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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (25 October 2024) | Viewed by 20505

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Special Issue Editors

Dr. Ana-Maria Singeap

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1. Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 2. Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, 700111 Iasi, Romania
Interests: metabolic dysfunction-associated steatotic liver disease; cirrhosis; liver transplantation; gastrointestinal bleeding
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Prof. Dr. Anca Trifan

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Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
Interests: hepatic fibrosis; steatohepatitis; inflammatory bowel disease; alcoholic liver disease; gastroenterology and hepatology; cardiovascular complications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver cirrhosis, traditionally defined as the end stage of advanced liver disease, remains a significant health challenge globally, impacting millions of individuals, and posing complex clinical and therapeutic considerations due to its severe complications. Recently, progress in the understanding of and approach to liver cirrhosis has been made, and new concepts such as regression, recompensation or disease modifiers are currently being debated. The optimal management of complication is an equally key issue. In liver transplantation, the present hot topics include extended criteria donors, organ preservation, precision medicine, and biomarkers for rejection. Also, appropriate palliative care in end-stage liver disease is of tremendous importance in terms of duration but especially the quality of a patient’s life.

We are pleased to announce and extend an invitation to submit manuscripts for a Special Issue of Journal of Clinical Medicine focused on “Updates in Liver Cirrhosis”. The goal of this Special Issue is to provide a comprehensive platform for researchers, clinicians, and experts in the field to share their latest findings, insights, and advancements related to liver cirrhosis. We welcome original research articles and reviews that contribute to the enhancement of knowledge in this critical area.

Topics of interest for this Special Issue include, but are not limited to:

Etiology and Pathogenesis of Liver Cirrhosis;
Diagnostic Innovations and Biomarkers;
Advances in Imaging Techniques for Cirrhosis Assessment;
Novel therapeutic Approaches and Drug Development;
Complications of Cirrhosis: Prevention and Management;
Liver Transplantation;
Multidisciplinary Approaches to Cirrhosis Care;
Quality of Life Enhancement.

Dr. Ana-Maria Singeap
Prof. Dr. Anca Trifan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatic fibrosis
portal hypertension
disease modifiers
cirrhosis complications
acute-on-chronic liver failure
hepatocellular carcinoma
liver transplantation
quality of life

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Published Papers (9 papers)

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Research

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13 pages, 2267 KiB

Open AccessArticle

The Use of Proton Pump Inhibitors in Patients with Liver Cirrhosis: Real Life Experience

by Raphaël Eftimie Spitz, Stefan Lucian Popa, Simona Grad, Dan Lucian Dumitrascu, Abdulrahman Ismaiel and Teodora Surdea-Blaga

J. Clin. Med. 2024, 13(17), 5155; https://doi.org/10.3390/jcm13175155 - 30 Aug 2024

Cited by 1 | Viewed by 2065

Abstract

(1) Background: Proton pump inhibitors (PPIs) are commonly prescribed for gastric disorders. In patients with liver cirrhosis, PPI use is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates; therefore, they should be used with caution. This study aims to evaluate the appropriateness of PPI prescriptions in hospitalized cirrhotic patients against current clinical guidelines to identify patterns of misuse and guide better prescribing practices. (2) Methods: A retrospective study was conducted on liver cirrhosis inpatients in an internal medicine department from January 2022 to May 2023. The primary measure was the proportion of PPI prescriptions aligned with clinical guidelines. Medical files were entirely reviewed by researchers to assess the appropriateness of PPI prescriptions using the current guidelines. Outcomes included the identification of common reasons for PPI prescription and the rate of inappropriate PPI use among the study population. (3) Results: The study included 189 cirrhotic patients, with PPIs prescribed to 95 (50.2%) patients during hospitalization and 75 (39.7%) patients at discharge. Among those, 47.4% of the inpatients and 34.7% at discharge had no valid indication for PPI administration. The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding. The most common inappropriate indication was portal hypertensive gastropathy (PHG), followed by treatment with corticosteroids and anticoagulants alone. We did not find an association between PPI administration during hospital stays and infections. Only in 4% of cases patients should have received PPIs and did not. (4) Conclusions: There is a concerning overprescription of PPIs in cirrhotic patients, often deviating from established guidelines. It subjects patients to unnecessary risks. There is an urgent need for increased awareness and adherence to clinical guidelines regarding PPI prescriptions in cirrhotic patients. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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13 pages, 983 KiB

Open AccessArticle

Quantitative Magnetic Resonance Cholangiopancreatography Scoring and Its Predictive Value for Outcomes in Adults with Primary Sclerosing Cholangitis

by Matei Mandea, Speranta Maria Iacob, Mugur Cristian Grasu, Cristian Anghel, Razvan Andrei Iacob, Mihaela Corina Ghioca, Cristian Gheorghe and Liliana Simona Gheorghe

J. Clin. Med. 2024, 13(15), 4548; https://doi.org/10.3390/jcm13154548 - 3 Aug 2024

Viewed by 1739

Abstract

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated disease that has an unfavorable prognosis and needs a liver transplant (LT). The aim of this paper was to show the usefulness of the Majoie classification on magnetic resonance cholangiopancreatography (MRCP) images in assessing the prognosis in adult patients with PSC. Methods: Our work presents a retrospective monocentric study performed on 64 adult patients with PSC of the large bile ducts. Two radiologists evaluated the MRCP of diagnosis and calculated MRCP scores using the Majoie classification. Liver-related outcome (LT or liver-related death) was marked as a primary endpoint. Results: Univariate analysis showed that patients with more severe lesions (sum score of intrahepatic and extrahepatic ducts > 3) had a lower age at diagnosis, of 37.2 years, complicated with liver cirrhosis (53.1% of patients) and recurrent cholangitis (28.1%) p < 0.05, without significant differences in mortality, association with IBD or LT. Concordance analysis between MRCP prognostic scores and progression to a PSC-related event showed a moderate relationship (c-statistic 0.662), and a good AUROC was observed for the UKPSC score (0.893) and the MRS (0.936). Conclusions: In the study, we observed a good correlation between the imaging scores based on the Majoie classification and the evolution of the patients. These scores were outperformed by the UKPSC, MRS, and PREsTo clinical models. Their utility was best in predicting recurrent cholangitis. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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11 pages, 858 KiB

Open AccessArticle

Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study

by Paolo Gallo, Antonio De Vincentis, Francesca Terracciani, Andrea Falcomatà, Valeria Pace Palitti, Maurizio Russello, Anthony Vignone, Domenico Alvaro, Raffaella Tortora, Marco Biolato, Maurizio Pompili, Vincenza Calvaruso, Veneziano Marzia, Marco Tizzani, Alessandro Caneglias, Francesco Frigo, Marcantonio Gesualdo, Alfredo Marzano, Valerio Rosato, Ernesto Claar, Rosanna Villani, Antonio Izzi, Raffaele Cozzolongo, Antonio Cozzolino, Aldo Airoldi, Chiara Mazzarelli, Marco Distefano, Claudia Iegri, Stefano Fagiuoli, Vincenzo Messina, Enrico Ragone, Rodolfo Sacco, Pierluigi Cacciatore, Flora Masutti, Saveria Lory Crocé, Alessandra Moretti, Valentina Flagiello, Giulia Di Pasquale, Antonio Picardi and Umberto Vespasiani-Gentilucci Show full author list Hide full author list

J. Clin. Med. 2024, 13(13), 3965; https://doi.org/10.3390/jcm13133965 - 6 Jul 2024

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Abstract

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the “Club Epatologi Ospedalieri” (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000–44,000/μL) to 58,000 (49,000–82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04–1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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14 pages, 2749 KiB

Open AccessArticle

Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents

by Anna Rycyk-Bojarzyńska, Beata Kasztelan-Szczerbińska, Halina Cichoż-Lach, Agata Surdacka and Jacek Roliński

J. Clin. Med. 2024, 13(5), 1237; https://doi.org/10.3390/jcm13051237 - 22 Feb 2024

Cited by 1 | Viewed by 1617

Abstract

Background: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). Methods: The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey’s Discriminant Function (mDF), and the presence of ALC complications. Results: The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. Conclusion: These findings suggest that alpha-defensins play an important role in the assessment of ALC. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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11 pages, 1296 KiB

Open AccessArticle

The Impact of Alcohol Consumption Pattern on Liver Fibrosis in Asymptomatic Patients

by Horia Minea, Ana-Maria Singeap, Catalin Victor Sfarti, Irina Girleanu, Stefan Chiriac, Cristina Muzica, Tudor Cuciureanu, Oana Cristina Petrea, Laura Huiban, Sebastian Zenovia, Robert Nastasa, Adrian Rotaru, Remus Stafie, Ermina Stratina, Camelia Cojocariu, Carol Stanciu and Anca Trifan

J. Clin. Med. 2023, 12(23), 7405; https://doi.org/10.3390/jcm12237405 - 29 Nov 2023

Cited by 3 | Viewed by 1718

Abstract

Introduction: Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10–20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. Methods: We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. Results: ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. Conclusions: Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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22 pages, 8196 KiB

Open AccessArticle

Nutrition and Mental Well-Being: Exploring Connections and Holistic Approaches

by Theodora Claudia Gheonea, Carmen-Nicoleta Oancea, Magdalena Mititelu, Elena Carmen Lupu, Corina-Bianca Ioniță-Mîndrican and Ion Rogoveanu

J. Clin. Med. 2023, 12(22), 7180; https://doi.org/10.3390/jcm12227180 - 20 Nov 2023

Cited by 6 | Viewed by 5182

Abstract

Quality of life, well-being, and psycho-emotional balance are closely related to the quality of the diet, the level of physical activity, the quality of rest, but also the absence of the consumption of narcotic substances and tobacco, or alcohol abuse. Based on the distribution of a questionnaire that included 30 questions, we aimed to statistically evaluate several factors that influence mental health and vices. It recorded a total of 1719 valid responses, which came from 78.3% female respondents and 21.7% male respondents. After processing the anthropometric data, it was observed that the majority of respondents are of normal weight (63.87%) and come from women in particular (36.13%). Based on the answers recorded, although over 60% of the respondents participating in the study are up to 40 years old, there is an increased tendency towards sedentarism (over 58% of the respondents declaring that they do sports very rarely or not at all), a low tendency regarding optimal consumption of vegetables and fruits, many respondents do not hydrate properly, which is why approximately 60% of respondents feel frequently tired, and over 32% are frequently nervous. The increased level of stress among the respondents and emotional eating are also generated by inadequate rest, reduced physical activity, and a diet that does not help the efficient detoxification of the body. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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Review

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31 pages, 1453 KiB

Open AccessReview

Innovative Drugs First Implemented in Type 2 Diabetes Mellitus and Obesity and Their Effects on Metabolic Dysfunction-Associated Steatohepatitis (MASH)-Related Fibrosis and Cirrhosis

by Georgiana-Diana Cazac-Panaite, Cristina-Mihaela Lăcătușu, Elena-Daniela Grigorescu, Adina-Bianca Foșălău, Alina Onofriescu and Bogdan-Mircea Mihai

J. Clin. Med. 2025, 14(4), 1042; https://doi.org/10.3390/jcm14041042 - 7 Feb 2025

Viewed by 1711

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), a progressive liver disease frequently associated with metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity, has the potential to progress symptomatically to liver cirrhosis and, in some cases, hepatocellular carcinoma. Hence, an urgent need arises to identify and approve new therapeutic options to improve patient outcomes. Research efforts have focused on either developing dedicated molecules or repurposing drugs already approved for other conditions, such as metabolic diseases. Among the latter, antidiabetic and anti-obesity agents have received the most extensive attention, with pivotal trial results anticipated shortly. However, the primary focus underlying successful regulatory approvals is demonstrating a substantial efficacy in improving liver fibrosis and preventing or ameliorating cirrhosis, the key advanced outcomes within MASLD progression. Besides liver steatosis, the ideal therapeutic candidate should reduce inflammation and fibrosis effectively. Although some agents have shown promise in lowering MASLD-related parameters, evidence of their impact on fibrosis and cirrhosis remains limited. This review aims to evaluate whether antidiabetic and anti-obesity drugs can be safely and effectively used in MASLD-related advanced fibrosis or cirrhosis in patients with T2DM. Our paper discusses the molecules closest to regulatory approval and the expectation that they can address the unmet needs of this increasingly prevalent disease. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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16 pages, 280 KiB

Open AccessReview

Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges

by Lorenza Forna, Laura Bozomitu, Vasile Valeriu Lupu, Ancuta Lupu, Laura Mihaela Trandafir, Anca Adam Raileanu, Camelia Cojocariu, Carmen Anton, Irina Girleanu and Cristina Maria Muzica

J. Clin. Med. 2024, 13(14), 4275; https://doi.org/10.3390/jcm13144275 - 22 Jul 2024

Viewed by 2075

Abstract

Background: Liver cirrhosis presents significant challenges in the pediatric population due to a complex interplay of etiological factors, clinical manifestations, and limited therapeutic options. The leading contributors to cirrhosis among pediatric patients are chronic cholestasis, metabolic disorders present from birth, and long-term hepatitis. Materials and method: Our narrative review aimed to synthesize literature data on the etiology, clinical picture, diagnostic techniques, optimal management of complications, and timely transplantation. Results: The epidemiology of liver cirrhosis in pediatric patients is evolving. The introduction of a universal vaccination and effective long-term viral suppression in viral hepatitis have significantly decreased complications rates. Liver transplantation programs worldwide have also improved the management of cirrhosis complications. Conclusions: Early diagnosis, comprehensive management strategies, and advancements in treatment modalities are critical for improving outcomes. Understanding these differences is crucial in providing age-appropriate care and support for those affected by cirrhosis. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

14 pages, 620 KiB

Open AccessReview

Non-Invasive Biomarkers for Differentiating Alcohol Associated Hepatitis from Acute Decompensation in Patients with ALD

by Mina Ignat and Horia Stefanescu

J. Clin. Med. 2024, 13(13), 3747; https://doi.org/10.3390/jcm13133747 - 27 Jun 2024

Cited by 1 | Viewed by 1803

Abstract

Alcohol-associated hepatitis (AH) is the most severe form of alcohol-related liver disease. The natural course of alcohol-related liver disease is influenced by heavy alcohol consumption and abstinence periods. Differentiating between AH and decompensated cirrhosis (DC) could be extremely challenging in clinical practice due to clinical and bioclinical similarities. The severity of AH is made on bioclinical grounds, the severe form necessitating corticotherapy treatment. Liver biopsy is still the standard of care for establishing the diagnosis in atypical presentations. The pathogenesis of AH is an interplay between gene expression, cytokine dysregulation, the immune system and the gut microbiota. Non-invasive tests are increasingly and widely used for the purpose of early diagnosis and reliable prognostication. The non-invasive tests are emerging in concordance with disease pathogenesis. In this review, we describe the non-invasive tools that can distinguish AH from DC. We outline the available cut-offs and their performance in diagnosis and prognosis, as well as in assessing the treatment response to corticotherapy. Promising circulating biomarkers like keratin 18, microRNAs and sphingolipids will be in the review. Full article

(This article belongs to the Special Issue Updates in Liver Cirrhosis)

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