|
1
|
Braillon A. Screening for Cirrhosis in People With Fatty Liver? Clin Gastroenterol Hepatol 2021; 19:850-851. [PMID: 33248094 DOI: 10.1016/j.cgh.2020.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/07/2020] [Accepted: 05/08/2020] [Indexed: 02/07/2023]
|
|
2
|
Nonalcoholic Fatty Liver Disease, Male Sexual Dysfunction, and Infertility: Common Links, Common Problems. Sex Med Rev 2020; 8:274-285. [DOI: 10.1016/j.sxmr.2019.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 12/28/2018] [Accepted: 01/14/2019] [Indexed: 12/18/2022]
|
|
3
|
Braillon A. Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma: Crying Wolf or Promoting Healthy Living? Clin Gastroenterol Hepatol 2019; 17:2383. [PMID: 31004760 DOI: 10.1016/j.cgh.2019.04.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 03/23/2019] [Accepted: 04/10/2019] [Indexed: 02/07/2023]
Affiliation(s)
- Alain Braillon
- Department of Medicine, University Hospital, Amiens, France
| |
Collapse
|
|
4
|
Minicozzi MR, von Hippel FA, Furin CG, Buck CL. Sodium perchlorate induces non-alcoholic fatty liver disease in developing stickleback. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2019; 251:390-399. [PMID: 31100570 PMCID: PMC6768070 DOI: 10.1016/j.envpol.2019.05.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 04/30/2019] [Accepted: 05/01/2019] [Indexed: 05/28/2023]
Abstract
Perchlorate is a pervasive, water-soluble contaminant that competitively inhibits the sodium/iodide symporter, reducing the available iodide for thyroid hormone synthesis. Insufficient iodide uptake can lead to hypothyroidism and metabolic syndromes. Because metabolism, obesity and non-alcoholic fatty liver disease (NAFLD) are tightly linked, we hypothesized that perchlorate would act as an obesogen and cause NAFLD via accumulation of lipids in liver of developing threespine stickleback (Gasterosteus aculeatus). We performed an upshift/downshift exposure regime (clean water to perchlorate treated water or perchlorate treated water to clean water) on stickleback embryos at two concentrations (30 mg/L and 100 mg/L) plus the control (0 mg/L) over the course of 305 days. Adult stickleback were euthanized, H&E stained and analyzed for liver morphology. Specifically, we counted the number of lipid droplets, and measured the area of each droplet and the total lipid area of a representative section of liver. We found that perchlorate treated fish had more and larger lipid droplets, and a larger percentage of lipid in their liver than control fish. These data indicate that perchlorate causes NAFLD and hepatic steatosis in stickleback at concentrations commonly found at contaminated sites. These data also indicate the potential of perchlorate to act as an obesogen. Future studies should investigate the obesogenic capacity of perchlorate by examining organ specific lipid accumulation and whether perchlorate induces these effects at concentrations commonly found in drinking water. Work is also needed to determine the mechanisms by which perchlorate induces lipid accumulation.
Collapse
Affiliation(s)
- Michael R Minicozzi
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA.
| | - Frank A von Hippel
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA
| | - Christoff G Furin
- Alaska Department of Environmental Conservation, Anchorage, AK, 99508, USA
| | - C Loren Buck
- Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, 86011, USA
| |
Collapse
|
|
5
|
|
|
6
|
Melatonin prevents chronic intermittent hypoxia-induced injury by inducing sirtuin 1-mediated autophagy in steatotic liver of mice. Sleep Breath 2018; 23:825-836. [PMID: 30411173 PMCID: PMC6700047 DOI: 10.1007/s11325-018-1741-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 09/27/2018] [Accepted: 10/08/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Hepatic steatosis that occasionally results in nonalcoholic steatohepatitis (NASH) is related to obstructive sleep apnea (OSA). Many studies have shown that autophagy exerts protective effects on liver damage caused by various diseases and melatonin exhibits hepatoprotective properties. However, the mechanisms of liver injury induced by chronic intermittent hypoxia (CIH) and the effect of melatonin on the regulation of liver injury remain unclear. PURPOSE This study was aimed to evaluate the role of CIH in steatohepatitis progression and the regulatory function of melatonin on fatty liver sensitivity to CIH injury, mainly focusing on autophagy signaling. METHODS A high-fat diet (FD)-induced obesity mouse model was subjected to intermittent hypoxia/normoxia events for approximately 8 h per day using an autophagy agonist, rapamycin, or an inhibitor, 3-methyladenine (3-MA), and SRT1720, a sirtuin 1 (SIRT1) activator, or sirtinol, a SIRT1 inhibitor, with or without melatonin for a total of six successive weeks, followed by assessment of expression of autophagy-related genes and activity of serum aminotransferase as well as histological evaluation of tissue morphology. RESULTS Neither FD nor CIH alone causes significant liver injury; however, the combination yielded higher serum aminotransferase activities and more severe histological changes, accompanied by a decrease in autophagy activity. Melatonin markedly inhibited FD/CIH-stimulated liver injury by enhancing autophagy. In contrast, SIRT1 inhibition resulted in a decrease in the expression of melatonin-induced autophagy-related genes as well as diminished its protective effects on FD/CIH-induced liver injury. CONCLUSION These results suggest that melatonin could ameliorate FD/CIH-induced hepatocellular damage by activating SIRT1-mediated autophagy signaling.
Collapse
|
|
7
|
Régnier M, Polizzi A, Guillou H, Loiseau N. Sphingolipid metabolism in non-alcoholic fatty liver diseases. Biochimie 2018; 159:9-22. [PMID: 30071259 DOI: 10.1016/j.biochi.2018.07.021] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 07/26/2018] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) involves a panel of pathologies starting with hepatic steatosis and continuing to irreversible and serious conditions like steatohepatitis (NASH) and hepatocarcinoma. NAFLD is multifactorial in origin and corresponds to abnormal fat deposition in liver. Even if triglycerides are mostly associated with these pathologies, other lipid moieties seem to be involved in the development and severity of NAFLD. That is the case with sphingolipids and more particularly ceramides. In this review, we explore the relationship between NAFLD and sphingolipid metabolism. After providing an analysis of complex sphingolipid metabolism, we focus on the potential involvement of sphingolipids in the different pathologies associated with NAFLD. An unbalanced ratio between ceramides and terminal metabolic products in the liver and plasma promotes weight gain, inflammation, and insulin resistance. In the etiology of NAFLD, some sphingolipid species such as ceramides may be potential biomarkers for NAFLD. We review the clinical relevance of sphingolipids in liver diseases.
Collapse
Affiliation(s)
- Marion Régnier
- INRA UMR1331, ToxAlim, Chemin de Tournefeuille, 31027 Toulouse, France
| | - Arnaud Polizzi
- INRA UMR1331, ToxAlim, Chemin de Tournefeuille, 31027 Toulouse, France
| | - Hervé Guillou
- INRA UMR1331, ToxAlim, Chemin de Tournefeuille, 31027 Toulouse, France
| | - Nicolas Loiseau
- INRA UMR1331, ToxAlim, Chemin de Tournefeuille, 31027 Toulouse, France.
| |
Collapse
|
|
8
|
|
|
9
|
Uetake Y, Ikeda H, Irie R, Tejima K, Matsui H, Ogura S, Wang H, Mu S, Hirohama D, Ando K, Sawamura T, Yatomi Y, Fujita T, Shimosawa T. High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice. Lipids Health Dis 2015; 14:6. [PMID: 25888871 PMCID: PMC4337194 DOI: 10.1186/s12944-015-0002-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 01/21/2015] [Indexed: 12/22/2022] Open
Abstract
Background It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome. Methods We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice. Results High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice. Conclusions We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH. Electronic supplementary material The online version of this article (doi:10.1186/s12944-015-0002-9) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Yuzaburo Uetake
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. .,Office for Research Ethics Support, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Hitoshi Ikeda
- Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. .,Department of Gastroenterology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Rie Irie
- Department of Pathology, Kawasaki Municipal Hospital, Kawasaki, Japan.
| | - Kazuaki Tejima
- Department of Gastroenterology, Toshiba General Hospital, Tokyo, Japan.
| | - Hiromitsu Matsui
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Sayoko Ogura
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. .,Division of Laboratory Medicine, Department of Pathology and Microbiology, Faculty of Medicine, Nihon University School of Medicine, Tokyo, Japan.
| | - Hong Wang
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - ShengYu Mu
- Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
| | - Daigoro Hirohama
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Katsuyuki Ando
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Tatsuya Sawamura
- Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. .,Department of Physiology, Shinshu University School of Medicine, Nagano, Japan.
| | - Yutaka Yatomi
- Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
| | - Toshiro Fujita
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. .,Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
| | - Tatsuo Shimosawa
- Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. .,Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
| |
Collapse
|
|
10
|
Braillon A. Hepatocellular carcinoma and the Newcastle-upon-Tyne area. J Hepatol 2014; 60:1329. [PMID: 24593924 DOI: 10.1016/j.jhep.2014.01.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Accepted: 01/19/2014] [Indexed: 12/04/2022]
Affiliation(s)
- Alain Braillon
- Alcohol Unit Treatment, University Hospital, 80000 Amiens, France.
| |
Collapse
|
|
11
|
Volumetric Gain of the Liver after Major Hepatectomy in Obese Patients. Ann Surg 2013; 258:696-702; discussion 702-4. [DOI: 10.1097/sla.0b013e3182a61a22] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
12
|
Castrillejo VM, Romero MM, Esteve M, Ardévol A, Blay M, Bladé C, Arola L, Salvadó MJ. Antioxidant effects of a grapeseed procyanidin extract and oleoyl-estrone in obese Zucker rats. Nutrition 2011; 27:1172-6. [DOI: 10.1016/j.nut.2010.12.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2009] [Revised: 11/30/2010] [Accepted: 12/10/2010] [Indexed: 10/18/2022]
|
|
13
|
Mirza MS. Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease. ISRN GASTROENTEROLOGY 2011; 2011:592404. [PMID: 21991518 PMCID: PMC3168494 DOI: 10.5402/2011/592404] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Accepted: 05/01/2011] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopathologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis and hepatocellular carcinoma. There is mounting evidence that NAFLD not only complicates obesity, but also perpetuates its metabolic consequences. Critical event that leads to progressive liver injury in NAFLD is unknown. Obesity reflects a generalized proinflammatory state with its increased inflammatory markers like C reactive protein, IL-6, IL-8, IL-10, PAI-1, TNF-α, and hepatocyte growth factor. The elevated production of these adipokines is increasingly considered to be important in the development of diseases linked to obesity and the metabolic syndrome. Disordered cytokine production is likely to play a role in the pathogenesis of NAFLD. There is no effective treatment for NAFLD, though weight loss may halt disease progression and revert histological changes, the underlying mechanism remaining elusive. All stages of the disease pathway from prevention, early identification/diagnosis, and treatment require an understanding of the pathogenesis of liver injury in NAFLD.
Collapse
Affiliation(s)
- M. S. Mirza
- SpR Surgery, Ninewells Hospital, 65 Lister Court, Dundee DD2 1UY, UK
| |
Collapse
|
|
14
|
Bekesi G, Tulassay Z, Lengyel G, Schaff Z, Szombath D, Stark J, Marczell I, Nagy-Repas P, Adler I, Dinya E, Racz K, Magyar K. The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model. J Neural Transm (Vienna) 2011; 119:25-30. [PMID: 21643961 DOI: 10.1007/s00702-011-0666-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Accepted: 05/22/2011] [Indexed: 01/21/2023]
Abstract
Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague-Dawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet + selegiline and (4) normal rat food + selegiline. Selegiline solution (2.5 µg/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20-30 ml/day), the daily dose was roughly equal with that used in the human therapy (5-10 mg/day). TSC was determined both at the beginning (0 day) and at the end of the study (28 days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers.
Collapse
Affiliation(s)
- Gabor Bekesi
- Second Department of Medicine, Faculty of Medicine, Semmelweis University, 46 Szentkiralyi utca, Budapest 1088, Hungary.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Sánchez-Garrido MA, Chico Y, González R, Ranchal I, González-Rubio S, Hidalgo AB, Díaz-López C, Costán G, Padillo FJ, De la Mata M, Ochoa B, Muntané J. Interleukin-6 is associated with liver lipid homeostasis but not with cell death in experimental hepatic steatosis. Innate Immun 2010; 15:337-49. [PMID: 19710104 DOI: 10.1177/1753425909104900] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Hepatic steatosis is a risk factor for the progression of non-alcoholic fatty liver disease. The role of pro-inflammatory interleukin (IL)-6 in hepatic steatosis etiology is controversial. We investigated in vivo and in primary hepatocyte cultures whether IL-6 has a modulator role in liver and mitochondria lipid composition and cell death in a choline-deficient (CD) diet rat model of hepatic steatosis. Dietary choline deficiency increased triglycerides and cholesterol, and reduced phosphatidylcholine (PC), phosphatidylethanolamine (PE) and the membrane integrity marker PC:PE ratio in liver. Choline-deficient diet enhanced systemic IL-6, and IL-6 receptor expression and cell death vulnerability in hepatocytes. Derangement of the mitochondrial electron transport chain and of its phospholipid environment was found in CD rat liver mitochondria, which exhibited elevated concentrations of triglycerides, cardiolipin and PC and elevated PC:PE ratio. The cell treatment with IL-6, but not PC, eliminated much of the CD-promoted lipid imbalance in mitochondria but not tumor-necrosis factor (TNF)-alpha-induced cell death. However, PC supplementation prevented the TNF-alpha-induced DNA fragmentation, cytochrome-c release and caspase-3 activity in control and CD hepatocytes. In conclusion, IL-6 ameliorated the mitochondria lipid disturbance in hepatocytes isolated from steatotic animals. Furthermore, PC is identified as a new survival agent that reverses several TNFalpha-inducible responses that are likely to promote steatosis and necrosis.
Collapse
|
|
16
|
Nonalcoholic fatty liver disease during valproate therapy. Eur J Pediatr 2009; 168:1391-4. [PMID: 19184102 DOI: 10.1007/s00431-009-0927-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2008] [Accepted: 01/13/2009] [Indexed: 12/31/2022]
Abstract
Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but its use can be associated with an increase in body weight. We report a case of nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin resistance. After the withdrawal of VPA therapy, our patient showed a significant weight loss, a decrease of body mass index, and normalization of metabolic and endocrine parameters; moreover, ultrasound measurements showed a complete normalization. The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal.
Collapse
|
|
17
|
|
|
18
|
Eriksson S, Eriksson KF, Bondesson L. Nonalcoholic steatohepatitis in obesity: a reversible condition. ACTA MEDICA SCANDINAVICA 2009; 220:83-8. [PMID: 3766211 DOI: 10.1111/j.0954-6820.1986.tb02733.x] [Citation(s) in RCA: 129] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Nonalcoholic steatohepatitis is a rare complication of obesity with laboratory and histological features indistinguishable from alcoholic hepatitis. Three patients with 50-60% overweight and steatohepatitis are reported. All responded with normalization of the biochemical and/or histological changes after modest weight reduction.
Collapse
|
|
19
|
Serfaty L, Lemoine M. Definition and natural history of metabolic steatosis: clinical aspects of NAFLD, NASH and cirrhosis. DIABETES & METABOLISM 2009; 34:634-7. [PMID: 19195623 DOI: 10.1016/s1262-3636(08)74597-x] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Metabolic steatosis or non-alcoholic fatty liver (NAFLD) is the most common cause of chronic liver injury in Western countries. Histological signs of necroinflammation, indicating the presence of non-alcoholic steatohepatitis (NASH), are present in 20-30% of cases. While steatosis on its own has a benign course, NASH may be associated with fibrosis and may progress to cirrhosis, terminal liver failure and hepatocellular carcinoma. NAFLD is closely associated with the metabolic syndrome, its prevalence reaching 50-90% in obese patients. The clinical impact of NAFLD has been demonstrated in large cohort studies by the overprevalence of cirrhosis and hepatocellular carcinoma in obese and diabetic patients. In terms of survival, liver disease is the third most common cause of mortality in patients with NAFLD. When associated with other causes of liver disease such as alcohol consumption or hepatitis C infection, metabolic steatosis may be a major risk factor for disease progression.
Collapse
Affiliation(s)
- L Serfaty
- Service d'Hépatologie, Hôpital Saint-Antoine, 75571 Paris cedex 12, France.
| | | |
Collapse
|
|
20
|
Predictors of nonalcoholic steatohepatitis in patients undergoing bariatric surgery: when is liver biopsy indicated? Surg Obes Relat Dis 2008; 4:612-7. [PMID: 18226970 DOI: 10.1016/j.soard.2007.11.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2007] [Revised: 11/06/2007] [Accepted: 11/14/2007] [Indexed: 12/26/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease is a frequent accompaniment of morbid obesity. A component of nonalcoholic fatty liver disease, steatosis, can, on occasion, lead to nonalcoholic steatohepatitis (NASH). Bariatric surgery has been shown to alter the course of this disease. Intraoperative liver biopsies might identify patients with NASH for more careful follow-up. We sought to determine noninvasive preoperative indicators of NASH. METHODS The patients scheduled for bariatric surgery underwent a preoperative assessment. The study variables included age, gender, race, body mass index, diabetes mellitus, hypertension, and the results of serum liver function tests and triglyceride, cholesterol, iron, and prealbumin measurements. Univariate and multivariate analyses were performed to identify significant variables associated with NASH as determined by subsequent core liver biopsies taken during open Roux-en-Y gastric bypass. RESULTS A total of 139 patients were entered into the study. NASH or NASH-associated fibrosis was found in 57 patients (41%). On univariate analyses, male gender (odds ratio [OR] 2.46, P = .06), diabetes mellitus (OR 2.60, P = .009), elevated serum triglyceride levels (OR 1.003, P = .02), elevated gamma glutamyl transferase (OR 1.015, P = .01), and decreased prealbumin (OR 0.94, P = .04) correlated with the presence of NASH. On multivariate analysis, only increased triglycerides (OR 1.004, P = .04) and decreased prealbumin (OR 0.88, P = .005) correlated with the presence of NASH. CONCLUSION NASH is a frequent accompaniment of morbid obesity in patients undergoing bariatric surgery. Univariate and multivariate analyses of the clinical parameters studied could not identify strong predictors of biopsy-verified NASH. Therefore, intraoperative biopsy remains instrumental in diagnosing NASH and providing information for additional follow-up.
Collapse
|
|
21
|
Abstract
Primary metabolic disorders and storage diseases are caused by endogenous factors, usually a gene mutation. Since the congenital defect is predominantly or exclusively located in the liver, the resulting diseases also become manifest in this organ.
Collapse
|
|
22
|
Qureshi K, Abrams GA. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2007; 13:3540-53. [PMID: 17659704 PMCID: PMC4146793 DOI: 10.3748/wjg.v13.i26.3540] [Citation(s) in RCA: 191] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.
Collapse
Affiliation(s)
- Kamran Qureshi
- Department of Medicine, University of Alabama at Birmingham, 1918 University Blvd 286 MCLM Birmingham, AL 35294, USA
| | | |
Collapse
|
|
23
|
García-Galiano D, Sánchez-Garrido MA, Espejo I, Montero JL, Costán G, Marchal T, Membrives A, Gallardo-Valverde JM, Muñoz-Castañeda JR, Arévalo E, De la Mata M, Muntané J. IL-6 and IGF-1 are Independent Prognostic Factors of Liver Steatosis and Non-Alcoholic Steatohepatitis in Morbidly Obese Patients. Obes Surg 2007; 17:493-503. [PMID: 17608262 DOI: 10.1007/s11695-007-9087-1] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Lipid accumulation and other histological liver markers characterize patients with non-alcoholic steatohepatitis (NASH). The identification of non-invasive prognostic factors of liver steatosis and NASH are relevant for the unravelling of the mechanisms of this disease, as well as for the clinical diagnoses of these patients. METHODS 36 patients with morbid obesity and 12 healthy subjects were consecutively enrolled in this cross-sectional study to determine the serological parameters associated with the degree of hepatic steatosis and NASH. Clinical, biochemical and histologic variables were examined in blood and liver biopsies by descriptive, univariate and multivariate regression analysis. RESULTS The patients were distributed as non-NASH (14), probably-NASH (13) and NASH (9), according to the Non-alcoholic fatty liver disease Activity Score (NAS). The study identified remarkable differences in liver steatosis, and glucose, insulin, IL-6 and IGF-1 concentrations in blood among patients with morbid obesity. IL-6 was correlated with the degree of liver steatosis until the morbidly obese patients fulfil the criteria of NASH. The patients with NASH reduced IL-6 concentration in blood. IGF-1 decreased throughout the progression of NASH. TNF-alpha concentration was not related to liver steatosis or NASH in morbidly obese patients. The multivariate regression analysis identified glucose >110 mg/dL, IL-6 >4.81 pg/mL and IGF-1 <130 ng/mL, and homeostasis model assessment (HOMA) >4.5 and IGF-1 <110 ng/mL as independent predictors of hepatic steatosis and NASH, respectively. CONCLUSIONS The concentration of glucose, insulin, IL-6 and IGF-1 in blood are useful markers for the selection of patients with liver steatosis or NASH.
Collapse
Affiliation(s)
- David García-Galiano
- Liver Research Unit, Reina Sofia University Hospital, CIBER HEPAD, Cordoba, Spain
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006; 45:600-6. [PMID: 16899321 DOI: 10.1016/j.jhep.2006.06.013] [Citation(s) in RCA: 376] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2006] [Revised: 06/05/2006] [Accepted: 06/07/2006] [Indexed: 12/21/2022]
Abstract
BACKGROUND/AIMS Obesity is one of the most important clinical associations with non-alcoholic steatohepatitis (NASH). Our aim was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD)/NASH in morbidly obese patients and the risk factors to more aggressive liver disease in this population. METHODS Review of available studies on prevalence of NAFLD/NASH in severely obese patients submitted to bariatric surgery. RESULTS Twelve observational and transversal studies were included, with consecutive recruitment, and prospective evaluation of data, summing 1620 patients with severe obesity. Prevalence of steatosis and NASH was 91% (range: 85-98%) and 37% (24-98%), respectively, with unexpected cirrhosis in 1.7% (1-7%). NASH was not related with age or body mass index, but there was an association between male sex and NASH/hepatic fibrosis. Diabetes mellitus and insulin resistance were the conditions most frequently associated with NASH, and hypertension with advanced hepatic fibrosis. CONCLUSIONS There is a very high prevalence of NAFLD in asymptomatic morbidly obese patients, more than one-third presenting histological criteria for NASH. This review underscores the large variations in prevalence of NASH between studies, calling for the need for a better agreement in the use of the histological criteria.
Collapse
Affiliation(s)
- Mariana Machado
- Departamento de Gastrenterologia, Instituto de Medicina Molecular (IMM), Faculdade de Medicina da Universidade de Lisboa, Portugal
| | | | | |
Collapse
|
|
25
|
Gill HK, Wu GY. Non-alcoholic fatty liver disease and the metabolic syndrome: Effects of weight loss and a review of popular diets. Are low carbohydrate diets the answer? World J Gastroenterol 2006; 12:345-53. [PMID: 16489632 PMCID: PMC4066051 DOI: 10.3748/wjg.v12.i3.345] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of fat-induced liver injury, ranging from relatively benign steatosis to cirrhosis and liver failure. The presence of obesity and insulin resistance is strongly associated with non-alcoholic fatty liver and confers on it a greater risk of histologically advanced disease. There is a growing concern in the medical profession as the prevalence of this disease continues to rise in parallel with the rise in obesity and the metabolic syndrome. Treatment options are limited and dietary weight loss is often advised. Low fat diets are difficult to adhere to and recent studies have shown the potential of low carbohydrate diets for weight loss and improving insulin resistance. Thus far, no study has evaluated the effect of low carbohydrate diets on NAFLD. Future studies will be required to address this question and others with regards to the nutritional adequacy and long-term side effects of these diets.
Collapse
|
|
26
|
Jaskiewicz K, Raczynska S, Rzepko R, Sledziński Z. Nonalcoholic fatty liver disease treated by gastroplasty. Dig Dis Sci 2006; 51:21-6. [PMID: 16416204 DOI: 10.1007/s10620-006-3077-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2005] [Accepted: 03/09/2005] [Indexed: 02/07/2023]
Abstract
Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in obese patients. The prevalence of NASH may increase with the rise in the rate of obesity and metabolic syndrome in affluent communities. The aim of this work is to describe clinical and histopathologic findings and correlate liver tissue damage to the length of duration of the obesity in the group of patients who underwent surgery as obesity treatment. Eighty-seven severely or morbidly obese patients underwent gastroplasty. Each patient was evaluated with complete clinical and laboratory medical assessment together with wedge liver biopsy taken from 59 unselected patients during the surgery. Patients were followed up for 41 months. Repeat liver biopsy was taken from 10 patients. Pathologic analysis recorded the presence and degree of steatosis, portal and lobular inflammation and fibrosis. Age, body mass index (BMI), and laboratory assessment correlated with pathologic data. Male patients showed more pronounced metabolic syndrome and fatty liver damage. Patients who become obese in childhood or as teenagers showed no differences in metabolic syndrome and NAFLD in mature age. There was statistically significant association between BMA, elevated transaminases, NAFLD, and fibrosis. Significant weight reduction was observed within first year after surgery, was slower in the second year, and stabilized within third year. Remarkable improvement followed in biological markers of metabolic syndrome. Ninety-six percent of initial liver biopsies had steatosis; 16% developed steatohepatitis and mild perivenular fibrosis. Significant improvement of the degenerative and inflammatory hepatic lesions in repeated biopsies and liver function readings was noted within 8 months after surgery. Obesity is a major and independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis. Surgical treatment improves metabolic abnormalities and hepatic lesions in long-term observations.
Collapse
Affiliation(s)
- K Jaskiewicz
- Departments of Pathology and General Surgery, University Medical School of Gdansk, Gdansk, Poland.
| | | | | | | |
Collapse
|
|
27
|
Ruhl CE, Everhart JE. Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin Gastroenterol Hepatol 2005; 3:1260-8. [PMID: 16361053 DOI: 10.1016/s1542-3565(05)00743-3] [Citation(s) in RCA: 178] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Both alcohol and obesity are associated with hepatic steatosis. However, little is known about whether the toxicity of alcohol to the liver is influenced by adiposity. We examined the relationship of alcohol drinking and binge drinking with abnormal serum aminotransferase activity in normal weight, overweight, and obese persons in a national, population-based study. METHODS Data were analyzed from 13,580 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, after excluding participants with hepatitis B or C or iron overload. Abnormal aminotransferase levels were defined by using sex-specific cutoffs for ALT and AST. Analyses were adjusted for other liver injury risk factors. RESULTS The prevalence of abnormal aminotransferase activity was elevated with consumption of >2 drinks per day or with overweight and obesity. In multivariate analysis, there was no association of alcohol intake with a higher prevalence of elevated aminotransferase levels among normal weight persons. In contrast, among overweight persons, consumption of >2 drinks per day increased the risk of elevated aminotransferase levels, and among the obese, > or = 1 drink per day was associated with a higher risk. Results were similar with elevated ALT alone as the outcome. With elevated AST alone as the outcome, intake of >2 drinks per day increased the risk, even among normal weight persons. Binge drinking was associated with aminotransferase elevation among obese consumers of 1-2 drinks per day. CONCLUSIONS In this large, national, population-based study, overweight and obesity increased the risk of alcohol-related abnormal aminotransferase activity.
Collapse
Affiliation(s)
- Constance E Ruhl
- Social and Scientific Systems, Inc, Silver Spring, Maryland 20910, USA.
| | | |
Collapse
|
|
28
|
Altunkaynak Z. EFFECTS OF HIGH FAT DIET INDUCED OBESITY ON FEMALE RAT LIVERS (A HISTOCHEMICAL STUDY). ELECTRONIC JOURNAL OF GENERAL MEDICINE 2005. [DOI: 10.29333/ejgm/82319] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
29
|
Liu CM, Tung TH, Liu JH, Chen VTK, Lin CH, Hsu CT, Chou P. A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan. World J Gastroenterol 2005; 11:1616-22. [PMID: 15786537 PMCID: PMC4305941 DOI: 10.3748/wjg.v11.i11.1616] [Citation(s) in RCA: 20] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan.
METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females).
RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females.
CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study.
Collapse
Affiliation(s)
- Chi-Ming Liu
- Community Medicine Research Center, National Yang-Ming University, Shih-Pai, 112, Taipei, Taiwan, China.
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40:1387-95. [PMID: 15565570 DOI: 10.1002/hep.20466] [Citation(s) in RCA: 2669] [Impact Index Per Article: 127.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined. In this study, we examined and compared the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects from a multiethnic, population-based sample (32.1% white, 48.3% black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy. HTGC varied over a wide range (0.0%-41.7%; median, 3.6%) in the population. Almost one third of the population had hepatic steatosis, and most subjects with hepatic steatosis had normal levels of serum alanine aminotransferase (79%). The frequency of hepatic steatosis varied significantly with ethnicity (45% in Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white women). The higher prevalence of hepatic steatosis in Hispanics was due to the higher prevalence of obesity and insulin resistance in this ethnic group. However, the lower frequency of hepatic steatosis in blacks was not explained by ethnic differences in body mass index, insulin resistance, ethanol ingestion, or medication use. The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics. The ethnic differences in the frequency of hepatic steatosis in this study mirror those observed previously for NAFLD-related cirrhosis (Hispanics > whites > blacks). In conclusion, the significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis-related liver disease.
Collapse
Affiliation(s)
- Jeffrey D Browning
- Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9046, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Abstract
Nonalcoholic fatty liver (NAFL) is increasingly recognized as an important and common public health problem that can lead to cirrhosis and hepatic failure. Because it is often asymptomatic,many people may not know that they have it. NAFL is closely linked to obesity, which in the United States and other developed countries is becoming more common. Consequently, the proportion of the population affected by NAFL will likely increase. Despite the growing importance of this condition, knowledge of the epidemiology of NAFL is limited by the lack of an accurate,noninvasive measure for use in screening of the general population. This article reviews information available from studies with relatively unselected samples with regard to prevalence, demographics,and risk factors for NAFL.
Collapse
Affiliation(s)
- Constance E Ruhl
- Social and Scientific Systems, Inc., 8757 Georgia Avenue, 12(th) floor, Silver Spring, MD 20910, USA.
| | | |
Collapse
|
|
32
|
Donati G, Stagni B, Piscaglia F, Venturoli N, Morselli-Labate AM, Rasciti L, Bolondi L. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut 2004; 53:1020-3. [PMID: 15194655 PMCID: PMC1774102 DOI: 10.1136/gut.2003.027086] [Citation(s) in RCA: 170] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The conditions associated with fatty liver disease presenting with normal liver enzymes and the mechanism involved in its development remain to be fully elucidated. AIMS The aim of the present study was to test the hypothesis that fatty liver with normal liver enzymes occurs more frequently in arterial hypertensive patients and to establish whether this condition is associated with insulin resistance. PATIENTS A total of 55 non-obese, non-diabetic, non-heavy alcohol drinking patients with arterial hypertensive and normal liver enzymes and 55 sex and age matched healthy subjects were enrolled into the study. METHODS Plasma metabolic parameters, body mass index, and the presence of fatty liver were investigated. Insulin resistance was estimated from plasma insulin and glucose as the homeostasis model assessment index. Stepwise logistic regression and multivariate regression analysis were used on the combined sample to identify variables independently associated with fatty liver and insulin resistance. RESULTS Hypertensive patients had a significantly higher prevalence of fatty liver (30.9% v 12.7%; p<0.041), higher insulin resistance (mean 2.27 (SD 1.81) v 1.56 (0.70); p = 0.022), and slightly higher body mass index (24.9 (3.0) v 24.0 (2.2); p = 0.043) than controls. Multivariate logistic regression identified insulin resistance (odds ratio 1.66 (95% confidence interval (CI) 1.03-2.52)) and body mass index (OR 1.22 (95% CI 1.00-1.49)) as factors independently associated with fatty liver. Multivariate regression analysis showed insulin resistance to be predicted by alanine transaminase (p = 0.002), presence of arterial hypertension (p = 0.029), and body mass index (p = 0.048). CONCLUSION The higher prevalence of non-alcoholic fatty liver in non-obese hypertensive patients with normal liver enzymes appears to be related to increases in insulin resistance and body weight.
Collapse
Affiliation(s)
- G Donati
- Division of Internal Medicine, Department of Internal Medicine and Gastroenterology, University of Bologna, Azienda S Orsola-Malpighi, Bologna, Italy
| | | | | | | | | | | | | |
Collapse
|
|
33
|
Wong VWS, Chan HLY, Hui AY, Chan KF, Liew CT, Chan FKL, Sung JJY. Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese. Aliment Pharmacol Ther 2004; 20:45-9. [PMID: 15225170 DOI: 10.1111/j.1365-2036.2004.02012.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease is prevalent in affluent countries and is a cause of cirrhosis and possibly hepatocellular carcinoma. AIM To examine the clinical and histological features of biopsy-proven non-alcoholic fatty liver disease and investigate the predictors of severe histological disease in Chinese patients. METHODS Electronic records of all patients (n = 247) who underwent liver biopsy between 1996 and 2003 in our hospital were retrieved. Patients who had histological features of non-alcoholic fatty liver disease were identified. The demographic, clinical, laboratory and histological (Brunt's criteria) parameters of these patients were analysed. RESULTS Forty-two patients had histology-proven non-alcoholic fatty liver disease. The median age was 47 years (range 23-69). All except one patient had features of metabolic syndrome. The median alanine aminotransferase was 93 (range 24-270) IU/L. Thirty-six (85.7%) patients had steatohepatitis and 11 (26.1%) also had fibrosis. Only one patient had stage 3 fibrosis. The presence of diabetes mellitus predicted higher grade steatohepatitis and fibrosis (P = 0.019) whereas alanine aminotransferase level had no correlation with histological severity of steatohepatitis. After a median follow-up of 42 months, no patient developed hepatic decompensation. CONCLUSIONS Most Chinese patients with non-alcoholic fatty liver disease had features of the metabolic syndrome. Histological activity was generally mild. Diabetes mellitus was the most important predictor of severe histological disease.
Collapse
Affiliation(s)
- V W-S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 2004; 126:586-97. [PMID: 14762795 DOI: 10.1053/j.gastro.2003.11.020] [Citation(s) in RCA: 334] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV)-related liver disease are common in the general population, but their concurrence is 2- to 3-fold higher than would be expected by chance alone. In patients with chronic HCV infection, steatosis is attributable to a variable combination of the mechanisms considered to play a role in the pathogenesis of NAFLD--insulin resistance in the obese and in the lean subject--along with a direct effect of HCV on hepatic lipid metabolism that leads to triglyceride accumulation through inhibition of export proteins that are required for very low density lipoprotein (VLDL) assembly and secretion. Accumulating evidence suggests that steatosis contributes to the progression of fibrosis in HCV-related disease in a pattern similar to that observed in NAFLD. Potential mechanisms of this effect include the increased sensitivity of steatotic livers to oxidative stress and cytokine-mediated injury. Steatosis-related hepatic insulin resistance may also play a role through the profibrogenic effects of the compensatory hyperinsulinemia and provides a potential explanation for the association between HCV and type 2 diabetes mellitus. Indeed, an appreciation of the importance of fat in HCV has recently led to trials of adjuvant therapy for HCV directed at steatosis-associated disease mechanisms, with encouraging results reported for various modalities, including weight loss and antioxidants. Future therapy should be aimed at exploiting the interactions of HCV with host insulin and lipid metabolism, particularly in nonresponders to standard antiviral schedules.
Collapse
Affiliation(s)
- Amedeo Lonardo
- Division of Internal Medicine and Gastroenterology, Modena City Hospital, Italy.
| | | | | | | | | | | |
Collapse
|
|
35
|
Abstract
BACKGROUND & AIMS The objective of this study was to address the hepatic effects of acute alcohol consumption in obesity by simulating an alcohol binge in genetically obese fa/fa rats compared with lean Fa/? rats. METHODS Ethanol 4 g/kg or saline was administered by gavage every 12 hours for 3 days. RESULTS Plasma alcohol levels were similar in both groups. Binge ethanol exposure caused liver injury in obese fa/fa but not in lean Fa/? rats, as assessed by alanine aminotransferase and H&E staining. Obesity impaired the antioxidant defense because basal levels of glutathione, glutamate cysteine ligase modulatory subunit, catalase, glutathione reductase, and superoxide dismutase were lower in fa/fa compared with Fa/? rats; the ethanol binge further decreased these antioxidants in fa/fa rats and also decreased glutathione peroxidase activity. Nonesterified fatty acids and lipid peroxidation were increased after ethanol treatment in fa/fa rats. Cytochrome P450 2E1 was down-regulated in fa/fa compared with Fa/? rats; however, the ethanol binge increased cytochrome P450 2E1 in both genotypes. Adenosine triphosphate decreased and uncoupling protein 2 increased in fa/fa rats treated with ethanol. 3-Nitrotyrosine protein adducts were detected only in fa/fa rats treated with ethanol, and this was accompanied by an induction of inducible nitric oxide synthase. Ethanol binge increased caspase-3 and caspase-8 activity, the expression of Fas ligand, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling in fa/fa rats. CONCLUSIONS These data indicate that binge drinking increases apoptosis and liver injury in obese rats more than in lean controls and suggest that the injury may involve oxidative and nitrosative damage.
Collapse
Affiliation(s)
- Michal Carmiel-Haggai
- Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, and Division of Livers Diseases, Mount Sinai Medical Center, New York, New York 10029, USA
| | | | | |
Collapse
|
|
36
|
Wójcicki J, Jaroszynska M, Droździk M, Pawlik A, Gawrońska-Szklarz B, Sterna R. Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects. Biopharm Drug Dispos 2003; 24:211-8. [PMID: 12784321 DOI: 10.1002/bdd.357] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The lipophilic beta-adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time-point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one-compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water-soluble atenolol, the AUC, C(max), Cl/(F x BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non-obese persons were clinically not relevant.
Collapse
Affiliation(s)
- Jerzy Wójcicki
- Department of Experimental and Clinical Pharmacology, Pomeranian Academy of Medicine, Szczecin, Poland
| | | | | | | | | | | |
Collapse
|
|
37
|
Affiliation(s)
- Juan Caballería
- Unidad de Hepatología. Institut Clínic de Malalties Digestives. Hospital Clínic. IDIBAPS. Universidad de Barcelona. Barcelona. España
| | | |
Collapse
|
|
38
|
Abstract
Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20-22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.
Collapse
|
|
39
|
Sørensen HT, Mellemkjaer L, Jepsen P, Thulstrup AM, Baron J, Olsen JH, Vilstrup H. Risk of cancer in patients hospitalized with fatty liver: a Danish cohort study. J Clin Gastroenterol 2003; 36:356-9. [PMID: 12642745 DOI: 10.1097/00004836-200304000-00015] [Citation(s) in RCA: 82] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
GOALS To examine the risk of cancer in patients with fatty liver. BACKGROUND The relation between liver disease, including fatty liver, and cancer risk is poorly understood. STUDY Using the population-based National Registry of Patients, we examined the incidence of cancer in 7,326 patients discharged with a diagnosis of fatty liver from a Danish hospital during 1977-1993. Patients with a prior diagnosis of liver cirrhosis were excluded. We identified cancers through the Danish Cancer Registry. The expected number of cancers was estimated from national age-, sex-, and site-specific incidence rates. RESULTS Overall, 523 cancers were diagnosed during 47,594 person-years of follow-up, yielding a 1.7-fold increased risk (95% confidence interval, 1.6-1.9) compared with the Danish general population. The risk of primary liver cancer was markedly elevated in patients with alcoholic as well as nonalcoholic fatty liver with a standardized incidence ratio of 9.5 (95% confidence interval, 5.7-14.8) and 4.4 (95% confidence interval, 1.2-11.4), respectively. Patients with alcoholic fatty liver also had substantially increased risks of several types of cancer associated with alcohol and tobacco use (cancers of the lung, pharynx, larynx, esophagus, and stomach) and a moderately increased risk for cancers of the colon and breast. Among patients with nonalcoholic fatty liver, an increased risk of some alcohol- and tobacco-related cancers was seen, and there was also an increased risk of colon and pancreas cancer. CONCLUSIONS Patients discharged with a diagnosis of fatty liver have an increased risk of cancer, in particular liver cancer, most prominently among patients with alcoholic fatty liver.
Collapse
|
|
40
|
Abstract
Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.
Collapse
Affiliation(s)
- André J Scheen
- Division of Diabetes, Nutrition & Metabolic Disorders, Department of Medicine, CHU Sart Tilman, Liège, Belgium
| | | |
Collapse
|
|
41
|
Affiliation(s)
- Arun J Sanyal
- Department of Internal Medicine Virginia Commonwealth University Medical College of Virginia Richmond, Virginia, USA
| |
Collapse
|
|
42
|
Abstract
Obesity and type 2 diabetes are associated strongly with NAFLD. It is not clear if one of these conditions causes the others, or if all are consequences of another process. Although NAFLD is known to occur in overly lean individuals, which indicates that excessive adiposity is not required for the development of NAFLD, the severities of insulin resistance and NAFLD tend to parallel each other, and the greatest prevalence of type 2 diabetes occurs in patients with NAFLD and cirrhosis. This observation suggests that insulin resistance and NAFLD may be related pathogenically. Experiments in mice demonstrate that insulin resistance and NAFLD result from a chronic inflammatory state that is characterized by increased levels of TNF alpha. The mechanisms that drive this chronic inflammation are unknown but might involve the oxidative stress that develops during fatty acid metabolism or when products from intestinal bacteria escape into the mesenteric blood to trigger a sustained hepatic inflammatory cytokine response in genetically susceptible individuals, promoting a positive feedback loop that reinforces insulin resistance and inflammation. This hypothesis is supported by some animal and human studies; however, more research is needed to evaluate this theory. Additional studies also are required to determine the benefits of treatments that interrupt this pathogenic cascade at various points. Preliminary work in animal and human studies suggests that diverse strategies that inhibit production of TNF alpha and improve insulin resistance also ameliorate NAFLD.
Collapse
Affiliation(s)
- Zhiping Li
- Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 912 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
| | | | | |
Collapse
|
|
43
|
Abstract
Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, prevalence has been predicted to increase along with the arsent epidemic of obesity and type II diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in 25% and 10% in these patients respectively over a 10-year period. This is of particular concern given the increasing recognition of NASH in children. Treatment consists of treating obesity and its co-morbidities; diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in body weight. Bariatric surgery is indicated in selected patients.A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.
Collapse
Affiliation(s)
- Wael I Youssef
- Division of Gastroenterology, The Robert Schwartz Center for Metabolism and Nutrition at Metro-Health Medical Center, Case Western Reserve University, Cleveland, OH 44109, USA
| | | |
Collapse
|
|
44
|
Abstract
OBJECTIVE Obesity and type 2 diabetes mellitus are considered risk factors for nonalcoholic steatohepatitis (NASH) and cryptogenic cirrhosis. Because obesity and type 2 diabetes are prevalent among African American females by the 5th and 6th decades, one would expect an increased number of African Americans among patients with NASH and cryptogenic cirrhosis. METHODS We determined the percentage of patients of African American and European American descent among all of the patients in our liver disease registry and those with NASH and cryptogenic cirrhosis. We also assessed the ethnicity of patients in our registry with other common liver diseases including hepatitis C, and we determined the ethnicity of patients seen at our center with type 2 diabetes and a primary diagnosis of obesity over a 4-yr period. Using census data, we compared these results to our local and regional ethnic demographics. RESULTS Overall, 199 of 2,253 patients (9%) in the registry were of African American descent, whereas 1,906 were of European American descent (85%). This distribution is similar to the ethnic mix in central Virginia (12% African American, 86% European American) and Albemarle County (12% African American, 83% European American). The prevalence of African American patients among individuals seen at our center for either type 2 diabetes or a primary diagnosis of obesity was over two times the prevalence of African Americans in the county or regional population. In contrast, of 159 NASH patients only one (0.6%) was of African American descent and 154 (97%) were of European American descent (p < 0.001 compared to the total registry, county, or region). Among 206 cryptogenic cirrhosis patients, only two (1%) were of African American descent, whereas 195 (95%) were of European American descent (p < 0.001 compared to the total registry). With regard to other liver diseases, African American patients were slightly overrepresented among hepatitis C patients and markedly overrepresented among patients with hepatic sarcoidosis, similar to previously reported national figures. CONCLUSION Although there is overrepresentation of African Americans among patients with major risk factors for NASH, individuals of primarily African American descent are infrequently represented among our patients with NASH or cryptogenic cirrhosis. This could result from underrecognition, underreferral, or a true lower prevalence of these disorders among African Americans.
Collapse
Affiliation(s)
- Stephen H Caldwell
- Department of Internal Medicine, University of Virginia, Charlottesville 22908-0708, USA
| | | | | | | |
Collapse
|
|
45
|
Abstract
Although non-alcoholic steatohepatitis (NASH) was considered relatively uncommon prior to the middle of the last decade, over the past three years there has been an explosion of studies on various aspects of NASH with one study reporting that after hepatitis C, NASH was the most common diagnosis in patients presenting largely with persistent abnormalities of liver function tests. The field of NASH has come a long way in a relatively short space of time. This article considers advances in knowledge that have arisen as a result of these studies and highlights areas for further work.
Collapse
Affiliation(s)
- C P Day
- Centre for Liver Research, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
| |
Collapse
|
|
46
|
Affiliation(s)
- Jeanne M Clark
- Department of Medicine, The Johns Hopkins University, 720 Rutland Street, Baltimore, MD 21205, USA
| | | | | |
Collapse
|
|
47
|
|
|
48
|
Mukai M, Ozasa K, Hayashi K, Kawai K. Various S-GOT/S-GPT ratios in nonviral liver disorders and related physical conditions and life-style. Dig Dis Sci 2002; 47:549-55. [PMID: 11911340 DOI: 10.1023/a:1017959801493] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
The relationship between the GOT/GPT ratio in nonviral liver disorders and underlying physical condition and life-style were evaluated. The subjects were 12,808 male railway company workers who underwent an annual health checkup. Nonviral liver disorders were defined as elevated transaminases (GOT > 76 IU/liter or GPT > 86 IU/liter, while negative for hepatitis B and C markers (282 cases). Controls were 9,783 males with normal findings for GOT, GPT, and y-GTP. By logistic regression analysis, GOT-dominant liver disorders were significantly related to alcohol consumption, hypertriglyceridemia, and diabetes mellitus. They were still significant on multivariate analysis. GPT-dominant liver disorders were significantly related to obesity, less exercise, hypercholesterolemia, and hypertriglyceridemia. Obesity and hypercholesterolemia were significant on multivariate analysis. In conclusion, the relationship between hypertriglyceridemia or diabetes mellitus and GOT-dominant disorders, which was not explained empirically, could indicate another pathogenesis for nonviral liver disorders, such as underlying insulin resistance.
Collapse
Affiliation(s)
- Masako Mukai
- Department of Social Medicine and Cultural Sciences, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine, Japan
| | | | | | | |
Collapse
|
|
49
|
Iwamoto N, Ogawa Y, Kajihara S, Hisatomi A, Yasutake T, Yoshimura T, Mizuta T, Hara T, Ozaki I, Yamamoto K. Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver. Clin Chim Acta 2001; 314:85-91. [PMID: 11718682 DOI: 10.1016/s0009-8981(01)00633-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI</=25.0 kg/m(2), n=100). The Gly16 homozygotes had a lower high-density lipoprotein cholesterol (HDL-C) level than the Arg16 homozygotes (1.50+/-0.4 vs. 1.32+/-0.3 mmol/l, p=0.014). However, no significant association with fatty liver was observed in the Gly16 allele frequency. The Gln27Glu27 heterozygotes showed higher concentrations of serum triglycerides (TG) than the Gln27Gln27 homozygotes (1.62+/-0.93 vs. 2.21+/-1.67 mmol/l, p=0.013). This correlation was also observed in all subjects regardless of weight classification. Univariate analysis indicated that subjects with the heterozygous Gln27Glu mutant alleles had a significantly higher prevalence of fatty liver vs. those without the mutation (Glu27 allele frequency, 0.07 vs. 0.12, p=0.047; odds ratio, 1.92; 95% confidence interval, 1.01-3.68). However, multivariate logistic regression models showed the prevalence of fatty liver to be significantly related to the homeostasis model assessment (HOMA) index, BMI, triglyceride and HDL-cholesterol. CONCLUSIONS These results suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene in codon 27 were associated with hypertryglyceridemia and independent of obesity, and thereby could be involved in the molecular pathogenesis of fatty liver.
Collapse
Affiliation(s)
- N Iwamoto
- Division of Metabolism and Endocrinology, Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Garcia RF, Morales E, Garcia CE, Saksena S, Hübscher SG, Elias E. Recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation. ARQUIVOS DE GASTROENTEROLOGIA 2001; 38:247-53. [PMID: 12068535 DOI: 10.1590/s0004-28032001000400007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
BACKGROUND Non-alcoholic steatohepatitis was coined in 1980 to describe pathological and clinical features of non-alcoholic disease associated with pathological features, commonly seen in alcoholic-liver disease itself. It is now a well-recognised cause of end-stage liver disease and a rare cause of orthotopic liver transplantation. A small number of cases with recurrent non-alcoholic steatohepatitis following liver transplantation have been reported, however de novo non-alcoholic steatohepatitis in the liver allograft is not well recognised. AIMS/RESULTS We report four cases of non-alcoholic steatohepatitis following orthotopic liver transplantation describing the factors related with the pathology. The recurrence of fatty infiltration occurred within 21 months and transition from mild steatosis to non-alcoholic steatohepatitis and early fibrosis was observed within 60 months post transplant in all four patients. All four cases had association with one or multiples risk factors (obesity, type 2 diabetes and/or hyperlipidemia). CONCLUSIONS Management of this risk factors may play a therapeutic role in the prevention of recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation.
Collapse
Affiliation(s)
- R F Garcia
- Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
| | | | | | | | | | | |
Collapse
|