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Al-Smadi K, Qureshi A, Buitrago M, Ashouri B, Kayali Z. Survival and Disease Progression in Older Adult Patients With Cirrhosis: A Retrospective Study. Int J Hepatol 2024; 2024:5852680. [PMID: 39149542 PMCID: PMC11326880 DOI: 10.1155/2024/5852680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/09/2024] [Accepted: 07/26/2024] [Indexed: 08/17/2024] Open
Abstract
Background: Cirrhosis incidence in older adult patients has been increasing with limited data on their survival. This study is aimed at investigating the survival and disease progression in older adult patients with cirrhosis compared to younger patients. Methods: This is a retrospective single-center study. Patients aged above 50 with a confirmed diagnosis of cirrhosis based on biopsy, FibroSure test, splenomegaly, and low platelets < 120 × 109/L) or imaging findings including FibroScan were included. Patients with active substance abuse, transjugular intrahepatic portosystemic shunt (TIPS), prior spontaneous bacterial peritonitis (SBP), variceal hemorrhage, model for end-stage liver disease-Na (MELD - Na) ≥ 20, had liver transplantation, malignancy except for squamous cell carcinoma, and other comorbidities such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and end-stage kidney disease with glomerular filtration rate (GFR) < 30 were excluded. Patients' records from the liver clinic were reviewed and demographics, laboratory, and compensation and decompensation status were collated. Patients were separated into two groups based on age 50-64 years and age ≥ 65. The primary endpoint was death, and the secondary endpoint was disease progression measured by the baseline to 12-month increase in MELD-Na score. The Kaplan-Meier analysis was conducted to compare the survival between the two groups. Cox regression analysis was performed to identify independent risk factors for poor survival. Results: A total of 191 patients diagnosed with cirrhosis met the inclusion and exclusion criteria. There were 80 patients aged 50-64 years and 111 patients aged ≥ 65 years. Significantly shorter survival times were seen among patients aged ≥ 65 years compared to those aged 50-64 years (73.3 ± 4.8 vs. 151.5 ± 22.7; p < .001). Age of diagnosis ≥ 65 years (p < 0.001), male gender (p = .013), body mass index (BMI) < 30 (p = 0.005), and decompensation (p = 0.008) were found to be independent risk factors for poor survival. MELD-Na scores increased significantly in 12 months of follow-up from baseline, but only in patients with decompensated cirrhosis (p = 0.013). Conclusions: Cirrhotic patients aged ≥ 65 years have significantly poor survival compared to younger patients. A prospective study is needed to further investigate the effect of age and obesity on survival and disease progression in older adult patients with cirrhosis.
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Affiliation(s)
- Khaled Al-Smadi
- Department of Gastroenterology and Hepatology University of California-Riverside School of Medicine, Riverside, USA
| | - Ammar Qureshi
- Department of Gastroenterology and Hepatology University of California-Riverside School of Medicine, Riverside, USA
| | - Michelle Buitrago
- Department of Biology State University of New York - Stony Brook, Stony Brook, USA
| | - Besher Ashouri
- Department of Gastroenterology and Hepatology University of California-Riverside School of Medicine, Riverside, USA
| | - Zeid Kayali
- Department of Gastroenterology and Hepatology University of California-Riverside School of Medicine, Riverside, USA
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Yen FS, Hou MC, Cheng-Chung Wei J, Shih YH, Hsu CY, Hsu CC, Hwu CM. Glucagon-like Peptide-1 Receptor Agonist Use in Patients With Liver Cirrhosis and Type 2 Diabetes. Clin Gastroenterol Hepatol 2024; 22:1255-1264.e18. [PMID: 37331413 DOI: 10.1016/j.cgh.2023.06.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 05/23/2023] [Accepted: 06/02/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND AND AIMS Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis. METHODS Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers. RESULTS The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32-0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41-0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49-0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36-0.97), and liver failure (aHR, 0.54; 95% CI, 0.34-0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse. CONCLUSIONS This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results.
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Affiliation(s)
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Ying-Hsiu Shih
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung City, Taiwan
| | - Chung Y Hsu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan; Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan; National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin, Taiwan.
| | - Chii-Min Hwu
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
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Yen FS, Hou MC, Liu JS, Hsu CC, Hwu CM. Severe hypoglycemia in patients with liver cirrhosis and type 2 diabetes. Front Med (Lausanne) 2023; 9:962337. [PMID: 36687427 PMCID: PMC9845885 DOI: 10.3389/fmed.2022.962337] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 12/09/2022] [Indexed: 01/06/2023] Open
Abstract
INTRODUCTION Advanced liver disease with massive liver damage may affect the metabolism of hypoglycemic agents and increase the risk of hypoglycemia. We conduct this research to compare the risk of severe hypoglycemia between patients with type 2 diabetes, with and without compensated liver cirrhosis. METHODS From Taiwan's National Health Insurance Research Database, we identified persons with type 2 diabetes with cirrhosis (n = 18,209) and without cirrhosis (n = 538,510) from January 1, 2000, to December 31, 2010. Cox proportional hazards models were adopted to assess risks of all-cause mortality and severe hypoglycemia. RESULTS The mean follow-up period of this study was 3.7 years. The incidence rates of death during follow-up were 26.54 and 2.75 per 1,000 patient-years [aHR 7.63 (6.70-8.70)] for patients with cirrhosis and without cirrhosis, respectively. The incidence rates of severe hypoglycemia during follow-up were 0.53 and 0.14 per 1,000 patient-years [aHR 2.74 (1.52-4.92)] for patients with and without cirrhosis, respectively. The subgroup analysis of hypoglycemia risks in patients with and without cirrhosis disclosed no significant interaction for variables such as age, sex, chronic kidney disease, sulfonylurea use, number of oral antidiabetic drugs, insulin, b-blocker, and fibrate. CONCLUSION This cohort study demonstrated that patients with type 2 diabetes and compensated cirrhosis showed a higher risk of mortality and severe hypoglycemia than those without liver cirrhosis.
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Affiliation(s)
| | - Ming-Chih Hou
- Department of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
| | - Jia-Sin Liu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
- National Center for Geriatrics and Welfare Research, National Health Research Institutes, Taipei City, Taiwan
| | - Chii-Min Hwu
- Department of Medicine, School of Medicine, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
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Yen FS, Hou MC, Wei JCC, Shih YH, Hsu CY, Hsu CC, Hwu CM. Liver-related long-term outcomes of alpha-glucosidase inhibitors in patients with diabetes and liver cirrhosis. Front Pharmacol 2022; 13:1049094. [PMID: 36618937 PMCID: PMC9812564 DOI: 10.3389/fphar.2022.1049094] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Adequate management of diabetes in patients with liver cirrhosis can be challenging. We conducted this study to investigate the liver-related long term outcomes of alpha-glucosidase inhibitors (AGIs) in patients with diabetes and cirrhosis. Methods: From National Health Insurance Research Database (NHIRD) in Taiwan, we recruited propensity-score matched alpha-glucosidase inhibitor users and non-users from a cohort of type 2 diabetes mellitus (T2DM) with compensated liver cirrhosis between 1 January 2000, and 31 December 2017, and followed them until 31 December 2018. Cox proportional hazards models with robust sandwich standard error estimates were used to assess the risk of main outcomes for alpha-glucosidase inhibitor users versus non-users. Results: The incidence rates of mortality during follow-up were 65.56 vs. 96.06 per 1,000 patient-years for alpha-glucosidase inhibitor users and non-users, respectively. The multivariable-adjusted model shows that alpha-glucosidase inhibitor users had significantly lower risks of all-cause mortality (aHR 0.63, 95% CI 0.56-0.71), hepatocellular carcinoma (aHR 0.55, 95% CI 0.46-0.67), decompensated cirrhosis (aHR 0.74 95% CI 0.63-0.87), hepatic encephalopathy (aHR 0.72, 95% CI 0.60-0.87), and hepatic failure (aHR 0.74, 95% CI 0.62-0.88) than alpha-glucosidase inhibitor non-users. Patients who received alpha-glucosidase inhibitors for a cumulative duration of more than 364 days had significantly lower risks of these outcomes than non-users. Conclusion: Alpha-glucosidase inhibitor use was associated with a lower risk of mortality, hepatocellular carcinoma, decompensated cirrhosis, and hepatic failure in patients with diabetes and compensated cirrhosis. alpha-glucosidase inhibitors may be useful for the management of diabetes in patients with compensated liver cirrhosis. Large-scale prospective studies are required to verify our results.
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Affiliation(s)
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Ying-Hsiu Shih
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Chung Y. Hsu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Taipei, Miaoli, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
- National Center for Geriatrics and Welfare Research, National Health Research Institutes, Taipei, Miaoli, Taiwan
| | - Chii-Min Hwu
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Yen F, Huang Y, Hou M, Hwu C, Lo Y, Shin S, Hsu C. Metformin use and cirrhotic decompensation in patients with type 2 diabetes and liver cirrhosis. Br J Clin Pharmacol 2022; 88:311-322. [PMID: 34198358 PMCID: PMC9292486 DOI: 10.1111/bcp.14970] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 04/19/2021] [Accepted: 05/26/2021] [Indexed: 12/11/2022] Open
Abstract
AIMS To compare the risks of all-cause mortality, hepatic outcomes, major adverse cardiovascular events between metformin users and nonusers for patients with diabetes and cirrhosis. METHODS From the Taiwan's National Health Insurance Research Database, we selected propensity-score matched metformin users and nonusers from the cohorts of type 2 diabetes mellitus with compensated (n = 26 164) or decompensated liver cirrhosis (n = 15 056) between 1 January 2000 and 31 December 2009, and followed them until 31 December 2010. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risk of investigated outcomes for metformin users. RESULTS The incidence rates of mortality during follow-up were 3.8 and 3.3 per 100 patient-years (adjusted hazard ratio [aHR] 1.13, 95% confidence interval 1.01-1.25) for metformin users and nonusers, respectively. The incidence rates of cirrhotic decompensation during follow-up were 5.9 and 4.9 per 100 patient-years (aHR 1.15, 95% confidence interval 1.04-1.27) for metformin users and nonusers. The risk of death (P for trend <.01) and cirrhotic decompensation (P for trend <.0001) associated with metformin use was significant for those taking metformin for >40 defined daily doses in 90 days or >1000 mg/d. The outcomes of metformin use vs nonuse for type 2 diabetes mellitus with decompensated liver cirrhosis were not statistically different, except that metformin users had higher risk of mortality (aHR 1.15). CONCLUSION Metformin use was associated with higher risks of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis. Prospective studies are required to confirm our results.
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Affiliation(s)
| | - Yi‐Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
- Faculty of Medicine, School of MedicineNational Yang‐Ming UniversityTaipeiTaiwan
| | - Ming‐Chih Hou
- Faculty of Medicine, School of MedicineNational Yang‐Ming UniversityTaipeiTaiwan
- Institute of Clinical Medicine, School of MedicineNational Yang‐Ming UniversityTaipeiTaiwan
| | - Chii‐Min Hwu
- Institute of Clinical Medicine, School of MedicineNational Yang‐Ming UniversityTaipeiTaiwan
- Section of Endocrinology and Metabolism, Department of MedicineTaipei Veterans General HospitalTaiwan
| | - Yu‐Ru Lo
- Institute of Population Health Sciences, National Health Research InstitutesMiaoli CountyTaiwan
| | - Shyi‐Jang Shin
- College of MedicineKaohsiung Medical UniversityKaohsiung CityTaiwan
- Division of Endocrinology and Metabolism, Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung CityTaiwan
- Department of Internal MedicineKaohsiung Municipal Ta‐Tung HospitalKaohsiung CityTaiwan
| | - Chih‐Cheng Hsu
- Institute of Population Health Sciences, National Health Research InstitutesMiaoli CountyTaiwan
- Department of Health Services AdministrationChina Medical UniversityTaichungTaiwan
- Department of Family MedicineMin‐Sheng General HospitalTaoyuanTaiwan
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Kadiri DD, Peela S, Ganguli D. Effect of cirrhosis and hepatitis on the prognosis of liver cancer. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA 2022:51-72. [DOI: 10.1016/b978-0-323-98806-3.00002-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Selvan M, Collins H, Griffiths W, Gelson W, Herre J. Case Report: Indwelling Pleural Catheter Based Management of Refractory Hepatic Hydrothorax as a Bridge to Liver Transplantation. Front Med (Lausanne) 2021; 8:695977. [PMID: 34322505 PMCID: PMC8311019 DOI: 10.3389/fmed.2021.695977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/14/2021] [Indexed: 11/24/2022] Open
Abstract
Introduction: Liver transplantation is the treatment of choice for decompensated liver disease, and by extension for hepatic hydrothorax. Persistent pleural effusions make it challenging for patients to maintain physiological fitness for transplantation. Indwelling pleural catheters (IPCs) provide controlled pleural fluid removal, including peri-operatively. The immune dysfunction of cirrhosis heightens susceptibility to bacterial infection and concerns exist regarding the sepsis potential from a tunnelled drain. Method: Six patients were identified who underwent IPC insertion for hepatic hydrothorax before successful liver transplantation, between November 2016 and November 2017. Results: All patients had recurrent transudative right sided pleural effusions. Mean age was 49 years (range 24–64) and mean United Kingdom Model for End-Stage Liver Disease score was 58. Four patients required correction of coagulopathy before insertion. There were no complications secondary to bleeding. Three patients were taught self-drainage at home of up to 1 litre (L) daily. A protocol was developed to ensure weekly review, pleural fluid culture and drainage of larger volumes in hospital. For every 2–3 L of pleural fluid drained, 100 mls of 20% Human Albumin Solution (HAS) was administered. On average an IPC was in situ for 58 days before surgery and drained 19 L of fluid in hospital. There was a small increase in average BMI (0.2) and serum albumin (2.1 g/L) at transplantation. There was one episode of stage one acute kidney injury secondary to high volume drainage. No further ascitic or pleural procedures were needed while an IPC was in situ. One thoracentesis was required after IPC removal. On average IPCs remained in situ for 7 days post transplantation and drained a further 2 L of fluid. Pleural fluid sampling was acquired on 92% of drainages in hospital. Of 44 fluid cultures, 2 cultured bacteria. Two patients had their IPCs and all other lines removed post transplantation due to suspected infection. Conclusion: Our case series describes a novel protocol and successful use of IPCs in the management of refractory hepatic hydrothorax as a bridge to liver transplantation. The protocol includes albumin replacement during pleural drainage, regular clinical review and culture of pleural fluid, with the option of self-drainage at home.
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Affiliation(s)
- Mayurun Selvan
- Respiratory Medicine, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
| | - Hannah Collins
- Respiratory Medicine, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
| | - William Griffiths
- Cambridge Liver Unit, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
| | - William Gelson
- Cambridge Liver Unit, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
| | - Jurgen Herre
- Respiratory Medicine, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom
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Yen FS, Lai JN, Wei JCC, Chiu LT, Hsu CC, Hou MC, Hwu CM. Is insulin the preferred treatment in persons with type 2 diabetes and liver cirrhosis? BMC Gastroenterol 2021; 21:263. [PMID: 34118892 PMCID: PMC8199810 DOI: 10.1186/s12876-021-01773-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/22/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis. METHODS From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan's National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes. RESULTS The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18-1.45), 1.18 (1.05-1.34), 1.53 (1.35-1.72), 1.26 (1.42-1.86), 1.41 (1.23-1.62), and 3.33 (2.45-4.53), respectively. CONCLUSIONS This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.
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Affiliation(s)
- Fu-Shun Yen
- Dr. Yen's Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan, 33354, Taiwan
| | - Jung-Nien Lai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, 3F., No. 373-2, Jianxing Road, Taichung, 40459, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung City, 40201, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan
| | - Lu-Ting Chiu
- Management Office for Health Data, China Medical University Hospital, 3F., No. 373-2, Jianxing Road, Taichung, 40459, Taiwan
- College of Medicine, China Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan
- Department of Health Services Administration, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, 168 ChingKuo Road, Taoyuan, 33044, Taiwan
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei, 11221, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan.
| | - Chii-Min Hwu
- Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei, 11221, Taiwan.
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan.
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Yen FS, Wei JCC, Yip HT, Hwu CM, Hou MC, Hsu CC. Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan. Hepatol Int 2021; 15:179-190. [PMID: 33423239 DOI: 10.1007/s12072-020-10122-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/15/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND/PURPOSE Management of type 2 diabetes mellitus (T2DM) in patients with liver cirrhosis is complex and suboptimal, but no clinical trial has adequately investigated antidiabetic drug use for such patients. We evaluate the risk of mortality, cardiovascular events, and hepatic outcomes between dipeptidyl peptidase-4 (DPP-4) inhibitor users and nonusers in patients with type 2 diabetes mellitus (T2DM) and cirrhosis. METHODS We selected 2828 paired propensity score matched DPP-4 inhibitor users and nonusers from a cohort of T2DM with compensated liver cirrhosis between January 1, 2007, and December 31, 2012. Cox proportional hazards models were used to assess the risk of main outcomes for DPP-4 inhibitor users. RESULTS The incidence rate of decompensated cirrhosis during follow-up was 2.20 and 1.53 per 100 patient-years (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.03-1.77) for DPP-4 inhibitor users and nonusers, respectively. The aHRs (95% CI) of variceal bleeding and hepatic failure were 1.67 (1.11-2.52) and 1.35 (1.02-1.79), respectively, for DPP-4 inhibitor users over nonusers. The risk of all-cause mortality, hepatocellular carcinoma, and major cardiovascular events between DPP-4 inhibitor users and nonusers were not statistically different. CONCLUSIONS This study found that DPP-4 inhibitor users were associated with higher risks of decompensated cirrhosis and hepatic failure than did nonusers among patients with T2DM and compensated liver cirrhosis. We must continue to search for appropriate antidiabetic drugs for patients with liver cirrhosis.
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Affiliation(s)
- Fu-Shun Yen
- Dr. Yen's Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan, 33354, Taiwan
| | - James Cheng-Chung Wei
- Division of Allergy, Immunology and Rheumatology Chung, Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan
| | - Hei-Tung Yip
- Management Office for Health Data, China Medical University Hospital, 3F., No. 373-2, Jianxing Road, Taichung, 40459, Taiwan
- College of Medicine, China Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan
| | - Chii-Min Hwu
- Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec.2, Linong Street, Taipei, 11221, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec.2, Linong Street, Taipei, 11221, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan.
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan.
- Department of Family Medicine, Min-Sheng General Hospital, 168 ChingKuo Road, Taoyuan, 33044, Taiwan.
- Department of Health Services Administration, China Medical University, No. 91, Xueshi Rd., North Dist., Taichung, 40402, Taiwan.
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Yen FS, Wei JCC, Chiu LT, Hsu CC, Hou MC, Hwu CM. Thiazolidinediones were associated with higher risk of cardiovascular events in patients with type 2 diabetes and cirrhosis. Liver Int 2021; 41:110-122. [PMID: 33124143 DOI: 10.1111/liv.14714] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 10/16/2020] [Accepted: 10/25/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND& AIMS Type 2 diabetes mellitus (T2DM) management in patients with cirrhosis is complicated. No clinical trials have investigated appropriate antidiabetic drug use in these patients. This study compared the risks of all-cause mortality, major adverse cardiovascular events (MACE) and hepatic outcomes between patients with T2DM and cirrhosis using and not using thiazolidinedione (TZD). METHODS We selected 1,705 propensity score-matched TZD users and nonusers from a Taiwan National Health Insurance Research Database cohort of T2DM patients with compensated cirrhosis between January 1, 2000, and December 31, 2012 and followed them until December 31, 2013. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risks of investigated outcomes for TZD users. RESULTS MACE incidence rates during follow-up were 2.14 and 1.30 per 100 patient-years for TZD users and nonusers, respectively (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI], 1.32-2.19). On the basis of TZD use, the aHRs (95% CIs) for stroke, ischemic heart disease and heart failure were 1.81 (1.28-2.55), 1.59 (1.03-2.44) and 2.09 (1.22-3.60) respectively. Compared with TZD nonusers, rosiglitazone users had significantly higher aHR [1.67 (1.26-2.20)] and pioglitazone users had no significant difference of aHR [1.12 (0.90-1.64)]. All-cause mortality, hepatocellular carcinoma, decompensated cirrhosis and hepatic failure risks did not differ significantly between TZD users and nonusers. CONCLUSIONS Compared with nonuser, TZD users demonstrated significantly higher MACE risks. Therefore, the risks of cardiovascular complications should be considered when prescribing TZDs to patients with T2DM and cirrhosis.
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Affiliation(s)
| | - James Cheng-Chung Wei
- Division of Allergy, Immunology and Rheumatology Chung, Shan Medical University Hospital, Taichung, Taiwan
| | - Lu-Ting Chiu
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chii-Min Hwu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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11
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Yen FS, Lai JN, Wei JCC, Chiu LT, Hwu CM, Hou MC, Hsu CC. Sulfonylureas may be useful for glycemic management in patients with diabetes and liver cirrhosis. PLoS One 2020; 15:e0243783. [PMID: 33315940 PMCID: PMC7735585 DOI: 10.1371/journal.pone.0243783] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 11/25/2020] [Indexed: 12/18/2022] Open
Abstract
This study aimed to investigate the long-term outcomes of sulfonylurea (SU) use in patients with T2DM and compensated liver cirrhosis. From January 1, 2000, to December 31, 2012, we selected the data of 3781 propensity-score-matched SU users and nonusers from Taiwan's National Health Insurance Research Database. The mean follow-up time for this study was 5.74 years. Cox proportional hazards models with robust sandwich standard error estimates were used to compare the risks of main outcomes between SU users and nonusers. The incidence of mortality during follow-up was 3.24 and 4.09 per 100 person-years for SU users and nonusers, respectively. The adjusted hazard ratios and 95% confidence intervals for all-cause mortality, major cardiovascular events, and decompensated cirrhosis in SU users relative to SU nonusers were 0.79 (0.71-0.88), 0.69 (0.61-0.80), and 0.82 (0.66-1.03), respectively. The SU-associated lower risks of death and cardiovascular events seemed to have a dose-response trend. This population-based cohort study demonstrated that SU use was associated with lower risks of death and major cardiovascular events compared with SU non-use in patients with T2DM and compensated liver cirrhosis. SUs may be useful for glycemic management for patients with liver cirrhosis.
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Affiliation(s)
| | - Jung-Nien Lai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
- Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan
| | - Lu-Ting Chiu
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung City, Taiwan
| | - Chii-Min Hwu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
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12
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Buechler C, Aslanidis C. Role of lipids in pathophysiology, diagnosis and therapy of hepatocellular carcinoma. Biochim Biophys Acta Mol Cell Biol Lipids 2020; 1865:158658. [PMID: 32058031 DOI: 10.1016/j.bbalip.2020.158658] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 12/05/2019] [Accepted: 02/06/2020] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive and widespread cancer. Patients with liver cirrhosis of different aetiologies are at a risk to develop HCC. It is important to know that in approximately 20% of cases primary liver tumors arise in a non-cirrhotic liver. Lipid metabolism is variable in patients with chronic liver diseases, and lipid metabolites involved therein do play a role in the development of HCC. Of note, lipid composition of carcinogenic tissues differs from non-affected liver tissues. High cholesterol and low ceramide levels in the tumors protect the cells from oxidative stress and apoptosis, and do also promote cell proliferation. So far, detailed characterization of the mechanisms by which lipids enable the development of HCC has received little attention. Evaluation of the complex roles of lipids in HCC is needed to better understand the pathophysiology of HCC, the later being of paramount importance for the development of urgently needed therapeutic interventions. Disturbed hepatic lipid homeostasis has systemic consequences and lipid species may emerge as promising biomarkers for early diagnosis of HCC. The challenge is to distinguish lipids specifically related to HCC from changes simply related to the underlying liver disease. This review article discusses aberrant lipid metabolism in patients with HCC.
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Affiliation(s)
- Christa Buechler
- Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
| | - Charalampos Aslanidis
- Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany
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Kockerling D, Nathwani R, Forlano R, Manousou P, Mullish BH, Dhar A. Current and future pharmacological therapies for managing cirrhosis and its complications. World J Gastroenterol 2019; 25:888-908. [PMID: 30833797 PMCID: PMC6397723 DOI: 10.3748/wjg.v25.i8.888] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 01/17/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
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Affiliation(s)
- David Kockerling
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Rooshi Nathwani
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Roberta Forlano
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Pinelopi Manousou
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Benjamin H Mullish
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Ameet Dhar
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
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Effects of Underlying Liver Disease on 30-Day Outcomes After Posterior Lumbar Fusion. World Neurosurg 2019; 125:e711-e716. [PMID: 30735863 DOI: 10.1016/j.wneu.2019.01.160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/15/2019] [Accepted: 01/17/2019] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To examine the effects of underlying liver disease on 30-day postoperative complications after elective posterior lumbar fusion (PLF). METHODS We performed a retrospective American College of Surgeons National Surgical Quality Improvement Program study of patients who had undergone elective PLF from 2011 to 2014. The patients were divided into 2 groups stratified by the presence of liver disease, assessed using the Model for End-stage Liver Disease plus sodium score (liver disease, ≥10; no liver disease, <10). The baseline patient and operative characteristics were compared between the 2 groups using univariate analysis. Subsequent multivariate regression analysis adjusted for differences in baseline characteristics was performed to identify 30-day postoperative complications independently associated with liver disease. RESULTS Of 2965 patients, 55.9% had underlying liver disease. Those with liver disease were more frequently aged >65 years, male, and underweight or overweight and had had American Society of Anesthesiologists class ≥3, diabetes, pulmonary comorbidity, cardiac comorbidity, renal comorbidity, bleeding disorder, preoperative dyspnea at rest, and a prolonged operative time. On univariate analysis, patients with liver disease had a greater incidence of cardiac complications, pulmonary complications, renal complications, blood transfusion, sepsis, urinary tract infection, and prolonged hospitalization. On adjusted multivariate regression analysis, liver disease was independently associated with renal complications, pulmonary complications, sepsis, urinary tract infection, prolonged hospitalization, and blood transfusion. CONCLUSIONS As the long-term survival of patients with liver disease continues to increase, a better understanding of the relationship between liver dysfunction and surgical outcomes is needed. The identification of modifiable risk factors would allow them to be addressed and optimized preoperatively to decrease the incidence and severity of complications and improve patient outcomes after PLF.
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15
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Boye A, Yang Y, Asenso J, Wei W. Anti-fibro-hepatocarcinogenic Chinese herbal medicines: A mechanistic overview. JOURNAL OF COMPLEMENTARY MEDICINE RESEARCH 2016; 5:278-89. [PMID: 27366355 PMCID: PMC4927134 DOI: 10.5455/jice.20160530032814] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 05/03/2016] [Indexed: 12/22/2022]
Abstract
Chinese herbal medicine (CHM) is an integral component of complementary/alternative medicine and it is increasingly becoming the preferred therapeutic modality for the treatment of liver fibrosis and hepatocellular carcinoma (HCC) worldwide. Accordingly, the World Health Organization (WHO) has attested to the popularity and efficacy of indigenous herbal therapies including CHM as a first line of treatment for some diseases including liver disorders. However, the WHO and drug discovery experts have always recommended that use of indigenous herbal remedies must go hand-in-hand with the requisite mechanistic elucidation so as to constitute a system of verification of efficacy within the ethnobotanical context of use. Although many CHM experts have advanced knowledge on CHM, nonetheless, more enlightenment is needed, particularly mechanisms of action of CHMs on fibro-hepato-carcinogenesis. We, herein, provide in-depth mechanisms of the action of CHMs which have demonstrated anti-fibro-hepatocarcinogenic effects, in pre-clinical and clinical studies as published in PubMed and other major scientific databases. Specifically, the review brings out the important signaling pathways, and their downstream targets which are modulated at multi-level by various anti-fibro-hepatocarcinogenic CHMs.
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Affiliation(s)
- Alex Boye
- Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
- Department of Pharmacology, Institute of Natural Medicine, Anhui Medical University, Hefei, Anhui Province, China
| | - Yan Yang
- Department of Pharmacology, Institute of Natural Medicine, Anhui Medical University, Hefei, Anhui Province, China
| | - James Asenso
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Wei Wei
- Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
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16
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Abstract
During the assessment of a patient with liver disease, finding the patient has decompensated cirrhosis, as defined by the presence of jaundice, ascites, variceal haemorrhage or hepatic encephalopathy, has major implications regarding management and prevention of cirrhosis-related complications, as well as consideration for a referral for liver transplantation evaluation. Prognosis is markedly worse in patients with decompensated compared with compensated cirrhosis. In general, any patient with decompensated cirrhosis should receive evaluation and medical care by a hepatologist. Since patients frequently present with more than one facet of liver decompensation, such cases pose a complex management challenge requiring input from a multidisciplinary team and close liaison with a liver transplant centre.
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17
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Bai YQ, Yang YX, Yang YG, Ding SZ, Jin FL, Cao MB, Zhang YR, Zhang BY. Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis. World J Gastroenterol 2014; 20:8660-8666. [PMID: 25024623 PMCID: PMC4093718 DOI: 10.3748/wjg.v20.i26.8660] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 04/10/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.
METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.
RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 109/L vs 63.3 ± 15.7 × 109/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.
CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.
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Badillo R, Rockey DC. Hepatic hydrothorax: clinical features, management, and outcomes in 77 patients and review of the literature. Medicine (Baltimore) 2014; 93:135-142. [PMID: 24797168 PMCID: PMC4632908 DOI: 10.1097/md.0000000000000025] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Hepatic hydrothorax is an important and difficult-to-manage complication of cirrhosis and portal hypertension. Here, we aimed to study its clinical features and natural history. Complete clinical data, including outcomes, were abstracted from hospital records of patients with cirrhosis and ascites admitted to University of Texas Southwestern University teaching hospitals from January 2001 to July 2012. Hepatic hydrothorax was diagnosed based on currently accepted clinical characteristics of the disease, including a known diagnosis of cirrhosis, the presence of portal hypertension, pleural fluid analysis, and the absence of primary cardiopulmonary disease.Seventy-seven of 495 (16%) hospitalized cirrhotic patients with pleural effusion (28 female; mean age, 52 yr) met the criteria for diagnosis of hepatic hydrothorax. Resting dyspnea and cough were the most prominent presenting symptoms, occurring in 34% and 22% of patients, respectively. Pleural effusions were most often right-sided (56/77; 73%), followed by left-sided only (13/77; 17%) and bilateral effusions (8/77; 10%); 7 (9%) patients did not have detectable ascites. The mean Model for End-Stage Liver Disease (MELD) score at presentation was 16. The serum to pleural fluid albumin gradient (SPAG) was ≥1.1 in all 48 patients in whom it was measured. Most patients (64/77; 83%) were managed with diuretics and/or thoracentesis, while 8 (10%) underwent transjugular intrahepatic portosystemic shunt (TIPS) and 5 (7%) underwent liver transplant. A total of 44 of 77 (57%) patients died during a mean follow-up of 12 months. The average time from presentation to death for all patients was 368 days, while for those after TIPS it was 845 days. No deaths were reported in the liver transplant group. The data indicate that a substantial number of patients with hepatic hydrothorax had what may be considered atypical presentations, including left-sided only effusions, or pleural effusion without ascites. Here, we propose that the term "serum to pleural fluid albumin gradient (SPAG)" be used to describe the gradient between serum and pleural fluid albumin levels and suggest that not only is it consistent with the portal hypertensive pathophysiology of hepatic hydrothorax, but also it is a useful criterion for diagnosis of hepatic hydrothorax. Finally, the overall outcome of hepatic hydrothorax was extremely poor, except in those undergoing TIPS or liver transplantation.
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Affiliation(s)
- Ricardo Badillo
- From the Department of Medicine (RB), University of Texas Southwestern, and Parkland Memorial Hospital (RB), Dallas, Texas; and Department of Medicine (DCR), Medical University of South Carolina, Charleston, South Carolina
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Levesque E, Saliba F, Ichaï P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014; 60:570-8. [PMID: 24280294 DOI: 10.1016/j.jhep.2013.11.012] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 10/25/2013] [Accepted: 11/18/2013] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Mortality rate of patients with cirrhosis admitted to the intensive care unit (ICU) and requiring mechanical ventilation varies between 60 and 91%. The aim of our study is to assess the prognosis of these patients, their 1-year outcome and to analyze predictive factors of long-term mortality. METHODS From May 2005 to May 2011, we studied 246 consecutive patients with cirrhosis requiring mechanical ventilation either at admission or during their ICU stay. RESULTS Alcohol was the most common etiology of the cirrhosis (69%). Bleeding related to portal hypertension (30%) and severe sepsis (33%) were the most common reasons for admission. ICU and hospital mortality were respectively 65.9% and 70.3%. Prognostic severity scores, the need for other organ support therapy, infection, and total bilirubin value at ICU admission were significantly associated with ICU mortality. Eighty-four patients (34.1%) were discharged from the ICU. Among these patients, the one-year survival was only of 32%. Logistic regression analysis, using survival at one year as the endpoint, identified two independent risk factors: the length of ventilation (odds ratio [OR] = 1.1; 95% CI, 1.0-1.2; p = 0.02) and total bilirubin at ICU discharge (OR = 1.3; 95% CI, 1.1-1.5; p = 0.006). CONCLUSION Patients with cirrhosis admitted to the liver ICU and who required mechanical ventilation have a poor prognosis with a 1-year mortality of 89%. At ICU discharge, a total bilirubin level higher than 64.5 μmol/L and length of ventilation higher than 9 days could help the hepatologists to identify patients at risk of death in the year following the ICU discharge.
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Affiliation(s)
- Eric Levesque
- AP-HP Hôpital Henri Mondor, Anesthésie et Réanimations Chirurgicales, Créteil, France; AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, 94800 Villejuif, France.
| | - Philippe Ichaï
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, 94800 Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, 94800 Villejuif, France
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Abolghasemi J, Eshraghian MR, Nasiri Toosi M, Mahmoodi M, Rahimi Foroushani A. Introducing an optimal liver allocation system for liver cirrhosis patients. HEPATITIS MONTHLY 2013; 13:e10479. [PMID: 24098306 PMCID: PMC3787686 DOI: 10.5812/hepatmon.10479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Revised: 02/08/2013] [Accepted: 02/20/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients. OBJECTIVES This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease. PATIENTS AND METHODS Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares. RESULTS During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients' age (year) by applying the Cox model: NMELD = 10 × (0.736 × ln (bilirubin) - 1.312 × ln (albumin) + 0.025 × age + 1.776). CONCLUSIONS The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested.
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Affiliation(s)
- Jamileh Abolghasemi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Mohammad Reza Eshraghian
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Mohammad Reza Eshraghian, Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2188989127, Fax: +98-2188989127, E-mail:
| | - Mohsen Nasiri Toosi
- Department of Gastroenterology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Mahmood Mahmoodi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Abbas Rahimi Foroushani
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran
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Kar K, Dasgupta A, Vijaya Bhaskar M, Sudhakar K. Alteration of micronutrient status in compensated and decompensated liver cirrhosis. Indian J Clin Biochem 2013; 29:232-7. [PMID: 24757308 DOI: 10.1007/s12291-013-0349-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 05/27/2013] [Indexed: 12/14/2022]
Abstract
Decompensation followed by death is the most serious outcome in patients suffering from cirrhosis of the liver. Alteration of trace elements may play a vital role in the process of decompensation. To examine the change in status of trace elements during the decompensation process, we analysed the zinc, copper, iron, magnesium, bilirubin and albumin levels in the serum of compensated (n = 34) and decompensated (n = 31) liver cirrhosis patients and compared them with healthy control group (n = 36) by post hoc ANOVA. We observed significant alteration in the selected micronutrients in the diseased group relative to healthy controls (P < 0.05). Moreover, mean serum zinc and iron levels were significantly lower with a higher level of serum copper in decompensated cirrhosis group than in compensated group (P < 0.05). However, no significant decrease of serum magnesium was found between the two diseased groups. Our findings imply that the trace elements like zinc, copper and iron might exert important contributory roles in decompensation process in liver cirrhosis and hence, may be utilized as important biomarkers for these patients. Furthermore, we propose that replacements of those micronutrients at an early stage can delay or prevent the severe outcomes like hepatic encephalopathy, gastrointestinal bleeding, severe jaundice or ascites in these patients.
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Affiliation(s)
- Kaushik Kar
- Department of Biochemistry, Mamata Medical College, Khammam, Andhra Pradesh India ; Department of Biochemistry, Calcutta National Medical College, CE 184 Salt Lake City, Sector 1, Kolkata, 700064 West Bengal India
| | - Anindya Dasgupta
- Department of Biochemistry, Calcutta National Medical College, Kolkata, West Bengal India
| | - M Vijaya Bhaskar
- Department of Biochemistry, Mamata Medical College, Khammam, Andhra Pradesh India
| | - K Sudhakar
- Department of Biochemistry, Mamata Medical College, Khammam, Andhra Pradesh India
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Abstract
The author draws attention on the importance surgical risk analysis from patient's safety point of view. Recently the development in quality assurance affected surgical practice as well, hence determination and evaluation of surgical risk are more exactly defined. This resulted in a significant decrease in mortality during surgical interventions on the liver despite a wider indication and increased numbers, recently. Importantly, surgical risk is much higher in patients with liver disease compared to patients with normal liver. The risk of surgical interventions for liver diseases (HCC, tumor) in patients with diffuse liver diseases (cirrhosis, chronic hepatitis, ALD) can be expressed numerically. For many years the Child-Turcotte-Pugh stadium could have been determined by using actual laboratory values. Recently the "50-50 rule" or more frequently the MELD score -- originally used in the practice of liver transplantation -- mean objective expression of surgical risk. Treatment optimalisation can reduce surgical risk, selected on the basis of risk analysis in multidisciplinary settings, which focus on the need of liver surgeons.
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Affiliation(s)
- Ferenc Jakab
- Uzsoki Utcai Kórház, 1145 Budapest, Uzsoki u. 29-41.
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23
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Dehghani SM, Imanieh MH, Haghighat M, Malekpour A, Falizkar Z. Etiology and complications of liver cirrhosis in children:report of a single center from southern iran. Middle East J Dig Dis 2013; 5:41-6. [PMID: 24829669 PMCID: PMC3990133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 12/22/2012] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Liver cirrhosis is one of the major causes of hospitalization and mortality in children. A wide spectrum of disorders including developmental abnormalities, infections, metabolic and genetic disorders can lead to liver cirrhosis in pediatric patients. Determination of its etiology is important for treatment, prevention of progressive liver damage, family counseling and prioritizing liver transplantation. The aim of this study is to evaluate causes of liver cirrhosis in children in Southern Iran. METHODS We included all cirrhotic children aged less than 18 years who referred to an outpatient pediatric gastroenterology clinic affiliated with Shiraz University of Medical Sciences between March 2009 and September 2010 in this cross-sectional study. The etiology of cirrhosis was determined according to clinical findings, laboratory tests, imaging studies such as ultrasonography or computed tomography scan, hepatobiliary scintigraphy and histopathologic examination of the liver biopsy. Cirrhosis with unknown etiology was considered as cryptogenic. RESULTS A total of 106 cirrhotic children aged between 5 months to 18 years with a mean age of 8.24 ± 6.12 years that included 60 boys (56.6%) and 46 girls (43.4%) were enrolled in the study. The most common causes of liver cirrhosis were Wilson disease (n=22; 20.7%), biliary atresia (n=19; 17.9%), and cryptogenic cirrhosis (n=14; 13.2%). Other causes were autoimmune hepatitis (n=12; 11.3%), idiopathic neonatal hepatitis (n=10; 9.4%), hepatorenal tyrosinemia (n=9; 8.5%), glycogen storage disease (n=6; 5.7%), and progressive familial intrahepatic cholestasis (n=4; 3.8%). CONCLUSION Considering the most common etiology of liver cirrhosis in children in this part of Iran we suggest testing for Wilson disease in all cirrhotic children.
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Affiliation(s)
- Seyed Mohsen Dehghani
- 1Associate Professor, Department of Pediatric Gastroenterology, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,Corresponding Author: Seyed Mohsen Dehghani, MD Associate Professor of Pediatric Gastroenterology,Gastroenterohepatology Research Center, Shiraz Transplant Research Center, Nemazee Teaching Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Tel: +98 711 626 1775 Fax:+98 711 647 4298
| | - Mohammad Hadi Imanieh
- 2Professor , Department of Pediatric Gastroenterology, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Haghighat
- 3Professor, Gastroenterohepatology Research Center, , Nemazee Teaching Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Abdorrasoul Malekpour
- 4Researcher, Gastroenterohepatology Research Center, Nemazee Teaching Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Falizkar
- 5Gastroenterohepatology Research Center, , Nemazee Teaching Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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