decompensated cirrhosis and invasive procedures have to be considered. In general, decompensated cirrhosis with ascites poses multiple issues to pharmacological treatment. In the present review, we discuss the challenges and controversies in the pharmacological treatment of ascites. Full article

(This article belongs to the Special Issue Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances)

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