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Wan X, Xu H, Li H, Zhong S, Lei Y, Deng H, Fu X, Zhou Z. Effectiveness and safety evaluation of terlipressin in the treatment of intestinal paralysis in end-stage liver disease. BMC Gastroenterol 2025; 25:286. [PMID: 40269714 PMCID: PMC12020273 DOI: 10.1186/s12876-025-03910-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 04/17/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND AND AIMS Intestinal paralysis is a common complication in end-stage liver disease (ESLD), our aim is to assess the effectiveness and safety of low-dose terlipressin for treating intestinal paralysis in ESLD. METHODS The study was divided into two phases, in the exploratory phase, we retrospectively analyzed the clinical data of patients with intestinal paralysis treated with low-dose terlipressin and explored its efficacy. In the clinical research phase, we designed a prospective cohort study, patients with intestinal paralysis were categorized into terlipressin treatment group (low-dose terlipressin was added to the conventional treatment) and conventional treatment group according to their wishes. The remission of intestinal paralysis, time to symptom remission, and differences in adverse reactions were compared between the two groups. RESULTS In the exploratory phase, 26 patients were exposed to low-dose terlipressin, 12 were cured, 11 were moderately effective, and 3 were ineffective. The mean time to abdominal bloating remission was 2 days, and the time to anal flatus and feces passage was 1 day. In the clinical research phase, a total of 131 patients were included at baseline, with the exception of one patient who discontinued medication due to severe vomiting, resulting in a final total of 130 patients included in the analysis. The mean time to abdominal pain and bloating remission in the terlipressin treatment group (32/130) was demonstrably shorter compared to the conventional treatment group (98/130) (P < 0.001), the mean time to anal flatus and feces passage was also shorter (P < 0.001), and the remission rate was higher (P < 0.05). The incidence of adverse events was similar. CONCLUSIONS Low-dose terlipressin treatment could considerably increase intestinal paralysis remission in ESLD patients with intestinal paralysis, and have good safety.
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Affiliation(s)
- Xia Wan
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Respiratory and Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Hua Xu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Shan Zhong
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yu Lei
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Huan Deng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiao Fu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhi Zhou
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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Gulyaeva K, Nadinskaia M, Maslennikov R, Aleshina Y, Goptar I, Lukashev A, Poluektova E, Ivashkin V. Gut microbiota analysis in cirrhosis and non-cirrhotic portal hypertension suggests that portal hypertension can be main factor of cirrhosis-specific dysbiosis. Sci Rep 2025; 15:8394. [PMID: 40069378 PMCID: PMC11897210 DOI: 10.1038/s41598-025-92618-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 03/03/2025] [Indexed: 03/15/2025] Open
Abstract
Gut dysbiosis plays an important role in cirrhosis, but the mechanism of its development was not established. The aim of the study was to test the hypothesis that portal hypertension can be the main factor in the development of gut dysbiosis in cirrhosis. This cross-sectional study included 25 patients with chronic non-cirrhotic portal hypertension due to extrahepatic portal vein obstruction after portal vein thrombosis (PVT) (NCPVT group), 29 cirrhotic patients without PVT (CirNoPVT), 15 cirrhotic patients with chronic PVT (CPVT), and 22 healthy controls. The fecal microbiota was assessed using 16S rRNA gene sequencing. The CirNoPVT and CPVT groups had largely similar differences in gut microbiota composition from the control group. Patients with NCPVT, as well as patients with cirrhosis, had a higher abundance of Streptococcus, Escherichia, Enterococcus, Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Bacilli, Gammaproteobacteria, Proteobacteria, and a lower abundance of Roseburia, Faecalibacterium, Methanobrevibacter, Ruminococcaceae, Methanobacteriaceae, Clostridia, Methanobacteria, and Euryarchaeota as they were compared with healthy individuals. Patients with NCPVT had a higher abundance of Bifidobacterium, Bifidobacteriaceae, Actinobacteria, and a lower abundance of Gemmiger and Catenibacterium compared to healthy individuals, which was not observed in the cirrhosis groups. The abundance of Porphyromonadaceae with the genus Parabacteroides was reduced in both groups with PVT, but not in CirNoPVT. There were no significant differences in gut microbiota beta-diversity among the CirNoPVT, CPVT and NCPVT groups. All these groups had significant differences in beta-diversity from the control group. Portal hypertension seems be the main factor in the development of gut dysbiosis in cirrhosis.
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Affiliation(s)
- Kseniya Gulyaeva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
| | - Maria Nadinskaia
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation.
| | - Yulia Aleshina
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
| | - Irina Goptar
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
| | - Alexander Lukashev
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation, 19991
- Research Institute for Systems Biology and Medicine, Moscow, Russian Federation, 117246
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow, Russian Federation, 19991
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya str., 1, bld. 1, Moscow, 119435, Russian Federation
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Gow-Lee B, Gaumnitz J, Alsadhan M, Garg G, Amoafo L, Zhang Y, Fang J, Rodriguez E. Cirrhosis and Portal Hypertension Worsen Bowel Preparation for Screening Colonoscopy. J Clin Gastroenterol 2025; 59:82-89. [PMID: 38567898 DOI: 10.1097/mcg.0000000000001990] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 02/12/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND Colonoscopy is a diagnostic and therapeutic procedure that reduces colorectal cancer incidence and mortality but requires adequate bowel cleansing for high-quality examination. Past studies have suggested cirrhosis as a risk factor for worse bowel preparation. METHODS We carried out a match-controlled retrospective study evaluating patients with and without cirrhosis who underwent outpatient screening colonoscopies to assess the effect of cirrhosis and portal hypertension complications on preparation quality and endoscopic measures. We also did a subgroup analysis excluding patients with obesity. RESULTS We examined 1464 patients with cirrhosis and matched controls. Cirrhotic patients had lower mean Boston Bowel Preparation Scale (BBPS) scores and slower cecal intubation times. We found a single point increase in the Model for End-stage Liver Disease (MELD) score, as well as ascites, hepatic encephalopathy, and variceal hemorrhage were all associated with a longer cecal intubation time. Subgroup analysis excluding patients with obesity again found a significantly lower BBPS score and longer cecal intubation time while also finding a 24% drop in polyp detection. CONCLUSIONS Patients with cirrhosis have worse BBPS scores and longer cecal intubation times. Nonobese cirrhotic patients additionally have a lower polyp detection rate. Portal hypertension complications were associated with worsened preparation quality and longer cecal intubation times. Each incremental increase in MELD score lengthened cecal intubation time. These findings support a more aggressive bowel preparation strategy for patients with cirrhosis, especially patients with severe disease or portal hypertension complications.
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Affiliation(s)
- Benjamin Gow-Lee
- Department of Internal Medicine, Spencer Fox Eccles School of Medicine
| | - John Gaumnitz
- Department of Internal Medicine, Spencer Fox Eccles School of Medicine
| | | | - Gauri Garg
- College of Social and Behavioral Sciences
| | - Linda Amoafo
- Division of Biostatistics, Department of Population Health Science, Spencer Fox Eccles School of Medicine
| | - Yue Zhang
- Division of Epidemiology, Department of Internal Medicine, Spencer Fox Eccles School of Medicine
| | - John Fang
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT
| | - Eduardo Rodriguez
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT
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Robinson-Papp J, Mehta M, Mueller BR, Neupane N, Zhao Z, Cedillo G, Coyle K, Campbell M, George MC, Benn EKT, Lee G, Semler J. Gastrointestinal Dysmotility, Autonomic Function and Small Intestinal Bacterial Overgrowth Among People with Well-Controlled HIV. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.25.24314370. [PMID: 39399020 PMCID: PMC11469347 DOI: 10.1101/2024.09.25.24314370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Introduction Gastrointestinal dysfunction, including microbiome changes and increased translocation across a compromised gastrointestinal barrier plays a role in the chronic inflammation experienced by people with HIV (PWH). It is unknown whether autonomic neuropathy (AN) may contribute to these mechanisms by altering gastrointestinal motility. Methods This is a cross-sectional study of 100 PWH and 89 controls. All participants underwent assessment of gastrointestinal transit times using a wireless motility capsule (WMC). All PWH and a subset of controls also underwent: a standardized battery of autonomic function tests summarized as the Modified Composite Autonomic Severity Score (MCASS) and its adrenergic, cardiovagal and sudomotor sub-scores, breath testing for small intestinal bacterial overgrowth (SIBO), and the Patient Assessment of Upper Gastrointestinal Disorders Symptoms (PAGI-SYM) and Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaires. Results PWH displayed shorter gastric emptying times (GET) and longer small bowel and colonic transit times (SBTT, CTT) compared to controls. Among PWH, GET was associated with PAGI-SYM score. The MCASS and its sudomotor sub-score (reflecting peripheral sympathetic function) were associated with SBTT but not GET or CTT. PWH with prolonged SBTT (>6h) were more likely to have SIBO. Conclusion Gastrointestinal motility is altered in PWH. This study provides preliminary evidence that changes in autonomic function may influence SBTT in PWH and that prolonged SBTT may contribute to the development of SIBO. Future studies are needed to more fully elucidate the pathophysiologic links between HIV-associated AN, altered gastrointestinal motility, the gastrointestinal microbiome, chronic inflammation, and resulting morbidity and mortality among PWH.
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Affiliation(s)
- Jessica Robinson-Papp
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Mitali Mehta
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Bridget R. Mueller
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Niyati Neupane
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Zhan Zhao
- Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy; New York City, NY, USA
| | - Gabriela Cedillo
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Kaitlyn Coyle
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Maya Campbell
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Mary Catherine George
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
| | - Emma KT Benn
- Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy; New York City, NY, USA
| | - Gina Lee
- Icahn School of Medicine at Mount Sinai, Department of Neurology; New York City, NY, USA
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Terbah R, Testro A, Gow P, Majumdar A, Sinclair M. Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis-Pathogenesis, Implications and Therapeutic Opportunities. Nutrients 2023; 16:35. [PMID: 38201864 PMCID: PMC10780673 DOI: 10.3390/nu16010035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.
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Affiliation(s)
- Ryma Terbah
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Adam Testro
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Paul Gow
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Avik Majumdar
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
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Weiler N, Bojunga J. Ernährung bei fortgeschrittener Leberzirrhose und perioperativ bei Lebertransplantation. DIE GASTROENTEROLOGIE 2023; 18:308-316. [DOI: 10.1007/s11377-023-00706-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2023] [Indexed: 01/04/2025]
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Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury. J Clin Med 2021; 10:jcm10235621. [PMID: 34884323 PMCID: PMC8658275 DOI: 10.3390/jcm10235621] [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: 11/02/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 12/15/2022] Open
Abstract
Hepatorenal syndrome (HRS) is a type of acute kidney injury (AKI), occurring in patients with decompensated liver cirrhosis and is associated with high mortality. We aim to describe the predictors associated with the development of HRS in cirrhotic patients with AKI. We retrospectively analyzed 529 cirrhotic patient encounters with AKI across all Northwell Health institutions between 1 January 2015 and 31 December 2018. We performed multivariate analyses to determine independent predictors of development of HRS. Alcoholic cirrhosis was the most common identified etiology of cirrhosis. The mean Model for End-Stage Liver Disease Scorewas18 (±7). Ascites was the most commonly identified clinical feature of portal hypertension. Infection was identified in 38.4% of patients with urinary tract infection/pyelonephritis being the most common. Spontaneous bacterial peritonitis occurred in 5.9% of patients. The most common cause of AKI was pre-renal. Hepatorenal syndrome was identified in 9.8% of patient encounters. Predictors of HRS were history of ascites, serum creatinine >2.5 mg/dL, albumin <3 g/dL, bilirubin >2 mg/dL and spontaneous bacterial peritonitis. We demonstrate strong predictors for the development of HRS which can aid clinicians to attain an early diagnosis of HRS, leading to prompt and targeted management and improving outcomes.
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Fukui H. Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update. Gut Liver 2021; 15:666-676. [PMID: 33071239 PMCID: PMC8444108 DOI: 10.5009/gnl20032] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 06/09/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022] Open
Abstract
Portal blood flows into the liver containing the gut microbiome and its products such as endotoxin and bacterial DNA. The cirrhotic liver acts and detoxifies as the initial site of microbial products. In so-called "leaky gut," the increased intestinal permeability for bacteria and their products constitutes an important pathogenetic factor for major complications in patients with liver cirrhosis. Prolonged gastric and small intestinal transit may induce intestinal bacterial overgrowth, a condition in which colonic bacteria translocate into the small gut. Cirrhotic patients further show gut dysbiosis characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous nonpathogenic bacteria. Pathological bacterial translocation (BT) is a contributing factor in the development of various severe complications. Bile acids (BAs) undergo extensive enterohepatic circulation and play important roles in the gut-liver axis. BT-induced inflammation prevents synthesis of BAs in the liver through inhibition of BA-synthesizing enzyme CYP7A1. A lower abundance of 7α-dehydroxylating gut bacteria leads to decreased conversion of primary to secondary BAs. Decreases in total and secondary BAs may play an important role in the gut dysbiosis characterized by a proinflammatory and toxic gut microbiome inducing BT and endotoxemia, as addressed in my previous reviews. Selective intestinal decontamination by the use of various antimicrobial drugs for management of complications has a long history. Lactobacillus GG decreasing endotoxemia is reported to improve the microbiome with beneficial changes in amino acid, vitamin and secondary BA metabolism. Current approaches for hepatic encephalopathy are the use of nonabsorbable antibiotics and disaccharides. Probiotics may become an additional therapeutic option for advanced liver cirrhosis.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Nara Medical University, Kashihara, Japan
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Sasso R, Rockey DC. Non-selective beta-blocker use in cirrhotic patients is associated with a reduced likelihood of hospitalisation for infection. Aliment Pharmacol Ther 2021; 53:418-425. [PMID: 33314175 DOI: 10.1111/apt.16156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/01/2020] [Accepted: 10/21/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Non-selective beta-blockers (NSBBs) reduce enteric bacterial translocation rates and the frequency of spontaneous bacterial peritonitis (SBP) in animal models. AIM To evaluate the effect of NSBBs on infection-related admissions. METHODS We performed a case-control study of cirrhotic patients' first in-patient admission between 1 January 2011 and 31 December 2016. We examined NSBB use and the development of infection. We performed a propensity score-matched analysis in those with NSBB use vs no use and calculated odds ratios on this matched cohort to determine the odds of outcomes based on NSBB use. RESULTS We identified 2165 cirrhotic patients who met our inclusion criteria. Most patients were Caucasian (69%), male (62%). Admission Model for End stage Liver Disease (MELD) score, Charlson comorbidity index and Child-Pugh score were 12 ± 1, 4 ± 2, and 8 ± 2, respectively. Ascites was the most common complication of portal hypertension (44%); 23% of patients used NSBBs at home. Infections occurred in 33% of admissions. In the propensity score-matched cohort, the use of NSBBs at home was associated with lower overall, and specific, infections. The effect was similar in patients taking NSBBs for either primary or secondary oesophageal variceal prophylaxis and for those on NSBBs for other indications. Patients not on NSBBs had higher odds of infection (OR = 2.5), SBP (OR = 4.0), and bacteraemia (OR = 6.0). CONCLUSION Home use of NSBBs by patients with cirrhosis was associated with fewer infection-related admissions. The data suggest that NSBBs in this group of patients reduce the risk of infection.
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Affiliation(s)
- Roula Sasso
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
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Skinner C, Thompson AJ, Thursz MR, Marchesi JR, Vergis N. Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention. Therap Adv Gastroenterol 2020; 13:1756284820942616. [PMID: 33149761 PMCID: PMC7580143 DOI: 10.1177/1756284820942616] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/25/2020] [Indexed: 02/04/2023] Open
Abstract
Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.
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Affiliation(s)
- Charlotte Skinner
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Alex J. Thompson
- Department of Surgery & Cancer, St. Mary’s Hospital Campus, Imperial College London, London, UK
| | - Mark R. Thursz
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Julian R. Marchesi
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
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Chopyk DM, Grakoui A. Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders. Gastroenterology 2020; 159:849-863. [PMID: 32569766 PMCID: PMC7502510 DOI: 10.1053/j.gastro.2020.04.077] [Citation(s) in RCA: 283] [Impact Index Per Article: 56.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/16/2020] [Accepted: 04/29/2020] [Indexed: 02/07/2023]
Abstract
Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora.
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Affiliation(s)
- Daniel M. Chopyk
- Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA
| | - Arash Grakoui
- Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
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Abstract
Acute on chronic liver failure (ACLF) is an inflammation-based disorder that occurs in patients with underlying liver disease and is characterized by hepatic and extrahepatic organ failure. Morbidity and mortality are high in patients with ACLF, and therefore prevention and early identification are critical to improve outcome. The purpose of this article is to define ACLF, describe ways to identify the expected outcome of ACLF after development, and illustrate interventions to prevent it and when it is not preventable reduce associated morbidity and mortality.
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Affiliation(s)
- Ariel Aday
- University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
| | - Jacqueline G O'Leary
- University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA; Dallas Veterans Affairs Medical Center, 4500 South Lancaster Road, Dallas, TX 75216, USA.
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Current Status and Prospects of Spontaneous Peritonitis in Patients with Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3743962. [PMID: 32724800 PMCID: PMC7364234 DOI: 10.1155/2020/3743962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 06/03/2020] [Indexed: 12/14/2022]
Abstract
Spontaneous bacterial peritonitis (SBP) is a common cirrhotic ascites complication which exacerbates the patient's condition. SBP is caused by gram-negative bacilli and, to a lesser extent, gram-positive cocci. Hospital-acquired infections show higher levels of drug-resistant bacteria. Geographical location influences pathogenic bacteria distribution; therefore, different hospitals in the same country record different bacteria strains. Intestinal changes and a weak immune system in patients with liver cirrhosis lead to bacterial translocation thus causing SBP. Early diagnosis and timely treatment are important in SBP management. When the treatment effect is not effective, other rare pathogens should be explored.
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Gundling F, Luxi M, Seidel H, Schepp W, Schmidt T. Small intestinal dysmotility in cirrhotic patients: correlation with severity of liver disease and cirrhosis-associated complications. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 59:540-550. [PMID: 32512591 DOI: 10.1055/a-1162-0357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Altered small intestinal motility has been observed in various manometry studies in patients with cirrhosis. Since small bowel manometry is available only in a few centers, interpretation of dysmotility in cirrhosis is controversial. PATIENTS AND METHODS In this study, both fasting and postprandial manometric tracings of 24-hour antroduodenojejunal manometries were analyzed using both visual analysis and computer-aided analysis. RESULTS In 34 patients (83 %), the mean migrating motor complex (MMC) cycle length was different compared with healthy controls. Phase II was prolonged in 27 patients (66 %), while phase I showed a reduced duration in 23 (56 %) and in phase III in 13 individuals (32 %). We also observed special motor patterns, e. g., migrating clustered contractions (MCCs) or retrograde clustered contractions (RCCs), which were present during fasting (69 %) and postprandial (92 %) motility, while none of the healthy controls showed any special motor patterns. Special motor patterns showed a significant correlation with the severity of cirrhosis (Child-Score; p > 0.05) and the existence of ascites (p < 0.05). DISCUSSION This study in a large cohort of patients with cirrhosis by using 24-hour, solid state portable manometry showed in most individuals disturbances of cyclic fasting motility. Special motor patterns like RCCs during fasting and postprandial motility could be observed exclusively in the cirrhosis group, showing a significant correlation with severity of cirrhosis and the occurence of associated complications.
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Affiliation(s)
- Felix Gundling
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Department of Internal Medicine - Division of Gastroenterology, Diabetology and Endocrinology, Kemperhof Koblenz, Koblenz, Germany
| | - Margo Luxi
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany
| | - Holger Seidel
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Isar Klinik, Munich, Germany
| | - Wolfgang Schepp
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany
| | - Thomas Schmidt
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Helios Klinik Attendorn, Attendorn, Germany
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Li B, Gao Y, Wang X, Qian Z, Meng Z, Huang Y, Deng G, Lu X, Liu F, Zheng X, Li H, Chen J. Clinical features and outcomes of bacterascites in cirrhotic patients: A retrospective, multicentre study. Liver Int 2020; 40:1447-1456. [PMID: 32128975 DOI: 10.1111/liv.14418] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 02/02/2020] [Accepted: 02/19/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Current guidelines on the management of bacterascites are limited. This multicentre, retrospective study investigated the clinical features and outcomes of cirrhosis patients with bacterascites. METHODS Two series of cirrhosis patients were evaluated. The first included 418 patients with ascites-positive cultures at 11 hospitals during 2012-2018. Clinical characteristics and outcomes were recorded. The second included 208 patients with sterile ascites from a prospective cohort (NCT02457637). Clinical features and outcomes of cirrhotic patients with or without bacterascites were investigated. RESULTS In the first series, bacterascites was diagnosed in 254/418 (60.8%) patients, and culture-positive spontaneous bacterial peritonitis (SBP) in 164/418 (39.2%) patients. Gram-positive bacteria were more prevalent in bacterascites patients than in culture-positive SBP patients (59.1% vs 22.0%; P < .001). For patients with acute-on-chronic liver failure (ACLF) in bacterascites and culture-positive SBP groups, the 28-day transplant-free mortality (41.3% vs 65.5%; P = .015) and the prevalence of in-hospital acute kidney injury (AKI) (84.8% vs 75%; P = .224). For patients without ACLF in the bacterascites (n = 208) and culture-positive SBP groups (n = 108), the 28-day transplant-free mortalities were 13% vs 13.9% (P = .822), the probabilities of progression to ACLF within 28 days were 10.1% vs 14.8% (P = .216) and the prevalences of in-hospital AKI were 14.4% vs 30.6% (P = .001). Bacterascites patients had higher 28-day mortality than those patients with sterile ascites, after propensity score matching (18.4% vs 8.6%; P = .010). CONCLUSION Bacterascites patients had non-negligible poor clinical outcomes, including in-hospital AKI, progression to ACLF and 28-day mortality. Future studies are warranted to expedite the diagnosis of bacterascites and optimize antibiotic treatment.
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Affiliation(s)
- Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University (JU), Jilin, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Zhiping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre (SPHCC), Fudan University, Shanghai, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Zhongji Meng
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Hubei, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Hunan, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xiaobo Lu
- Infectious Disease Centre, The First Affiliated Hospital of Xinjiang Medical University (XMU), Xinjiang, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Feng Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University (SDU), Jinan, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
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Zhao Q, Xing F, Tao Y, Liu H, Huang K, Peng Y, Feng N, Liu C. Xiaozhang Tie Improves Intestinal Motility in Rats With Cirrhotic Ascites by Regulating the Stem Cell Factor/c-kit Pathway in Interstitial Cells of Cajal. Front Pharmacol 2020; 11:1. [PMID: 32116689 PMCID: PMC7011082 DOI: 10.3389/fphar.2020.00001] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 01/03/2020] [Indexed: 11/13/2022] Open
Abstract
We previously discovered that Xiaozhang Tie (XZT) was helpful for cirrhotic ascites, with obvious abdominal distention relief, suggesting that it may improve gastrointestinal (GI) motility. However, the underlying mechanisms of GI motility in cirrhotic ascites are unclear. Here, we aimed to discover explored the effect of XZT on GI motility in animal cirrhotic ascites and probed the action mechanism affecting GI motility by regulating the stem cell factor (SCF)/c-kit pathway in interstitial cells of Cajal (ICCs) and GI hormones. First, rat models of cirrhotic ascites were developed and then divided randomly into the following three subgroups: model control, XZT group, and mosapride group. The efficacy of XZT on treating cirrhotic ascites was evaluated on the basis of ascites weight and volume, 24 h urine volume, and feces water content. GI motility of the cirrhotic model, intestine propulsion, and gastric residue were detected using the migration distance of ink in vivo, and the frequency of contraction and tension of isolated gastric and jejunal muscle strips were measured after incubation with XZT extracts. Serum GI hormone content, including motilin (MTL), substance P (SP), somatostatin (SS), and vasoactive intestinal polypeptide were assayed. Subsequently, ICCs were isolated from jejunum, and primarily cultured ICCs were incubated with and without XZT and SCF. The cell vitality of the ICCs was measured. A whole-cell patch recording technique was used to record the current of K+ and Na+ channels in the ICC membrane. Expressions of c-kit/p-c-kit, p-Akt, p-STAT3, and p-Erk1/2 were detected in vivo and in vitro. The results revealed that XZT significantly reduced ascites weight and increased urine volume and fecal water content in model rats. XZT promoted intestinal motility and increased MTL level but reduced SP and SS levels. It enhanced the current of Na+ and K+ in ICCs and improved c-kit expression and signaling mediator phosphorylation in SCF/c-kit, which was inhibited by imatinib in vitro and downregulated in model rats in vivo. Our study concluded that XZT reduced the amount of ascites and improved intestinal motility in cirrhotic rats, which may be associated with its effect on ascites and was involved in the mechanisms regulating the SCF/c-kit signaling pathway in ICCs and improving gastrointestinal hormone secretion.
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Affiliation(s)
- Qiang Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Feng Xing
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yanyan Tao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongliang Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Kai Huang
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
| | - Yuan Peng
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Nianping Feng
- Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China.,Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai, China.,Shanghai Innovation Center of TCM Health Service, Shanghai, China
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Zhao Q, Xing F, Tao Y, Liu H, Huang K, Peng Y, Feng N, Liu C. Xiaozhang Tie Improves Intestinal Motility in Rats With Cirrhotic Ascites by Regulating the Stem Cell Factor/c-kit Pathway in Interstitial Cells of Cajal. Front Pharmacol 2020. [PMID: 32116689 DOI: 10.3389/fphar.2020.603926/bibtex] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023] Open
Abstract
We previously discovered that Xiaozhang Tie (XZT) was helpful for cirrhotic ascites, with obvious abdominal distention relief, suggesting that it may improve gastrointestinal (GI) motility. However, the underlying mechanisms of GI motility in cirrhotic ascites are unclear. Here, we aimed to discover explored the effect of XZT on GI motility in animal cirrhotic ascites and probed the action mechanism affecting GI motility by regulating the stem cell factor (SCF)/c-kit pathway in interstitial cells of Cajal (ICCs) and GI hormones. First, rat models of cirrhotic ascites were developed and then divided randomly into the following three subgroups: model control, XZT group, and mosapride group. The efficacy of XZT on treating cirrhotic ascites was evaluated on the basis of ascites weight and volume, 24 h urine volume, and feces water content. GI motility of the cirrhotic model, intestine propulsion, and gastric residue were detected using the migration distance of ink in vivo, and the frequency of contraction and tension of isolated gastric and jejunal muscle strips were measured after incubation with XZT extracts. Serum GI hormone content, including motilin (MTL), substance P (SP), somatostatin (SS), and vasoactive intestinal polypeptide were assayed. Subsequently, ICCs were isolated from jejunum, and primarily cultured ICCs were incubated with and without XZT and SCF. The cell vitality of the ICCs was measured. A whole-cell patch recording technique was used to record the current of K+ and Na+ channels in the ICC membrane. Expressions of c-kit/p-c-kit, p-Akt, p-STAT3, and p-Erk1/2 were detected in vivo and in vitro. The results revealed that XZT significantly reduced ascites weight and increased urine volume and fecal water content in model rats. XZT promoted intestinal motility and increased MTL level but reduced SP and SS levels. It enhanced the current of Na+ and K+ in ICCs and improved c-kit expression and signaling mediator phosphorylation in SCF/c-kit, which was inhibited by imatinib in vitro and downregulated in model rats in vivo. Our study concluded that XZT reduced the amount of ascites and improved intestinal motility in cirrhotic rats, which may be associated with its effect on ascites and was involved in the mechanisms regulating the SCF/c-kit signaling pathway in ICCs and improving gastrointestinal hormone secretion.
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Affiliation(s)
- Qiang Zhao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Feng Xing
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yanyan Tao
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongliang Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Kai Huang
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
| | - Yuan Peng
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Nianping Feng
- Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai, China
- Shanghai Innovation Center of TCM Health Service, Shanghai, China
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Snell DB, Cohen-Mekelburg S, Weg R, Ghosh G, Buckholz AP, Mehta A, Ma X, Christos PJ, Jesudian AB. Gastric food retention at endoscopy is associated with severity of liver cirrhosis. World J Hepatol 2019; 11:725-734. [PMID: 31772719 PMCID: PMC6856021 DOI: 10.4254/wjh.v11.i11.725] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/22/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis. Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis. However, the contributing factors have not been fully elucidated. Retained gastric food on esophagogastroduodenoscopy (EGD) has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity. Therefore, we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease. Additionally, we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.
AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.
METHODS We performed a retrospective case-control study of cirrhotic subjects who underwent EGD at an academic medical center between 2000 and 2015. Three hundred sixty-four patients with confirmed cirrhosis, who underwent a total of 1044 EGDs for the indication of esophageal variceal screening or surveillance, were identified. During the same period, 519 control patients without liver disease, who underwent a total of 881 EGDs for the indication of anemia, were identified. The presence of retained food on EGD was used as a surrogate for delayed gastric emptying. The relative frequency of delayed gastric emptying among cirrhotics was compared to non-cirrhotics. Characteristics of patients with and without retained food on EGD were compared using univariable and multivariable logistic regression analysis to identify associated factors.
RESULTS Overall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics were more likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P < 0.001). Characteristics associated with retained food on univariable analysis included age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004), Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P = 0.007), and lower platelet count (P = 0.027). On multivariate logistic regression analysis, in addition to the presence of cirrhosis (adjusted OR = 5.83; 95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34; 95%CI: 1.08-5.06, P = 0.031), opioid use (OR = 3.08; 95%CI: 1.29-7.34, P = 0.011), and Child-Pugh class C (OR = 4.29; 95%CI: 1.43-12.9, P = 0.01) were also associated with a higher likelihood of food retention on EGD.
CONCLUSION Cirrhotics have a higher frequency of retained food at EGD than non-cirrhotics. Decompensated cirrhosis, defined by Child-Pugh class C, is associated with a higher likelihood of delayed gastric emptying.
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Affiliation(s)
- David B Snell
- Division of Gastroenterology and Hepatology, New York University, New York, NY 10016, United States
| | - Shirley Cohen-Mekelburg
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Russell Weg
- Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14642, United States
| | - Gaurav Ghosh
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY 10065, United States
| | - Adam P Buckholz
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY 10065, United States
| | - Amit Mehta
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Xiaoyue Ma
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY 10065, United States
| | - Paul J Christos
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY 10065, United States
| | - Arun B Jesudian
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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Stirnimann J, Stirnimann G. Nutritional Challenges in Patients with Advanced Liver Cirrhosis. J Clin Med 2019; 8:jcm8111926. [PMID: 31717529 PMCID: PMC6912781 DOI: 10.3390/jcm8111926] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 11/05/2019] [Accepted: 11/05/2019] [Indexed: 12/13/2022] Open
Abstract
Patients with advanced liver cirrhosis are at risk of malnutrition and nutrition-associated complications. Significant ascites, a frequent finding in these patients, has an especially negative impact on oral nutrition. A negative caloric and protein balance can further deteriorate the already impaired synthetic function of the cirrhotic liver. An important factor in this situation is the diminished capacity of glycogen production and storage in the cirrhotic liver and, consequently, a reduced tolerability for fasting episodes. These episodes are frequently observed in hospitalized patients, e.g., while waiting for investigations, interventions or surgery. A comprehensive work-up of patients with advanced liver cirrhosis should include not only a thorough assessment regarding nutritional deficits, but also a muscularity analysis to identify patients with sarcopenia. The overall nutritional treatment goal is to cover caloric deficits and assure a sufficiently high protein intake. Furthermore, vitamin and micronutrient deficiencies should be identified and corrective measures implemented where required. Ideally, optimal nutrition management can not only prevent the progression of malnutrition and sarcopenia in patients with advanced liver cirrhosis, but positively influence the evolution of the liver disease.
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Affiliation(s)
- Jessica Stirnimann
- Division of Diabetology, Endocrinology, Nutritional Medicine and Metabolism, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland;
| | - Guido Stirnimann
- University Clinic for Visceral Surgery and Medicine, University Hospital Inselspital and University of Bern, 3010 Bern, Switzerland
- Correspondence: or ; Tel.: +41-31-632-2111
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21
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The Effect of Obesity on the Quality of Bowel Preparation for Colonoscopy: Results From a Large Observational Study. J Clin Gastroenterol 2019; 53:e214-e220. [PMID: 29738352 DOI: 10.1097/mcg.0000000000001045] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Obesity has been linked to suboptimal bowel preparation but this association has not been conclusively investigated in prospective studies. GOALS Our objective was to determine whether any relationship exists between obesity as measured by body mass index (BMI) and quality of bowel preparation. STUDY Adult patients who presented for outpatient colonoscopy at a single urban ambulatory surgery center within a 6-month period and fulfilled inclusion criteria were prospectively enrolled for the study. Patients were divided by BMI into subcategories based on the World Health Organization international classification of obesity. The Modified Aronchick scale was used to assess bowel preparation for colonoscopy. A univariate and multivariate analysis was used to determine a possible association between BMI and poor preparation. RESULTS A total of 1429 patients were evaluated. On the basis of inclusion criteria, 1314 subjects were analyzed, out of which 73% were overweight or obese. Inadequate bowel preparation was noted in 21.1% of patients. There was no correlation between obesity and the quality of the bowel preparation. Male gender (P=0.002), diabetes mellitus (P<0.0001), liver cirrhosis (P=0.001), coronary artery disease (P=0.003), refractory constipation (P<0.0001), and current smoking (P=0.01) were found to be independently predictive of poor bowel preparation. CONCLUSIONS Increased BMI is not predictive of suboptimal bowel preparation for colonoscopy. The results of our study are pivotal given the increased risk of colorectal cancer in obese patients and their known lower rate of colorectal cancer screening in certain populations. It is important to avoid subjecting these patients to an intensive bowel preparation that may further discourage screening in a patient population that requires it.
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Ghosh G, Jesudian AB. Small Intestinal Bacterial Overgrowth in Patients With Cirrhosis. J Clin Exp Hepatol 2019; 9:257-267. [PMID: 31024208 PMCID: PMC6477138 DOI: 10.1016/j.jceh.2018.08.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 08/19/2018] [Indexed: 02/07/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is defined by increased density and/or abnormal composition of microbiota in the small bowel. SIBO is often encountered in patients with cirrhosis as a result of impaired intestinal motility and delayed transit time, both of which are exacerbated by more severe liver disease. Additional risk factors for SIBO commonly encountered in cirrhotic patients include coexisting diabetes, autonomic neuropathy, and/or alcoholic use. Diagnosis of SIBO is performed by breath testing or jejunal aspiration, the gold standard. In cirrhotic patients, the presence of SIBO can lead to profound clinical consequences. Increased intestinal permeability in these patients predisposes to bacterial translocation into the systemic circulation. As a result, SIBO is implicated as a significant risk factor in the pathogenesis of both spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhotics. Antibiotics, especially rifaximin, are the best studied and most effective treatment options for SIBO. However, prokinetics, probiotics, nonselective beta-blockers, and treatment of underlying liver-related pathophysiology with transjugular intrahepatic portosystemic shunt placement or liver transplantation are also being investigated. This review will discuss the risk factors, diagnosis, manifestations in cirrhosis, and treatment options of SIBO.
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Key Words
- 51Cr-EDTA, 51Cr-Ethylenediaminetetraacetic Acid
- CFUs, Colony-Forming Units
- CP, Child-Pugh Score
- FODMAPS, Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols
- GI, Gastrointestinal
- HBV, Hepatitis B Virus
- HE, Hepatic Encephalopathy
- IBS, Irritable Bowel Syndrome
- MHE, Minimal Hepatic Encephalopathy
- MMC, Migrating Motor Complex
- OCTT, Orocecal Transit Time
- PH, Portal Hypertension
- PPI, Proton Pump Inhibitor
- SBP, Spontaneous Bacterial Peritonitis
- SBRT, Small Bowel Residence Time
- SBTT, Small Bowel Transit Time
- SIBO, Small Intestinal Bacterial Overgrowth
- TIPS, Transjugular Intrahepatic Portosystemic Shunt
- bacterial translocation
- cirrhosis
- liver disease
- mL, Milliliter
- ppm, Parts Per Million
- small intestinal bacterial overgrowth
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Affiliation(s)
- Gaurav Ghosh
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, 525 E. 68th Street, M-532, New York, NY, 10065, USA
| | - Arun B. Jesudian
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, 1305 York Avenue, 4th Floor, New York, NY, 10065, USA,Address for correspondence: Arun B. Jesudian, 1305 York Avenue, 4th Floor, New York, NY, 10065, USA
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Wang P, Zhang YJ, Li YR, Xia XY, Lv SY. STORE-gastrointestinal functions and gastrointestinal hormones in patients with liver failure. Medicine (Baltimore) 2018; 97:e13167. [PMID: 30508896 PMCID: PMC6283146 DOI: 10.1097/md.0000000000013167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This study aims to investigate the gastrointestinal functions of patients with liver failure (LF) based on gastrointestinal dysfunction (GD) scores and serum gastrointestinal hormone levels.The GD in LF patients was scored using the gastrointestinal dysfunction scoring criteria. Serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels were determined in LF patients. In addition, liver function and prothrombin activity were detected, and ultrasonography was performed.The GD score was significantly higher in the LF groups than in the control group. Compared with the control group, serum GAS, CCK, and MTL levels significantly increased in the LF groups, and was positively correlated with the severity of LF. Furthermore, in the LF groups, GD was positively correlated with the severity of LF. However, the GD score and serum GAS, CCK, and MTL levels in the acute LF group were not statistically different, when compared with those in the subacute LF group, acute-on-chronic LF group and chronic LF group.LF plays a key role in the development of GD, and may be the main cause of obvious gastrointestinal symptoms, such as abdominal distension, nausea, vomiting and anorexia, in LF patients. The severity of GD is not associated with LF type, but is positively correlated with the severity of LF, suggesting that GD in LF patients may have complicated mechanisms.
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Affiliation(s)
- Ping Wang
- Department of Preventive Medicine, Medical College, Henan University of Science and Technology
| | - Ying-Jian Zhang
- Department of Gastroenterology, First Affiliated Hospital Henan University of Science and Technology, Luoyang, China
| | - Yi-Ran Li
- Department of Gastroenterology, First Affiliated Hospital Henan University of Science and Technology, Luoyang, China
| | - Xiao-Yan Xia
- Department of Preventive Medicine, Medical College, Henan University of Science and Technology
| | - Shu-Yan Lv
- Department of Preventive Medicine, Medical College, Henan University of Science and Technology
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Liu Y, Jin Y, Li J, Zhao L, Li Z, Xu J, Zhao F, Feng J, Chen H, Fang C, Shilpakar R, Wei Y. Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis. Front Physiol 2018; 9:470. [PMID: 29780327 PMCID: PMC5946013 DOI: 10.3389/fphys.2018.00470] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/13/2018] [Indexed: 12/13/2022] Open
Abstract
Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child–Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child–Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(>F) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child–Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI (r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway “bacterial invasion of epithelial cells” in patients, was highly negatively correlated with SBT (r = -0.57, p < 0.01). The severity of microbiota dysbiosis in LC patients depends on SBT rather than Child–Pugh score. SBT per se might be significantly related to the gut microbiota abnormalities observed in patients with LC.
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Affiliation(s)
- Yang Liu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ye Jin
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jun Li
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lei Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhengtian Li
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jun Xu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fuya Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jing Feng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huinan Chen
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chengyuan Fang
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rojina Shilpakar
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Gastrointestinal Motility Disorders and Their Clinical Implications in Cirrhosis. Gastroenterol Res Pract 2017; 2017:8270310. [PMID: 28584525 PMCID: PMC5444003 DOI: 10.1155/2017/8270310] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 04/13/2017] [Indexed: 12/21/2022] Open
Abstract
Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.
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Cirrhotic Patients Have Worse Bowel Preparation at Screening Colonoscopy than Chronic Liver Disease Patients without Cirrhosis. J Clin Exp Hepatol 2016; 6:297-302. [PMID: 28003719 PMCID: PMC5157875 DOI: 10.1016/j.jceh.2016.08.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 08/12/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Cirrhosis has been shown in small studies to be a predictor of suboptimal bowel preparation at screening colonoscopy. It has yet to be established whether patients with chronic liver disease in the absence of cirrhosis experience equally poor colon cleansing. Intestinal dysmotility related to cirrhosis might impair bowel preparation in this population more than those with chronic liver disease without cirrhosis. OBJECTIVE This study compared the quality of bowel preparation in cirrhotic and non-cirrhotic patients with chronic liver disease and determined whether this influenced polyp detection rate. METHODS A retrospective study of patients with chronic liver disease, both cirrhotic and non-cirrhotic, who underwent screening colonoscopy was performed. Patient characteristics, concomitant medication use, adequacy of bowel preparation, and the total number and types of polyps found were compared between cirrhotic and non-cirrhotic groups. RESULTS 330 patients fulfilled inclusion criteria; 36% (n = 120) were cirrhotic. Cirrhotic patients had significantly worse bowel preparation scores compared with non-cirrhotics (mean 3.4 ± 1.1 vs. 3.7 ± 0.9, P = 0.003). Worse bowel preparation scores in cirrhotics vs. non-cirrhotics persisted despite controlling for age, sex, and concomitant diabetes mellitus (DM) (P = 0.0027). Among the cirrhotics, 48% had the lowest preparation scores compared with 30% of non-cirrhotics. No difference in polyp detection rate was found between cirrhotics and non-cirrhotics. Severity of cirrhosis as assessed by the MELD score did not predict worse bowel preparation. CONCLUSIONS Cirrhotics have significantly worse bowel preparation scores compared to non-cirrhotics with chronic liver disease. No correlation between MELD score and bowel preparation score was observed in the cirrhotic cohort.
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Aguirre Valadez JM, Rivera-Espinosa L, Méndez-Guerrero O, Chávez-Pacheco JL, García Juárez I, Torre A. Intestinal permeability in a patient with liver cirrhosis. Ther Clin Risk Manag 2016; 12:1729-1748. [PMID: 27920543 PMCID: PMC5125722 DOI: 10.2147/tcrm.s115902] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A "leaky gut" is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications.
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Affiliation(s)
| | | | - Osvely Méndez-Guerrero
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición”Salvador Zubirán
| | | | - Ignacio García Juárez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición”Salvador Zubirán
| | - Aldo Torre
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición”Salvador Zubirán
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Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci Rep 2016; 6:34055. [PMID: 27687977 PMCID: PMC5043180 DOI: 10.1038/srep34055] [Citation(s) in RCA: 149] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 08/22/2016] [Indexed: 12/13/2022] Open
Abstract
Cirrhosis-associated duodenal dysbiosis is not yet clearly defined. In this research, duodenal mucosal microbiota was analyzed in 30 cirrhotic patients and 28 healthy controls using 16S rRNA gene pyrosequencing methods. The principal coordinate analysis revealed that cirrhotic patients were colonized by remarkable different duodenal mucosal microbiota in comparison with controls. At the genus level, Veillonella, Megasphaera, Dialister, Atopobium, and Prevotella were found overrepresented in cirrhotic duodenum. And the duodenal microbiota of healthy controls was enriched with Neisseria, Haemophilus, and SR1 genera incertae sedis. On the other hand, based on predicted metagenomes analyzed, gene pathways related to nutrient absorption (e.g. sugar and amino acid metabolism) were highly abundant in cirrhosis duodenal microbiota, and functional modules involved in bacterial proliferation and colonization (e.g. bacterial motility proteins and secretion system) were overrepresented in controls. When considering the etiology of cirrhosis, two operational taxonomic units (OTUs), OTU-23 (Neisseria) and OTU-36 (Gemella), were found discriminative between hepatitis-B-virus related cirrhosis and primary biliary cirrhosis. The results suggest that the structure of duodenal mucosa microbiota in cirrhotic patients is dramatically different from healthy controls. The duodenum dysbiosis might be related to alterations of oral microbiota and changes in duodenal micro-environment.
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Vilz TO, Pantelis D, Lingohr P, Fimmers R, Esmann A, Randau T, Kalff JC, Coenen M, Wehner S. SmartPill® as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study). BMJ Open 2016; 6:e011014. [PMID: 27401360 PMCID: PMC4947765 DOI: 10.1136/bmjopen-2015-011014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill(®), a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill(®) immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. METHODS AND ANALYSIS The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill(®) will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill(®) in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill(®) to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill(®) will be analysed. ETHICS AND DISSEMINATION The protocol was approved by the federal authority (94.1.05-5660-8976) and the local ethics committee (092/14-MPG). Findings will be disseminated through publications and conference presentations. TRIAL REGISTRATION NUMBER NCT02329912; Pre-results.
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Affiliation(s)
- Tim O Vilz
- Department of Surgery, University of Bonn, Bonn, Germany
| | | | | | - Rolf Fimmers
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Bonn, Germany
- Institute of Medical Biometrics, Informatics and Epidemiology, Study Center Bonn, University of Bonn, Bonn, Germany
| | - Anke Esmann
- Department of Surgery, University of Bonn, Bonn, Germany
| | - Thomas Randau
- Department of Orthopedics and Trauma Surgery, University of Bonn, Bonn, Germany
| | - Jörg C Kalff
- Department of Surgery, University of Bonn, Bonn, Germany
| | - Martin Coenen
- Clinical Study Core Unit, Study Center Bonn (SZB), University of Bonn, Bonn, Germany
- Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany
| | - Sven Wehner
- Department of Surgery, University of Bonn, Bonn, Germany
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Abstract
Background Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. Summary Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. Key Messages This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan
| | - Reiner Wiest
- Department of Gastroenterology, University Hospital of Visceral Surgery and Medicine, Bern, Switzerland
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Fukui H, Wiest R. Changes of Intestinal Functions in Liver Cirrhosis. Inflamm Intest Dis 2016; 1:24-40. [PMID: 29922655 PMCID: PMC5988129 DOI: 10.1159/000444436] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Accepted: 02/04/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. SUMMARY Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. KEY MESSAGES This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan
| | - Reiner Wiest
- Department of Gastroenterology, University Hospital of Visceral Surgery and Medicine, Bern, Switzerland
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Abstract
Background Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core of this interesting research field. Summary Most investigators noted small intestinal dysmotility in their patients with liver cirrhosis. Marked changes in the contraction pattern were observed in early manometric studies. The orocecal transit time, particularly small intestinal transit, has generally been reported to be prolonged, which has been demonstrated in multiple investigations to be related to the severity of the liver disease (e.g., Child-Pugh class), the presence of small intestinal bacterial overgrowth (SIBO) and hepatic encephalopathy (HE) as well as a history of spontaneous bacterial peritonitis. Bacteriologically proven SIBO in proximal jejunal aspiration has been reported to be present in up to 59% of cirrhotic patients and is associated with systemic endotoxemia. Clinical and experimental studies suggest that delayed small bowel transit in liver cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea. In addition to autonomic neuropathy, metabolic derangements and diabetic state, SIBO itself may delay intestinal transit in cirrhotic patients. Several studies, both from the West and the East, have shown that the gut microbiota is altered in cirrhotic patients and particularly those with HE. Further, a quantitative change in Bacteroides/Firmicutes ratio, with a prevalence of potentially pathogenic bacteria (e.g., Enterobacteriaceae) and reduction in specific commensals (e.g., Lachnospiraceae), has been described. Structural and functional changes in the intestinal mucosa that contribute to increases in intestinal permeability for bacteria and their products have been observed in patients with liver cirrhosis, which is considered as an important pathogenetic factor for several complications. The mechanism of intestinal barrier dysfunction in cirrhosis is multifactorial, including alcohol, portal hypertension (vascular congestion and dysregulation), endotoxemia, SIBO, local inflammation and, most likely, immunological factors and medications. Key Messages This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research. The question of whether this intestinal barrier dysfunction is accompanied and/or at least partly caused by structural and functional changes in the epithelial tight junction proteins is as yet unsolved. Development of new strategies to modulate gut-liver interaction is urgently needed.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan
| | - Reiner Wiest
- Department of Gastroenterology, University Hospital of Visceral Surgery and Medicine, Bern, Switzerland
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Abstract
INTRODUCTION Bacterial infections are a serious complication of cirrhosis, as they can lead to decompensation, multiple organ failure, and/or death. Preventing infections is therefore very relevant. Because gut bacterial translocation is their main pathogenic mechanism, prevention of infections is mostly based on the use of orally administered poorly absorbed antibiotics such as norfloxacin (selective intestinal decontamination). However, antibiotic prophylaxis leads to antibiotic resistance, limiting therapy and increasing morbidity and mortality. Prevention of bacterial infections in cirrhosis should therefore move away from antibiotics. AREAS COVERED This review focuses on various potentially novel methods to prevent infections in cirrhosis focusing on non-antibiotic strategies. The use of probiotics, nonselective intestinal decontamination with rifaximin, prokinetics and beta-blockers or fecal microbiota transplant as means of targeting altered gut microbiota, bile acids and FXR agonists are all potential alternatives to selective intestinal decontamination. Prokinetics and beta-blockers can improve intestinal motility, while bile acids and FXR agonists help by improving the intestinal barrier. Finally, granulocyte colony stimulating factor (G-CSF) and statins are emerging therapeutic strategies that may improve immune dysfunction in cirrhosis. EXPERT OPINION Evidence for these strategies has been restricted to animal studies and proof-of concept studies but we expect this to change in coming years.
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Workplace Health Promotion and Wellbeing. ScientificWorldJournal 2015; 2015:606875. [PMID: 26380362 PMCID: PMC4563109 DOI: 10.1155/2015/606875] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 07/13/2015] [Indexed: 12/25/2022] Open
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Li Y, Han T. Mechanisms of susceptibility to bacterial infections in cirrhotic patients. Shijie Huaren Xiaohua Zazhi 2015; 23:3560-3566. [DOI: 10.11569/wcjd.v23.i22.3560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections are very common in cirrhotic patients, and the incidence is 4-5 times higher than that in the general population. The mechanisms of susceptibility to bacterial infections in cirrhotic patients include intestinal bacterial overgrowth, bacterial translocation, increased number of potentially pathogenic bacteria accompanied by reduced number of beneficial bacteria; small bowel motility disturbances and delayed gut transit, increased intestinal permeability; genetic predisposition to bacterial infections; immunodeficiency accompanied by persistent activation of the immune cells with production of pro-inflammatory cytokines. In this paper, we will discuss the mechanisms of susceptibility to bacterial infections in cirrhotic patients.
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Keuchel M, Kurniawan N, Baltes P, Bandorski D, Koulaouzidis A. Quantitative measurements in capsule endoscopy. Comput Biol Med 2015; 65:333-47. [PMID: 26299419 DOI: 10.1016/j.compbiomed.2015.07.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 07/16/2015] [Accepted: 07/17/2015] [Indexed: 12/14/2022]
Abstract
This review summarizes several approaches for quantitative measurement in capsule endoscopy. Video capsule endoscopy (VCE) typically provides wireless imaging of small bowel. Currently, a variety of quantitative measurements are implemented in commercially available hardware/software. The majority is proprietary and hence undisclosed algorithms. Measurement of amount of luminal contamination allows calculating scores from whole VCE studies. Other scores express the severity of small bowel lesions in Crohn׳s disease or the degree of villous atrophy in celiac disease. Image processing with numerous algorithms of textural and color feature extraction is further in the research focuses for automated image analysis. These tools aim to select single images with relevant lesions as blood, ulcers, polyps and tumors or to omit images showing only luminal contamination. Analysis of motility pattern, size measurement and determination of capsule localization are additional topics. Non-visual wireless capsules transmitting data acquired with specific sensors from the gastrointestinal (GI) tract are available for clinical routine. This includes pH measurement in the esophagus for the diagnosis of acid gastro-esophageal reflux. A wireless motility capsule provides GI motility analysis on the basis of pH, pressure, and temperature measurement. Electromagnetically tracking of another motility capsule allows visualization of motility. However, measurement of substances by GI capsules is of great interest but still at an early stage of development.
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Affiliation(s)
- M Keuchel
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany.
| | - N Kurniawan
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
| | - P Baltes
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
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Yang YY, Hsieh SL, Lee PC, Yeh YC, Lee KC, Hsieh YC, Wang YW, Lee TY, Huang YH, Chan CC, Lin HC. Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites. J Hepatol 2014; 61:1004-13. [PMID: 24953022 DOI: 10.1016/j.jhep.2014.05.049] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 05/29/2014] [Accepted: 05/31/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Intestinal hyperpermeability, impaired peritoneal macrophages (PMs) phagocytosis, and bacterial translocation (BT), resulting in increased systemic and local infection/inflammation such as spontaneous bacterial peritonitis (SBP) together with increased tumor necrosis factor-α (TNFα) levels, are all implicated in the pathogenesis of cirrhosis-related complications. Manipulation of the cannabinoid receptors (CB1R and CB2R), which are expressed on the gut mucosa and PMs, has been reported to modulate intestinal inflammation and systemic inflammatory cytokine release. Our study aims to explore the effects of chronic CB1R/CB2R agonist/antagonist treatments on relevant abnormalities in cirrhotic ascitic rats. METHODS Vehicle, archidonyl-2-chloroethylamide (ACEA, CB1R agonist), JWH133 (CB2R agonist), and AM630 (CB2R antagonist) were given to thioacetamide (TAA) and common bile duct ligation (BDL) cirrhotic rats with ascites for two weeks and various measurement were performed. RESULTS Compared to sham rats, CB2Rs were downregulated in cirrhotic rat intestines and PMs. The two-week JWH133 treatment significantly decreased systemic/intestinal oxidative stress, TNFα and inflammatory mediators, infection, intestinal mucosal damage and hyperpermeability; the JWH133 treatment also decreased bacterial overgrowth/adhesion, BT and SBP, upregulated intestinal tight junctions and downregulated the PM TNFα receptor/NFκBp65 protein expression in cirrhotic rats. Acute and chronic JWH133 treatment corrected the TNFα-induced suppression of phagocytosis of cirrhotic rat PMs, which then could be reversed by concomitant AM630 treatment. CONCLUSIONS Our study suggests that CB2R agonists have the potential to treat BT and various relevant abnormalities through inhibition of systemic/intestinal oxidative stress, inflammatory cytokines and TNFα release in cirrhosis. Overall, the chronic CB2R agonist treatment affects multiple approach mechanisms, and its direct effect on the hyperdynamic circulation is only minor.
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Affiliation(s)
- Ying-Ying Yang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Clinical Skill Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
| | - Shie-Liang Hsieh
- Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Institute of Infection and Immunology Center & Institute of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Pei-Chang Lee
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Chen Yeh
- Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yun-Cheng Hsieh
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ying-Wen Wang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Tzung-Yan Lee
- Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Che-Chang Chan
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
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Kalaitzakis E. Gastrointestinal dysfunction in liver cirrhosis. World J Gastroenterol 2014; 20:14686-14695. [PMID: 25356031 PMCID: PMC4209534 DOI: 10.3748/wjg.v20.i40.14686] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 04/27/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis.
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Dabos KJ, Koulaouzidis A. Portal hypertensive enteropathy, occult bleeding, and capsule endoscopy: where do we go from here? Dig Dis Sci 2014; 59:899-901. [PMID: 24652110 DOI: 10.1007/s10620-014-3103-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Konstantinos J Dabos
- Endoscopy Unit, Centre for Liver and Digestive Disorders, The Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK
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Abstract
PURPOSE OF REVIEW To critically review recent literature on small intestinal bacterial overgrowth (SIBO). RECENT FINDINGS When originally described, SIBO was added to the list of causes of the malabsorption syndrome and the pathophysiology of its consequences for the digestion and absorption of various nutrients was gradually revealed. More recently, SIBO was incriminated as a cause of diarrhea, especially in the elderly. However, the suggestion that SIBO may be a causative factor in irritable bowel syndrome and of its constituent symptoms has sparked debate and controversy on the very definition of SIBO. This debate revolves around the tests employed and the diagnostic cut-off values (for bacterial numbers) used to diagnose SIBO in clinical practice. SUMMARY A fundamental problem with SIBO, and one that allows controversy to simmer, is the lack of a universally accepted and applied gold standard for the diagnosis of SIBO. Hopefully, the application of molecular microbiological methods to the characterization of the small intestinal microbiome will tell us, once and for all, what is normal and when 'abnormality' is truly responsible for symptoms and disease. Meanwhile, therapy remains, for the most part, empirical and is based on the correction, wherever possible, of any underlying cause, attention to nutritional deficiencies, and the use of antibiotics.
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Miura K, Tanaka A, Yamamoto T, Adachi M, Takikawa H. Proton pump inhibitor use is associated with spontaneous bacterial peritonitis in patients with liver cirrhosis. Intern Med 2014; 53:1037-42. [PMID: 24827481 DOI: 10.2169/internalmedicine.53.2021] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Accumulating evidence suggests that the use of proton pump inhibitors (PPIs) is associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients, although the results are inconsistent. We aimed to examine whether PPI use is associated with SBP in Japan, where the administration of PPIs is strictly regulated. METHODS In this single-center retrospective study, we reviewed 65 patients with liver cirrhosis who were admitted between January 2008 and January 2013 due to ascites. The administration of any PPI for at least one week prior to admission was regarded as PPI use. RESULTS Eighteen cirrhotic patients with SBP and 47 without SBP were identified. Both the serum bilirubin levels and international normalized ratio (INR) values were significantly elevated in the patients with SBP (p=0.007, 0.002). The model for end-stage liver disease scores (mean±SD) were 16.1±9.9 and 12.5±9.3 in those with and without SBP (p=0.009), respectively. PPIs were used in 16 out 18 in patients with SBP and 27 of 47 patients without SBP (p=0.002). A multivariate analysis identified INR (odds ratio (OR)=15.3, 95% CI 2.96-76.9, p=0.001) and PPI use (OR=6.41, 95% CI=1.16-35.7, p=0.033) to be independent risk factors for SBP. CONCLUSION The use of PPIs in cirrhotic patients with ascites is independently associated with SBP in the Japanese clinical setting.
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Affiliation(s)
- Kotaro Miura
- Department of Medicine, Teikyo University School of Medicine, Japan
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