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Yoo T, Lee KW, Yi NJ, Hong SK, Lee JM, Kim H, Lim J, Seo S, Suh KS. Impact of PNPLA3 (rs738409-G) polymorphism on post-transplant outcomes after liver transplantation for alcohol-related liver disease. Clin Transplant 2020; 34:e14011. [PMID: 32557704 DOI: 10.1111/ctr.14011] [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: 03/30/2020] [Revised: 05/16/2020] [Accepted: 06/07/2020] [Indexed: 11/29/2022]
Abstract
INTRODUCTION We aimed to evaluate the association between PNPLA3 polymorphism and post-liver transplantation (LT) outcomes related to alcohol relapse (AR). METHOD We retrospectively analyzed data from patients receiving LT for alcoholic liver disease (ALD) from 04/2014 to 12/2017. Liver-related clinical outcomes were assessed by the gamma-glutamyltransferase (GGT) level and alcohol-related liver failure (ARLF). Genotyping was performed using prospectively collected DNA samples in both donors and recipients. RESULTS A total of 83 recipients were enrolled. Post-LT AR occurred in 31 patients (37.3%). Thirty-one patients (14 AR, 9 abstainers) showed elevated GGT levels, and 3 AR patients experienced ARLF. In the multivariate analysis, rs738409 G allele carrier and heavy drinking (HRAR score ≥ 4) were independent risk factors for elevated GGT levels (odds ratio [OR] = 8.69, P < .01; OR = 13.07, P = .01) and ARLF (OR = 4.52, P = .04; OR = 19.62, P = .03). Among 15 heavy AR patients, being an rs738409 G allele carrier was related to GGT elevation (P = .03) and ARLF (P = .04), but it was not related to GGT elevation in mild drinkers (n = 16) or abstainers (n = 52). CONCLUSION PNPLA3 polymorphism of the recipient genotype can independently affect the post-LT prognosis of LT patients for ALD, especially in heavy AR patients. Therefore, strong abstinence education is recommended in patients with this single nucleotide polymorphism.
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Affiliation(s)
- Tae Yoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Hallym University College of Medicine, Gyeonggi-do, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyeyoung Kim
- Department of Surgery, Eulji University College of Medicine, Daejeon, Republic of Korea
| | - Jieun Lim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sooin Seo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Abstract
The frequency of psychiatric illness presenting with liver disease occurs at rates higher than pure chance. This reflects the association between alcohol and drug dependence with acute and chronic liver toxicity and disease. Because mood and anxiety disorders are more common in substance use disorder, the link extends to higher rates of these disorders in patients with liver disease. Finally, liver disease can represent a chronic and painful condition that presents a significant physical and psychological stress for patients.
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Affiliation(s)
- William R. Yates
- 4201 East 41st Street, Tulsa, OK 74135, william-yates @ouhsc.edu
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Wild Edible Fruit of Prunus nepalensis Ser. (Steud), a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice. PLoS One 2015; 10:e0144280. [PMID: 26633891 PMCID: PMC4669143 DOI: 10.1371/journal.pone.0144280] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 10/27/2015] [Indexed: 12/17/2022] Open
Abstract
The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud), a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME) exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 30.92 ± 0.40 μg/ml). PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38). On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.
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Is chronic feeding of low dose alcohol hepatotoxic or genotoxic?: A time course study in mice. THE NUCLEUS 2014. [DOI: 10.1007/s13237-014-0120-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Nusrat S, Khan MS, Fazili J, Madhoun MF. Cirrhosis and its complications: Evidence based treatment. World J Gastroenterol 2014; 20:5442-5460. [PMID: 24833875 PMCID: PMC4017060 DOI: 10.3748/wjg.v20.i18.5442] [Citation(s) in RCA: 147] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 01/17/2014] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis results from progressive fibrosis and is the final outcome of all chronic liver disease. It is among the ten leading causes of death in United States. Cirrhosis can result in portal hypertension and/or hepatic dysfunction. Both of these either alone or in combination can lead to many complications, including ascites, varices, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary syndrome, and coagulation disorders. Cirrhosis and its complications not only impair quality of life but also decrease survival. Managing patients with cirrhosis can be a challenge and requires an organized and systematic approach. Increasing physicians’ knowledge about prevention and treatment of these potential complications is important to improve patient outcomes. A literature search of the published data was performed to provide a comprehensive review regarding the management of cirrhosis and its complications.
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Abstract
There are insufficient data available on the epidemiology of fatty liver to design a complete and correct view of the prevalence, incidence and natural history of this disorder. This article, mainly based on the revision of recently published papers in this field, attempts to give an overview of the current findings on the epidemiology of fatty liver worldwide. The possible factors involved in the development of fat accumulation in the liver, and their potential role in the progression of the disorder will be also addressed.
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Khocht A, Janal M, Schleifer S, Keller S. The influence of gingival margin recession on loss of clinical attachment in alcohol-dependent patients without medical disorders. J Periodontol 2003; 74:485-93. [PMID: 12747453 DOI: 10.1902/jop.2003.74.4.485] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The objective of this study was to examine the effects of alcohol and cocaine misuse on periodontal status in a group of alcohol-dependent patients. METHODS Forty verified alcoholics, either exclusively (n = 10) or with cocaine abuse (n = 30), and a matched comparison group of 25 non-alcoholic subjects, 14 of whom abused cocaine, were entered in the study. All subjects were free from systemic illnesses. Blood levels of gamma glutamyl transpeptidase (GGTP), a liver enzyme indicator of alcohol drinking, were determined. A comprehensive periodontal examination was performed on 6 sites per tooth. The gingival index (GI) and plaque index (PI) were recorded. Attachment levels (AL) were computed as probing depth (PD) plus gingival margin level (GM). RESULTS No statistically significant differences were noted between the groups for average AL, PD, GM, GI, and PI. In alcoholics, Pearson correlation showed a positive association between GGTP levels and loss of periodontal attachment (P<0.05). A series of regression analyses predicting AL from selected periodontal and demographic factors showed that alcoholics manifest AL by greater increases in GM than non-alcoholics (P<0.07). Severe alcohol use as measured by GGTP >51 iu/l worsens PI (P<0.07), which adversely impacts GM, GI, PD, and ultimately AL. No significant associations were found between cocaine use and AL. CONCLUSIONS The results suggest that persistent alcohol abuse increases periodontitis development by heightening the loss of attachment through recession of gingival margins.
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Affiliation(s)
- Ahmed Khocht
- Medical College of Georgia, School of Dentistry, Augusta, GA 30912-1220, USA.
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Westin J, Lagging LM, Spak F, Aires N, Svensson E, Lindh M, Dhillon AP, Norkrans G, Wejstål R. Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection. J Viral Hepat 2002; 9:235-41. [PMID: 12010513 DOI: 10.1046/j.1365-2893.2002.00356.x] [Citation(s) in RCA: 97] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Although excessive alcohol consumption in combination with hepatitis C virus (HCV) infection is known to increase the risk of liver cirrhosis, the effect of moderate alcohol intake remains to be elucidated. The aim of this study was to evaluate the effect of moderate alcohol consumption on fibrosis progression in HCV infection. A group of 78 patients with HCV infection and moderate alcohol consumption were analysed retrospectively. All patients had undergone two liver biopsies, with a median time between biopsies of 6.3 years, and had not received any antiviral therapy. Their lifetime drinking history was recorded. All patients except one had daily alcohol consumption below 40 g of ethanol (median 4.8 g/day, interquartile range 1.1-11.6 g/day) during the period between the biopsies. The patients whose liver fibrosis had deteriorated had a higher total alcohol consumption and higher drinking frequency between the biopsies. The degree of fibrosis progression was greater in patients with a total alcohol intake and drinking frequency above the median level for the group. A multiple logistic regression analysis showed that drinking frequency and time between biopsies were independently associated with fibrosis progression. Hence, even moderate alcohol intake seems to increase fibrosis progression in HCV-infected patients. From that point of view, total abstention ought to be recommended. If this is not achieved, occasional use of alcohol is probably less harmful than daily drinking for patients with low or moderate alcohol consumption.
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Affiliation(s)
- Johan Westin
- Department of Infectious Diseases, Göteborg University, Göteborg Sweden.
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Bellentani S, Saccoccio G, Masutti F, Giacca M, Miglioli L, Monzoni A, Tiribelli C. Risk factors for alcoholic liver disease. Addict Biol 2000; 5:261-8. [PMID: 20575840 DOI: 10.1111/j.1369-1600.2000.tb00190.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Abstract Alcoholic liver disease (ALD) is still a frequent disorder, even though its incidence appears to be decreasing. In spite of intense investigation, the precise mechanisms leading to ALD are still imprecisely known. This is due in part to the lack of a reliable animal model; in part to the difficulty of obtaining clinical data of adequate sample size and derived from unblased populations and finally from the lack of uniformity of the criteria used to define ALD. This paper will review what is known of the various pieces of this puzzle, with particular emphasis not only on the total amount of alcohol consumed, but also on drinking patterns and type of alcoholic beverage ingested. The other potential factors such as age, gender, genetic background, nutritional status, occupational hazards and viral diseases (especially HCV infection) will be touched upon.
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Affiliation(s)
- S Bellentani
- Fondo per lo Studio delle Malattie del Fegato, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy ICGEB, AREA Ricerca, Padriciano, Trieste, Italy
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Yates WR, Reed DA, Booth BM, Masterson BJ, Brown K. Prognostic validity of short-term abstinence in alcoholism. Alcohol Clin Exp Res 1994; 18:280-3. [PMID: 8048728 DOI: 10.1111/j.1530-0277.1994.tb00015.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
A demonstrated period of abstinence is often viewed as a good prognostic sign in alcoholism. For example, short-term abstinence is one factor often considered important as a selection criteria for alcoholics who are being evaluated as liver transplant candidates. However, the prognostic validity of short-term abstinence is unclear. We evaluated the effects of 3 and 6 months of abstinence on readmission rates in a series of 299 alcoholics following discharge from inpatient treatment. Readmission rates were stratified using a 3-factor model of alcoholism severity. This 3-factor model defined groups with 1-year readmission rates, ranging from 15.8% to 62.7%. Short-term abstinence did not have strong effects on readmission rates for the most severe alcoholics, nor did short-term abstinence produce clinically significant reduction for readmission rates for the least severe alcoholics. We conclude that short-term abstinence has minimal effect on prognosis for alcoholics with various levels of baseline severity.
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Affiliation(s)
- W R Yates
- Department of Psychiatry, University of Iowa College of Medicine, Iowa City
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Gavaler JS, Smith WI, Van Thiel DH, Rosenblum ER, Deal SR, Allan MJ. "Binge" versus steady drinking: effects on the liver in the ovariectomized rat. Alcohol Clin Exp Res 1993; 17:355-8. [PMID: 8488979 DOI: 10.1111/j.1530-0277.1993.tb00775.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Substantial interest exists as to whether or not differential effects in liver injury based on the pattern of alcohol intake exist; and further, if they do, are they simply a function of the total dose over time. A rat model in which ethanol (ETOH) at doses of 12%, 24%, or 36% of total calories was isocalorically administered for 4 months either daily or intermittently (4 days of ETOH, 3 days of control diet, repeatedly) was used to assess this question. There were significant differences in the two feeding pattern groups between 36% ETOH rats for the liver weight corrected for body weight, the fat infiltration score, the total amount of ETOH consumed/mg body weight, the proportion of animals with a fat infiltration score > 2, and albumin levels. There was a significant difference between 12% ETOH rats for the liver weight corrected for body weight. Of particular relevance is the comparison to be made between Daily 12% ETOH and Binge 24% ETOH animals, because these two groups consumed an identical total amount of ETOH/mg body weight (Daily: 445 +/- 5 vs. Binge: 468 +/- 15) and thus these animals are comparable in terms of ETOH dose over time but different in terms of the pattern of ETOH exposure. There were no differences in the liver/body ratio (Daily: 235 +/- 6 vs. Binge: 232 +/- 4), fat infiltration score (Daily: 2.5 +/- 4 vs. Binge: 2.4 +/- 0.3), the proportion of animals with a fat infiltration score > 2 (Daily: 5/10 vs. Binge: 4/8), or albumin levels (Daily: 3.0 +/- 0.1 vs. Binge: 3.1 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- J S Gavaler
- Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania
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