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Alnimer L, Arellano D, Brombosz E, Noureddin M. Metabolic issues in patients with metabolic dysfunction-associated steatohepatitis (MASH) and their impact on MASH recurrence following liver transplantation: A narrative review. Liver Transpl 2024:01445473-990000000-00524. [PMID: 39621112 DOI: 10.1097/lvt.0000000000000544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 11/12/2024] [Indexed: 01/03/2025]
Abstract
Decompensated cirrhosis secondary to metabolic dysfunction-associated steatohepatitis (MASH) is not only a common indication for liver transplant (LT) but is becoming the leading cause of LT in postmenopausal women in the United States. Given the different complex mechanisms involved in the occurrence of MASH, it is being recognized as the hepatic manifestation of the metabolic syndrome. There are multiple metabolic issues associated with MASH, including obesity, DMT2, cardiovascular disease, and chronic kidney disease, which need to be addressed in the pretransplant and posttransplant setting for better patient outcomes. Recurrence of MASH following LT can occur due to many reasons including reversal of the catabolic state seen in cirrhosis, improvement in appetite, and the effect of certain post-LT medications on the graft; however, managing recurrence can be challenging and thus urges addressing these issues before transplant, in addition to recognizing, and treating them in the posttransplant setting. In this review, we discuss the various metabolic issues that face patients with MASH and the medical and surgical management options available to improve outcomes and reduce chances of recurrence.
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Affiliation(s)
- Lynna Alnimer
- Department of Medicine, Division of Gastroenterology, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, Michigan, USA
| | - Diego Arellano
- Department of Medicine, Houston Methodist Hospital, Houston Research Institute, Houston, Texas, USA
| | | | - Mazen Noureddin
- Department of Medicine, Houston Liver Institute, Houston Research Institute, Houston, Texas, USA
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2
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Chen B, Lu Q, Hu B, Sun D, Ying T. Protocol of quantitative ultrasound techniques for noninvasive assessing of hepatic steatosis after bariatric surgery. Front Surg 2024; 10:1244199. [PMID: 38239667 PMCID: PMC10794322 DOI: 10.3389/fsurg.2023.1244199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 11/27/2023] [Indexed: 01/22/2024] Open
Abstract
Introduction Roux-en-Y gastric bypass surgery can effectively improve steatosis, necroinflammatory activity, and hepatic fibrosis in individuals diagnosed with morbid obesity or nonalcoholic steatohepatitis (NASH). Common methods such as body mass index (BMI) to evaluate the postoperative effect of clinical bariatric surgery cannot differentiate subcutaneous fats from visceral fats and muscles. Several Quantitative ultrasound (QUS)-based approaches have been developed to quantify hepatic steatosis. QUS techniques (tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI)) from radio frequency (RF) data analysis as a means for the detection and grading of hepatic steatosis has been posited as an objective and noninvasive approach. The implementation and standardization of QUS techniques (TAI, TSI) in assessing hepatic steatosis quantitatively after bariatric surgery is of high-priority. Our study is aimed to assess hepatic steatosis with QUS techniques (TAI, TSI) in morbidly obese individuals before and after bariatric surgery, and to compare with anthropometric measurements, laboratory assessments and other imaging methods. Methods and analysis The present investigation, a self-discipline examination of navigational capacity devoid of visual cues, is designed as a single-site, forward-looking evaluation of efficacy with the imprimatur of the institutional review board. The duration of the study has been provisionally determined to span from 1 January 2023 through 31 December 2025. Our cohort shall encompass one hundred participants, who was scheduled to undergo Roux-en-Y gastric bypass (RYGB) at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All patients will undergo anthropometric measurements, blood-based biochemical analyses, ultrasonic examination and magnetic resonance imaging proton density fat fraction (MRI-PDFF). The primary endpoint is the analysis of evaluating the efficacy of QUS techniques assessing hepatic steatosis compared to other methods before and after bariatric surgery. Results Prior to the fomal study, we recruited 21 obese Chinese participants who received ultrasonic examination (TAI, TSI) and MRI-PDFF. AC-TAI showed moderate correlations with MRI-PDFF (adjusted r = 0.632; P < 0.05). For MRI-PDFF ≥10%, SC-TSI showed moderate correlations with MRI-PDFF (adjusted r = 0.677; P < 0.05). Conclusion Our pre-experiment results signified that using QUS techniques for postoperative evaluation of bariatric surgery is promising. QUS techniques will be signed a widespread availability, real-time functionality, and low-cost approach for assessing hepatic steatosis before and after bariatric surgery in obese individuals, thus is capable for subsequent scale-up liver fat quantification. Ethics and dissemination The present research endeavor has been bestowed with the imprimatur of the Ethics Committee of the Hospital, as indicated by its Approval Number: 2023-KY-015. In due course, upon completion of the study, we intend to disseminate our findings by publishing them in a suitable academic journal, thereby facilitating their widespread utilization. Registration The trial is duly registered with the Chinese Clinical Trial Registry, and with a unique Trial Registration Number, ChiCTR2300069892, approved on March 28, 2023.
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Affiliation(s)
- Bin Chen
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qijie Lu
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bing Hu
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Di Sun
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Ying
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Tsamos G, Vasdeki D, Koufakis T, Michou V, Makedou K, Tzimagiorgis G. Therapeutic Potentials of Reducing Liver Fat in Non-Alcoholic Fatty Liver Disease: Close Association with Type 2 Diabetes. Metabolites 2023; 13:metabo13040517. [PMID: 37110175 PMCID: PMC10141666 DOI: 10.3390/metabo13040517] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/21/2023] [Accepted: 03/29/2023] [Indexed: 04/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.
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Affiliation(s)
- Georgios Tsamos
- Division of Gastroenterology, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK
| | - Dimitra Vasdeki
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Vassiliki Michou
- Sports Medicine Laboratory, School of Physical Education & Sport Science, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece
| | - Kali Makedou
- Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
| | - Georgios Tzimagiorgis
- Laboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece
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Gunturu NS, Castillo-Larios R, Bowers S, Edwards M, Burns J, Perry D, Elli EF. Combined Sleeve Gastrectomy with Liver Transplant in Patients with Obesity: a Feasibility Study. Obes Surg 2022; 32:3600-3604. [PMID: 36169908 DOI: 10.1007/s11695-022-06289-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 09/13/2022] [Accepted: 09/15/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) associated with obesity is one of the leading causes of liver failure requiring transplant, yet guidelines for the management of obesity in these scenarios are not always followed. In order to decrease incidence of NASH in the new liver, we studied the feasibility of simultaneous liver transplant and bariatric surgery. MATERIALS AND METHODS We retrospectively identified patients who underwent simultaneous liver transplant and sleeve gastrectomy at our hospital site between November 24, 2019, and April 14, 2022. Demographics, surgical data, postoperative adverse events, and weight loss data were collected. RESULTS Ten patients met inclusion criteria. Mean body mass index (BMI) at the time of transplant was 43.1 ± 5.3 kg/m2, and mean length of hospital stay was 10.8 ± 5.22 days. Within 30 days after surgery, 7 patients reported adverse effects, and 2 were readmitted. Mean BMI at 6-month follow-up was 30.6 ± 2.5 kg/m2. Mean percentage excess weight (in pounds) loss was 48.1 ± 11.4%, 58.6 ± 8.9%, and 66.1 ± 15.3% at 3-, 6-, and 12-month follow-up, respectively. Three patients had an increase in weight at 12-month follow-up when compared to 6-month follow-up. Most patients required fewer comorbidity-related medications, and none reported adverse effects related to sleeve gastrectomy. CONCLUSIONS Bariatric surgery at the time of liver transplant is safe and has minimal adverse effects. Results include substantial postoperative weight loss, improvement in comorbidities, and decreased risk of NASH in the new liver. Further studies with larger cohorts are required to confirm the findings of this study.
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Affiliation(s)
- Naga Swati Gunturu
- Department of General Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Rocio Castillo-Larios
- Department of General Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Steven Bowers
- Department of General Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Michael Edwards
- Department of General Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Justin Burns
- Department of Transplant, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Danna Perry
- Department of Transplant, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA
| | - Enrique F Elli
- Department of General Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
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Ahmed Z, Khan MA, Vazquez-Montesino LM, Ahmed A. Bariatric surgery, obesity and liver transplantation. Transl Gastroenterol Hepatol 2022; 7:25. [PMID: 35892056 PMCID: PMC9257534 DOI: 10.21037/tgh-2020-14] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 07/06/2020] [Indexed: 06/01/2024] Open
Abstract
The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.
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Affiliation(s)
| | - Muhammad Ali Khan
- Division of Gastroenterology and Hepatology, University of Alabama Birmingham, AL, USA
| | | | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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6
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Abstract
Currently, there are no approved medications to treat patients with nonalcoholic steatohepatitis (NASH) with fibrosis or cirrhosis. Although the management goal in these patients is weight reduction by 7-10% with lifestyle modifications, only less than 10% of patients achieve this target at 1-year, and fewer maintain the weight loss at 5 years. Bariatric surgery is an option that may be considered in those who fail to lose weight by lifestyle changes. Bariatric surgery has been shown to improve liver histology including fibrosis secondary to NASH, in addition to other benefits including an improvement or resolution of type 2 diabetes mellitus, dyslipidemia, and hypertension, and a reduction of cardiovascular morbidity or mortality. There are no guidelines of bariatric surgery indications for the management of NASH. The purpose of this review is to critically appraise the current knowledge of the role of bariatric surgery and the potential mechanisms for its perceived benefits in the management of patients with NASH-related liver disease.
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Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Non-Alcoholic Fatty Liver Disease: A 12-Month Follow-Up Study with Paired Liver Biopsies. J Clin Med 2021; 10:jcm10173783. [PMID: 34501231 PMCID: PMC8432029 DOI: 10.3390/jcm10173783] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/20/2021] [Accepted: 08/22/2021] [Indexed: 12/25/2022] Open
Abstract
Roux-en-Y gastric bypass (RYGB) improves, and can sometimes resolve, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) but data based on histological assessment for the efficacy of sleeve gastrectomy (SG) in resolving NAFLD are sparse. Consequently, we aimed to compare the efficacy of RYGB vs. SG on NAFLD 12 months after surgery. In a prospective cohort study, 40 patients with obesity underwent bariatric surgery (16 RYGB and 24 SG). During surgery, a liver biopsy was taken and repeated 12 months later. NAFLD severity was evaluated using the NAFLD Activity Score (NAS) and Kleiner Fibrosis score. RYGB and SG patients were comparable at baseline. Mean (standard deviation, SD) NAS was 3.3 (0.9) in RYGB and 3.1 (1.4) in SG (p = 0.560) with similar degrees of steatosis, inflammation, and ballooning. Two RYGB patients, and six SG patients, had NASH (p = 0.439). Twelve months after surgery, NAS was significantly and comparably (p = 0.241) reduced in both RYGB (−3.00 (95% CI −3.79–−2.21), p < 0.001) and SG (−2.25 (95% CI −2.92–−1.59), p < 0.001) patients. RYGB patients had significantly more reduced (p = 0.007) liver steatosis (−0.91 (95% CI −1.47–−1.2) than SG patients (−0.33 (95% CI −0.54–−0.13) and greater improvement in the plasma lipid profile. Fibrosis declined non-significantly. NASH was resolved in seven of eight patients without a worsening of their fibrosis. RYGB and SG have similar beneficial effects on NAS and NASH without the worsening of fibrosis. RYGB is associated with a more pronounced reduction in liver steatosis.
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8
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Bariatric Surgery and Liver Disease: General Considerations and Role of the Gut-Liver Axis. Nutrients 2021; 13:nu13082649. [PMID: 34444807 PMCID: PMC8399840 DOI: 10.3390/nu13082649] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 07/23/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023] Open
Abstract
Weight loss is a therapeutic solution for many metabolic disorders, such as obesity and its complications. Bariatric surgery aims to achieve lasting weight loss in all patients who have failed after multiple dietary attempts. Among its many benefits, it has been associated with the regression of non-alcoholic fatty liver disease (NAFLD), which is often associated with obesity, with evidence of substantial improvement in tissue inflammation and fibrosis. These benefits are mediated not only by weight loss, but also by favorable changes in systemic inflammation and in the composition of the gut microbiota. Changes in microbial metabolites such as short-chain fatty acids (SCFAs), capable of acting as endocrine mediators, and bile acids (BAs) as well as modifications of the gut-brain axis, are among the involved mechanisms. However, not all bariatric surgeries show beneficial effects on the liver; those leading to malabsorption can cause liver failure or a marked worsening of fibrosis and the development of cirrhosis. Nevertheless, there are still many unclear aspects, including the extent of the benefits and the magnitude of the risks of bariatric surgery in cirrhotic patients. In addition, the usefulness and the safety of these procedures in patients who are candidates to or who have undergone liver transplant need solid supporting evidence. This paper aims to review literature data on the use of bariatric surgery in the setting of chronic liver disease.
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9
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Finotti M, Romano M, Auricchio P, Scopelliti M, Brizzolari M, Grossi U, Piccino M, Benvenuti S, Morana G, Cillo U, Zanus G. Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives. J Pers Med 2021; 11:499. [PMID: 34199535 PMCID: PMC8229090 DOI: 10.3390/jpm11060499] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.
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Affiliation(s)
- Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Pasquale Auricchio
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Ugo Grossi
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Piccino
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Stefano Benvenuti
- Gastroenterology Unit (IV), Cà Foncello Regional Hospital, 31100 Treviso, Italy;
| | - Giovanni Morana
- Division of Radiology, Treviso Regional Hospital, 31100 Treviso, Italy;
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
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10
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Pomenti S, Mehta S, Guo A, Wattacheril J. Bariatric Surgery in the Peritransplant Period. Clin Liver Dis (Hoboken) 2021; 17:282-291. [PMID: 33968390 PMCID: PMC8087907 DOI: 10.1002/cld.1052] [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: 07/16/2020] [Revised: 10/04/2020] [Accepted: 10/11/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Sydney Pomenti
- Division of Digestive and Liver DiseasesDepartment of MedicineColumbia University Irving Medical Center
| | - Sanket Mehta
- Columbia University Vagelos College of Physicians and Surgeons
| | - Averill Guo
- Department of MedicineColumbia University Irving Medical CenterNew YorkNY
| | - Julia Wattacheril
- Division of Digestive and Liver DiseasesDepartment of MedicineColumbia University Irving Medical Center
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11
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Toman D, Vavra P, Jelinek P, Ostruszka P, Ihnat P, Foltys A, Pelikan A, Roman J. Effect of bariatric surgery on fatty liver disease in obese patients: A prospective one year follow-up study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021; 166:195-203. [PMID: 33885048 DOI: 10.5507/bp.2021.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 04/07/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), often associated with obesity and metabolic syndrome, manifests itself as steatosis, hepatic fibrosis, cirrhosis, or even end-stage liver disease. NAFLD causes inflammation, insulin resistance and cardiovascular complications. The current study aimed to evaluate the beneficial effects of bariatric surgery on biochemical parameters of hepatic functions in obese patients by comparing them before and one-year after the surgery. METHODS A total of 72 morbidly obese patients underwent bariatric surgery between 2016 and 2018. The incidence of diabetes mellitus in this group was 29%, median body weight was 124.5 kg (109.0-140.0) and mean body mass index (BMI) was 44.38 ± 6.770 kg/m2. The used surgical procedures included gastric bypass, sleeve gastrectomy, laparoscopic gastric plication, and single anastomosis duodeno-ileal bypass-sleeve gastrectomy. Biochemical parameters including ALT/AST ratio (AAR), NAFLD fibrosis score (NFS), hepatic fibrosis index (FIB-4) and Fatty Liver Index (FLI) were evaluated in all patients at the time of surgery and one year after the intervention. RESULTS Significant improvement after the intervention was observed in 64 patients. A significant reduction in body weight (P<0.0001), waist circumference (P<0.0001), and body mass index (P<0.0001) were observed. NAFLD liver fibrosis index changed significantly (P<0.0001), suggesting a trend of improvement from advanced fibrosis towards stages 0-2. The FIB-4 fibrosis index indicated significant improvement (P=0.0136). Besides, a significant decline in hepatic steatosis (P<0.0001) was observed after bariatric surgery as compared to the pre-surgery fatty liver conditions. CONCLUSION Among the strategies to overcome NAFLD-associated impediments, bariatric surgery can be considered effective in reducing obesity and metabolic co-morbidities. TRIAL REGISTRATION ClinicalTrials.gov (NCT04569396).
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Affiliation(s)
- Daniel Toman
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Petr Vavra
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Petr Jelinek
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Petr Ostruszka
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Peter Ihnat
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Ales Foltys
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
| | - Anton Pelikan
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic.,Department of Surgery, St. Mary's Hospital, Newport, Isle of Wight, United Kingdom.,Department of Health Care Sciences, Faculty of Humanities, Tomas Bata University Zlin, Czech Republic
| | - Jan Roman
- Department of Surgery, Faculty of Medicine, Ostrava University, Czech Republic.,Department of Surgery, University Hospital Ostrava, Czech Republic
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SILVA MBDBE, TUSTUMI F, DANTAS ACB, MIRANDA BCJ, PAJECKI D, DE-CLEVA R, SANTO MA, NAHAS SC. OBESIDADE E ESTEATOSE GRAVE: A IMPORTÂNCIA DA AVALIAÇÃO BIOQUÍMICA E ESCORES. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2021; 34:e1626. [PMID: 35107488 PMCID: PMC8846460 DOI: 10.1590/0102-672020210002e1626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 09/15/2021] [Indexed: 11/23/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered a public health problem,
mainly in severely obese patients.
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13
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Van Gaal LF, Mertens J, Francque S, De Block C. Therapeutic approaches for non-alcoholic steatohepatitis. Ther Adv Endocrinol Metab 2021; 12:20420188211034300. [PMID: 34497708 PMCID: PMC8419532 DOI: 10.1177/20420188211034300] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be associated with a number of endocrine pathologies. Despite the epidemic, the complex pathophysiology and major complications, ranging from metabolic disturbances (diabetes and more) to cardiovascular disease, people with NASH are left with very few management options. The best and most approved therapeutic option is lifestyle intervention. Although pharmacotherapies based on pathophysiological background are in development, response rates appear modest, mainly for fibrosis treatment, which is the reason for lack of approved drug therapy. Previous drugs analyzed, such as pioglitazone and vitamin E, show weak efficacy. From different phase II trials, antidiabetic (injectable) drugs seem to be promising, both in mono- or bitherapy. Also, derivatives of peroxisome proliferator-activated receptors may have an interesting future, as well. For that reason, more focus should be given on prevention of this novel disease entity. In view of this booming epidemic, with a background of obesity and type 2 diabetes, and the important medical consequences, early recognition, prevention and intervention of NAFLD/NASH seems appropriate. In this review, we will focus on the different current and future therapeutic intervention options, taking into consideration the complex pathophysiology of this disease.
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Affiliation(s)
| | | | - Sven Francque
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Edegem, Belgium
- University of Antwerp, Faculty of Medicine & Health Sciences, LEMP, Wilrijk, Belgium
| | - Christophe De Block
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Edegem, Belgium
- University of Antwerp, Faculty of Medicine & Health Sciences, LEMP, Wilrijk, Belgium
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Mohammed ED, Abdel-Naim AB, Kangpeng J, Jiang R, Wei J, Sun B. The mother relationship between insulin resistance and non-alcoholic steatohepatitis: Glucosinolates hydrolysis products as a promising insulin resistance-modulator and fatty liver-preventer. Life Sci 2020; 264:118615. [PMID: 33096115 DOI: 10.1016/j.lfs.2020.118615] [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: 09/18/2020] [Revised: 10/09/2020] [Accepted: 10/14/2020] [Indexed: 11/25/2022]
Abstract
Non-alcoholic fatty liver disease (NFLD) is one of the present public health problems which have no specific and effective treatment. The speed of the disease progression depends on the patient's lifestyle. Due to life stresses and lack of time, a high number of people depend on fast food containing a high amount of fats which one of the main causes of insulin resistance (IR). IR is one of the metabolic disorders which strongly intersected with molecular NAFLD and leading to its progression into non-alcoholic steatohepatitis (NASH). In this review, we introduced the updated statistics of NAFLD and NASH progression all over the world shows its importance, etiologies, and pathogenesis. Also, IR and its role in NASH initiation and progression explored, and current treatments with its limitations have been explained. Glucosinolates (GLS) is a group of phytochemicals which known by its potent hydrolysis products with promising anti-cancer effect. In this review, we have collected the recent experimental studies of different GLS hydrolysis products against IR and chronic liver diseases supported by our lab finding. Finally, we recommend this group of phytochemicals as promising molecules to be studied experimentally and clinically against a wide range of chronic liver diseases with an acceptable safety margin.
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Affiliation(s)
- Eman D Mohammed
- Department of Clinical Pharmacology, Nanjing Drum Tower Hospital, Pharmacy Collage of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, Jiangsu Province, China; Natural Products Unit, Medicinal and Aromatic Plants Department, Desert Research Centre, Cairo, Egypt
| | - Ashraf B Abdel-Naim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Jin Kangpeng
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, Jiangsu Province, China
| | - Runqiu Jiang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, Jiangsu Province, China
| | - Jifu Wei
- Research Division of Clinical Pharmacology, The First Affiliated Hospital, Pharmacy College of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
| | - Beicheng Sun
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, Jiangsu Province, China; Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China.
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15
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Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep 2020; 2:100192. [PMID: 33163950 PMCID: PMC7607500 DOI: 10.1016/j.jhepr.2020.100192] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.
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Key Words
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- DM, diabetes mellitus
- DPP-4, dipeptidyl peptidase-4
- ELTR, European Liver Transplant Registry
- ESLD, end-stage liver disease
- GLP1 RAs, glucagon-like peptide-1 receptor agonists
- Graft survival
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- Hypertension
- IRR, incidence rate ratio
- Immunosuppressant
- LT, liver transplant
- MAFLD, metabolic dysfunction-associated fatty liver disease
- Metabolic complication
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- New-onset diabetes after transplantation
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis
- OR, odds ratio
- Obesity
- Patient survival
- SGLT2, sodium-glucose co-transporter-2
- Solid organ transplantation
- UNOS, United Network for Organ Sharing
- mTORi, mammalian target of rapamycin inhibitors
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Corresponding author. Address: Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital. Tel.: +39 0498212892; fax: + 390498217848.
| | - Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
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Prabhakar O, Bhuvaneswari M. Role of diet and lifestyle modification in the management of nonalcoholic fatty liver disease and type 2 diabetes. Tzu Chi Med J 2020; 33:135-145. [PMID: 33912410 PMCID: PMC8059462 DOI: 10.4103/tcmj.tcmj_86_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/11/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic evidence of insulin resistance which is the hallmark of type 2 diabetes. NAFLD is considered as the risk factor for developing type 2 diabetes and has a high frequency of occurrence in those with existing type 2 diabetes. Compared with patients with only NAFLD or type 2 diabetes, these patients show a poor metabolic profile and increase mortality. Hence, effective treatment strategies are necessary. Here, we review the role of diet and lifestyle modification in the management of NAFLD and type 2 diabetes. Based on the available studies, it has been shown that the addition of any kind of physical activity or exercise is beneficial for patients with both NAFLD and type 2 diabetes. Proper dietary management leads to weight loss are also effective in improving metabolic parameters in patients with both NAFLD and type 2 diabetes. In conclusion, it is clear that increasing physical activity or exercise is effective in improving metabolic parameters in patients who are suffering with both NAFLD and type 2 diabetes.
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Affiliation(s)
- Orsu Prabhakar
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
| | - Mylipilli Bhuvaneswari
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
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The Effect of Laparoscopic Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease. Surg Laparosc Endosc Percutan Tech 2020; 29:509-512. [PMID: 31107849 DOI: 10.1097/sle.0000000000000672] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Obesity is associated with nonalcoholic fatty liver disease which is one of the most common causes of chronic liver disease. FibroScan is a noninvasive tool for liver stiffness measurement and controlled attenuation parameter to evaluate liver steatosis and fibrosis. We aimed to demonstrate the effect of laparoscopic sleeve gastrectomy on liver steatosis and fibrosis. Of the 120 consecutive patients screened, 72 were enrolled in this study. FibroScan M probe and XL probe were used for the evaluation of liver steatosis and fibrosis. Fifty-two patients (72.2%) were female individuals and 20 (27.8%) were male individuals; the mean age was 37.9±10.4 years. Percentage of excess weight loss was significant at the third and sixth months: 57.2±18.3 (P<0.05) and 81.4±24.6 (P<0.05), respectively. Mean preoperative controlled attenuation parameter and liver stiffness measurement values were 309.2±68.7 dB/m and 7.5±5.0 kPa, respectively, and significantly declined to 217.4±56.4 dB/m and 5.6±2.5 kPa, respectively, at sixth postoperative month (P<0.001 and <0.01, respectively). These results suggest that laparoscopic sleeve gastrectomy is associated with significant improvement in liver steatosis and fibrosis. Bariatric surgery has a beneficial effect on nonalcoholic fatty liver disease in morbidly obese patients.
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Chakravarthy MV, Waddell T, Banerjee R, Guess N. Nutrition and Nonalcoholic Fatty Liver Disease: Current Perspectives. Gastroenterol Clin North Am 2020; 49:63-94. [PMID: 32033765 DOI: 10.1016/j.gtc.2019.09.003] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis are diseases in their own right as well as modifiable risk factors for cardiovascular disease and type 2 diabetes. With expanding knowledge on NAFLD pathogenesis, insights have been gleaned into molecular targets for pharmacologic and nonpharmacologic approaches. Lifestyle modifications constitute a cornerstone of NAFLD management. This article reviews roles of key dietary macronutrients and micronutrients in NAFLD pathogenesis and their effects on molecular targets shared with established or emerging pharmacotherapies. Based on current evidence, a recommendation for a dietary framework as part of the comprehensive management strategy for NAFLD is provided.
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Affiliation(s)
| | - Thomas Waddell
- Perspectum Diagnostics, 23-38 Hythe Bridge Street, Oxford OX1 2ET, UK
| | - Rajarshi Banerjee
- Perspectum Diagnostics, 23-38 Hythe Bridge Street, Oxford OX1 2ET, UK; Oxford University Hospitals NHS Foundation Trust, Headley Way, Headington, Oxford OX3 9DU, UK
| | - Nicola Guess
- King's College London, 150 Stamford Street, London SE1 9NH, UK; University of Westminster, 101 New Cavendish St, Fitzrovia, London W1W 6XH, United Kingdom
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Ma N, Ma R, Tang K, Li X, He B. Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway. J Diabetes Res 2020; 2020:4326549. [PMID: 32309446 PMCID: PMC7136782 DOI: 10.1155/2020/4326549] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 01/28/2020] [Accepted: 02/12/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics and find new therapeutic basis on obese type 2 diabetes mellitus (T2DM) patients. Materials and Methods. Thirty-two rats were divided into nondiabetic group, diabetic group, sham group, and RYGB group. The Dual-energy X-ray absorptiometry (DEXA) was used to detect short-term curriculum vitae for rat body component and fat and lean mass. Hepatic lipid content and triglyceride levels were detected by Oil Red O staining. Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. The carbon dioxide production from the oxidation of [14C] oleate was measured. Plasma glucose was measured by glucose oxidase assay. The insulin and C-peptide were detected. Triacylglyceride (TG) and free fat acid (FFA) in plasma were determined by enzymatic colorimetric assays. RESULTS RYGB improved metabolic parameters and enhanced plasma GLP-1 level, ameliorated the lipopexia, and increased insulin sensitivity in the liver; RYGB promoted the hepatic autophagy and inhibited the mTOR/p70S6K signaling pathway. GLP-1 reduced fat load and increased fatty acid β-oxidation by activated autophagy to regulate the hepatic lipid pathway through mTOR/p70S6K signaling pathway. CONCLUSIONS RYGB may reduce liver lipid toxicity and improve insulin sensitivity through activating the hepatic fat hydrolysis pathway and inhibiting the liver fat synthesis pathway. However, the transport pathway of liver fat does not play a key role.
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Affiliation(s)
- Nanxi Ma
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Rui Ma
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Kaixin Tang
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Xuesong Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Bing He
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
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Chu X, Karasinski K, Donellan S, Kaniper S, Wood GC, Shi W, Edwards MA, Soans R, Still CD, Gerhard GS. A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease. Langenbecks Arch Surg 2019; 405:165-172. [PMID: 31828503 DOI: 10.1007/s00423-019-01848-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 11/28/2019] [Indexed: 12/20/2022]
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue. METHODS Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record. RESULTS The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples. CONCLUSION Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.
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Affiliation(s)
- Xin Chu
- Obesity Research Institute, Geisinger Clinic, Danville, PA, USA
| | - Kelsey Karasinski
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA
| | - Sean Donellan
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA
| | - Scott Kaniper
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA
| | - G Craig Wood
- Obesity Research Institute, Geisinger Clinic, Danville, PA, USA
| | - Weixing Shi
- Obesity Research Institute, Geisinger Clinic, Danville, PA, USA
| | - Michael A Edwards
- Department of Surgery, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA
| | - Rohit Soans
- Department of Surgery, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA
| | | | - Glenn S Gerhard
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
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Laparoscopic Sleeve Gastrectomy Resolves NAFLD: Another Formal Indication for Bariatric Surgery? Obes Surg 2019; 28:4022-4033. [PMID: 30121855 DOI: 10.1007/s11695-018-3466-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Obesity is strongly associated with non-alcoholic fatty liver disease (NAFLD); 66-99% of the obese population could suffer some grade of NAFLD. It can progress into cirrhosis, which is associated to hepatocellular carcinoma, and a liver transplant could be indicated. NAFLD represents the third cause of liver transplant, and it is expected to be the first by 2025. Sleeve gastrectomy (SG) is the most common bariatric procedure over the world. There is scant literature regarding NAFLD after SG, and there are no prospective studies published up to date. OBJECTIVE To evaluate the evolution of NAFLD in patients with obesity after 1 year of SG. METHODS From January 2009 to December 2013, intraoperative liver biopsy was performed in 63 obese patients who underwent SG. Forty-three patients were again biopsied 1 year after surgery. Demographics, body mass index, percentage of excess weight loss, liver function test, lipid panel, glucose panel, and histological changes were prospectively analyzed. RESULTS One hundred percent of the patients reversed or reduced the stage of steatosis or steatohepatitis 12 months after surgery, obtaining a statistically significant difference for both steatosis and steatohepatitis. One patient presented complete cirrhosis regression in the pathology. Neither of the patients had worsened liver histology. CONCLUSIONS NAFLD could be dealt with laparoscopic sleeve gastrectomy, preventing its progression into cirrhosis. SG can be performed in patients with obesity and metabolic syndrome, with NAFLD showing satisfactory results 12 months after surgery. NAFLD should be a formal indication for bariatric surgery.
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Abstract
Background Obesity is associated with chronic inflammation, liver steatosis and increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are a biomarker reflecting inflammation and the degree of fibrosis in NAFLD. We investigated alterations in PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric bypass (RYGBP). Methods One hundred twenty-four morbidly obese non-diabetic patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP. Results Body mass index (BMI) was reduced from 43.5 kg/m2 (baseline) to 31.1 kg/m2 (follow-up), and p < 0.001 and weight declined from 126.2 to 89.0 kg. PCs decreased from 303 × 109 to 260 × 109/l, p < 0.001. GGT was reduced from 0.63 to 0.38 μkat/l, p < 0.001. ALT decreased from 0.69 to 0.59 μkat/l, p = 0.006. CRP was lowered from 7.3 to 5.4 mg/l p < 0.001 and ferritin from 106 to 84 μg/l p < 0.001. The alterations in PCs correlated with the changes in CRP (r = 0.38, p = 0.001), BMI (r = 0.25, p = 0.012), weight (r = 0.24, p = 0.015) and inversely correlated with ferritin (r = 21, p = 0.036). Conclusions PCs, GGT and ALT (markers for NAFLD), and CRP and ferritin (markers for inflammation) decreased in morbidly obese after RYGBP. The decrease in PCs correlated with alterations in CRP, BMI, weight and ferritin. The lowering of liver enzymes may reflect a lowered liver fat content and decreased general inflammation.
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Tzifi F, Fretzayas A, Chrousos G, Kanaka-Gantenbein C. Non-alcoholic fatty liver infiltration in children: an underdiagnosed evolving disease. Hormones (Athens) 2019; 18:255-265. [PMID: 31140156 DOI: 10.1007/s42000-019-00107-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/25/2019] [Indexed: 12/21/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease, one that is still underdiagnosed in pediatric populations (as well as in the general population), this due to the progressive increase in childhood obesity observed both in developed and developing countries during the last few decades. The pathophysiology of the disease has not been thoroughly clarified yet. The condition displays common pathways in adults and children; however, there are age-related differences. Unlike adults, children with NAFLD require extensive laboratory analysis, because underlying pathologies other than obesity may contribute to the evolution of the disease. Despite the presence of several serum markers and imaging techniques that contribute to NAFLD diagnosis, liver biopsy remains the gold standard diagnostic procedure. Early intervention and obesity prevention are mandatory, as NAFLD is reversible at an early stage. If left undiagnosed and untreated, NAFLD can progress to steatohepatitis (NASH) and subsequent liver failure, a potentially lethal complication. Of note, there are no treatment options when advanced liver fibrosis occurs. This review summarizes literature data on NAFLD in childhood indicating that this is an evolving disease and a significant component of the metabolic syndrome. Pediatricians should be aware of this entity, screening children at high risk and providing appropriate early management, in collaboration with pediatric subspecialists.
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Affiliation(s)
- Flora Tzifi
- First Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, Medical School, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.
- Athens Medical Group, Marousi, Greece.
| | | | - George Chrousos
- First Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, Medical School, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece
| | - Christina Kanaka-Gantenbein
- First Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, Medical School, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece
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Lee Y, Doumouras AG, Yu J, Brar K, Banfield L, Gmora S, Anvari M, Hong D. Complete Resolution of Nonalcoholic Fatty Liver Disease After Bariatric Surgery: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17:1040-1060.e11. [PMID: 30326299 DOI: 10.1016/j.cgh.2018.10.017] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 09/27/2018] [Accepted: 10/01/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Bariatric surgery has been reported to lead to complete resolution of nonalcoholic fatty liver disease (NAFLD) following the sustained weight loss induced in obese patients. We performed a systematic review and meta-analysis to evaluate the effects of bariatric surgery on NAFLD in obese patients. METHODS We searched MEDLINE, EMBASE, CENTRAL, and Web of Science databases through May 2018 for studies that compared liver biopsy results before and after bariatric surgery in obese patients. Primary outcomes were biopsy-confirmed resolution of NAFLD and NAFLD activity score. Secondary outcomes were worsening of NAFLD after surgery and liver volume. The Grading of Recommendations, Assessment, Development, and Evidence approach was conducted to assess overall quality of evidence. RESULTS We analyzed data from 32 cohort studies comprising 3093 biopsy specimens. Bariatric surgery resulted in a biopsy-confirmed resolution of steatosis in 66% of patients (95% CI, 56%-75%), inflammation in 50% (95% CI, 35%-64%), ballooning degeneration in 76% (95% CI, 64%-86%), and fibrosis in 40% (95% CI, 29%-51%). Patients' mean NAFLD activity score was reduced significantly after bariatric surgery (mean difference, 2.39; 95% CI, 1.58-3.20; P < .001). However, bariatric surgery resulted in new or worsening features of NAFLD, such as fibrosis, in 12% of patients (95% CI, 5%-20%). The overall Grading of Recommendations, Assessment, Development, and Evidence quality of evidence was very low. CONCLUSIONS Through this systematic review and meta-analysis, we found that bariatric surgery leads to complete resolution of NAFLD in obese patients. However, some patients develop new or worsened features of NAFLD. Randomized controlled trials are needed to further examine the therapeutic benefits of bariatric surgery for patients with NAFLD.
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Affiliation(s)
- Yung Lee
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Aristithes G Doumouras
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - James Yu
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Karanbir Brar
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Laura Banfield
- Health Sciences Library, McMaster University, Hamilton, Ontario, Canada
| | - Scott Gmora
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Mehran Anvari
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Dennis Hong
- Division of General Surgery, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
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Laursen TL, Hagemann CA, Wei C, Kazankov K, Thomsen KL, Knop FK, Grønbæk H. Bariatric surgery in patients with non-alcoholic fatty liver disease - from pathophysiology to clinical effects. World J Hepatol 2019; 11:138-149. [PMID: 30820265 PMCID: PMC6393715 DOI: 10.4254/wjh.v11.i2.138] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/01/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), is important in NAFLD. Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2D. Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD. Therefore, bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients. In the present review, we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways. We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients. The specific focus was liver histopathology as assessed by the invasive liver biopsy. Additionally, we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.
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Affiliation(s)
- Tea L Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Christoffer A Hagemann
- Gubra ApS, Hørsholm 2970, Denmark
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup 2900, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
| | - Chunshan Wei
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China
| | - Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Karen L Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Filip K Knop
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup 2900, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38:485-521. [PMID: 30712783 DOI: 10.1016/j.clnu.2018.12.022] [Citation(s) in RCA: 392] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.
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Affiliation(s)
- Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
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Tan CH, Al-Kalifah N, Lee WJ, Ser KH, Lee YC, Chen JC. HSCRP as surrogate marker in predicting long term effect of bariatric surgery on resolution of non-alcoholic steatohepatitis. Asian J Surg 2019; 42:203-208. [DOI: 10.1016/j.asjsur.2018.04.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 02/12/2018] [Accepted: 04/30/2018] [Indexed: 12/13/2022] Open
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Diwan TS, Rice TC, Heimbach JK, Schauer DP. Liver Transplantation and Bariatric Surgery: Timing and Outcomes. Liver Transpl 2018; 24:1280-1287. [PMID: 30080949 DOI: 10.1002/lt.25303] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Accepted: 06/18/2018] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is projected to become the leading indication for liver transplantation (LT) in the next decade in the United States. Strategies to treat the underlying etiology of NASH, which is almost always obesity, are being pursued. One such strategy is the utilization of bariatric surgery (BS) in the peritransplant period. The use of BS prior to LT could prevent the progression of NASH and abrogate the need for LT. BS at the time of LT or postoperatively has the potential to not only improve obesity-associated conditions such as diabetes, but also the potential to influence the incidence of NASH in the post-LT setting. However, there continues to be no consensus on the use and timing of BS in this patient population. This review aims to discuss the current literature and possible future action.
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Affiliation(s)
- Tayyab S Diwan
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
| | - Teresa C Rice
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
| | - Julie K Heimbach
- Division of Transplantation Surgery, Mayo Clinic College of Medicine, Rochester, MN
| | - Daniel P Schauer
- Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati Collaborative on Obesity Research, Cincinnati, OH
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Abstract
PURPOSE OF REVIEW The goal of this paper is to review current literature on nutritional ketosis within the context of weight management and metabolic syndrome, namely, insulin resistance, lipid profile, cardiovascular disease risk, and development of non-alcoholic fatty liver disease. We provide background on the mechanism of ketogenesis and describe nutritional ketosis. RECENT FINDINGS Nutritional ketosis has been found to improve metabolic and inflammatory markers, including lipids, HbA1c, high-sensitivity CRP, fasting insulin and glucose levels, and aid in weight management. We discuss these findings and elaborate on potential mechanisms of ketones for promoting weight loss, decreasing hunger, and increasing satiety. Humans have evolved with the capacity for metabolic flexibility and the ability to use ketones for fuel. During states of low dietary carbohydrate intake, insulin levels remain low and ketogenesis takes place. These conditions promote breakdown of excess fat stores, sparing of lean muscle, and improvement in insulin sensitivity.
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Affiliation(s)
- Victoria M Gershuni
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
| | - Stephanie L Yan
- Department of Internal Medicine, University of California Davis, Davis, CA, USA
| | - Valentina Medici
- Division of Gastroenterology, University of California Davis, Davis, CA, USA
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Mendez-Sanchez N, Cruz-Ramon VC, Ramirez-Perez OL, Hwang JP, Barranco-Fragoso B, Cordova-Gallardo J. New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis. Int J Mol Sci 2018; 19:2034. [PMID: 30011790 PMCID: PMC6073816 DOI: 10.3390/ijms19072034] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 07/09/2018] [Accepted: 07/11/2018] [Indexed: 02/08/2023] Open
Abstract
NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotoxicity, and bile acid (BA) toxicity, have been reported to be associated with NASH progression. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, which is caused by the ectopic accumulation of triglyceride-derived toxic metabolites and the subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. Adipose tissue (AT), especially visceral AT, comprises multiple cell populations that produce adipokines and insulin-like growth factor, plus macrophages and other immune cells that stimulate the development of lipotoxic liver disease. These biomolecules have been recently linked with many digestive diseases and gastrointestinal malignancies such as hepatocellular carcinoma. This made us question what role lipotoxicity has in the natural history of liver fibrosis. Therefore, this review focuses on the close relationship between AT and NASH. A good comprehension of the pathways that are related to dysregulated AT, metabolic dysfunction, and hepatic lipotoxicity will result in the development of prevention strategies and promising therapeutics for patients with NASH.
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Affiliation(s)
| | | | | | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Beatriz Barranco-Fragoso
- Department of Gastroenterology, National Medical Center "20 Noviembre", 03229 Mexico City, Mexico.
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Kirkpatrick V, Moon RC, Teixeira AF, Jawad MA. Cirrhosis following single anastomosis duodeno-ileal switch: A case report. Int J Surg Case Rep 2018; 45:130-132. [PMID: 29605778 PMCID: PMC6000903 DOI: 10.1016/j.ijscr.2018.03.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 03/02/2018] [Indexed: 12/27/2022] Open
Abstract
We report a rare case of a liver cirrhosis in a patient who underwent single anastomosis duodenal switch procedure. We describe the possible presentation of the patient with a liver cirrhosis. Management of single anastomosis duodenal switch patients should include close monitoring of liver function. Introduction Single anastomosis duodeno-ileal switch (SADI-S) involves a single, loop duodeno-ileal anastomosis with omission of the traditional Roux-en-Y distal ileo-ileal anastomosis. Not much has been published on the complications of SADI-S. Presentation of case The patient is a 40 year-old male who underwent robot-assisted SADI-S three years prior. At the time of surgery, his body mass index (BMI) was 69 kg/m2. His BMI was 31 kg/m2 at the time of presentation. Computed tomography of the abdomen and pelvis showed a liver with a nodular appearance and moderate ascites throughout the abdomen and above the liver. Liver function showed AST 73 U/L, ALT 63 U/L, alkaline phosphatase 128 U/L, bilirubin 1.0 mg/dL, and albumin 2.8 g/dL. He underwent diagnostic and therapeutic paracentesis with removal of 6L of fluid that was negative for infection or malignant cells. Esophagogastroduodenoscopy showed grade I esophageal varices and diffuse mild gastritis. Discussion Mild hepatic dysfunction is common after biliopancreatic diversion and usually manifests as a temporary rise in liver enzymes that peak several months after surgery and normalize by one year. Cirrhosis and liver failure are rare sequelae that may develop at any time after surgery. Potential mechanisms include the absorption of hepatotoxic compounds from the bypassed small intestine in the context of bacterial overgrowth, protein malnutrition, and excessive free fatty acid mobilization causing steatosis and oxidative damage to hepatocytes. Conclusion Close laboratory monitoring is important after SADI-S in order to detect worsening hepatic dysfunction, which may occur many years after the surgery in the absence of other etiologies for liver failure.
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Affiliation(s)
- Vincent Kirkpatrick
- Department of Bariatric Surgery, Orlando Regional Medical Center, Orlando Health, USA
| | - Rena C Moon
- Department of Bariatric Surgery, Orlando Regional Medical Center, Orlando Health, USA
| | - Andre F Teixeira
- Department of Bariatric Surgery, Orlando Regional Medical Center, Orlando Health, USA
| | - Muhammad A Jawad
- Department of Bariatric Surgery, Orlando Regional Medical Center, Orlando Health, USA.
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Alsina ME, Ruiz-Tovar J, Bernabeu A. Evolution of Liver Steatosis Quantified by MR Imaging and MR Spectroscopy, in Morbidly Obese Patients Undergoing Sleeve Gastrectomy: Short-Term Outcomes. Obes Surg 2018; 27:1724-1728. [PMID: 27885531 DOI: 10.1007/s11695-016-2473-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Currently, the standard procedure used to evaluate hepatic steatosis is the liver biopsy. This is an invasive practice that presents inherent risks. Increasing evidence suggests that magnetic resonance imaging (MRI) and MR spectroscopy (MRS) may represent an accurate method to determine the hepatic lipid content. The aim of this study was to evaluate the effect of sleeve gastrectomy on liver steatosis, quantified by MRI and MRS. PATIENTS AND METHODS A prospective observational study of patients undergoing laparoscopic sleeve gastrectomy was performed. All patients underwent a MRI and a MRS study 2 weeks before the intervention and 6 months after the surgery. Anthropometric, biochemical, and radiological parameters were analyzed. RESULTS Twenty-three patients were included, 21 females and 2 males, with a mean age of 47.6 ± 10.6 years and mean pre-op BMI 47.6 ± 6.7 Kg/m2. Six months after surgery, mean BMI was 32.2 ± 5.1 Kg/m2, with a mean excess weight loss of 68.2 ± 18.6%. Mean preoperative hepatic volume was 1999.9 ± 436.2 ml and 6 months after surgery it decreased to 1568 ± 170.3 ml (p = 0.005). Mean preoperative percentage of lipid content was 14.2 ± 15.4% and 6 months after surgery, it decreased to 4.3 ± 3.2% (p = 0.007). A significant reduction of steatosis grade was observed, with disappearance of preoperative steatosis in 54.9% of the patients. CONCLUSION Six months after sleeve gastrectomy, a significant reduction of liver steatosis is observed, as demonstrated by reduction in the percentage of intrahepatocitary lipids and liver volume, determined by MRS and MRI. These imaging techniques can be considered as noninvasive, accurate methods for monitoring liver steatosis in morbidly obese patients undergoing bariatric surgery.
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Affiliation(s)
| | - Jaime Ruiz-Tovar
- Department of Surgery, Bariatric Surgery Unit, University Hospital Rey Juan Carlos, Gladiolo s/n, 28933, Madrid, Spain.
| | - Angela Bernabeu
- Magnetic Resonance Department, Inscanner SL, Alicante, Spain
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Ruiz-Tovar J, Alsina ME, Alpera MR. Improvement of nonalcoholic fatty liver disease in morbidly obese patients after sleeve gastrectomy: association of ultrasonographic findings with lipid profile and liver enzymes. Acta Chir Belg 2017; 117:363-369. [PMID: 28585487 DOI: 10.1080/00015458.2017.1334858] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND After bariatric surgery an improvement or even complete resolution of nonalcoholic fatty liver disease (NAFLD) in morbidly obese patients is achieved, but little is known about the effect of laparoscopic sleeve gastrectomy (LSG). PATIENTS AND METHODS A prospective observational study of patients undergoing LSG was performed. An abdominal ultrasonography and blood sample extraction (investigating liver enzymes and lipid profile) were performed preoperatively and 12 months after surgery. RESULTS Fifty patients were included in the study. Preoperatively, 84% of the patients presented liver steatosis. A significant reduction of steatosis could be observed 12 months after surgery (p < .001). Preoperative degree of steatosis showed a direct correlation with AST (p = .008) and ALT (p = .007) and an inverse correlation with HDL-cholesterol (p = .019). The reduction of liver steatosis showed an inverse correlation with the increase of HDL-cholesterol between pre- and postoperative determinations (p = .008). CONCLUSIONS Liver steatosis, as measured by ultrasonography, improves after sleeve gastrectomy, achieving a complete resolution in 90% of the cases. Preoperative steatosis correlates directly with AST and ALT levels and inversely with HDL-cholesterol. The postoperative increase of HDL-cholesterol shows an inverse correlation with liver steatosis improvement, suggesting that it could be a good marker for monitoring the postoperative liver status.
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Affiliation(s)
- Jaime Ruiz-Tovar
- Department of Surgery, Obesity Unit, General University Hospital Elche, Alicante, Spain
| | - Maria Engracia Alsina
- Department of Radiology, Obesity Unit, General University Hospital Elche, Alicante, Spain
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Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease. Gastroenterol Res Pract 2017; 2017:3932491. [PMID: 29348746 PMCID: PMC5733887 DOI: 10.1155/2017/3932491] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Revised: 10/01/2017] [Accepted: 10/12/2017] [Indexed: 12/13/2022] Open
Abstract
Obesity now affects millions of people and places them at risk of developing metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models, time-restricted feeding resets the hepatic circadian clock and enhances transcription of key metabolic regulators of glucose and lipid homeostasis. Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time-restricted feeding model, have also identified significant improvement in body mass index, serum lipid profiles, and oxidative stress parameters. Based on the findings of studies conducted on human subjects, dawn-to-sunset fasting has the potential to be a cost-effective intervention for obesity, metabolic syndrome, and NAFLD.
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Kalidari B, Mahmoudieh M, Melali H, Nazari Moghadam M, Kolahdouzan M. Predictive Factors of Steatosis and Non-Alcoholic Steatohepatitis in Morbidly Obese Patients Undergoing Bariatric Surgery. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.14088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Safwan M, Collins KM, Abouljoud MS, Salgia R. Outcome of liver transplantation in patients with prior bariatric surgery. Liver Transpl 2017; 23:1415-1421. [PMID: 28752920 DOI: 10.1002/lt.24832] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 07/23/2017] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease is becoming the leading cause of disease resulting in liver transplantation (LT). As a result of this trend, more LT candidates are presenting with prior history of bariatric surgery (BS). Over the last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior BS. The most common type of BS was Roux-en-Y gastric bypass (n = 9) with 1 sleeve gastrectomy and 1 jejunoileal bypass. A total of 9 patients underwent LT alone, and 2 underwent simultaneous liver-kidney transplantation. The most common indication for LT was nonalcoholic steatohepatitis (n = 10) with 5 having additional diagnosis of alcoholic liver disease. The 30-day reoperation rate was 36.4% (n = 4); indications were bile duct repair (n = 3) and wound repair (n = 1). In the first 6 months after LT, biliary complications were seen in 54.5% (n = 6) of the patients. Both patient and graft survival rates at 1 and 2 years were 81.8% (n = 9) and 72.7% (n = 8), respectively. A total of 8 patients (72.7%) had indications for liver biopsy after LT; significant macrovesicular steatosis was found in 2 (18.2%). In patients with a history of alcohol consumption, 2 (40.0%) relapsed after LT. Two patients (18.2%) had a history of diet-controlled diabetes before LT; 1 of these patients became insulin dependent after LT. Mean body mass index (BMI) at LT was 31.0 ± 5.7 kg/m2 . Mean BMI at 1, 6, and 12 months after LT was 28.3 ± 5.8, 28.0 ± 3.2, and 31.0 ± 6.6 kg/m2 , respectively. Mean preoperative albumin was 2.6 ± 0.6 mg/dL. Patients showed improvement in albumin after LT, with mean albumin of 2.7 ± 0.6 and 3.2 ± 0.5 mg/dL at 1 and 3 months, respectively. The liver profile was stable after LT, with mean aspartate aminotransferase of 32.9 ± 18.4 and 26.6 ± 19.8 IU/L and alanine aminotransferase of 28.0 ± 17.5 and 30.2 ± 17.0 IU/L at 6 and 12 months, respectively. In conclusion, outcomes of LT patients with prior BS are comparable with other transplant recipients with regards to patient and graft survival and post-LT complication rates. Liver Transplantation 23 1415-1421 2017 AASLD.
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Affiliation(s)
| | | | | | - Reena Salgia
- Department of Gastroenterology, Henry Ford Hospital, Detroit, MI
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Parker BM, Wu J, You J, Barnes DS, Yerian L, Kirwan JP, Schauer PR, Sessler DI. Reversal of fibrosis in patients with nonalcoholic steatohepatosis after gastric bypass surgery. BMC OBESITY 2017; 4:32. [PMID: 28919979 PMCID: PMC5596497 DOI: 10.1186/s40608-017-0168-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 08/23/2017] [Indexed: 12/26/2022]
Abstract
Background Roux-en-Y gastric bypass (RYGB) improves the pathophysiology that contributes to obesity-related nonalcoholic steatohepatitis (NASH). Whether obesity-related fibrosis improves is unclear. We hypothesized that RYGB reverses NASH and fibrosis, and indocyanine green (ICG) clearance provides a sensitive measure for detecting asymptomatic fatty liver disease. Methods One hundred six obese adults scheduled for RYGB had preoperative liver function assessed using standard tests and ICG clearance and core liver biopsies obtained during RYGB. Once patients lost 60% of their preoperative weight or weight loss plateaued, liver function was reassessed. Repeat liver biopsies were obtained on patients with NASH at the time of RYGB. Results RYGB improved steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. Serum albumin, AST, and ALT decreased the most in patients with NASH and NASH plus fibrosis. Twenty seven (26%) patients had normal baseline liver histology and 45 (43%) had NASH or NASH plus fibrosis. Nine of 13 patients with substantial fatty liver had normalized histology after weight loss, while severity of disease in the rest had stabilized or was reduced. Mean ICG clearance in patients with normal/mild fatty liver disease and those with histological fatty livers did not differ significantly. Conclusions RYGB surgery reverses NASH and liver fibrosis. Underlying mechanisms that facilitate improvement remain unclear.
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Affiliation(s)
- Brian M Parker
- Department of General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH USA.,Department of Anesthesiology, Allegheny Health Network, Pittsburgh, PA USA
| | - Jiang Wu
- Department of Anesthesiology & Pain Medicine, University of Washington Medical Center, Seattle, WA USA
| | - Jing You
- Departments of Quantitative Health Sciences and OUTCOMES RESEARCH, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH USA
| | - David S Barnes
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH USA
| | - Lisa Yerian
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH USA
| | - John P Kirwan
- Department of Pathobiology, Cleveland Clinic, Cleveland, OH USA
| | - Philip R Schauer
- Department of General Surgery, Cleveland Clinic, Cleveland, OH USA
| | - Daniel I Sessler
- Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH USA
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Shouhed D, Steggerda J, Burch M, Noureddin M. The role of bariatric surgery in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol 2017; 11:797-811. [PMID: 28712339 DOI: 10.1080/17474124.2017.1355731] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects between 25% and 33% of the population, is more common in obese individuals, and is the most common cause of chronic liver disease in the United States. However, despite rising prevalence, effective treatments remain limited. Areas covered: We performed a literature search across multiple databases (Pubmed, Medline, etc.) to identify significant original research and review articles to provide an up-to-date and concise overview of disease pathogenesis and diagnostic evaluation and to expand on available treatment options with a specific focus on the potential role of bariatric surgery. Here we provide the most comprehensive review of bariatric surgery for the management of NAFLD, noting benefits from different procedures and multiple reports showing improvements in steatosis, inflammation and fibrosis over the duration of follow-up. Expert commentary: The morbidity of NAFLD is significant as it may become the most common indication for liver transplantation within the next 5 years. In addition to known benefits of weight loss and diabetes resolution, bariatric surgery has the potential to halt and reverse disease progression and future controlled trials should be performed to further define its benefit in the treatment of NAFLD in morbidly obese patients.
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Affiliation(s)
- Daniel Shouhed
- a Department of Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA.,b Division of Bariatric Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA
| | - Justin Steggerda
- a Department of Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA
| | - Miguel Burch
- a Department of Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA.,b Division of Bariatric Surgery , Cedars-Sinai Medical Center , Los Angeles , CA , USA
| | - Mazen Noureddin
- c Fatty Liver Disease Program, Division of Digestive and Liver Diseases, Department of Medicine , Comprehensive Transplant Center, Cedars-Sinai Medical Center , Los Angeles , CA , USA
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Abstract
PURPOSE OF REVIEW Obesity is recognized as a chronic and recurring disease, often accompanied by other weight-related comorbid conditions such as obstructive sleep apnea, hypertension, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). This chapter will seek to focus on the effect of weight loss surgery (WLS), in particular Roux-en-Y gastric bypass (RYGB), on NAFLD. RECENT FINDINGS Among several modalities available to treat NAFLD, the one most likely to achieve rapid, significant, and sustained improvement of liver disease is WLS. The most commonly studied WLS procedure at this time is RYGB, and there is significant evidence that this is a safe and effective procedure both for weight loss and to bring about improvement of multiple associated comorbid conditions, including NAFLD. Further research focusing on non-surgical approaches that might mimic the effect of WLS on liver pathology is needed.
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Affiliation(s)
- Vamsi Alli
- Division of Minimally Invasive and Bariatric Surgery, Penn State Hershey Medical Center, 500 University Drive, Mail Code H-149, Hershey, PA, 17033, USA
| | - Ann M Rogers
- Division of Minimally Invasive and Bariatric Surgery, Penn State Hershey Medical Center, 500 University Drive, Mail Code H-149, Hershey, PA, 17033, USA.
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Cazzo E, Pareja JC, Chaim EA. Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review. SAO PAULO MED J 2017; 135:277-295. [PMID: 28562737 PMCID: PMC10019840 DOI: 10.1590/1516-3180.2016.0306311216] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 12/31/2016] [Indexed: 02/06/2023] Open
Abstract
CONTEXT AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been increasingly diagnosed worldwide and is now recognized as a source of public health concern. It comprises a wide spectrum of histological features that range from simple steatosis to severe forms of fibrosis, steatohepatitis and even cirrhosis. The impact of bariatric surgery on the course of NAFLD in individuals with obesity has been extensively studied. DESIGN AND SETTING: Narrative review; public university hospital. METHODS: A comprehensive review was conducted based on an online search on the electronic databases MEDLINE and LILACS using the MeSH terms "fatty liver" and "bariatric surgery". RESULTS: The exact mechanisms that lead to improvement in NAFLD following bariatric surgery are not completely understood. Since Roux-en-Y gastric bypass (RYGB) is the bariatric surgical procedure most performed worldwide, it is also the one from which the effects on NAFLD have been most studied, although there is also consistent evidence regarding the effects from gastric banding, sleeve gastrectomy and biliopancreatic diversions. CONCLUSION: According to the currently available evidence, bariatric surgery leads to significant improvement in NAFLD. Further research, especially by means of randomized controlled trials enrolling larger cohorts of individuals, is needed to determine the optimal procedure for this group of subjects.
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Affiliation(s)
- Everton Cazzo
- MD, MSc, PhD. Assistant Professor, Department of Surgery, Universidade Estadual de Campinas (UNICAMP), Campinas (SP), Brazil.
| | - José Carlos Pareja
- MD, PhD. Associate Professor, Department of Surgery, Universidade Estadual de Campinas (UNICAMP), Campinas (SP), Brazil.
| | - Elinton Adami Chaim
- MD, MSc, PhD. Full Professor, Department of Surgery, Universidade Estadual de Campinas (UNICAMP), Campinas, (SP), Brazil.
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Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges. Nutr Res Rev 2017; 30:97-105. [PMID: 28222828 DOI: 10.1017/s0954422416000287] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.
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The Effects of Metabolic Surgery on Fatty Liver Disease and Nonalcoholic Steatohepatitis. Surg Clin North Am 2017; 96:703-15. [PMID: 27473796 DOI: 10.1016/j.suc.2016.03.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an under-recognized but increasingly important manifestation of the metabolic syndrome. Bariatric surgery, both through direct weight loss and more indirect effects on insulin resistance and improvements in inflammatory proteins, can have a profound effect on NAFLD, resulting in improvement or resolution of even high-grade liver disease.
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Clinical and Metabolic Effects of Biliopancreatic Diversion Persist After Reduction of the Gastric Pouch and Elongation of the Common Alimentary Tract. Preliminary Report in a Series of Patients with a 10-Year Follow-Up. Obes Surg 2016; 27:1493-1500. [DOI: 10.1007/s11695-016-2479-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Abstract
Outcomes after bariatric surgery can vary widely and seem to have a significant genetic component. Only a small number of candidate gene and genome-wide association studies have analyzed bariatric surgery outcomes. The role of bile acids in mediating the beneficial effects of bariatric surgery implicate genes regulated by the farnesoid X receptor transcription factor.
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Affiliation(s)
- Olivier F Noel
- Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, Philadelphia, PA 19140, USA; Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA; DNAsimple, Philadelphia, PA, USA
| | - Christopher D Still
- Department of Gastroenterology and Nutrition, Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822, USA
| | - Glenn S Gerhard
- Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, 960 Medical Education and Research Building (MERB), 3500 North Broad Street, Philadelphia, PA 19140, USA.
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Aguilar-Olivos NE, Almeda-Valdes P, Aguilar-Salinas CA, Uribe M, Méndez-Sánchez N. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome. Metabolism 2016; 65:1196-1207. [PMID: 26435078 DOI: 10.1016/j.metabol.2015.09.004] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Revised: 09/03/2015] [Accepted: 09/08/2015] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD.
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Affiliation(s)
| | - Paloma Almeda-Valdes
- Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carlos A Aguilar-Salinas
- Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Misael Uribe
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
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Bower G, Toma T, Harling L, Jiao LR, Efthimiou E, Darzi A, Athanasiou T, Ashrafian H. Bariatric Surgery and Non-Alcoholic Fatty Liver Disease: a Systematic Review of Liver Biochemistry and Histology. Obes Surg 2016; 25:2280-9. [PMID: 25917981 DOI: 10.1007/s11695-015-1691-x] [Citation(s) in RCA: 183] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of global liver disease that is associated with the rising prevalence of obesity worldwide. There is now increasing clinical and mechanistic evidence reporting on the metabolic and weight loss effects of bariatric surgery on improving NAFLD in obese patients. OBJECTIVES The aim of this paper was to quantify the effects of bariatric surgery on NAFLD by appraising the modulation between pre- and post-operative liver enzyme levels (as markers of liver injury) and liver histology. METHODS A systematic review of studies reporting pre-operative and post-operative liver enzymes or liver histology was done in obese patients with NAFLD undergoing bariatric surgery. Data were meta-analysed using random-effects modelling. Subgroup analysis, quality scoring and risk of bias were assessed. RESULTS Bariatric surgery is associated with a significant reduction in the weighted incidence of a number of histological features of NAFLD including steatosis (50.2 and 95 %CI of 35.5-65.0), fibrosis (11.9 and 95 %CI of 7.4-16.3 %), hepatocyte ballooning (67.7 and 95 %CI 56.9-78.5) and lobular inflammation (50.7 and 95 %CI 26.6-74.8 %). Surgery is also associated with a reduction in liver enzyme levels, with statistically significant reductions in ALT (11.36 u/l, 95 %CI 8.36-14.39), AST (3.91 u/l, 95 %CI 2.23-5.59), ALP (10.55 u/l, 95 %CI 4.40-16.70) and gamma-GT (18.39 u/l, 95 %CI 12.62-24.16). Heterogeneity in results was high. CONCLUSIONS Bariatric surgery is associated with a significant improvement in both histological and biochemical markers of NAFLD. Future studies must focus on higher levels of evidence to better identify the benefits of bariatric surgery on liver disease in order to enhance future treatment strategies in the management of NAFLD.
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Affiliation(s)
- Guy Bower
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Tania Toma
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Leanne Harling
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Long R Jiao
- Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Hepatobiliary and Pancreatic Surgery, Imperial College Healthcare NHS Trust, London, UK
| | - Evangelos Efthimiou
- Department of Surgery and Cancer, Imperial College London, London, UK.,Department of Bariatric Surgery, Chelsea and Westminster Hospital, London, UK
| | - Ara Darzi
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Thanos Athanasiou
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Hutan Ashrafian
- Department of Surgery and Cancer, Imperial College London, London, UK. .,Department of Bariatric Surgery, Chelsea and Westminster Hospital, London, UK. .,Department of Hepatobiliary and Pancreatic Surgery, Imperial College Healthcare NHS Trust, London, UK.
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Combined Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Sleeve Gastrectomy or Gastric Bypass?—a Controlled Matched Pair Study of 34 Patients. Obes Surg 2015; 26:1867-74. [DOI: 10.1007/s11695-015-2006-y] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Mahawar KK, Parmar C, Graham Y, Abouleid A, Carr WRJ, Jennings N, Schroeder N, Small PK. Routine Liver Biopsy During Bariatric Surgery: an Analysis of Evidence Base. Obes Surg 2015; 26:177-81. [PMID: 26428254 DOI: 10.1007/s11695-015-1916-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and alleviates liver fat accumulation in a diabetic rat model. Obes Surg 2015; 24:2152-60. [PMID: 24898720 DOI: 10.1007/s11695-014-1308-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ). METHODS Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively. RESULTS Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively. CONCLUSIONS DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.
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