|
1
|
Ulrich H, Glaser T, Thomas AP. Purinergic signaling in liver disease: calcium signaling and induction of inflammation. Purinergic Signal 2025; 21:69-81. [PMID: 39320433 PMCID: PMC11958897 DOI: 10.1007/s11302-024-10044-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 08/15/2024] [Indexed: 09/26/2024] Open
Abstract
Purinergic signaling regulates many metabolic functions and is implicated in liver physiology and pathophysiology. Liver functionality is modulated by ionotropic P2X and metabotropic P2Y receptors, specifically P2Y1, P2Y2, and P2Y6 subtypes, which physiologically exert their influence through calcium signaling, a key second messenger controlling glucose and fat metabolism in hepatocytes. Purinergic receptors, acting through calcium signaling, play an important role in a range of liver diseases. Ionotropic P2X receptors, such as the P2X7 subtype, and certain metabotropic P2Y receptors can induce aberrant intracellular calcium transients that impact normal hepatocyte function and initiate the activation of other liver cell types, including Kupffer and stellate cells. These P2Y- and P2X-dependent intracellular calcium increases are particularly relevant in hepatic disease states, where stellate and Kupffer cells respond with innate immune reactions to challenges, such as excess fat accumulation, chronic alcohol abuse, or infections, and can eventually lead to liver fibrosis. This review explores the consequences of excessive extracellular ATP accumulation, triggering calcium influx through P2X4 and P2X7 receptors, inflammasome activation, and programmed cell death. In addition, P2Y2 receptors contribute to hepatic steatosis and insulin resistance, while inhibiting the expression of P2Y6 receptors can alleviate alcoholic liver steatosis. Adenosine receptors may also contribute to fibrosis through extracellular matrix production by fibroblasts. Thus, pharmacological modulation of P1 and P2 receptors and downstream calcium signaling may open novel therapeutic avenues.
Collapse
Affiliation(s)
- Henning Ulrich
- Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, 05508-000, Brazil.
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
| | - Talita Glaser
- Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, 05508-000, Brazil.
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
| | - Andrew P Thomas
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
| |
Collapse
|
|
2
|
Ha NB, Yao F. Alcohol and Hepatocellular Carcinoma. Clin Liver Dis 2024; 28:633-646. [PMID: 39362712 DOI: 10.1016/j.cld.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Alcohol-associated liver disease (ALD) poses a significant risk for hepatocellular carcinoma (HCC), comprising various liver conditions from steatosis to cirrhosis. Despite accounting for a third of global HCC cases and deaths, ALD-related HCC lacks characterization compared to viral hepatitis-related HCC. Proposed mechanisms for ALD-related HCC include acetaldehyde toxicity, increased reactive oxygen species, and inflammation. This review examines ALD-associated HCC epidemiology, co-factors like viral hepatitis and metabolic syndrome, surveillance, and treatment challenges. Despite advances in screening and management, ALD-related HCC often presents at advanced stages, limiting treatment options and survival.
Collapse
Affiliation(s)
- Nghiem B Ha
- Hepatology, Liver Transplant, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, S-357, San Francisco, CA 94112, USA
| | - Francis Yao
- Hepatology, Liver Transplant, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, S-357, San Francisco, CA 94112, USA.
| |
Collapse
|
|
3
|
Fukushima M, Miyaaki H, Nakao Y, Sasaki R, Haraguchi M, Takahashi K, Ozawa E, Miuma S, Akazawa Y, Soyama A, Eguchi S, Okano S, Nakao K. Characterizing alcohol-related and metabolic dysfunction-associated steatotic liver disease cirrhosis via fibrotic pattern analysis. Sci Rep 2024; 14:23679. [PMID: 39390024 PMCID: PMC11466976 DOI: 10.1038/s41598-024-73739-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/20/2024] [Indexed: 10/12/2024] Open
Abstract
This study aimed to address the diagnostic challenges in distinguishing between alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized whole-slide imaging technology to conduct a comprehensive digital analysis of liver specimens collected from patients undergoing transplantation. This study included 36 and 17 patients with ALD and MASLD cirrhosis, respectively, who underwent transplantation at our institution. Digital slides were analyzed for fibrosis patterns using FibroNest™. Patient background characteristics were comparable between ALD (n = 36) and MASLD (n = 17) groups, except for sex. The ALD group exhibited thicker collagen per strand, longer and more flexural fibrosis, and a more heterogeneous distribution than the MASLD group. In patients with ALD and concomitant metabolic dysfunction, fiber distribution became relatively uniform, resembling MASLD. Application of the phenotypic fibrosis composite score achieved 100% sensitivity and specificity for ALD/MASLD diagnosis. Digital pathological analysis of the fibrosis patterns showed morphological differences between ALD and MASLD. This approach holds promise for histological differentiation, providing valuable insights beyond the current definitions based solely on alcohol intake. This study emphasizes the potential of digital pathology in refining the diagnostic criteria for hepatic disorders.
Collapse
Affiliation(s)
- Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Yasuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Kosuke Takahashi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Eisuke Ozawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| | - Yuko Akazawa
- Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinji Okano
- Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan
| |
Collapse
|
|
4
|
Du M, Liu Y, Cao J, Li X, Wang N, He Q, Zhang L, Zhao B, Dugarjaviin M. Food from Equids-Commercial Fermented Mare's Milk (Koumiss) Products: Protective Effects against Alcohol Intoxication. Foods 2024; 13:2344. [PMID: 39123538 PMCID: PMC11312395 DOI: 10.3390/foods13152344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 07/19/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
Fermented mare's milk (koumiss), a traditional Central Asian dairy product derived from fermented mare's milk, is renowned for its unique sour taste and texture. It has long been consumed by nomadic tribes for its nutritional and medicinal benefits. This study aimed to comprehensively analyze the protective effects of koumiss against alcohol-induced harm across behavioral, hematological, gastrointestinal, hepatic, and reproductive dimensions using a mouse model. Optimal intoxicating doses of alcohol and koumiss doses were determined, and their effects were explored through sleep tests and blood indicator measurements. Pretreatment with koumiss delayed inebriation, accelerated sobering, and reduced mortality in mice, mitigating alcohol's impact on blood ethanol levels and various physiological parameters. Histopathological and molecular analyses further confirmed koumiss's protective role against alcohol-induced damage in the liver, stomach, small intestine, and reproductive system. Transcriptomic studies on reproductive damage indicated that koumiss exerts its benefits by influencing mitochondrial and ribosomal functions and also shows promise in mitigating alcohol's effects on the reproductive system. In summary, koumiss emerges as a potential natural agent for protection against alcohol-induced harm, opening avenues for future research in this field.
Collapse
Affiliation(s)
- Ming Du
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Yuanyi Liu
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Jialong Cao
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Xinyu Li
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Na Wang
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Qianqian He
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Lei Zhang
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Bilig Zhao
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Manglai Dugarjaviin
- Key Laboratory of Equus Germplasm Innovation, Ministry of Agriculture and Rural Affairs, Hohhot 010018, China; (M.D.); (Y.L.); (J.C.); (X.L.); (N.W.); (Q.H.); (L.Z.); (B.Z.)
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China
- Equus Research Center, Inner Mongolia Agricultural University, Hohhot 010018, China
| |
Collapse
|
|
5
|
Ali NAM, Abdelhamid AM, El-Sayed NM, Radwan A. Alpha-Asarone attenuates alcohol-induced hepatotoxicity in a murine model by ameliorating oxidative stress, inflammation, and modulating apoptotic-Autophagic cell death. Toxicol Appl Pharmacol 2024; 490:117041. [PMID: 39059505 DOI: 10.1016/j.taap.2024.117041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/01/2024] [Accepted: 07/21/2024] [Indexed: 07/28/2024]
Abstract
Alcoholic liver disease (ALD) is a major cause of chronic liver injury characterized by steatosis, inflammation, and fibrosis. This study explored the hepatoprotective mechanisms of alpha-asarone in a mouse model of chronic-binge alcohol feeding. Adult male mice were randomized into control, alcohol, and alcohol plus alpha-asarone groups. Serum aminotransferases and histopathology assessed liver injury. Oxidative stress was evaluated via malondialdehyde content, glutathione, superoxide dismutase, and catalase activities. Pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified by ELISA. P53-mediated apoptosis was determined by immunohistochemistry. Key autophagy markers phospho-AMPK, AMPK, Beclin-1, LC3-I/LC3-II ratio, and LC3 were examined by immunoblotting. Alcohol administration increased serum ALT, AST and ALP, indicating hepatocellular damage. This liver dysfunction was associated with increased oxidative stress, inflammation, p53 expression and altered autophagy. Alpha-asarone treatment significantly decreased ALT, AST and ALP levels and improved histological architecture versus alcohol alone. Alpha-asarone also mitigated oxidative stress, reduced TNF-α, IL-1β and IL-6 levels, ameliorated p53 overexpression and favorably modulated autophagy markers. Our findings demonstrate that alpha-asarone confers protective effects against ALD by enhancing antioxidant defenses, suppressing hepatic inflammation, regulating apoptotic signaling, and restoring autophagic flux. This preclinical study provides compelling evidence for the therapeutic potential of alpha-asarone in attenuating alcohol-induced liver injury and warrants further evaluation as a pharmacotherapy for ALD.
Collapse
Affiliation(s)
- Nada A M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Amir Mohamed Abdelhamid
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
| | - Norhan M El-Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Asmaa Radwan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
| |
Collapse
|
|
6
|
Ribback S, Peters K, Yasser M, Prey J, Wilhelmi P, Su Q, Dombrowski F, Bannasch P. Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming. J Clin Transl Hepatol 2024; 12:52-61. [PMID: 38250461 PMCID: PMC10794273 DOI: 10.14218/jcth.2023.00242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/22/2023] [Accepted: 09/05/2023] [Indexed: 01/23/2024] Open
Abstract
Background and Aims Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development. Methods Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections. Results BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis. Conclusions BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.
Collapse
Affiliation(s)
- Silvia Ribback
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Kristin Peters
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Mohd Yasser
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Jessica Prey
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Paula Wilhelmi
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Qin Su
- Cell Marque, Millipore-Sigma, Rocklin, CA, USA
| | - Frank Dombrowski
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Peter Bannasch
- German Cancer Research Center (DKFZ), Heidelberg, Germany
| |
Collapse
|
|
7
|
Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
8
|
|
|
9
|
Testino G, Pellicano R. Corrected and republished from: Metabolic associated liver disease. Panminerva Med 2023; 65:391-399. [PMID: 37750860 DOI: 10.23736/s0031-0808.23.04850-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.
Collapse
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o Polyclinic San Martino Hospital, Genoa, Italy -
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-SGAS Hospital, Turin, Italy, Corrected and republished from: Panminerva Medica 2022 December
| |
Collapse
|
|
10
|
Chaudhry H, Sohal A, Iqbal H, Roytman M. Alcohol-related hepatitis: A review article. World J Gastroenterol 2023; 29:2551-2570. [PMID: 37213401 PMCID: PMC10198060 DOI: 10.3748/wjg.v29.i17.2551] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/10/2023] [Accepted: 04/13/2023] [Indexed: 05/23/2023] Open
Abstract
Alcohol-related hepatitis (ARH) is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by significant alcohol use. It ranges in severity from mild to severe and carries significant morbidity and mortality. The refinement of scoring systems has enhanced prognostication and guidance of clinical decision-making in the treatment of this complex disease. Although treatment focuses on supportive care, steroids have shown benefit in select circumstances. There has been a recent interest in this disease process, as coronavirus disease 2019 pandemic led to substantial rise in cases. Although much is known regarding the pathogenesis, prognosis remains grim due to limited treatment options. This article summarizes the epidemiology, genetics, pathogenesis, diagnosis and treatment of ARH.
Collapse
Affiliation(s)
- Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA 93701, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Humzah Iqbal
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA 93701, United States
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA 93701, United States
| |
Collapse
|
|
11
|
Testino G, Pellicano R. Metabolic associated liver disease. Panminerva Med 2022; 64:555-563. [PMID: 36533665 DOI: 10.23736/s0031-0808.22.04730-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
In real practice the patient with liver disease is often the carrier of multiple etiological factors such as metabolic syndrome (MS) and alcohol consumption (AC). Their copresence is often underestimated and AC is not adequately studied. Traditionally to diagnose non-alcoholic fatty liver disease (NAFLD), AC must not exceed 30 gr for men and 20 gr for women per day. This limit should still be reduced, especially in relation to the AC and fibrogenesis ratio and also frequent misestimation of AC or unrecognized MS may underestimate multi caused liver injury. AC is a contributing cause of MS and alcoholic and non-alcoholic liver disease have a substantially overlapping histopathological picture. Moreover, AC and MS are cause and contributing cause of extra-hepatic morbidity and mortality. It can be concluded that the possible simplification of terminology at metabolic associated liver disease (MALD) makes clinical activity more usable and immediate, facilitates better communication and cooperation between scientific societies and specialists who apparently deal with different medical sectors, facilitates early identification of related hepatic and extra-hepatic pathology, allows to "see the person in a unitary way," to create more streamlined care pathways, to reduce the hospitalization rate with relative cost-benefit advantage and to create unitary prevention and health promotion policies.
Collapse
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o Polyclinic San Martino Hospital, Genoa, Italy -
| | | |
Collapse
|
|
12
|
He Z, Guo T, Cui Z, Xu J, Wu Z, Yang X, Hu H, Mei H, Zhou J, Zhang Y, Wang K. New understanding of Angelica sinensis polysaccharide improving fatty liver: The dual inhibition of lipid synthesis and CD36-mediated lipid uptake and the regulation of alcohol metabolism. Int J Biol Macromol 2022; 207:813-825. [PMID: 35358574 DOI: 10.1016/j.ijbiomac.2022.03.148] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 03/20/2022] [Accepted: 03/23/2022] [Indexed: 12/01/2022]
Abstract
Angelica sinensis polysaccharide (ASP) has presented increasingly recognized lipid regulation and antioxidant abilities. However, there is little direct evidence to explain why ASP possesses the observed lipid-lowering and anti-oxidation effects. In vivo and in vitro models of alcoholic fatty liver disease (AFLD) were established to examine the direct effect of ASP on hepatic fat accumulation. Our results showed that the lipid-lowering effect of ASP might result from the dual inhibition of lipid synthesis and CD36-mediated lipid uptake. The antioxidation of ASP might be attributed to the reversal of alcohol metabolic pathways from CYP2E1 catalysis to ADH catalysis. Taken together, the study demonstrated the direct role of ASP in lipid metabolism for the first time and revealed the underlying mechanism of reducing ROS, providing an available strategy for ASP as a potential agent to treat AFLD.
Collapse
Affiliation(s)
- Zihao He
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Tingting Guo
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Zheng Cui
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Jingya Xu
- Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, 430030 Wuhan, PR China
| | - Zhijing Wu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Xiawen Yang
- Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, 430030 Wuhan, PR China
| | - Huiping Hu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Hao Mei
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Jing Zhou
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China
| | - Yu Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China; Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 430030 Wuhan, PR China.
| | - Kaiping Wang
- Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, 430030 Wuhan, PR China.
| |
Collapse
|
|
13
|
Yan X, Liu X, Wang Y, Ren X, Ma J, Song R, Wang X, Dong Y, Fan Q, Wei J, Yu A, Sui H, She G. Multi-omics integration reveals the hepatoprotective mechanisms of ursolic acid intake against chronic alcohol consumption. Eur J Nutr 2022; 61:115-126. [PMID: 34215920 DOI: 10.1007/s00394-021-02632-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 06/28/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively. METHODS The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber-DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively. RESULTS The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione-S-transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways. CONCLUSION UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management.
Collapse
Affiliation(s)
- Xin Yan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Xiaoyun Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Yu Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Xueyang Ren
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Jiamu Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Ruolan Song
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Xiuhuan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Ying Dong
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Qiqi Fan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Jing Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Axiang Yu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Hong Sui
- School of Chinese Pharmacy, Ningxia Medical University, Yinchuan, 750004, China
| | - Gaimei She
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| |
Collapse
|
|
14
|
Kolaric TO, Nincevic V, Kuna L, Duspara K, Bojanic K, Vukadin S, Raguz-Lucic N, Wu GY, Smolic M. Drug-induced Fatty Liver Disease: Pathogenesis and Treatment. J Clin Transl Hepatol 2021; 9:731-737. [PMID: 34722188 PMCID: PMC8516847 DOI: 10.14218/jcth.2020.00091] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 02/08/2021] [Accepted: 07/01/2021] [Indexed: 12/12/2022] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.
Collapse
Affiliation(s)
- Tea Omanovic Kolaric
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
| | - Vjera Nincevic
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
| | - Lucija Kuna
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
| | | | - Kristina Bojanic
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
- Health Center Osijek, Osijek, Croatia
| | - Sonja Vukadin
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
| | - Nikola Raguz-Lucic
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Martina Smolic
- University of Osijek, Faculty of Medicine, Osijek, Croatia
- University of Osijek, Faculty of Dental Medicine and Health, Osijek, Croatia
- Correspondence to: Martina Smolic, University of Osijek, Faculty of Medicine, Department of Pharmacology; Faculty of Dental Medicine and Health, Department of Pharmacology and Biochemistry, J. Huttlera 4, Osijek 31000, Croatia. ORCID: https://orcid.org/0000-0002-6867-826X. Tel: + 385-31-512-800, Fax: +385-31-512-833, E-mail:
| |
Collapse
|
|
15
|
Yan X, Ren X, Liu X, Wang Y, Ma J, Song R, Wang X, Dong Y, Fan Q, Wei J, Yu A, She G. Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:7074-7083. [PMID: 34152776 DOI: 10.1021/acs.jafc.1c02362] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.
Collapse
Affiliation(s)
- Xin Yan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Xueyang Ren
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Xiaoyun Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Yu Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Jiamu Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Ruolan Song
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Xiuhuan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Ying Dong
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Qiqi Fan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Jing Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Axiang Yu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| | - Gaimei She
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, People's Republic of China
| |
Collapse
|
|
16
|
Rorat M, Hałoń A, Jurek T. Histology of Liver of the Deceased Due to Harmful Use of Alcohol. Alcohol Alcohol 2021; 55:518-523. [PMID: 32626893 DOI: 10.1093/alcalc/agaa059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/04/2020] [Accepted: 06/02/2020] [Indexed: 11/13/2022] Open
Abstract
AIM To study types and incidence of histological changes in liver of people deceased due to harmful use of alcohol. METHODS A retrospective review of medico-legal autopsy of 236 adults who died in the years 2015-2016 due to harmful use of alcohol was done. Histopathological liver samples taken during autopsies were evaluated. Blood alcohol content was analyzed. Serological tests for hepatitis B surface antigen and anti-hepatitis C virus (HCV) were performed. RESULTS The most common liver pathology (83.1%) was steatosis, mainly mixed type (50%); 66.9% had high-grade steatosis. Liver fibrosis was detected in 39.4% of cases, with fibrosis of higher than or equal to third grade in 14%, hepatitis in 44.5% and steatohepatitis in 19.1%. Toxic hepatocyte injury features (ballooning degeneration, Mallory-Denk bodies) were found in 20.8% cases and degenerative-damage changes in 41.1%. The correlation between the grade of steatosis and fibrosis (P = 0.0005), toxic injury (0.00000101) and degenerative-traumatic changes (P = 0.00000741) was found. The correlation was found between hepatitis and higher than or equal to third grade steatosis (P = 0.037), cholestasis (P = 0.0139), toxic injury features (P = 2.58 × 10-13), degenerative-damage changes (P = 7.9 × 10-12) and presence of anti-HCV (P = 0.00723) and between progression of fibrosis and presence of toxic injury features (2.28 × 10-19), degenerative-damage changes (P = 4.25 × 10-11) and anti-HCV (P = 0.0263). CONCLUSIONS Spectrum of histopathological liver changes is broad regardless of sex, and various traits are present in various patterns. Comorbidities have strong influence on the picture of changes in the liver. Exact evaluation how often and what histopathological changes will develop in alcohol liver disease is not possible by reason of variability of external factors.
Collapse
Affiliation(s)
- Marta Rorat
- Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4 Str., 50-345 Wrocław, Poland
| | - Agnieszka Hałoń
- Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213 Str., 50-556 Wrocław, Poland
| | - Tomasz Jurek
- Department of Forensic Medicine, Wroclaw Medical University, J. Mikulicza-Radeckiego 4 Str., 50-345 Wrocław, Poland
| |
Collapse
|
|
17
|
Shi C, Wang L, Zhou K, Shao M, Lu Y, Wu T. Targeted Metabolomics Identifies Differential Serum and Liver Amino Acids Biomarkers in Rats with Alcoholic Liver Disease. J Nutr Sci Vitaminol (Tokyo) 2021; 66:536-544. [PMID: 33390395 DOI: 10.3177/jnsv.66.536] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
To investigate changes in serum and hepatic levels of amino acids in ALD and to provide novel evidence and approaches for the prevention and treatment of ALD. Twenty specific pathogen-free SD male rats were devided into two groups, ten for the control group, and ten for the model group. Serum biochemical markers, including alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronidase were measured. Histological analysis of liver tissues was performed. Serum and liver amino acids levels were quantitatively determined by ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-TQMS)-based targeted metabolomics. Compared with the normal group, ALD rats showed an obvious increase in the levels of β-alanine, alanine, serine, ornithine, tyrosine and the tyrosine ratio, while there was a decrease in arginine levels, the BTR ratio and Fischer's ratio in serum. Additionally, ALD rats exhibited a significant increase in the levels of cysteine and putrescine, while there was a decrease in sarcosine, β-alanine, serine, proline, valine, threonine, ornithine, lysine, histidine, tyrosine, symmetric dimethylarginine, methionine, isoleucine and methionine-sulfoxide levels in liver tissues compared with the normal group. The serum and liver amino acids showed significant changes in ALD rats and can be considered as potential specific diagnostic biomarkers for ALD.
Collapse
Affiliation(s)
- Chenze Shi
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine
| | - Lei Wang
- Department of Hepatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine
| | - Kejun Zhou
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research
| | - Mingmei Shao
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine
| | - Yifei Lu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine
| |
Collapse
|
|
18
|
Suresh D, Srinivas AN, Kumar DP. Etiology of Hepatocellular Carcinoma: Special Focus on Fatty Liver Disease. Front Oncol 2020; 10:601710. [PMID: 33330100 PMCID: PMC7734960 DOI: 10.3389/fonc.2020.601710] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 10/30/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular Carcinoma (HCC) is a highly aggressive cancer with mortality running parallel to its incidence and has limited therapeutic options. Chronic liver inflammation and injury contribute significantly to the development and progression of HCC. Several factors such as gender, age, ethnicity, and demographic regions increase the HCC incidence rates and the major risk factors are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), carcinogens (food contaminants, tobacco smoking, and environmental toxins), and inherited diseases. In recent years evidence highlights the association of metabolic syndrome (diabetes and obesity), excessive alcohol consumption (alcoholic fatty liver disease), and high-calorie intake (nonalcoholic fatty liver disease) to be the prime causes for HCC in countries with a westernized sedentary lifestyle. HCC predominantly occurs in the setting of chronic liver disease and cirrhosis (80%), however, 20% of the cases have been known in patients with non-cirrhotic liver. It is widely believed that there exist possible interactions between different etiological agents leading to the involvement of diverse mechanisms in the pathogenesis of HCC. Understanding the molecular mechanisms of HCC development and progression is imperative in developing effective targeted therapies to combat this deadly disease. Noteworthy, a detailed understanding of the risk factors is also critical to improve the screening, early detection, prevention, and management of HCC. Thus, this review recapitulates the etiology of HCC focusing especially on the nonalcoholic fatty liver disease (NAFLD)- and alcoholic fatty liver disease (AFLD)-associated HCC.
Collapse
Affiliation(s)
- Diwakar Suresh
- Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Jagadguru Sri Shivarathreeshwara (JSS) Medical College, JSS Academy of Higher Education and Research, Mysuru, India
| | - Akshatha N Srinivas
- Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Jagadguru Sri Shivarathreeshwara (JSS) Medical College, JSS Academy of Higher Education and Research, Mysuru, India
| | - Divya P Kumar
- Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Jagadguru Sri Shivarathreeshwara (JSS) Medical College, JSS Academy of Higher Education and Research, Mysuru, India
| |
Collapse
|
|
19
|
Abstract
An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, cirrhosis, and lead to hepatocellular carcinoma (HCC). The aim of this review is to clarify the present condition and the mechanisms of alcohol-related hepatocarcinogenesis and clinical risk factors for alcohol-related HCC. There are several possible mechanisms through which alcohol may induce hepatocarcinogenesis, including the mutagenic effects of acetaldehyde toxicity through the formation of protein and DNA adducts and the production of reactive oxygen species due to the excessive hepatic deposition of iron, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. Furthermore, it has been reported that alcohol accelerates liver carcinogenesis through several signaling pathways including gut-liver axis. From a clinical perspective, it is well known that alcohol interacts with other factors, such as age, gender, viral hepatitis, obesity, and diabetes leading to an increased risk of HCC.
Collapse
Affiliation(s)
- Makiko Taniai
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| |
Collapse
|
|
20
|
Han H, Desert R, Das S, Song Z, Athavale D, Ge X, Nieto N. Danger signals in liver injury and restoration of homeostasis. J Hepatol 2020; 73:933-951. [PMID: 32371195 PMCID: PMC7502511 DOI: 10.1016/j.jhep.2020.04.033] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 04/08/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023]
Abstract
Damage-associated molecular patterns are signalling molecules involved in inflammatory responses and restoration of homeostasis. Chronic release of these molecules can also promote inflammation in the context of liver disease. Herein, we provide a comprehensive summary of the role of damage-associated molecular patterns as danger signals in liver injury. We consider the role of reactive oxygen species and reactive nitrogen species as inducers of damage-associated molecular patterns, as well as how specific damage-associated molecular patterns participate in the pathogenesis of chronic liver diseases such as alcohol-related liver disease, non-alcoholic steatohepatitis, liver fibrosis and liver cancer. In addition, we discuss the role of damage-associated molecular patterns in ischaemia reperfusion injury and liver transplantation and highlight current studies in which blockade of specific damage-associated molecular patterns has proven beneficial in humans and mice.
Collapse
Affiliation(s)
- Hui Han
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Romain Desert
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Sukanta Das
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Zhuolun Song
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Dipti Athavale
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Xiaodong Ge
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA
| | - Natalia Nieto
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL 60612, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, 840 S. Wood St., Suite 1020N, MC 787, Chicago, IL 60612, USA.
| |
Collapse
|
|
21
|
Kondo R, Iwakiri Y. The lymphatic system in alcohol-associated liver disease. Clin Mol Hepatol 2020; 26:633-638. [PMID: 32951411 PMCID: PMC7641555 DOI: 10.3350/cmh.2020.0179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 12/18/2022] Open
Abstract
The lymphatic system plays vital roles in interstitial fluid balance and immune cell surveillance. The effect of alcohol on the lymphatic system is poorly understood. This review article explores the role of the lymphatic system in the pathogenesis of alcohol-related disease including alcoholic liver disease (ALD) and the therapeutic potential of targeting hepatic lymphatics for the treatment of ALD.
Collapse
Affiliation(s)
- Reiichiro Kondo
- Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Yasuko Iwakiri
- Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
22
|
Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma. Cancers (Basel) 2020; 12:cancers12061419. [PMID: 32486341 PMCID: PMC7352397 DOI: 10.3390/cancers12061419] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/19/2020] [Accepted: 05/27/2020] [Indexed: 12/11/2022] Open
Abstract
: Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.
Collapse
|
|
23
|
Ferreira RC, Batista TM, Duarte SS, Silva DKF, Lisboa TMH, Cavalcanti RFP, Leite FC, Mangueira VM, Sousa TKGD, Abrantes RAD, Trindade EOD, Athayde-Filho PFD, Brandão MCR, Medeiros KCDP, Farias DF, Sobral MV. A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions. Biomed Pharmacother 2020; 128:110247. [PMID: 32450524 DOI: 10.1016/j.biopha.2020.110247] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 05/01/2020] [Accepted: 05/10/2020] [Indexed: 02/08/2023] Open
Abstract
Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and micronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC50 (lethal concentration 50%) higher than 100 μg/mL. On the acute toxicity assay in mice, LD50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1β, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.
Collapse
Affiliation(s)
- Rafael Carlos Ferreira
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Tatianne Mota Batista
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Sâmia Sousa Duarte
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Daiana Karla Frade Silva
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Thaís Mangeon Honorato Lisboa
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Raquel Fragoso Pereira Cavalcanti
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Fagner Carvalho Leite
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Vivianne Mendes Mangueira
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Tatyanna Kélvia Gomes de Sousa
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Renata Albuquerque de Abrantes
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | | | | | | | - Karina Carla de Paula Medeiros
- Department of Morphology, Center of Biosciences, Federal University of Rio Grande Do Norte, 59078-970, Rio Grande do Norte, Brazil
| | - Davi Felipe Farias
- Department of Molecular Biology, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil
| | - Marianna Vieira Sobral
- Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, 58051-970, João Pessoa, Paraíba, Brazil.
| |
Collapse
|
|
24
|
Efficacy of Polymethoxylated Flavonoids from Citrus depressa Extract on Alcohol-induced Liver Injury in Mice. BIOTECHNOL BIOPROC E 2019. [DOI: 10.1007/s12257-019-0310-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
25
|
Fonseca TL, Fernandes GW, Bocco BMLC, Keshavarzian A, Jakate S, Donohue TM, Gereben B, Bianco AC. Hepatic Inactivation of the Type 2 Deiodinase Confers Resistance to Alcoholic Liver Steatosis. Alcohol Clin Exp Res 2019; 43:1376-1383. [PMID: 30908637 PMCID: PMC6602874 DOI: 10.1111/acer.14027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/15/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A mouse with hepatocyte-specific deiodinase type II inactivation (Alb-D2KO) is resistant to diet-induced obesity, hepatic steatosis, and hypertriglyceridemia due to perinatal epigenetic modifications in the liver. This phenotype is linked to low levels of Zfp125, a hepatic transcriptional repressor that promotes liver steatosis by inhibiting genes involved in packaging and secretion of very-low-density lipoprotein. METHODS Here, we used chronic and binge ethanol (EtOH) in mice to cause liver steatosis. RESULTS The EtOH treatment causes a 2.3-fold increase in hepatic triglyceride content; Zfp125 levels were approximately 50% higher in these animals. In contrast, Alb-D2KO mice did not develop EtOH-induced liver steatosis. They also failed to elevate Zfp125 to the same levels, despite being on the EtOH-containing diet for the same period of time. Their phenotype was associated with 1.3- to 2.9-fold up-regulation of hepatic genes involved in lipid transport and export that are normally repressed by Zfp125, that is, Mttp, Abca1, Ldlr, Apoc1, Apoc3, Apoe, Apoh, and Azgp1. Furthermore, genes involved in the EtOH metabolic pathway, that is, Aldh2 and Acss2, were also 1.6- to 3.1-fold up-regulated in Alb-D2KO EtOH mice compared with control animals kept on EtOH. CONCLUSIONS EtOH consumption elevates expression of Zfp125. Alb-D2KO animals, which have lower levels of Zfp125, are much less susceptible to EtOH-induced liver steatosis.
Collapse
Affiliation(s)
- Tatiana L. Fonseca
- Section of Endocrinology, Diabetes & Metabolism, University of Chicago, Chicago, IL
| | - Gustavo W. Fernandes
- Section of Endocrinology, Diabetes & Metabolism, University of Chicago, Chicago, IL
| | | | - Ali Keshavarzian
- Division of Digestive Diseases and Nutrition, Rush University, Chicago IL
| | | | - Terrence M. Donohue
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha NE
| | - Balázs Gereben
- Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
| | - Antonio C. Bianco
- Section of Endocrinology, Diabetes & Metabolism, University of Chicago, Chicago, IL
| |
Collapse
|
|
26
|
Epidemiology of Alcohol Consumption and Societal Burden of Alcoholism and Alcoholic Liver Disease. Clin Liver Dis 2019; 23:39-50. [PMID: 30454831 DOI: 10.1016/j.cld.2018.09.011] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Alcohol abuse is a major determinant of public health outcomes. Worldwide data from 2016 indicate that alcohol is the seventh leading risk factor in terms of disability-adjusted life years, an increase of more than 25% from 1990 to 2016. Understanding the epidemiology of alcoholic liver disease, including the regional variations in consumption and public policy, is an area of active research. In countries where the per capita consumption of alcohol decreases, there appears to be an associated decrease in disease burden. Given alcohol's health burden, an increased focus on alcohol control policies is needed.
Collapse
|
|
27
|
Butler DC, Lewin DN, Batalis NI. Differential Diagnosis of Hepatic Necrosis Encountered at Autopsy. Acad Forensic Pathol 2018; 8:256-295. [PMID: 31240042 DOI: 10.1177/1925362118782056] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 04/13/2018] [Indexed: 12/13/2022]
Abstract
The liver is subject to a variety of extrinsic and intrinsic insults that manifest with both specific and nonspecific patterns of necrosis. In the autopsy setting, these patterns are often encountered as incidental findings or even causes of death. There are several etiologies of hepatic necrosis, including toxins, drug injuries, viral infections, ischemic injuries, and metabolic disease, all of which possess overlapping gross and histologic presentations. Nonetheless, patterned necrosis in the context of clinical and demographic history allows for the forensic pathologist to develop a differential diagnosis, which may then be pruned into a specific or likely cause. The aim of the following review is to elucidate these patterns in the context of the liver diseases from which they arise with the goal developing a differential diagnosis and ultimate determination of etiology. Acad Forensic Pathol. 2018 8(2): 256-295.
Collapse
|
|
28
|
Basisty NB, Liu Y, Reynolds J, Karunadharma PP, Dai DF, Fredrickson J, Beyer RP, MacCoss MJ, Rabinovitch PS. Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment. J Gerontol A Biol Sci Med Sci 2018; 73:561-570. [PMID: 28958078 PMCID: PMC6380815 DOI: 10.1093/gerona/glx047] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 08/16/2017] [Indexed: 12/30/2022] Open
Abstract
Accumulation of protein aggregates with age was first described in aged human tissue over 150 years ago and has since been described in virtually every human tissue. Ubiquitin modifications are a canonical marker of insoluble protein aggregates; however, the composition of most age-related inclusions remains relatively unknown. To examine the landscape of age-related protein aggregation in vivo, we performed an antibody-based pulldown of ubiquitinated proteins coupled with metabolic labeling and mass spectrometry on young and old mice on calorie restriction (CR), rapamycin (RP)-supplemented, and control diets. We show increased abundance of many ubiquitinated proteins in old mice and greater retention of preexisting (unlabeled) ubiquitinated proteins relative to their unmodified counterparts-fitting the expected profile of age-increased accumulation of long-lived aggregating proteins. Both CR and RP profoundly affected ubiquitinome composition, half-live, and the insolubility of proteins, consistent with their ability to mobilize these age-associated accumulations. Finally, confocal microscopy confirmed the aggregation of two of the top predicted aggregating proteins, keratins 8/18 and catalase, as well as their attenuation by CR and RP. Stable-isotope labeling is a powerful tool to gain novel insights into proteostasis mechanisms, including protein aggregation, and could be used to identify novel therapeutic targets in aging and protein aggregation diseases.
Collapse
Affiliation(s)
- Nathan B Basisty
- Department of Pathology, University of Washington, Seattle
- Buck Institute for Research on Aging, Novato, California
| | - Yuxin Liu
- Department of Medicine, SUNY Upstate Medical University, Syracuse, New York
| | - Jason Reynolds
- Department of Medicine, University of Washington, Seattle
| | | | - Dao-Fu Dai
- Department of Pathology, University of Washington, Seattle
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City
| | | | - Richard P Beyer
- Department of Environmental Health, University of Washington, Seattle
| | | | | |
Collapse
|
|
29
|
|
|
30
|
Gonçalves JL, Lacerda-Queiroz N, Sabino JF, Marques PE, Galvão I, Gamba CO, Cassali GD, de Carvalho LM, da Silva e Silva DA, Versiani A, Teixeira MM, de Faria AMC, Vieira AT, Brunialti-Godard AL. Evaluating the effects of refined carbohydrate and fat diets with acute ethanol consumption using a mouse model of alcoholic liver injury. J Nutr Biochem 2017; 39:93-100. [DOI: 10.1016/j.jnutbio.2016.08.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 06/13/2016] [Accepted: 08/10/2016] [Indexed: 02/07/2023]
|
|
31
|
Todoric J, Antonucci L, Karin M. Targeting Inflammation in Cancer Prevention and Therapy. Cancer Prev Res (Phila) 2016; 9:895-905. [PMID: 27913448 DOI: 10.1158/1940-6207.capr-16-0209] [Citation(s) in RCA: 270] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 10/03/2016] [Indexed: 12/14/2022]
Abstract
Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol, and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common nonsteroidal anti-inflammatory drugs (NSAID) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches on the basis of tumor resection, radiation, and cytotoxic chemicals. Cancer Prev Res; 9(12); 895-905. ©2016 AACR.
Collapse
Affiliation(s)
- Jelena Todoric
- Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California.,Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Laura Antonucci
- Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California
| | - Michael Karin
- Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California. .,Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California
| |
Collapse
|
|
32
|
VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2016; 2016:9607054. [PMID: 27660750 PMCID: PMC5021862 DOI: 10.1155/2016/9607054] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 07/10/2016] [Accepted: 08/04/2016] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.
Collapse
|
|
33
|
Jang SH, Cho SW, Yoon HM, Jang KJ, Song CH, Kim CH. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury. J Pharmacopuncture 2015; 17:16-24. [PMID: 25780705 PMCID: PMC4332019 DOI: 10.3831/kpi.2014.17.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 09/11/2014] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. METHODS Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. RESULTS GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. CONCLUSION The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.
Collapse
Affiliation(s)
- Sun-Hee Jang
- Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University, Busan, Korea
| | - Sung-Woo Cho
- Department of Oriental Rehabilitation Medicine, College of Korean Medicine, Dong-Eui University, Busan, Korea
| | - Hyun-Min Yoon
- Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University, Busan, Korea
| | - Kyung-Jeon Jang
- Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University, Busan, Korea
| | - Chun-Ho Song
- Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University, Busan, Korea
| | - Cheol-Hong Kim
- Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University, Busan, Korea
| |
Collapse
|
|
34
|
IREDALE JOHNP, BATALLER RAMON. Identifying molecular targets to improve immune function in alcoholic hepatitis. Gastroenterology 2015; 148:498-501. [PMID: 25613314 PMCID: PMC4410810 DOI: 10.1053/j.gastro.2015.01.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- JOHN P. IREDALE
- Centre for Inflammation Research, Queen’s Medical Research Institute, Edinburgh, United Kingdom
| | - RAMON BATALLER
- Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| |
Collapse
|
|
35
|
Ceccarelli S, Nobili V, Alisi A. Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease. World J Gastroenterol 2014; 20:16443-16451. [PMID: 25469012 PMCID: PMC4248187 DOI: 10.3748/wjg.v20.i44.16443] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 08/08/2014] [Accepted: 09/30/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other pro-inflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD.
Collapse
|
|
36
|
Sakhuja P. Pathology of alcoholic liver disease, can it be differentiated from nonalcoholic steatohepatitis? World J Gastroenterol 2014; 20:16474-9. [PMID: 25469015 PMCID: PMC4248190 DOI: 10.3748/wjg.v20.i44.16474] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 07/28/2014] [Accepted: 09/12/2014] [Indexed: 02/06/2023] Open
Abstract
The liver involvement in alcoholic liver disease (ALD) classically ranges from alcoholic steatosis, alcoholic hepatitis or steatohepatitis, alcoholic cirrhosis and even hepatocellular carcinoma. The more commonly seen histologic features include macrovesicular steatosis, neutrophilic lobular inflammation, ballooning degeneration, Mallory-Denk bodies, portal and pericellular fibrosis. Nonalcoholic steatohepatitis (NASH) is a condition with similar histology in the absence of a history of alcohol intake. Although the distinction is essentially based on presence or absence of a history of significant alcohol intake, certain histologic features favour one or the other diagnosis. This review aims at describing the histologic spectrum of alcoholic liver disease and at highlighting the histologic differences between ALD and NASH.
Collapse
|
|
37
|
Testino G, Leone S, Borro P. Alcohol and hepatocellular carcinoma: A review and a point of view. World J Gastroenterol 2014; 20:15943-15954. [PMID: 25473148 PMCID: PMC4239482 DOI: 10.3748/wjg.v20.i43.15943] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 04/30/2014] [Accepted: 07/22/2014] [Indexed: 02/06/2023] Open
Abstract
It is well recognized that one cause of chronic liver disease and hepatocellular carcinoma (HCC) is alcohol consumption. Research in Italy and the United States concludes that the most common cause of HCC (responsible for 32% to 45% of HCC) is alcohol. It has recently been shown that a significant relationship between alcohol intake, metabolic changes, and hepatitis virus infection does exist. Alcohol may be a factor in the development of HCC via direct (genotoxic) and indirect mechanisms (cirrhosis). There is only one way of diagnosing HCC, which is early identification through surveillance, when curative treatments become possible. After stopping alcohol intake the risk of liver cancer decreases by 6% to 7% a year, and an estimated time period of 23 years is also needed. Therefore, surveillance is also important in former drinkers and, in our opinion, independently from the presence of compensated cirrhosis. In cases of very early stage (VES) and early stage with portal hypertension, liver transplantation is the optimal option; and in cases of associated disease, percutaneous ethanol injections, radiofrequency and microwave ablation are the ideal treatments. Despite the possibility of detecting microvascular invasion with HR, several studies and some randomized controlled trials revealed that overall survival and DSF rates in patients with VES HCC are much the same after ablation and HR. Therefore, ablation can be regarded as a first-line choice for patients with VES HCC. It is important to emphasize that the choice of treatment should be weighed carefully in the context of a multidisciplinary cancer team.
Collapse
|
|
38
|
Ray S, Khanra D, Sonthalia N, Kundu S, Biswas K, Talukdar A, Saha M, Bera H. Clinico-biochemical correlation to histological findings in alcoholic liver disease: a single centre study from eastern India. J Clin Diagn Res 2014; 8:MC01-5. [PMID: 25478382 PMCID: PMC4253200 DOI: 10.7860/jcdr/2014/8763.4968] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Accepted: 07/14/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects. MATERIALS AND METHODS A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. RESULT Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. CONCLUSION The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.
Collapse
Affiliation(s)
- Sayantan Ray
- Residential Medical Officer, Department of Medicine, Calcutta National Medical College and Hospital, Kolkata, India
| | - Dibbendhu Khanra
- Resident, Department of Medicine, Medical College and Hospital, Kolkata, India
| | - Nikhil Sonthalia
- Resident, Department of Medicine, Medical College and Hospital, Kolkata, India
| | - Supratip Kundu
- Resident, Department of Cardiology, Medical College and Hospital, Kolkata, India
| | - Kaushik Biswas
- Senior Resident, Department of Endocrinology, Institute of Post Graduate Medical Education & Research (IPGMER) and SSKM Hospital, Kolkata, India
| | - Arunansu Talukdar
- Professor, Department of Medicine, Medical College and Hospital, Kolkata, India
| | - Manjari Saha
- Assistant Professor, Department of Medicine, Medical College and Hospital, Kolkata, India
| | - Himel Bera
- Assistant Professor, Department of Pathology, Bankura Sammilani Medical College & Hospital, Bankura, India
| |
Collapse
|
|
39
|
Fujii H, Kawada N. Fibrogenesis in alcoholic liver disease. World J Gastroenterol 2014; 20:8048-8054. [PMID: 25009376 PMCID: PMC4081675 DOI: 10.3748/wjg.v20.i25.8048] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2013] [Revised: 01/28/2014] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Alcohol abstinence is the most effective therapy for ALD. However, targeted therapies are urgently needed for patients with severe ALD (i.e., alcoholic hepatitis) or those who do not abstain from alcohol. The lack of studies and the availability of animal models that do not reflect all the features of this disease in humans inhibit the development of new drugs for ALD. In ALD-associated fibrosis, hepatic stellate cells are the principal cell type responsible for extracellular matrix production. Although the mechanisms underlying fibrosis in ALD are largely similar to those observed in other chronic liver diseases, oxidative stress, methionine metabolism abnormalities, hepatocyte apoptosis, and endotoxin lipopolysaccharides that activate Kupffer cells may play unique roles in disease-related fibrogenesis. Lipogenesis during the early stages of ALD has recently been implicated as a risk factor for the progression of cirrhosis. Other topics include osteopontin, interleukin-1 signaling, and genetic polymorphism. In this review, we discuss the basic pathogenesis of ALD and focus on liver fibrogenesis.
Collapse
|
|
40
|
Vonghia L, Michielsen P, Dom G, Francque S. Diagnostic challenges in alcohol use disorder and alcoholic liver disease. World J Gastroenterol 2014; 20:8024-8032. [PMID: 25009373 PMCID: PMC4081672 DOI: 10.3748/wjg.v20.i25.8024] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/07/2014] [Accepted: 02/17/2014] [Indexed: 02/06/2023] Open
Abstract
Alcohol use disorders represent a heterogeneous spectrum of clinical manifestations that have been defined by the Diagnostic and Statistical Manual of Mental Disorders-5. Excessive alcohol intake can lead to damage of various organs, including the liver. Alcoholic liver disease includes different injuries ranging from steatosis to cirrhosis and implicates a diagnostic assessment of the liver disease and of its possible complications. There is growing interest in the possible different tools for assessing previous alcohol consumption and for establishing the severity of liver injury, especially by non-invasive methods.
Collapse
|
|
41
|
Exocrine pancreatic insufficiency and chronic pancreatitis in chronic alcoholic liver disease: coincidence or shared toxicity? Pancreas 2014; 43:730-4. [PMID: 24713840 DOI: 10.1097/mpa.0000000000000085] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aims of this study were to determine the prevalence of exocrine pancreatic insufficiency (EPI) and chronic pancreatitis (CP) in patients with chronic alcoholic liver disease and to analyze the possible associated factors. METHODS This is an analytical observational study of cases and controls for a sample of patients with chronic alcoholic and nonalcoholic liver disease. Exocrine pancreatic insufficiency was diagnosed using the C mixed-triglyceride breath test. Patients with abdominal pain underwent endoscopic ultrasonography for CP evaluation using the Wiersema criteria. RESULTS A total of 154 patients were included, 129 with alcoholic liver disease (83 with cirrhosis) and 25 with nonalcoholic liver disease. Exocrine pancreatic insufficiency was found in 55.2% versus 16.7% (P < 0.001), 70% of patients without cirrhosis compared with 46.2% of patients with cirrhosis had pancreatic insufficiency (P = 0.017), and 82.7% of patients with alcoholic liver disease and abdominal pain had CP (P < 0.001). Exocrine pancreatic insufficiency was associated with the male sex, alcohol intake, abdominal pain, degree of liver failure, and the absence of portal hypertension. Chronic pancreatitis was correlated with age younger than 55 years and abdominal pain. CONCLUSIONS Patients with alcoholic liver disease had a high prevalence of EPI and CP; this prevalence was even higher in patients who have not yet developed cirrhosis with liver failure or portal hypertension.
Collapse
|
|
42
|
Celli R, Zhang X. Pathology of Alcoholic Liver Disease. J Clin Transl Hepatol 2014; 2:103-9. [PMID: 26357621 PMCID: PMC4521259 DOI: 10.14218/jcth.2014.00010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 04/14/2014] [Accepted: 04/16/2014] [Indexed: 02/05/2023] Open
Abstract
Alcohol-attributable burden on global health is increasing, and the relationship between population alcohol consumption and liver-related deaths is strong. Longstanding scientific and clinical work has led to a relatively thorough, if not complete, understanding of the effects of alcohol consumption on the liver. Pathologic features of alcoholic liver disease (ALD) are recognized by pathologists and used to assist clinicians in diagnosing and determining severity of disease in patients suspected of ALD. In this review, we discuss the pathologic manifestations of ALD and provide salient points on their pathophysiology. In addition, the benefits and indications of liver biopsy and important differential diagnoses, including features distinguishing these entities, are reviewed.
Collapse
Affiliation(s)
- Romulo Celli
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Xuchen Zhang
- Pathology and Laboratory Service, VA Connecticut Health System and Department of Pathology, Yale University School of Medicine, West Haven, CT, USA
| |
Collapse
|
|
43
|
Hayashi M, Kanda T, Nakamura M, Miyamura T, Yasui S, Nakamoto S, Wu S, Arai M, Imazeki F, Yokosuka O. Acute liver injury in a patient with alcohol dependence: a case resembling autoimmune hepatitis or drug-induced liver injury. Case Rep Gastroenterol 2014; 8:129-33. [PMID: 24847195 PMCID: PMC4025146 DOI: 10.1159/000362442] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Some patients with alcohol dependence may initially present with atypical laboratory and histological features resembling autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). Even with liver biopsy, it may be difficult to diagnose certain patients with alcohol dependence. However, careful follow-up of our patient and consultations with the attending psychiatrist were successful in diagnosing alcohol dependence and its liver injury. The immune mechanisms of alcoholic liver diseases, AIH and DILI may be overlapping. Certain patients are suffering from AIH with flares on a background of alcohol abuse. Certain patients with alcohol abuse may have a past history of DILI. This might be consistent with the fact that alcohol dependence initially presents with atypical laboratory features of AIH or DILI. With careful observation, the clinician should remind himself that alcohol dependence is not always required for developing liver disease, since many patients with liver disease do not meet the criteria for alcohol dependence.
Collapse
Affiliation(s)
- Masahiro Hayashi
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tatsuo Miyamura
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Fumio Imazeki
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan
| |
Collapse
|
|
44
|
Aggarwal S, Fiel MI, Schiano TD. Obliterative portal venopathy: a clinical and histopathological review. Dig Dis Sci 2013; 58:2767-76. [PMID: 23812828 DOI: 10.1007/s10620-013-2736-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Accepted: 05/29/2013] [Indexed: 12/12/2022]
Abstract
Non-cirrhotic portal hypertension (NCPH) is characterized by the elevation of the portal pressure in the absence of cirrhosis. Obliterative portal venopathy (OPV) as a cause of NCPH is being increasingly diagnosed, especially after recent reports of its occurrence in patients with HIV using didanosine. Patients usually present with episodes of variceal hemorrhage and other features of portal hypertension including jaundice, ascites, encephalopathy and hepatopulmonary syndrome. Hepatic synthetic function is typically well preserved and the laboratory evaluation in OPV patients typically reveals only mild nonspecific hematological abnormalities chiefly related to hypersplenism. Its diagnosis remains a challenge and patients are often mistakenly diagnosed as having cirrhosis. Despite the increasing recognition of OPV, its etiology and pathogenesis are still unclear. A number of etiologies have been proposed including genetic predisposition, recurrent bacterial infections, HIV infection and highly active antiretroviral therapy, an altered immune response, hypercoagulability, and exposure to chemicals and certain medications. Histopathological evaluation remains critical in excluding cirrhosis and other causes of portal hypertension, and is the only way of definitively establishing the diagnosis of OPV. Clinicians should have a high index of suspicion for OPV in patients who present with variceal bleeding and splenomegaly and who do not have other features of cirrhosis. The purpose of this review is to summarize the known etiologies for OPV and its associated clinical aspects and correlations, and to also provide ample histophotomicrographs of OPV to aid in the diagnosis. It will also help raise awareness of this entity amongst pathologists and clinicians alike.
Collapse
Affiliation(s)
- Sourabh Aggarwal
- School of Medicine, Western Michigan University, Kalamazoo, MI, USA
| | | | | |
Collapse
|
|
45
|
Theise ND. Histopathology of alcoholic liver disease. Clin Liver Dis (Hoboken) 2013; 2:64-67. [PMID: 30992826 PMCID: PMC6448621 DOI: 10.1002/cld.172] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 01/25/2013] [Accepted: 02/17/2013] [Indexed: 02/04/2023] Open
Affiliation(s)
- Neil D. Theise
- Departments of Pathology and Medicine (Division of Digestive Diseases), Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY
| |
Collapse
|