Advances in Pathogenesis and Treatment of Chronic Liver Disease

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Gastroenterology & Hepatology".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 3441

Special Issue Editors


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Guest Editor
Academic Department of Gastroenterology, "Laiko" General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece
Interests: hepatocellular carcinoma; cirrhosis; portal hypertension; elastography; liver fibrosis
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Guest Editor
Academic Department of Gastroenterology, "Laiko" General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
Interests: liver; hepatitis; liver cirrhosis

Special Issue Information

Dear Colleagues,

Chronic liver disease represents a significant contributor to global morbidity and mortality. Its etiology encompasses diverse factors, including chronic viral hepatitis, metabolic-associated steatotic liver disease (MASLD), alcoholic liver disease, autoimmune liver diseases, and cholestatic liver diseases. The resulting chronic inflammatory state can culminate in liver fibrosis, cirrhosis, and the development of portal hypertension, leading to severe complications such as ascites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome, and liver cancer. A comprehensive understanding of how each causative factor triggers liver inflammation and fibrosis is imperative for advancing future therapeutic strategies aimed at curtailing inflammation and impeding fibrosis, ultimately mitigating the prevalence of liver cirrhosis and its associated complications. This Special Issue endeavors to elucidate the current knowledge on the underlying pathways of chronic liver disease causative factors, underscore existing treatment modalities, and disseminate the latest evidence relating to ongoing therapeutic interventions.

Dr. Dimitrios Karagiannakis
Dr. Margarita Papatheodoridi
Guest Editors

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Keywords

  • chronic liver disease
  • cirrhosis
  • portal hypertension
  • pathogenesis
  • treatment

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Published Papers (3 papers)

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15 pages, 1484 KiB  
Article
High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease
by Ivan Budimir Bekan, Dino Šisl, Alan Šućur, Ana Bainrauch, Valerija Bralić Lang, Pavao Planinić, Nataša Kovačić, Danka Grčević, Anna Mrzljak and Tomislav Kelava
Medicina 2025, 61(7), 1293; https://doi.org/10.3390/medicina61071293 - 18 Jul 2025
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Abstract
Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 [...] Read more.
Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). Materials and Methods: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. Results: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (p > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, p = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (p > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. Conclusions: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Chronic Liver Disease)
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15 pages, 4196 KiB  
Article
Aerobic-Resistance Training with Royal Jelly Supplementation Has a Synergistic Effect on Paraoxonase 1 Changes and Liver Function in Women with MASLD
by Roya Askari, Nazanin Rabani, Hamid Marefati, Marzie Sadat Azarnive, Matteo Pusceddu and Gian Mario Migliaccio
Medicina 2025, 61(2), 349; https://doi.org/10.3390/medicina61020349 - 17 Feb 2025
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Abstract
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and [...] Read more.
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and its prevalence increases with age and obesity, and after menopause. Among the ways to treat it, we can mention regular sports exercises and the use of natural supplements. Therefore, the aim of this research is to investigate and compare the effects of aerobic-resistance training with royal jelly supplementation on changes in paraoxonase 1, oxidized LDL, liver function, and lipid profile in postmenopausal women with Dysfunction-Associated Steatotic Liver Disease. Materials and Methods: This semi-experimental study involved 23 women with Dysfunction-Associated Steatotic Liver Disease with an average weight (71.34 ± 11.63 kg), age (48.54 ± 3.88 years), and body mass index (27.63 ± 4.20 kg/m2). They were randomly divided into two groups: exercise + supplement (n = 12) and exercise + placebo (n = 11). Both groups performed eight-station resistance exercises (8–12 repetitions in 2–4 sets) for 8 weeks, with three sessions per week (for 35–40 min, from 10-15 RPE), and then, for 10–15 min of active rest, they performed aerobic exercises with an intensity of 40–85% of the target heart rate, in two-minute intervals with 45 s of active rest. Royal jelly supplement (500 mg on training days, before each training session) was consumed. Blood sampling was done before and 48 h after the last training session. Statistical analysis was performed using a variance test with repeated measures (two groups × two stages of pre-test-post-test) in SPSS software (Version 26) with a significance level of p < 0.05. Results: The results of the statistical analysis show that the effects of eight weeks of exercise + supplement and exercise + placebo on PON1, oxLDL, lipid profiles (HDL, LDL, TC, and TG), and liver enzymes (ALT, AST) in women with non-alcoholic fatty liver showed a significant difference (p < 0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. But significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015) and AST (p = 0.009) were observed in the exercise + supplement group compared to the exercise + placebo group (<0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. However, significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015), and AST (p = 0.009) was observed in the exercise + supplement group compared to the exercise + placebo group. Conclusions: Based on the results, it can be concluded that aerobic-resistance exercises with the addition of royal jelly can probably be an efficient and recommended strategy to minimize the harmful effects of Dysfunction-Associated Steatotic Liver Disease by affecting the activity of liver enzymes, paraoxonase 1, LDL oxidation, and lipid profile. Although exercise alone also yielded favorable results, according to the findings of this research, it can be said that exercise, combined with the use of royal jelly supplements, may have more positive effects on reducing liver complications and improving body function. However, in order to obtain more accurate scientific evidence, it is necessary to investigate more doses and timing of royal jelly in future studies. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Chronic Liver Disease)
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21 pages, 2969 KiB  
Systematic Review
Value of Probiotics on Outcome in Patients Following Liver Surgery: A Systematic Review and Meta-Analysis
by Robert Karitnig, Andreas Bogner, Nora Jahn, Christos Vlachos, Andri Lederer, Antonia Geisler, Robert Sucher and Hans Michael Hau
Medicina 2025, 61(6), 1068; https://doi.org/10.3390/medicina61061068 - 10 Jun 2025
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Abstract
Background and Objectives: The gut–liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver’s detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients [...] Read more.
Background and Objectives: The gut–liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver’s detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients develop bacterial infections, with a high risk of bacteremia or even sepsis-related liver failure and death. The potential advantages of administering pro- or synbiotics before/after surgery remain a topic of discussion. Therefore, a systematic review of randomized clinical trials comparing patients with and without supplementation and their outcomes and effects after liver resection (LR) or liver transplantation (LT) was conducted. Materials and Methods: A computer-based search of electronic databases was conducted to gather randomized controlled trials (RCTs) that focused on probiotic/synbiotic use during the perioperative period for liver surgery patients. Two researchers independently screened the studies, extracted the data, evaluated the risk of bias, and performed a meta-analysis using RevMan Web. Results: Our research revealed 19 relevant randomized controlled studies that included a total of 1698 patients on the perioperative use of pro-/symbiotic administration in liver surgery. Eight studies were performed on liver transplantation (LT), and 11 studies were performed for liver resection (LR). The results of the meta-analysis demonstrated that the probiotic group exhibited lower rates of postoperative infectious complications (OR = 0.34; 95%CI 0.25 to 0.45; p < 0.0001), hospital stay duration (SMD = −0.13; 95%CI −0.25 to −0.00; p = 0.05), lower serum endotoxin levels (SMD = −0.39%CI −0.59 to −19; p < 0.0001), and white blood cell counts (SMD = −SMD = −0.35; 95%CI −0.56 to −0.13; p = 0.002) compared to the control group. Further, with regard to liver function, we observed significant postoperative differences in alanine aminotransferase (ALT)-levels (SMD = −0.46; 95%CI −0.63 to −0.29; p < 0.0001), aspartate aminotransferase (AST) levels (SMD = −0.53; 95%CI −0.71 to −0.34; p < 0.0001), bilirubin levels (SMD = −0.35; 95%CI −0.50 to −0.19; p < 0.0001), and international ratio (INR) levels (SMD = −0.1; 95%CI −0.12 to −0.08; p ≤ 0.0001), favoring the symbiotic group compared to the control group. Conclusions: The use of pro-/synbiotics during the perioperative period reduces the risk of postoperative infections, support postoperative liver function, and recovery and shortens hospital stays for liver surgery patients. However, they do not appear to particularly aid in inflammation reduction. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Chronic Liver Disease)
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