Gastroenterology Insights

Research

13 pages, 1089 KiB

Open AccessArticle

Genetic Variation in Angiotensin II Type 1 Receptor Is Linked to Lipid Levels and Hepatic Steatosis in Alcohol-Associated Liver Disease, but Not to Cirrhosis or Hepatocellular Carcinoma

by Hans Dieter Nischalke, Franziska Schmalz, Janett Fischer, Christine Möller, Madlen Matz-Soja, Benjamin Krämer, Bettina Langhans, Jacob Nattermann, Thomas Berg, Christian P. Strassburg and Philipp Lutz

Gastroenterol. Insights 2024, 15(1), 19-31; https://doi.org/10.3390/gastroent15010002 - 3 Jan 2024

Viewed by 1445

Abstract

Background: Development of cirrhosis and hepatocellular carcinoma (HCC) in patients with high alcohol intake is modulated by genetic predispositions. Genetic variation in angiotensin II type 1 receptor (AGTR1) has been described as a risk factor for non-alcoholic fatty liver disease in [...] Read more.

Background: Development of cirrhosis and hepatocellular carcinoma (HCC) in patients with high alcohol intake is modulated by genetic predispositions. Genetic variation in angiotensin II type 1 receptor (AGTR1) has been described as a risk factor for non-alcoholic fatty liver disease in Asian patients. Methods: We analysed Caucasian patients with alcohol–associated cirrhosis without (n = 238) and with (n = 339) HCC, healthy controls (n = 200), and HCV–infected cirrhotic patients with and without HCC (n = 263) for association with the polymorphisms rs3772622 and rs2276736 in AGTR1. Results: Rs2276736 in AGTR1 was associated with both low–density lipoprotein (LDL) cholesterol levels and hepatic steatosis in patients with alcohol–associated liver disease. The distribution of genotypes for both rs3772622 and rs2276736 in AGTR1 were comparable between controls, cirrhosis patients, and those with HCC. Minor allele frequencies were 32% (44%) in healthy controls, 35%/34% (46%/45%) in alcohol–associated liver disease without/with HCC and 31%/38% (43%/39%) in HCV cirrhosis and HCV HCC, respectively. The genotype of the most important genetic risk factor for fatty liver disease, PNPLA3 I148M, did not interact with the AGTR1 polymorphisms. Conclusion: Genetic variation in AGTR1, although associated with blood lipid levels and hepatic steatosis, is not a risk factor for alcohol–associated cirrhosis or HCC in Caucasians. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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11 pages, 1541 KiB

Open AccessArticle

Lysosomal Acid Lipase Deficiency in the Etiological Investigation of Cryptogenic Liver Disease in Adults: A Multicenter Brazilian Study

by Aline Coelho Rocha Candolo, Guilherme Grossi Lopes Cançado, Patricia Momoyo Zitelli, Daniel Ferraz de Campos Mazo, Claudia Pinto Marques Oliveira, Marlone Cunha-Silva, Raquel Dias Greca, Roberta Chaves Araújo, Amanda Sacha Paulino Tolentino Alustau, Claudia Alves Couto, Mateus Jorge Nardelli, Roque Gabriel Rezende de Lima, Alberto Queiroz Farias, Flair José Carrilho and Mário Guimarães Pessôa

Gastroenterol. Insights 2023, 14(4), 564-574; https://doi.org/10.3390/gastroent14040040 - 9 Nov 2023

Viewed by 1725

Abstract

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of [...] Read more.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m². The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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10 pages, 1893 KiB

Open AccessArticle

Blood-Based Non-Invasive Tests of Hepatic Fibrosis in Autoimmune Hepatitis: Application among Selected Patients Leads to Higher Accuracy

by Marco Ferronato, Marco Lenzi, Paolo Muratori and Luigi Muratori

Gastroenterol. Insights 2022, 13(3), 286-295; https://doi.org/10.3390/gastroent13030029 - 9 Sep 2022

Cited by 2 | Viewed by 2064

Abstract

Background. Assessment of liver fibrosis is essential to guide treatment in autoimmune hepatitis (AIH), but non-invasive tests (NITs) showed poor accuracy. Our study aims to evaluate the performance of NITs among different AIH presentations. Methods. Monocentric retrospective study among 122 AIH patients. NITs [...] Read more.

Background. Assessment of liver fibrosis is essential to guide treatment in autoimmune hepatitis (AIH), but non-invasive tests (NITs) showed poor accuracy. Our study aims to evaluate the performance of NITs among different AIH presentations. Methods. Monocentric retrospective study among 122 AIH patients. NITs were compared to histological grading of liver fibrosis. We performed an accuracy analysis among acute (jaundice and/or transaminases > 10 times upper limit of normal) and non-acute patients. Results. A significant difference in the distribution of NIT values for each Ishak stage was found for spleen-diameter-to-platelet-count ratio (SD/PC) (p < 0.001), fibrosis-4-score (FIB-4) (p = 0.002), AST-to-ALT ratio (AAR) (p = 0.002), red-blood-cell-width-distribution-to-platelet-count ratio (RDW/PC) (p = 0.008) and AST-to-platelet-count ratio (APRI) (p = 0.029). The AUC for advanced fibrosis of SD/PC, FIB-4, RDW/PC, APRI and AAR were, respectively, 0.814, 0.770, 0.768, 0.708 and 0.694. The AUC of SD/PC, FIB-4 and APRI in non-acute subgroup were 0.902, 0.834 and 0.758, while in acute patients they were 0.754, 0.724 and 0.716. RDW/PC and AAR weren’t different among the two subgroups. Conclusions. For SD/PC, FIB-4 and APRI, diagnostic accuracy is higher in patients with non-acute presentation. In this context, SD/PC and FIB-4 showed an overall performance that could be of interest in clinical practice alongside other non-invasive techniques. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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Review

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15 pages, 703 KiB

Open AccessReview

Anabolic Androgenic Steroids and Hepatocellular Adenoma and Carcinoma: Molecular Mechanisms and Clinical Implications

by Luca Ielasi, Enrico Fulco, Nicola Reggidori, Marco Domenicali and Francesco Giuseppe Foschi

Gastroenterol. Insights 2024, 15(3), 599-613; https://doi.org/10.3390/gastroent15030044 - 4 Jul 2024

Viewed by 2471

Abstract

Anabolic androgenic steroids (AAS) are a class of hormones that are used for hormonal replacement therapy in cases of male hypogonadism and for a few other medical conditions, mainly anemias, as well as for the female-to-male transition process. At the same time, AAS [...] Read more.

Anabolic androgenic steroids (AAS) are a class of hormones that are used for hormonal replacement therapy in cases of male hypogonadism and for a few other medical conditions, mainly anemias, as well as for the female-to-male transition process. At the same time, AAS are widely abused for their muscle-building and strength-increasing properties. Among their side effects, androgens can exert a toxic effect on the liver, causing hepatotoxicity, but they can also induce hepatocyte proliferation and malignant transformation. Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) are two primary liver lesions that have been described as potentially related to AAS. This review provides an up-to-date analysis of how androgens can induce liver carcinogenesis and a comprehensive overview on the available data in the literature about AAS and primary liver tumors. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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12 pages, 789 KiB

Open AccessReview

Benign Recurrent Intrahepatic Cholestasis: Where Are We Now?

by Eleni V. Geladari, Natalia G. Vallianou, Evangelia Margellou, Dimitris Kounatidis, Vassilios Sevastianos and Alexandra Alexopoulou

Gastroenterol. Insights 2024, 15(1), 156-167; https://doi.org/10.3390/gastroent15010011 - 6 Feb 2024

Cited by 1 | Viewed by 2433

Abstract

Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is [...] Read more.

Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is marked by recurrent episodes of jaundice accompanied by intense pruritus, enduring from weeks to years across the lifespan. Normal gamma-glutamyl transferase (GGT) levels are a characteristic laboratory finding. Initially considered unlikely to progress to chronic liver disease or cirrhosis, some reports suggest BRIC may evolve into a continuous and progressive form of cholestasis. Moreover, these recurrent cholestatic episodes significantly impact quality of life, and certain mutations elevate the risk of hepatobiliary malignancy. Between episodes, histological findings of centrilobular cholestasis and abnormal laboratory parameters revert to normal, potentially obviating the need for liver biopsy. This review focuses on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis. Additionally, it outlines triggering factors and available treatment options. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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22 pages, 1334 KiB

Open AccessReview

Hepatitis C and Nonalcoholic Steatohepatitis in the 21st Century: Impact on Liver Disease and Liver Transplantation

by Sonia Samuel, Ahmad Abulawi and Raza Malik

Gastroenterol. Insights 2023, 14(3), 249-270; https://doi.org/10.3390/gastroent14030018 - 29 Jun 2023

Cited by 3 | Viewed by 2623

Abstract

Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause [...] Read more.

Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause of liver disease. It is predicted to surpass hepatitis C as a leading indication for transplant. The introduction of direct-acting antivirals (DAAs) decreased the prevalence of chronic hepatitis C infections, but the obesity epidemic and metabolic syndrome have increased the prevalence of NASH. Weight loss and dietary modifications are recommended NASH therapies, but unlike for hepatitis C, federally approved agents are lacking and currently under investigation. Clinical trials face many barriers in NASH treatment because of the difficulty of diagnosis and a lack of standardized and accurate clinical and histologic responses. Mortality and morbidity in NASH are heightened because of the presence of multiple comorbidities including cardiovascular disease, diabetes, and renal dysfunction. A liver transplant may be indicated, but a thorough screening of candidates, including a comprehensive cardiovascular assessment, is essential to ensuring successful outcomes pre- and post-transplant. Therapeutic agents for NASH are warranted before it becomes a significant and leading cause of morbidity and mortality worldwide. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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10 pages, 667 KiB

Open AccessReview

Clinical and Safety Evaluation of Liv.52 in Alcoholic Liver Disease: A Review

by Subramanian Ganesh, Neeraj Joshi, Mukesh Kumar Jain, Lokendra Sharma, Anish Desai, Mohamed Rafiq, Uddagiri Venkanna Babu and Rajesh Kumawat

Gastroenterol. Insights 2022, 13(4), 377-386; https://doi.org/10.3390/gastroent13040037 - 13 Nov 2022

Cited by 3 | Viewed by 45369

Abstract

Alcoholic liver disease (ALD) has been a growing concern in developed and developing nations. Oxidative stress and lipid peroxidation are the most common cause of the development and progression of ALD. Due to paucity in the number and efficacy of hepatoprotective drugs currently [...] Read more.

Alcoholic liver disease (ALD) has been a growing concern in developed and developing nations. Oxidative stress and lipid peroxidation are the most common cause of the development and progression of ALD. Due to paucity in the number and efficacy of hepatoprotective drugs currently available, and with the easy availability of natural therapy and herbal medicines, ALD is managed using a combination of pharmaceutical interventions and herbal medications. However, the effectiveness of these hepatoprotectives is controversial. Preclinical and clinical studies have demonstrated that Liv.52 modulates the lipotropic activity of hepatocytes, reduces inflammation, enhances alcohol and acetaldehyde metabolism, and protects the hepatic parenchyma by restoring the antioxidant levels of hepatocytes. Clinical studies further support that there is improvement in the subjective symptoms of patients as well as improvements in liver function test parameters. Studies suggest that Liv.52 is well tolerated and has no reported side effects. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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Other

Jump to: Research, Review

7 pages, 538 KiB

Open AccessCase Report

A Case of Advanced Hepatocellular Carcinoma with Bone Metastases Managed with Tyrosine Kinase Inhibitors and Aggressive Palliative Radiation Therapy: Role of Combination Therapy for Extending Survival

by Luca Ielasi, Bernardo Stefanini, Fabio Piscaglia, Alessandro Granito and Francesco Tovoli

Gastroenterol. Insights 2023, 14(1), 38-44; https://doi.org/10.3390/gastroent14010005 - 12 Feb 2023

Cited by 2 | Viewed by 2364

Abstract

We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued [...] Read more.

We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued and multiple radiation therapy (RT) sessions with a palliative purpose were performed. Thanks to this aggressive radiotherapy approach in order to control the bone tumor burden, the patient has continued sorafenib for 34.6 months achieving an overall survival (OS) of 41.3 months. This result highlights the importance of a tailored management of patients with advanced HCC and the role of the RT for BM control, even if at lower cumulative radiation dose, for extending patient survival. Full article

(This article belongs to the Special Issue Feature Papers in Liver Research)

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