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Sodoma AM, Pellegrini JR, Greenberg S, Sodoma A, Munshi R, Pellegrini RG, Singh J. Outcomes of Coronary Artery Bypass Grafting (CABG) Patients With and Without a History of Liver Transplant. Cureus 2024; 16:e75820. [PMID: 39822448 PMCID: PMC11737807 DOI: 10.7759/cureus.75820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Liver transplant (LT) patients face various challenges, including an increased risk of coronary artery disease (CAD) for a variety of reasons, with 70% of LT recipients having one cardiovascular event. Coronary artery bypass grafting (CABG) remains one of the most commonly performed major surgical procedures in the United States, with 20-30% of LT patients requiring a CABG. Many studies have analyzed when to perform a CABG and CAD workup pre-LT, but this population remains a problem. The patient population is challenging to study due to their rarity and complexity. Our study aimed to compile many patients through the National Inpatient Sample (NIS) database to gauge the outcomes of CABG in patients with and without a history of LT. Methods: Patients who underwent CABG with or without a history of LT were selected from the NIS from 2008 to 2020. The International Classification of Diseases (ICD) 9 and 10 codes were used to identify suitable records. Primary outcomes of interest were all-cause hospital mortality, shock, acute myocardial infarction, acute kidney injury (AKI), and a composite of these. Secondary outcomes included length of stay and total charges. Results: A weighted total of 2,407,349 CABG hospitalizations were included in this study. Of these, 1,833 had a history of LT. Overall, patients with a history of LT were more likely to be younger (65.16 vs. 66.16; p<0.001), male (81.6% vs. 73.66%; p<0.001), and more complex (Charlson Comorbidity Index (CCI) 5.89 vs. 4.16; p<0.001) than patients without a history of LT. Patients with a history of LT also had higher rates of diabetes mellitus type 2 (57.02% vs. 43.39%; p<0.001), end-stage renal disease (11.21% vs. 2.95%; p<0.001), and gastroesophageal reflux disease (GERD) (28.39% vs. 21.26%; p<0.001). CABG patients with a history of LT were less likely, however, to have hyperlipidemia (56.72% vs. 74.26%; p<0.001), hypertension (25.95% vs. 58.45%; p<0.001), obesity (19% vs. 23.42%; p=0.046), a history of smoking (12.06% vs. 18.66%; p<0.01), or alcohol use disorder (9.04% vs. 13.44%; p=0.017). We found that patients admitted for CABG with a history of LT had significantly higher adjusted odds of mortality (OR 1.84; p<0.01), AKI (OR 2.65; p<0.001), and composite outcome (OR 2.04; p<0.001). They also experienced a longer length of stay (1.7 days; p=0.02) and greater hospital charges ($26,761; p=0.029). CONCLUSION We found that CABG patients with a history of LT had nearly twofold higher odds of mortality, nearly threefold higher odds of AKI, and twofold higher odds of composite outcomes than CABG patients without LT. This corresponded to longer lengths of stay and increased hospital charges. Patients should require lower thresholds for left heart catheterization and more strict CAD testing before an LT due to the increased risk of adverse outcomes with the current standard of care.
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Affiliation(s)
- Andrej M Sodoma
- Internal Medicine, South Shore University Hospital, Bay Shore, USA
| | | | - Samuel Greenberg
- Anesthesia and Critical Care, Renaissance School of Medicine at Stony Brook University, Stony Brook, USA
| | - Andrej Sodoma
- Chemistry Faculty, College of Natural Sciences, Grand Canyon University, Phoenix, USA
| | - Rezwan Munshi
- Internal Medicine, Nassau University Medical Center, East Meadow, USA
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Samuvel DJ, Lemasters JJ, Chou CJ, Zhong Z. LP340, a novel histone deacetylase inhibitor, decreases liver injury and fibrosis in mice: role of oxidative stress and microRNA-23a. Front Pharmacol 2024; 15:1386238. [PMID: 38828459 PMCID: PMC11140137 DOI: 10.3389/fphar.2024.1386238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/24/2024] [Indexed: 06/05/2024] Open
Abstract
Effective therapy for liver fibrosis is lacking. Here, we examined whether LP340, the lead candidate of a new-generation of hydrazide-based HDAC1,2,3 inhibitors (HDACi), decreases liver fibrosis. Liver fibrosis was induced by CCl4 treatment and bile duct ligation (BDL) in mice. At 6 weeks after CCl4, serum alanine aminotransferase increased, and necrotic cell death and leukocyte infiltration occurred in the liver. Tumor necrosis factor-α and myeloperoxidase markedly increased, indicating inflammation. After 6 weeks, α-smooth muscle actin (αSMA) and collagen-1 expression increased by 80% and 575%, respectively, indicating hepatic stellate cell (HSC) activation and fibrogenesis. Fibrosis detected by trichrome and Sirius-red staining occurred primarily in pericentral regions with some bridging fibrosis in liver sections. 4-Hydroxynonenal adducts (indicator of oxidative stress), profibrotic cytokine transforming growth factor-β (TGFβ), and TGFβ downstream signaling molecules phospho-Smad2/3 also markedly increased. LP340 attenuated indices of liver injury, inflammation, and fibrosis markedly. Moreover, Ski-related novel protein-N (SnoN), an endogenous inhibitor of TGFβ signaling, decreased, whereas SnoN expression suppressor microRNA-23a (miR23a) increased markedly. LP340 (0.05 mg/kg, ig., daily during the last 2 weeks of CCl4 treatment) decreased 4-hydroxynonenal adducts and miR23a production, blunted SnoN decreases, and inhibited the TGFβ/Smad signaling. By contrast, LP340 had no effect on matrix metalloproteinase-9 expression. LP340 increased histone-3 acetylation but not tubulin acetylation, indicating that LP340 inhibited Class-I but not Class-II HDAC in vivo. After BDL, focal necrosis, inflammation, ductular reactions, and portal and bridging fibrosis occurred at 2 weeks, and αSMA and collagen-1 expression increased by 256% and 560%, respectively. LP340 attenuated liver injury, ductular reactions, inflammation, and liver fibrosis. LP340 also decreased 4-hydroxynonenal adducts and miR23a production, prevented SnoN decreases, and inhibited the TGFβ/Smad signaling after BDL. In vitro, LP340 inhibited immortal human hepatic stellate cells (hTERT-HSC) activation in culture (αSMA and collagen-1 expression) as well as miR23a production, demonstrating its direct inhibitory effects on HSC. In conclusions, LP340 is a promising therapy for both portal and pericentral liver fibrosis, and it works by inhibiting oxidative stress and decreasing miR23a.
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Affiliation(s)
- Devadoss J. Samuvel
- Departments of Drug Discovery and Biomedical Sciences, Charleston, SC, United States
| | - John J. Lemasters
- Departments of Drug Discovery and Biomedical Sciences, Charleston, SC, United States
- Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, United States
| | - C. James Chou
- Departments of Drug Discovery and Biomedical Sciences, Charleston, SC, United States
- Lydex Pharmaceuticals, Mount Pleasant, SC, United States
| | - Zhi Zhong
- Departments of Drug Discovery and Biomedical Sciences, Charleston, SC, United States
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Muacevic A, Adler JR, Awan SA, Shaikh AJ, Abbasi AA. Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation. Cureus 2023; 15:e33932. [PMID: 36819375 PMCID: PMC9937675 DOI: 10.7759/cureus.33932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2023] [Indexed: 01/19/2023] Open
Abstract
Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices (GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reduce the occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.
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Abstract
AIM The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. METHODS Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. RESULTS Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 μg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P < 0.0001, respectively). During the 3 years prior to oral L-carnitine administration, the enrolled patients were hospitalized a total of 29 times for hepatic encephalopathy. However, during the 3 years following oral L-carnitine administration, they were admitted a total of six times for hepatic encephalopathy (P < 0.001). Median survival time was 40.9 months. Child-Pugh scores before and after oral L-carnitine administration differed significantly, whereas liver reserve function, nutritional status, and muscle index did not change significantly. CONCLUSIONS Oral L-carnitine administration is effective and free of adverse effects in patients with hyperammonemia and reduces the number of hospital admissions for hepatic encephalopathy.
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Wang F, So KF, Xiao J, Wang H. Organ-organ communication: The liver's perspective. Am J Cancer Res 2021; 11:3317-3330. [PMID: 33537089 PMCID: PMC7847667 DOI: 10.7150/thno.55795] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/28/2020] [Indexed: 12/11/2022] Open
Abstract
Communication between organs participates in most physiological and pathological events. Owing to the importance of precise coordination among the liver and virtually all organs in the body for the maintenance of homeostasis, many hepatic disorders originate from impaired organ-organ communication, resulting in concomitant pathological phenotypes of distant organs. Hepatokines are proteins that are predominantly secreted from the liver, and many hepatokines and several signaling proteins have been linked to diseases of other organs, such as the heart, muscle, bone, and eyes. Although liver-centered interorgan communication has been proposed in both basic and clinical studies, to date, the regulatory mechanisms of hepatokine production, secretion, and reciprocation with signaling factors from other organs are obscure. Whether other hormones and cytokines are involved in such communication also warrants investigation. Herein, we summarize the current knowledge of organ-organ communication phenotypes in a variety of diseases and the possible involvement of hepatokines and/or other important signaling factors. This provides novel insight into the underlying roles and mechanisms of liver-originated signal transduction and, more importantly, the understanding of disease in an integrative view.
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Chai J, Wang K, Kong X, Pan C, Jiang W, Zhou W, Chen H, Xue F, Zhang L, Shen Z. Coronary artery bypass graft combined with liver transplantation in patients with advanced alcoholic liver cirrhosis: A case report. Exp Ther Med 2020; 19:3197-3202. [PMID: 32266015 PMCID: PMC7132228 DOI: 10.3892/etm.2020.8594] [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: 11/23/2018] [Accepted: 08/30/2019] [Indexed: 11/17/2022] Open
Abstract
Performing cardiothoracic surgery on patients with advanced liver failure and liver cirrhosis is high-risk for patients. Coronary artery bypass grafting is the most effective treatment for patients with liver failure that is complicated with severe coronary heart disease, and who cannot be treated using coronary stent intervention. In the current study, one case of coronary artery bypass grafting combined with liver transplantation was assessed, with the patient exhibiting advanced alcoholic liver cirrhosis. A coronary artery bypass graft was performed to relieve angina pectoris. Following surgery, wound exudation, secondary infection, liver failure, pleuroperitoneal fluid leakage, hypoproteinemia and other adverse treatment results occurred, and the chest wound did not heal. Allograft liver transplantation was subsequently performed and, following surgery, the chest wound healed gradually after debridement, and the patient recovered.
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Affiliation(s)
- Junwu Chai
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Kai Wang
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Xiangrong Kong
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Cheng Pan
- Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, P.R. China
| | - Wentao Jiang
- Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, P.R. China
| | - Wei Zhou
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Honglei Chen
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Fenlong Xue
- Department of Cardiovascular Surgery, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation, Tianjin, 300074, P.R. China
| | - Li Zhang
- Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, P.R. China
| | - Zhongyang Shen
- Department of Liver Transplantation, Tianjin First Central Hospital, Tianjin 300192, P.R. China
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Wimborne HJ, Takemoto K, Woster PM, Rockey DC, Lemasters JJ, Zhong Z. Aldehyde dehydrogenase-2 activation by Alda-1 decreases necrosis and fibrosis after bile duct ligation in mice. Free Radic Biol Med 2019; 145:136-145. [PMID: 31557514 PMCID: PMC6880805 DOI: 10.1016/j.freeradbiomed.2019.09.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 09/11/2019] [Accepted: 09/22/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM Liver fibrosis is a leading cause of mortality worldwide. Oxidative stress is a key component in the pathogenesis of liver fibrosis. We investigated the role of aldehyde formation resulting from lipid peroxidation in cholestatic liver injury and fibrosis. METHODS C57Bl/6J mice underwent bile duct ligation (BDL) or sham operation. One hour after surgery and daily thereafter, animals were given Alda-1 (20 mg/kg, s.c.), an aldehyde dehydrogenase-2 activator, or equivalent volume of vehicle. Blood and livers were collected after 3 and 14 days. RESULTS Serum alanine aminotransferase (ALT) increased from 39.8 U/L after sham operation to 537 U/L 3 days after BDL, which Alda-1 decreased to 281 U/L. Biliary infarcts with a periportal distribution developed with an area of 7.8% at 14 days after BDL versus 0% area after sham operation. Alda-1 treatment with BDL decreased biliary infarcts to 1.9%. Fibrosis detected by picrosirius red staining increased from 1.6% area in sham to 7.3% after BDL, which decreased to 3.8% with Alda-1. Alda-1 suppression of fibrosis was additionally confirmed by second harmonic generation microscopy. After BDL, collagen-I mRNA increased 12-fold compared to sham, which decreased to 6-fold after Alda-1 treatment. Smooth muscle α-actin expression in the liver, a marker of activated stellate cells, increased from 1% area in sham to 18.7% after BDL, which decreased to 5.3% with Alda-1. CD68-positive macrophages increased from 33.4 cells/field in sham to 134.5 cells/field after BDL, which decreased to 64.9 cells/field with Alda-1. Lastly, 4-hydroxynonenal adduct (4-HNE) immunofluorescence increased from 2.5% area in sham to 14.1% after BDL. Alda-1 treatment decreased 4-HNE to 2.2%. CONCLUSION Accelerated aldehyde degradation by Alda-1 decreases BDL-induced liver necrosis, inflammation, and fibrosis, implying that aldehydes play an important role in the pathogenesis of cholestatic liver injury and fibrosis.
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Affiliation(s)
- Hereward J Wimborne
- Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, 29425, United States; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, 29425, United States
| | - Kenji Takemoto
- Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, 29425, United States; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, 29425, United States
| | - Patrick M Woster
- Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, 29425, United States
| | - Don C Rockey
- Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, United States
| | - John J Lemasters
- Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, 29425, United States; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, 29425, United States; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, United States; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, United States
| | - Zhi Zhong
- Center for Cell Death, Injury & Regeneration, Medical University of South Carolina, Charleston, SC, 29425, United States; Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC, 29425, United States.
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Wang C, Ma DQ, Luo S, Wang CM, Ding DP, Tian YY, Ao KJ, Zhang YH, Chen Y, Meng ZJ. Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure. World J Clin Cases 2019; 7:2204-2216. [PMID: 31531315 PMCID: PMC6718793 DOI: 10.12998/wjcc.v7.i16.2204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/20/2019] [Accepted: 07/20/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND In China, hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality. Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality. Bacterial translocation from the intestine, impaired hepatic clearance, and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure. The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes. Active prevention, early diagnosis, and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF. AIM To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF. METHODS Patients with HBV-ACLF hospitalized at Taihe Hospital, Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled. Patient-related information was retrieved from the hospital case database, including general information, blood biochemistry, complications, etc. According to the occurrence of secondary infection or not, the patients were divided into an infection group and a non-infection group. The sites, types, and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed. The risk factors for infections were assessed by unconditional logistic regression. RESULTS There were 174 cases of HBV-ACLF that met the enrollment criteria, of which 114 (65.52%) were diagnosed with infectious complications. Infections occurred in the abdominal cavity (87 cases), respiratory tract (51 cases), urinary tract (18 cases), and biliary tract (10 cases). Patients with infectious complications had a significantly higher 28-d mortality (70.18%, 80/114) than those without (40.00%, 24/60) (70.18% vs 40.00%, P < 0.05). And patients with infectious complications had a much higher incidence of non-infectious complications (54.39%, 62/114) (54.39% vs 15.00%, P < 0.05), leading to an extremely high 28-d mortality of 88.71% (55/62) (P < 0.05). The grade of liver failure, period of hospital stay ≥ 30 d, age ≥ 45 years, and percentage of neutrophils > 70% were identified as risk factors for infectious complications. CONCLUSION The high incidence of infectious complications in patients with HBV-ACLF is associated with severity and deterioration of the disease and may contribute to the extremely high mortality of these patients.
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Affiliation(s)
- Chen Wang
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - De-Qiang Ma
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Sen Luo
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Chuan-Min Wang
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - De-Ping Ding
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - You-You Tian
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Kang-Jian Ao
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Yin-Hua Zhang
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Yue Chen
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
| | - Zhong-Ji Meng
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
- Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China
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Wang C, Ma DQ, Luo S, Wang CM, Ding DP, Tian YY, Ao KJ, Zhang YH, Chen Y, Meng ZJ. Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure. World J Clin Cases 2019. [DOI: 10.12998/wjge.v7.i16.2204] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Martí‐Carvajal AJ, Gluud C, Arevalo‐Rodriguez I, Martí‐Amarista CE. Acetyl-L-carnitine for patients with hepatic encephalopathy. Cochrane Database Syst Rev 2019; 1:CD011451. [PMID: 30610762 PMCID: PMC6353234 DOI: 10.1002/14651858.cd011451.pub2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatic encephalopathy is a common and devastating neuropsychiatric complication of acute liver failure or chronic liver disease. Ammonia content in the blood seems to play a role in the development of hepatic encephalopathy. Treatment for hepatic encephalopathy is complex. Acetyl-L-carnitine is a substance that may reduce ammonia toxicity. This review assessed the benefits and harms of acetyl-L-carnitine for patients with hepatic encephalopathy. OBJECTIVES To assess the benefits and harms of acetyl-L-carnitine for patients with hepatic encephalopathy. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and Science Citation Index Expanded for randomised clinical trials. We sought additional randomised clinical trials from the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. We performed all electronic searches until 10 September 2018. We looked through the reference lists of retrieved publications and review articles, and we searched the FDA and EMA websites. SELECTION CRITERIA We searched for randomised clinical trials in any setting, recruiting people with hepatic encephalopathy. Trials were eligible for inclusion if they compared acetyl-L-carnitine plus standard care (e.g. antibiotics, lactulose) versus placebo or no acetyl-L-carnitine plus standard care. We are well aware that by selecting randomised clinical trials, we placed greater focus on potential benefits than on potential harms. DATA COLLECTION AND ANALYSIS We selected randomised clinical trials, assessed risk of bias in eight domains, and extracted data in a duplicate and independent fashion. We estimated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. We measured statistical heterogeneity using I² and D² statistics. We subjected our analyses to fixed-effect and random-effects model meta-analyses. We assessed bias risk domains to control systematic errors. We assessed overall quality of the data for each individual outcome by using the GRADE approach. MAIN RESULTS We identified five randomised clinical trials involving 398 participants. All trials included only participants with cirrhosis as the underlying cause of hepatic encephalopathy. Trials included participants with covert or overt hepatic encephalopathy. All trials were conducted in Italy by a single team and assessed acetyl-L-carnitine compared with placebo. Oral intervention was the most frequent route of administration. All trials were at high risk of bias and were underpowered. None of the trials were sponsored by the pharmaceutical industry.None of the identified trials reported information on all-cause mortality, serious adverse events, or days of hospitalisation. Only one trial assessed quality of life using the Short Form (SF)-36 scale (67 participants; very low-quality evidence). The effects of acetyl-L-carnitine compared with placebo on general health at 90 days are uncertain (MD -6.20 points, 95% confidence interval (CI) -9.51 to -2.89). Results for additional domains of the SF-36 are also uncertain. One trial assessed fatigue using the Wessely and Powell test (121 participants; very low-quality evidence). The effects are uncertain in people with moderate-grade hepatic encephalopathy (mental fatigue: MD 0.40 points, 95% CI -0.21 to 1.01; physical fatigue: MD -0.20 points, 95% CI -0.92 to 0.52) and mild-grade hepatic encephalopathy (mental fatigue: -0.80 points, 95% CI -1.48 to -0.12; physical fatigue: 0.20 points, 95% CI -0.72 to 1.12). Meta-analysis showed a reduction in blood ammonium levels favouring acetyl-L-carnitine versus placebo (MD -13.06 mg/dL, 95% CI -17.24 to -8.99; 387 participants; 5 trials; very low-quality evidence). It is unclear whether acetyl-L-carnitine versus placebo increases the risk of non-serious adverse events (8/126 (6.34%) vs 3/120 (2.50%); RR 2.51, 95% CI 0.68 to 9.22; 2 trials; very low-quality evidence). Overall, adverse events data were poorly reported and harms may have been underestimated. AUTHORS' CONCLUSIONS This Cochrane systematic review analysed a heterogeneous group of five trials at high risk of bias and with high risk of random errors conducted by only one research team. We assessed acetyl-L-carnitine versus placebo in participants with cirrhosis with covert or overt hepatic encephalopathy. Hence, we have no data on the drug for hepatic encephalopathy in acute liver failure. We found no information about all-cause mortality, serious adverse events, or days of hospitalisation. We found no clear differences in effect between acetyl-L-carnitine and placebo regarding quality of life, fatigue, and non-serious adverse events. Acetyl-L-carnitine reduces blood ammonium levels compared with placebo. We rated all evidence as of very low quality due to pitfalls in design and execution, inconsistency, small sample sizes, and very few events. The harms profile for acetyl-L-carnitine is presently unclear. Accordingly, we need further randomised clinical trials to assess acetyl-L-carnitine versus placebo conducted according to the SPIRIT statements and reported according to the CONSORT statements.
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Affiliation(s)
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Ingrid Arevalo‐Rodriguez
- Hospital Universitario Ramon y Cajal (IRYCIS)Clinical Biostatistics UnitMadridSpain
- CIBER Epidemiology and Public Health (CIBERESP)MadridSpain
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Abstract
BACKGROUND Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. OBJECTIVES To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. SELECTION CRITERIA We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias.We found no effect on all-cause mortality when probiotics were compared with placebo or no treatment (7 trials; 404 participants; RR 0.58, 95% CI 0.23 to 1.44; low-quality evidence). No-recovery (as measured by incomplete resolution of symptoms) was lower for participants treated with probiotic (10 trials; 574 participants; RR 0.67, 95% CI 0.56 to 0.79; moderate-quality evidence). Adverse events were lower for participants treated with probiotic than with no intervention when considering the development of overt hepatic encephalopathy (10 trials; 585 participants; RR 0.29, 95% CI 0.16 to 0.51; low-quality evidence), but effects on hospitalisation and change of/or withdrawal from treatment were uncertain (hospitalisation: 3 trials, 163 participants; RR 0.67, 95% CI 0.11 to 4.00; very low-quality evidence; change of/or withdrawal from treatment: 9 trials, 551 participants; RR 0.70, 95% CI 0.46 to 1.07; very low-quality evidence). Probiotics may slightly improve quality of life compared with no intervention (3 trials; 115 participants; results not meta-analysed; low-quality evidence). Plasma ammonia concentration was lower for participants treated with probiotic (10 trials; 705 participants; MD -8.29 μmol/L, 95% CI -13.17 to -3.41; low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial.When probiotics were compared with lactulose, the effects on all-cause mortality were uncertain (2 trials; 200 participants; RR 5.00, 95% CI 0.25 to 102.00; very low-quality evidence); lack of recovery (7 trials; 430 participants; RR 1.01, 95% CI 0.85 to 1.21; very low-quality evidence); adverse events considering the development of overt hepatic encephalopathy (6 trials; 420 participants; RR 1.17, 95% CI 0.63 to 2.17; very low-quality evidence); hospitalisation (1 trial; 80 participants; RR 0.33, 95% CI 0.04 to 3.07; very low-quality evidence); intolerance leading to discontinuation (3 trials; 220 participants; RR 0.35, 95% CI 0.08 to 1.43; very low-quality evidence); change of/or withdrawal from treatment (7 trials; 490 participants; RR 1.27, 95% CI 0.88 to 1.82; very low-quality evidence); quality of life (results not meta-analysed; 1 trial; 69 participants); and plasma ammonia concentration overall (6 trials; 325 participants; MD -2.93 μmol/L, 95% CI -9.36 to 3.50; very low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. AUTHORS' CONCLUSIONS The majority of included trials suffered from a high risk of systematic error ('bias') and a high risk of random error ('play of chance'). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence is very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics.
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Affiliation(s)
- Rohan Dalal
- Sydney Medical School, Westmead Hospital, Sydney, Australia
| | - Richard G McGee
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, The Prince of Wales, Barker St, Randwick, Australia, NSW 2031
| | - Angela C Webster
- Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, Sydney, NSW, Australia, 2006
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12
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Nojkov B, Cappell MS. Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis. World J Gastroenterol 2016; 22:446-466. [PMID: 26755890 PMCID: PMC4698507 DOI: 10.3748/wjg.v22.i1.446] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/11/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy's lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. METHODS Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: "alcoholic liver disease", "alcoholic hepatitis"," alcoholic cirrhosis", "cirrhosis", "liver disease", "upper gastrointestinal bleeding", "non-variceal upper gastrointestinal bleeding", "PUD", ''DL'', ''Mallory-Weiss tear", and "MWS''. RESULTS While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics. Pre-endoscopic management of acute GI bleeding in patients with aALD unrelated to portal hypertension is similar to the management of aALD patients with GI bleeding from portal hypertension, because clinical distinction before endoscopy is difficult. Most patients require intensive care unit admission and attention to avoid over-transfusion, to correct electrolyte abnormalities and coagulopathies, and to administer antibiotic prophylaxis. Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal. Prompt endoscopy, after initial resuscitation, is essential to diagnose and appropriately treat these patients. Generally, the same endoscopic hemostatic techniques are used in patients bleeding from PUD, DL, or MWS in patients with aALD as in the general population. CONCLUSION Nonvariceal upper GI bleeding in patients with aALD has clinically important differences from that in the general population without aALD, including: more frequent and more severe bleeding from PUD, DL, or MWS.
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13
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Coombes J, Swiderska-Syn M, Dollé L, Reid D, Eksteen B, Claridge L, Briones-Orta MA, Shetty S, Oo YH, Riva A, Chokshi S, Papa S, Mi Z, Kuo PC, Williams R, Canbay A, Adams DH, Diehl AM, van Grunsven LA, Choi SS, Syn WK. Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice. Gut 2015; 64:1120-31. [PMID: 24902765 PMCID: PMC4487727 DOI: 10.1136/gutjnl-2013-306484] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 05/22/2014] [Indexed: 12/29/2022]
Abstract
BACKGROUND Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN may modulate liver progenitor cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralisation on murine liver fibrosis. METHODS Liver progenitors (603B and bipotential mouse oval liver) were treated with OPN-neutralising aptamers in the presence or absence of transforming growth factor (TGF)-β, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN-neutralising antibodies) on liver progenitor cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and semiquantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. RESULTS OPN is overexpressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound healing by modulating TGF-β signalling. In vivo, OPN-neutralisation attenuates the liver progenitor cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS OPN upregulation during liver injury is a conserved repair response, and influences liver progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell response and fibrogenesis in mouse models of liver fibrosis.
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Affiliation(s)
- J Coombes
- Regeneration and Repair Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - M Swiderska-Syn
- Division of Gastroenterology, Department of Medicine, Duke University, NC, USA
| | - L Dollé
- Liver Cell Biology Lab (LIVR), Department of Cell Biology (CYTO), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
| | - D Reid
- Snyder Institute for Chronic Diseases, Health Research and Innovation Centre (HRIC), University of Calgary, Canada
| | - B Eksteen
- Snyder Institute for Chronic Diseases, Health Research and Innovation Centre (HRIC), University of Calgary, Canada
| | - L Claridge
- Centre for Liver Research, NIHR Institute for Biomedical Research, University of Birmingham, UK
| | - MA Briones-Orta
- Regeneration and Repair Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - S Shetty
- Centre for Liver Research, NIHR Institute for Biomedical Research, University of Birmingham, UK
| | - YH Oo
- Centre for Liver Research, NIHR Institute for Biomedical Research, University of Birmingham, UK
| | - A Riva
- Viral Hepatitis Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - S Chokshi
- Viral Hepatitis Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - S Papa
- Cell Signaling Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - Z Mi
- Department of Surgery, Loyola University, Chicago, USA
| | - PC Kuo
- Department of Surgery, Loyola University, Chicago, USA
| | - R Williams
- Regeneration and Repair Group, The Institute of Hepatology, Foundation for Liver Research, London, UK
| | - A Canbay
- Department of Gastroenterology and Hepatology, Essen University Hospital, Essen, Germany
| | - DH Adams
- Centre for Liver Research, NIHR Institute for Biomedical Research, University of Birmingham, UK
| | - AM Diehl
- Division of Gastroenterology, Department of Medicine, Duke University, NC, USA
| | - LA van Grunsven
- Liver Cell Biology Lab (LIVR), Department of Cell Biology (CYTO), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
| | - SS Choi
- Division of Gastroenterology, Department of Medicine, Duke University, NC, USA,Section of Gastroenterology, Department of Medicine, Durham Veteran Affairs Medical Center, Durham, NC, USA
| | - WK Syn
- Regeneration and Repair Group, The Institute of Hepatology, Foundation for Liver Research, London, UK,Centre for Liver Research, NIHR Institute for Biomedical Research, University of Birmingham, UK,Department of Hepatology, Barts Health NHS Trust, London, UK,Senior and Corresponding Author: Dr Wing-Kin Syn, Head of Liver Regeneration and Repair, The Institute of Hepatology, Foundation for Liver Research, London WC1E 6HX, Tel: 44-20272559837,
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14
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Comorbidities have a limited impact on post-transplant survival in carefully selected cirrhotic patients: a population-based cohort study. Ann Hepatol 2015. [DOI: 10.1016/s1665-2681(19)31172-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2023]
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Lo EAG, Wilby KJ, Ensom MHH. Use of proton pump inhibitors in the management of gastroesophageal varices: a systematic review. Ann Pharmacother 2015; 49:207-19. [PMID: 25583938 DOI: 10.1177/1060028014559244] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVE To review the efficacy and safety of proton pump inhibitors (PPIs) in gastroesophageal varices (GEVs). DATA SOURCES MEDLINE (1946 to September 2014), EMBASE (1974 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), Cochrane Central Register of Controlled Trials (1991 to September 2014), Google, and Google Scholar were searched using the following terms: esophageal varices, gastroesophageal varices, variceal hemorrhage, variceal bleeding, banding ligation, endoscopic variceal ligation, sclerotherapy, proton pump inhibitor, PPI, omeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, and esomeprazole. STUDY SELECTION AND DATA EXTRACTION Published and unpublished studies evaluating the clinical outcomes of PPI use for GEVs were included regardless of study design. Non-English and nonhuman studies were excluded. DATA SYNTHESIS Of 1156 studies, 20 were included after assessment. There was wide methodological heterogeneity and moderately high risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal ulcer size post-elective esophageal ligation; the clinical importance of such findings is not known given the self-limiting nature of esophageal ulcer. Available evidence does not support a role of PPIs for long-term prophylaxis of portal hypertension-related bleeding and high-dose infusion for acute management of GEV hemorrhage. Retrospective data demonstrate a potential increase in the incidence of spontaneous bacterial peritonitis in patients with cirrhosis receiving PPIs. CONCLUSIONS The best available evidence supports the use of short-course (10 days) PPI post-endoscopic variceal ligation to reduce ulcer size if ulcer healing is a concern. Practices such as high-dose infusion and prolonged use should be discouraged until evidence of benefit becomes available.
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Affiliation(s)
- Elaine A G Lo
- University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Mary H H Ensom
- University of British Columbia, Vancouver, British Columbia, Canada Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada
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17
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Lactulose accelerates liver regeneration in rats by inducing hydrogen. J Surg Res 2015; 195:128-35. [PMID: 25700936 DOI: 10.1016/j.jss.2015.01.034] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Revised: 01/04/2015] [Accepted: 01/21/2015] [Indexed: 11/23/2022]
Abstract
BACKGROUND Oxidative stress and inflammation are implicated in the process of liver regeneration. Lactulose orally administered can be bacterially fermented and induces dramatic amounts of endogenous hydrogen. Hydrogen has been confirmed to have antioxidant and anti-inflammatory properties. This study investigated the potential influence of lactulose administration on liver regeneration. MATERIALS AND METHODS Antibiotics were used to suppress bacterial fermentation of lactulose, and hydrogen-rich saline was used as a supplementary measure of exogenous hydrogen. The liver regeneration model was produced in Sprague-Dawley rats through 70% partial hepatectomy. RESULTS Compared with non-lactulose-treated group, lactulose administration remarkably increased the weights of remnant liver and inhibited increases in serum levels of transaminases more notably. In the lactulose-treated group, increases of markers for regeneration, such as proliferating cell nuclear antigen and cyclin D1, were highly elevated. Biochemically, lactulose administration increased liver superoxide dismutase activity and decreased malondialdehyde content. In the lactulose-treated group, excessive increases in inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, were inhibited significantly. Increased heme oxygenase-1 and superoxide dismutase 2 expression were also observed after lactulose treatment. The antibiotics suppressed the regeneration-promoting effect of lactulose by reducing hydrogen production, whereas supplementing hydrogen by hydrogen-rich saline would get a similar regeneration-promoting effect as lactulose administration. CONCLUSIONS Lactulose administration accelerates posthepatectomized liver regeneration in rats by inducing hydrogen, which may result from attenuation of the oxidative stress response and excessive inflammatory response.
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Progressive Familial Intrahepatic Cholestasis: A Rare Cause of Cirrhosis in Young Adult Patients. Case Rep Med 2015; 2015:428638. [PMID: 26136783 PMCID: PMC4468343 DOI: 10.1155/2015/428638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 05/21/2015] [Indexed: 12/03/2022] Open
Abstract
Hepatic cirrhosis is an important cause of morbidity and mortality. An unusual case of cirrhosis and portal hypertension in an 18-year-old patient secondary to Progressive Intrahepatic Cholestasis is discussed. The clinical and biochemical findings are discussed and a clinical approach to determining the underlying etiology of cirrhosis is outlined. Significant complications of portal hypertension include ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, varices, and hepatic encephalopathy. A clinical approach to these complications of cirrhosis is presented. Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare congenital metabolic abnormality. There are 3 subtypes and Type 3 PFIC commonly presents in late adolescence and early adulthood. Clinical and laboratory findings as well as management for the condition are described.
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Martí-Carvajal AJ, Gluud C, Arevalo-Rodriguez I. Acetyl-L-carnitine for patients with hepatic encephalopathy. Hippokratia 2014. [DOI: 10.1002/14651858.cd011451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital; The Cochrane Hepato-Biliary Group; Blegdamsvej 9 Copenhagen Denmark DK-2100
| | - Ingrid Arevalo-Rodriguez
- Fundación Universitaria de Ciencias de la Salud; Division of Research; Carrera 19 Nº 8a - 32 Bogotá D.C. Bogota DC Colombia 11001
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Gómez-Hurtado I, Such J, Sanz Y, Francés R. Gut microbiota-related complications in cirrhosis. World J Gastroenterol 2014; 20:15624-15631. [PMID: 25400446 PMCID: PMC4229527 DOI: 10.3748/wjg.v20.i42.15624] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized.
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Abstract
OPINION STATEMENT The careful review of drug-drug interactions is vital to the safe prescribing of medications for chronic medical conditions. The elderly population suffers from multiple medical problems, and polypharmacy leads to further morbidity in this vulnerable group of patients. We discuss gastrointestinal conditions such as GERD, peptic ulcer disease, gastroparesis, diarrhea, constipation, irritable bowel syndrome, inflammatory bowel disease, chronic liver disease and the commonly used medications in these conditions. Treatment options must be individualized and tailored to accommodate the underlying pharmacokinetics and known drug-drug interactions. The indication for the use of a therapeutic agent in the elderly and the duration of use must be frequently readdressed to help prevent polypharmacy and adverse drug reactions. Medications should be started at a low dose with careful titration to achieve a clinical response to prevent toxicity. The aim of this article is to increase awareness of important drug-drug interactions of commonly prescribed gastrointestinal medications in the elderly.
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Bruns H, Lozanovski VJ, Schultze D, Hillebrand N, Hinz U, Büchler MW, Schemmer P. Prediction of postoperative mortality in liver transplantation in the era of MELD-based liver allocation: a multivariate analysis. PLoS One 2014; 9:e98782. [PMID: 24905210 PMCID: PMC4048202 DOI: 10.1371/journal.pone.0098782] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Accepted: 05/06/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIMS Liver transplantation is the only curative treatment for end-stage liver disease. While waiting list mortality can be predicted by the MELD-score, reliable scoring systems for the postoperative period do not exist. This study's objective was to identify risk factors that contribute to postoperative mortality. METHODS Between December 2006 and March 2011, 429 patients underwent liver transplantation in our department. Risk factors for postoperative mortality in 266 consecutive liver transplantations were identified using univariate and multivariate analyses. Patients who were <18 years, HU-listings, and split-, living related, combined or re-transplantations were excluded from the analysis. The correlation between number of risk factors and mortality was analyzed. RESULTS A labMELD ≥20, female sex, coronary heart disease, donor risk index >1.5 and donor Na+>145 mmol/L were identified to be independent predictive factors for postoperative mortality. With increasing number of these risk-factors, postoperative 90-day and 1-year mortality increased (0-1: 0 and 0%; 2: 2.9 and 17.4%; 3: 5.6 and 16.8%; 4: 22.2 and 33.3%; 5-6: 60.9 and 66.2%). CONCLUSIONS In this analysis, a simple score was derived that adequately identified patients at risk after liver transplantation. Opening a discussion on the inclusion of these parameters in the process of organ allocation may be a worthwhile venture.
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Affiliation(s)
- Helge Bruns
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Vladimir J. Lozanovski
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Daniel Schultze
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Norbert Hillebrand
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Ulf Hinz
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Markus W. Büchler
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
| | - Peter Schemmer
- Department of General and Transplant Surgery, Ruprecht-Karls University, Heidelberg, Germany
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Kang YJ, Bae EJ, Hwang K, Jeon DH, Jang HN, Cho HS, Chang SH, Park DJ. Initial serum sodium concentration determines the decrease in sodium level after terlipressin administration in patients with liver cirrhosis. SPRINGERPLUS 2013; 2:519. [PMID: 24156092 PMCID: PMC3797913 DOI: 10.1186/2193-1801-2-519] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 10/03/2013] [Indexed: 02/07/2023]
Abstract
Background Terlipressin, as a prodrug of vasopressin, has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial. Methods This study retrospectively investigated 127 patients with liver cirrhosis to examine the incidence and risk factors for the decrease in serum sodium level following terlipressin administration. Results Terlipressin was prescribed for bleeding control (99) and management of hepatorenal syndrome (28). Serum sodium level decreased from 134.0 ± 6.5 mmol/L to 130.4 ± 6.2 mmol/L during or after terlipressin treatment (P < 0.001) in all patients. In 45 patients (35.4%), the serum sodium concentration decreased by > 5 mmol/L, in 29 patients (22.8%); by 5–10 mmol/L; and in 16 patients (12.6%), by > 10 mmol/L. Five patients in the latter group showed neurological manifestations. In the univariate analysis, several factors including age, purpose of use, serum creatinine, and Model for End-Stage Liver Disease score, representing liver function, were significantly associated with the decrease in serum sodium after terlipressin administration. However, a multivariate analysis revealed that only initial sodium level was the most powerful predictor of terlipressin-induced reduction in serum sodium. Conclusion An acute reduction in serum sodium concentration was not uncommon during terlipressin treatment, and the baseline serum sodium level was closely related to the reduction in serum sodium concentration.
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Affiliation(s)
- Yeo-Jin Kang
- Department of Internal Medicine, School of Medicine Gyeongsang University, 816 Beongil 15 Jinju-daero, Jinju, Gyeongnam South Korea
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A current update on the rule of alternative and complementary medicine in the treatment of liver diseases. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:321234. [PMID: 24109491 PMCID: PMC3784269 DOI: 10.1155/2013/321234] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 08/02/2013] [Indexed: 02/05/2023]
Abstract
There is a vast body of knowledge which is ever-increasing about the treatment of liver disease with alternative and complementary medicine for which hundreds of thousands of literatures have been documented. Liver disease is a general term. This term covers all the potential problems that cause the liver to fail to perform its specified operations. Liver disease has a variety of presentations and causes a great public health problem worldwide which threatens the wellness of billions of people. Incidences of many types of liver disease are currently rising. Although there is still a debate about the entity of alternative and complementary medicine, it is now widely used and it is improving. And it covers the shortages and compensates for the weaknesses of conventional methods in the treatment of liver diseases. Alternative and complementary medicine for liver diseases provides benefits by regulating immunity, controlling disease progression, improving quality of life, and prolonging survival. This paper reviews the increasing interest and growing research into alternative and complementary medicine for liver diseases, with a look at the rough classification, principle of management, evidence-based applications, and issues for prescription and perspectives.
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