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New Therapies of Liver Diseases
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New Therapies of Liver Diseases

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 (31 July 2021) | Viewed by 53478

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Pierluigi Toniutto

E-Mail Website
Guest Editor
Hepatology and Liver Transplantation Unit, Department of Specialized Medicine Azienda Sanitaria Universitaria Integrata, Academic Hospital, Udine, Italy
Interests: hepatocellular carcinoma; hepatitis B; hepatitis C; liver cirrhosis; liver diseases; liver transplantation; cirrhosis; chronic hepatitis C; hepatology

Special Issue Information

Dear Colleagues,

For many years, liver diseases were thought to be incurable. Hepatologists were resigned to witnessing the progressive decay of liver function, up to the onset of liver failure, without being able to significantly modify the natural history of the disease with pharmacological therapies. Over the past few years, however, we have seen very rapid progress in scientific research in hepatology, which has led to two important results. The first was the availability of new drugs for the treatment of hepatitis C, which made it possible to heal all patients with the disease. The second is the growing understanding of the pathophysiological mechanisms responsible for the progression of liver damage and the development of clinical complications. This has led to the identification, for numerous liver diseases, of precise drug therapy targets, which for the first time have been shown to substantially modify patient survival.

Never before this very recent period has there been a real therapeutic revolution in the hepatology field that is expected to significantly improve the prognosis of liver diseases in the near future. In the present Special Issue, we aim to collect a number of review and original articles that highlight significant advances in the discovery and application of new treatment options for many liver diseases. Specific chapters will be dedicated to the advances of pharmacological treatment of cholestatic liver diseases and to the new treatment options to obtain a functional cure in hepatitis B virus infection. A specific section of the issue will be dedicated to the more recent advances in pharmacological treatments to prevent and/or reverse the main complications of end stage liver disease as the development of ascites, gastrointestinal bleeding, hepatic encephalopathy, and acute on chronic liver failure. New treatment modalities for hepatocellular carcinoma and cholangiocarcinoma will be extensively discussed, taking into account the recent availability of immunotherapy in addition to the established treatment options. A particular attention will be reserved for liver transplantation, analyzing the new potential indications as well as the use of DCD donors, and the potential support of stem cell transplantation.

In summary, this Special Issue will help readers to get an up-to-date and authoritative view of how new therapies will continue to improve the clinical management of patients with liver diseases in the forthcoming future.

Dr. Pierluigi Toniutto
Guest Editor

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

  • Cholestatic Liver diseases
  • a. Primary Biliary Cirrhosis (PBC)
  • b. Primary Sclerosing Cholangitis (PSC)
  • Viral hepatitis
  • a. HBV and HDV new treatments on horizon
  • Cirrhosis
  • a. Prevention of cirrhosis complications
  • b. Ascites
  • c. Gastrointestinal bleeding
  • d. Hepatic encephalopathy
  • e. Acute on chronic liver failure
  • Hepatocellular carcinoma
  • a. New medical treatments and new potential combination treatment strategies
  • Cholangiocarcinoma
  • a. New treatment options
  • Liver Transplantation
  • a. HCC exceeding Milan criteria
  • b. New indications for liver transplantation
  • c. Stem cell transplantation

Published Papers (15 papers)

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Editorial

Jump to: Research, Review

7 pages, 183 KiB  
Editorial
Special Issue “New Therapies of Liver Diseases”
by Pierluigi Toniutto
J. Clin. Med. 2022, 11(7), 1798; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11071798 - 24 Mar 2022
Cited by 2 | Viewed by 1609
Abstract
Medical and surgical treatments aimed at curing severe liver diseases and prolonging the survival of patients have improved dramatically in recent years [...] Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)

Research

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11 pages, 1527 KiB  
Article
Real-World Clinical Management of Patients with Primary Biliary Cholangitis—A Retrospective Multicenter Study from Germany
by Anne-Christin Beatrice Wilde, Charlotte Lieb, Elise Leicht, Lena Maria Greverath, Lara Marleen Steinhagen, Nina Wald de Chamorro, Jörg Petersen, Wolf Peter Hofmann, Holger Hinrichsen, Renate Heyne, Thomas Berg, Uwe Naumann, Jeannette Schwenzer, Johannes Vermehren, Andreas Geier, Frank Tacke and Tobias Müller
J. Clin. Med. 2021, 10(5), 1061; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10051061 - 04 Mar 2021
Cited by 12 | Viewed by 2300
Abstract
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate [...] Read more.
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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10 pages, 1374 KiB  
Article
Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites
by Atsushi Hosui, Takafumi Tanimoto, Toru Okahara, Munehiro Ashida, Kohsaku Ohnishi, Yuhhei Wakahara, Yukihiro Kusumoto, Toshio Yamaguchi, Yuka Sueyoshi, Motohiro Hirao, Takuya Yamada and Naoki Hiramatsu
J. Clin. Med. 2021, 10(2), 294; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020294 - 14 Jan 2021
Cited by 3 | Viewed by 1838
Abstract
(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with [...] Read more.
(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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Review

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13 pages, 283 KiB  
Review
Management of Ascites in Patients with Cirrhosis: An Update
by Giacomo Zaccherini, Manuel Tufoni, Giulia Iannone and Paolo Caraceni
J. Clin. Med. 2021, 10(22), 5226; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10225226 - 10 Nov 2021
Cited by 14 | Viewed by 5013
Abstract
Ascites represents a critical event in the natural history of liver cirrhosis. From a prognostic perspective, its occurrence marks the transition from the compensated to the decompensated stage of the disease, leading to an abrupt worsening of patients’ life expectancy. Moreover, ascites heralds [...] Read more.
Ascites represents a critical event in the natural history of liver cirrhosis. From a prognostic perspective, its occurrence marks the transition from the compensated to the decompensated stage of the disease, leading to an abrupt worsening of patients’ life expectancy. Moreover, ascites heralds a turbulent clinical course, characterized by acute events and further complications, frequent hospitalizations, and eventually death. The pathophysiology of ascites classically relies on hemodynamic mechanisms, with effective hypovolemia as the pivotal event. Recent discoveries, however, integrated this hypothesis, proposing systemic inflammation and immune system dysregulation as key mechanisms. The mainstays of ascites treatment are represented by anti-mineralocorticoids and loop diuretics, and large volume paracentesis. When ascites reaches the stage of refractoriness, however, diuretics administration should be cautious due to the high risk of adverse events, and patients should be treated with periodic execution of paracentesis or with the placement of a trans-jugular intra-hepatic portosystemic shunt (TIPS). TIPS reduces portal hypertension, eases ascites control, and potentially modify the clinical course of the disease. Further studies are required to expand its indications and improve the management of complications. Long-term human albumin administration has been studied in two RCTs, with contradictory results, and remains a debated issue worldwide, despite a potential effectiveness both in ascites control and long-term survival. Other treatments (vaptans, vasoconstrictors, or implantable drainage systems) present some promising aspects but cannot be currently recommended outside clinical protocols or a case-by-case evaluation. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
11 pages, 240 KiB  
Review
Emerging Therapies for Advanced Cholangiocarcinoma: An Updated Literature Review
by Anthony Vignone, Francesca Biancaniello, Marco Casadio, Ludovica Pesci, Vincenzo Cardinale, Lorenzo Ridola and Domenico Alvaro
J. Clin. Med. 2021, 10(21), 4901; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10214901 - 24 Oct 2021
Cited by 8 | Viewed by 2099
Abstract
Cholangiocarcinoma is a group of malignancies with poor prognosis. Treatments for the management of advanced-stage cholangiocarcinoma are limited, and the 5-year survival rate is estimated to be approximately 5–15%, considering all tumor stages. There is a significant unmet need for effective new treatment [...] Read more.
Cholangiocarcinoma is a group of malignancies with poor prognosis. Treatments for the management of advanced-stage cholangiocarcinoma are limited, and the 5-year survival rate is estimated to be approximately 5–15%, considering all tumor stages. There is a significant unmet need for effective new treatment approaches. The present review is provided with the aim of summarizing the current evidence and future perspectives concerning new therapeutic strategies for cholangiocarcinoma. The role of targeted therapies and immunotherapies is currently investigational in cholangiocarcinoma. These therapeutic options might improve survival outcomes, as shown by the promising results of several clinical trials illustrated in the present review. The co-presence of driver mutations and markers of susceptibility to immunotherapy may lead to rational combination strategies and clinical trial development. A better understanding of immunologically based therapeutic weapons is needed, which will lead to a form of a precision medicine strategy capable of alleviating the clinical aggressiveness and to improve the prognosis of cholangiocarcinoma. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
20 pages, 936 KiB  
Review
Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents
by Giacomo Zaccherini, Manuel Tufoni, Mauro Bernardi and Paolo Caraceni
J. Clin. Med. 2021, 10(19), 4590; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10194590 - 05 Oct 2021
Cited by 4 | Viewed by 5493
Abstract
The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, [...] Read more.
The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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11 pages, 814 KiB  
Review
Acute-on-Chronic Liver Failure in Cirrhosis
by Carmine Gambino, Salvatore Piano and Paolo Angeli
J. Clin. Med. 2021, 10(19), 4406; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10194406 - 26 Sep 2021
Cited by 12 | Viewed by 5355
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite [...] Read more.
Acute-on-chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated chronic liver disease. It is characterised by high 28-day mortality, the presence of one or more organ failures (OFs) and a variable but severe grade of systemic inflammation. Despite the peculiarity of each one, every definition proposed for ACLF recognizes it as a proper clinical entity. In this paper, we provide an overview of the diagnostic criteria proposed by the different scientific societies and the clinical characteristics of the syndrome. Established and experimental treatments are also described. Among the former, the most relevant are directed to support organ failures, treat precipitating factors and carry out early assessment for liver transplantation (LT). Further studies are needed to better clarify pathophysiology of the syndrome and discover new therapies. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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14 pages, 290 KiB  
Review
HBV and HDV: New Treatments on the Horizon
by Valentina Zuccaro, Erika Asperges, Marta Colaneri, Lea Nadia Marvulli and Raffaele Bruno
J. Clin. Med. 2021, 10(18), 4054; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10184054 - 08 Sep 2021
Cited by 5 | Viewed by 2356
Abstract
Despite the accumulating knowledge, chronic hepatitis B (CHB) and HDV infection represent a global health problem, and there are still several critical issues, which frequently remain uncovered. In this paper, we provided an overview of the current therapeutic options and summarized the investigational [...] Read more.
Despite the accumulating knowledge, chronic hepatitis B (CHB) and HDV infection represent a global health problem, and there are still several critical issues, which frequently remain uncovered. In this paper, we provided an overview of the current therapeutic options and summarized the investigational therapies in the pipeline. Furthermore, we discussed some critical issues such as a “functional cure” approach, the futility of long-term NA therapy and the relevance of understanding drug actions and safety of antivirals, especially in special populations. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
11 pages, 263 KiB  
Review
New Therapies of Liver Diseases: Hepatic Encephalopathy
by Chiara Mangini and Sara Montagnese
J. Clin. Med. 2021, 10(18), 4050; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10184050 - 07 Sep 2021
Cited by 9 | Viewed by 3712
Abstract
Hepatic encephalopathy (HE) is a common complication of advanced liver disease which has profound implications in terms of the patients’ ability to fulfil their family and social roles, to drive and to provide for themselves. Recurrent and persistent HE is still a serious [...] Read more.
Hepatic encephalopathy (HE) is a common complication of advanced liver disease which has profound implications in terms of the patients’ ability to fulfil their family and social roles, to drive and to provide for themselves. Recurrent and persistent HE is still a serious management challenge, translating into a significant burden for patients and their families, health services and society at large. The past few years have been characterized by significantly more attention towards HE and its implications; its definition has been refined and a small number of new drugs/alternative management strategies have become available, while others are underway. In this narrative review we summarize them in a pragmatic and hopefully useful fashion. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
22 pages, 1076 KiB  
Review
COVID-19 in Liver Transplant Recipients: A Systematic Review
by Chiara Becchetti, Sarah Gabriela Gschwend, Jean-François Dufour and Vanessa Banz
J. Clin. Med. 2021, 10(17), 4015; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10174015 - 05 Sep 2021
Cited by 17 | Viewed by 2870
Abstract
Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We [...] Read more.
Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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15 pages, 520 KiB  
Review
Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review
by Pierluigi Toniutto, Elisa Fumolo, Ezio Fornasiere and Davide Bitetto
J. Clin. Med. 2021, 10(17), 3932; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173932 - 31 Aug 2021
Cited by 14 | Viewed by 2278
Abstract
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit [...] Read more.
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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18 pages, 562 KiB  
Review
New Indications for Liver Transplantation
by Alberto Zanetto, Sarah Shalaby, Martina Gambato, Giacomo Germani, Marco Senzolo, Debora Bizzaro, Francesco Paolo Russo and Patrizia Burra
J. Clin. Med. 2021, 10(17), 3867; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173867 - 28 Aug 2021
Cited by 19 | Viewed by 3503
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, [...] Read more.
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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14 pages, 306 KiB  
Review
Recent Advances in the Management of Acute Variceal Hemorrhage
by Alberto Zanetto, Sarah Shalaby, Paolo Feltracco, Martina Gambato, Giacomo Germani, Francesco Paolo Russo, Patrizia Burra and Marco Senzolo
J. Clin. Med. 2021, 10(17), 3818; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10173818 - 25 Aug 2021
Cited by 11 | Viewed by 6144
Abstract
Gastrointestinal bleeding is one of the most relevant causes of death in patients with cirrhosis and clinically significant portal hypertension, with gastroesophageal varices being the most frequent source of hemorrhage. Despite survival has improved thanks to the standardization on medical treatment aiming to [...] Read more.
Gastrointestinal bleeding is one of the most relevant causes of death in patients with cirrhosis and clinically significant portal hypertension, with gastroesophageal varices being the most frequent source of hemorrhage. Despite survival has improved thanks to the standardization on medical treatment aiming to decrease portal hypertension and prevent infections, mortality remains significant. In this review, our goal is to discuss the most recent advances in the management of esophageal variceal hemorrhage in cirrhosis with specific attention to the treatment algorithms involving the use of indirect measurement of portal pressure (HVPG) and transjugular intrahepatic portosystemic shunt (TIPS), which aim to further reduce mortality in high-risk patients after acute variceal hemorrhage and in the setting of secondary prophylaxis. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
21 pages, 1576 KiB  
Review
Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors and Applicability of First-Line Atezolizumab/Bevacizumab in a Real-Life Setting
by Maria Corina Plaz Torres, Quirino Lai, Fabio Piscaglia, Eugenio Caturelli, Giuseppe Cabibbo, Elisabetta Biasini, Filippo Pelizzaro, Fabio Marra, Franco Trevisani and Edoardo G. Giannini
J. Clin. Med. 2021, 10(15), 3201; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10153201 - 21 Jul 2021
Cited by 15 | Viewed by 3546
Abstract
Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with [...] Read more.
Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with advanced hepatocellular carcinoma (HCC). As a matter of fact, the overall survival and objective response rates reported in patients with advanced HCC treated with ICIs are the highest ever reported in the second-line setting and, most recently, the combination of the anti-programmed death ligand protein-1 atezolizumab with bevacizumab—an anti-vascular endothelial growth factor monoclonal antibody—demonstrated superiority to sorafenib in a Phase III randomized clinical trial. Therefore, this regimen has been approved in several countries as first-line treatment for advanced HCC and is soon expected to be widely used in clinical practice. However, despite the promising results of trials exploring ICIs alone or in combination with other agents, there are still some critical issues to deal with to optimize the prognosis of advanced HCC patients. For instance, the actual proportion of patients who are deemed eligible for ICIs in the real-life ranges from 10% to 20% in the first-line setting, and is even lower in the second-line scenario. Moreover, long-term data regarding the safety of ICIs in the population of patients with cirrhosis and impaired liver function are lacking. Lastly, no biomarkers have been identified to predict response, and thus to help clinicians to individually tailor treatment. This review aimed to summarize the state of the art immunotherapy in HCC and, by analyzing a large, multicenter cohort of Italian patients with HCC, to assess the potential applicability of the combination of atezolizumab/bevacizumab in the real-life setting. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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20 pages, 756 KiB  
Review
The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities
by Marta Mazzetti, Giulia Marconi, Martina Mancinelli, Antonio Benedetti, Marco Marzioni and Luca Maroni
J. Clin. Med. 2021, 10(8), 1763; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081763 - 18 Apr 2021
Cited by 17 | Viewed by 3826
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number [...] Read more.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number of clinical trials and possible new targets for therapy. In this review, we provide an update on the treatments in clinical use and summarize the new drugs in trials for PBC and PSC patients. Farnesoid X Receptor (FXR) agonists and Pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonists are the most promising agents and have shown promising results in both PBC and PSC. Fibroblast Growth Factor 19 (FGF19) analogues also showed good results, especially in PBC, while, although PBC and PSC are autoimmune diseases, immunosuppressive drugs had disappointing effects. Since the gut microbiome could have a potential role in the pathogenesis of PSC, recent research focused on molecules that could change the microbiome, with good results. The near future of the medical management of these diseases may include new treatments or a combination of multiple drugs targeting different signaling pathways at different stages of the diseases. Full article
(This article belongs to the Special Issue New Therapies of Liver Diseases)
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