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1
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Li H, Luo Y, Zhang Q, Dong L, Liu H, Yue W, Zhu Q, Huang D. Ultrasound-based assessment of impaired gastric emptying in patients with hepatitis B cirrhosis. Clin Exp Med 2025; 25:121. [PMID: 40254679 PMCID: PMC12009778 DOI: 10.1007/s10238-025-01650-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 03/25/2025] [Indexed: 04/22/2025]
Abstract
This study aims to evaluate the utility of gastric ultrasound in assessing gastric emptying dysfunction in patients with hepatitis B cirrhosis and its correlation with alterations in portal venous flow and liver stiffness. Gastric motility and emptying parameters, portal venous flow parameters, and liver stiffness were measured by ultrasound in 42 patients with hepatitis B cirrhosis and 48 healthy controls. Statistical analysis was performed to compare the differences in these parameters between the two groups and to analyze the correlation between gastric ultrasound parameters and alternations in portal venous blood flow and liver stiffness. Firstly, the Gastric Motility Index was significantly lower in the experimental group than in the control group, while other gastric ultrasound parameters were significantly higher (p < 0.01). Secondly, measurements obtained from two-dimensional ultrasound, Color Doppler Flow Imaging, and two-dimensional Shear Wave Elastography revealed that Portal Vein Diameter (PVD) and Liver Stiffness (LS) were significantly higher in the experimental group compared to the control group, while the maximum portal vein velocity (PVmax) was significantly lower (p < 0.01). Finally, correlation analysis demonstrated that gastric ultrasound parameters correlated with PVD, PVmax, and LS. Gastric function is significantly impaired in patients with hepatitis B cirrhosis compared to controls, and gastric ultrasound parameters demonstrate a notable correlation with PVD, PVmax, and LS. Gastric ultrasound effectively evaluates gastric motility and emptying function in these patients, offering a reliable foundation for clinical diagnosis and management.
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Affiliation(s)
- Hongxing Li
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
- Department of Ultrasound, Nanbu People's Hospital, Nanchong, 637300, Sichuan, China
| | - Yi Luo
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Qinhui Zhang
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Linghong Dong
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Hanyang Liu
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Wensheng Yue
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Qirong Zhu
- Department of Infection, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Duo Huang
- Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
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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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3
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Nishimura N, Kaji K, Kitagawa K, Sawada Y, Furukawa M, Ozutsumi T, Fujinaga Y, Tsuji Y, Takaya H, Kawaratani H, Moriya K, Namisaki T, Akahane T, Fukui H, Yoshiji H. Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis. Int J Mol Sci 2021; 22:6921. [PMID: 34203178 PMCID: PMC8267717 DOI: 10.3390/ijms22136921] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/22/2021] [Accepted: 06/24/2021] [Indexed: 12/12/2022] Open
Abstract
Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called "leaky gut". Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.
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Affiliation(s)
- Norihisa Nishimura
- Department of Gastroenterology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan; (K.K.); (K.K.); (Y.S.); (M.F.); (T.O.); (Y.F.); (Y.T.); (H.T.); (H.K.); (K.M.); (T.N.); (T.A.); (H.F.); (H.Y.)
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Enderes J, Teschke J, Manekeller S, Vilz TO, Kalff JC, Glowka TR. Chronic Liver Disease Increases Mortality Following Pancreatoduodenectomy. J Clin Med 2021; 10:jcm10112521. [PMID: 34200183 PMCID: PMC8201140 DOI: 10.3390/jcm10112521] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 05/29/2021] [Accepted: 06/02/2021] [Indexed: 12/13/2022] Open
Abstract
According to the International Study Group of Pancreatic Surgery (ISGPS), data about the impact of pre-existing liver pathologies on delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) according to the definitions of the International Study Group of Pancreatic Surgery (ISGPS) are lacking. We therefore investigated the impact of DGE after PD according to ISGPS in patients with liver cirrhosis (LC) and advanced liver fibrosis (LF). Patients were analyzed with respect to pre-existing liver pathologies (LC and advanced LF, n = 15, 6% vs. no liver pathologies, n = 240, 94%) in relation to demographic factors, comorbidities, intraoperative characteristics, mortality and postoperative complications, with special emphasis on DGE. DGE was equally distributed (DGE grade A, p = 1.000; B, p = 0.396; C, p = 0.607). Particularly, the first day of solid food intake (p = 0.901), the duration of intraoperative administered nasogastric tube (NGT) (p = 0.812), the rate of re-insertion of NGT (p = 0.072), and the need for parenteral nutrition (p = 0.643) did not differ. However, patients with LC and advanced LF showed a higher ASA (American Society of Anesthesiologists) score (p = 0.016), intraoperatively received more erythrocyte transfusions (p = 0.029), stayed longer in the intensive care unit (p = 0.010) and showed more intraabdominal abscess formation (p = 0.006). Moreover, we did observe a higher mortality rate amongst patients with pre-existing liver diseases (p = 0.021), and reoperation was a risk factor for higher mortality (p ≤ 0.001) in the multivariate analysis. In our study, we could not detect a difference with respect to DGE classified by ISGPS; however, we did observe a higher mortality rate amongst these patients and thus, they should be critically evaluated for PD.
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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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Losurdo G, D’Abramo FS, Indellicati G, Lillo C, Ierardi E, Di Leo A. The Influence of Small Intestinal Bacterial Overgrowth in Digestive and Extra-Intestinal Disorders. Int J Mol Sci 2020; 21:3531. [PMID: 32429454 PMCID: PMC7279035 DOI: 10.3390/ijms21103531] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 05/13/2020] [Accepted: 05/15/2020] [Indexed: 02/07/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is a condition hallmarked by an increase in the concentration of colonic-type bacteria in the small bowel. Watery diarrhea, bloating, abdominal pain and distension are the most common clinical manifestations. Additionally, malnutrition and vitamin (B12, D, A, and E) as well as minerals (iron and calcium) deficiency may be present. SIBO may mask or worsen the history of some diseases (celiac disease, irritable bowel disease), may be more common in some extra-intestinal disorders (scleroderma, obesity), or could even represent a pathogenetic link with some diseases, in which a perturbation of intestinal microbiota may be involved. On these bases, we performed a review to explore the multiple links between SIBO and digestive and extra-intestinal diseases.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
- PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy
| | - Fulvio Salvatore D’Abramo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
| | - Giuseppe Indellicati
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
| | - Chiara Lillo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (F.S.D.); (G.I.); (C.L.); (E.I.); (A.D.L.)
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Fukui H. Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far? Diseases 2019; 7:diseases7040058. [PMID: 31726747 PMCID: PMC6956030 DOI: 10.3390/diseases7040058] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 10/29/2019] [Accepted: 10/29/2019] [Indexed: 02/07/2023] Open
Abstract
Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8522, Japan
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Liu Chen Kiow J, Vincent C, Sidani S, Bouin M. High occurrence of small intestinal bacterial overgrowth in primary biliary cholangitis. Neurogastroenterol Motil 2019; 31:e13691. [PMID: 31373141 DOI: 10.1111/nmo.13691] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 07/11/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease affecting mainly middle-aged women. An alteration in intestinal motility has been well documented in cirrhosis predisposing to small intestinal bacterial overgrowth (SIBO). Patients with PBC frequently complain of various gastrointestinal symptoms compatible with SIBO. No study has specifically been published to this day to determine the occurrence of SIBO in PBC. Our objective was to determine the prevalence of SIBO in patients with PBC. METHODS Retrospective study from 2010 to 2018. All patients diagnosed with PBC during this period had a systematic screening for SIBO in their diagnostic workup. The diagnosis of SIBO was made by a carbohydrate breath test (lactulose and/or glucose). Clinical and paraclinical factors of patients were compared with a control group of healthy subjects. KEY RESULTS Ninety-eight subjects were included in the study (mean age 49, range 21-88 years) including 58 patients with PBC and 40 healthy subjects. The PBC group was older than the control group (mean age 56, range 31-88 vs 39, range 21-62 years; P < .001), but identical for gender and body mass index. The prevalence of SIBO was higher in PBC versus controls (32.8% vs 2.5%; P < .001). The PBC group with SIBO had significantly more diarrhea (78.9% vs 35.9%; P < .05) than the PBC group without SIBO, but the prevalence of abdominal pain and bloating was similar. CONCLUSIONS & INFERENCES The high occurrence of SIBO in PBC may explain some of the frequently reported gastrointestinal symptoms. This study justifies the systematic screening for SIBO in PBC.
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Affiliation(s)
- Jeremy Liu Chen Kiow
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Catherine Vincent
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Sacha Sidani
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Mickael Bouin
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
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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: 38] [Impact Index Per Article: 6.3] [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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10
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Pantham G, Post A, Venkat D, Einstadter D, Mullen KD. A New Look at Precipitants of Overt Hepatic Encephalopathy in Cirrhosis. Dig Dis Sci 2017; 62:2166-2173. [PMID: 28560484 DOI: 10.1007/s10620-017-4630-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 05/23/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Overt hepatic encephalopathy (HE) is a major cause of significant morbidity and mortality in patients with liver cirrhosis. We examined the frequency and profile of the precipitating factors resulting in hospitalizations for overt HE. METHODS We conducted both retrospective and prospective studies to identify clinical precipitants of overt HE in patients with cirrhosis. The retrospective study patients were hospitalized at a large urban safety-net hospital, and the prospective study included the patients admitted at a liver transplant center. RESULTS There were a total of 149 patients with cirrhosis and overt HE (91 males, mean age 55.3 ± 8.6 years) in the retrospective group and 45 patients (27 males, mean age 58.3 ± 8.2 years) in the prospective group of the study. The average MELD score was 16 ± 6.8 in the retrospective group and 22.7 ± 7.2 in the prospective group. Dehydration (46-76%), acute kidney injury (32-76%), lactulose nonadherence (about 50%), constipation (about 40%), and infections (20-42%) were the most frequently identified precipitants for hospitalization in retrospective and prospective groups. Multiple precipitants were identified in 60 (40.3%) patients in the retrospective group and 34 (76%) patients in the prospective group. CONCLUSIONS Multiple concurrent precipitating factors were identified in the majority of patients with overt HE requiring hospitalization. Dehydration due to various causes was the most common precipitant of overt HE, followed by acute kidney injury (AKI), constipation, and infections. Prevention of dehydration, AKI, and constipation by close outpatient monitoring may be an effective measure to prevent hospitalization for overt HE in patients with cirrhosis.
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Affiliation(s)
- Ganesh Pantham
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
| | - Anthony Post
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Deepak Venkat
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Douglas Einstadter
- Departments of Medicine, Epidemiology and Biostatistics, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Kevin D Mullen
- Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Cleveland, OH, USA
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11
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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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12
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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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Gut Microbiota and Host Reaction in Liver Diseases. Microorganisms 2015; 3:759-91. [PMID: 27682116 PMCID: PMC5023261 DOI: 10.3390/microorganisms3040759] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 10/08/2015] [Accepted: 10/21/2015] [Indexed: 02/07/2023] Open
Abstract
Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.
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Tapper EB, Jiang ZG, Patwardhan VR. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy. Mayo Clin Proc 2015; 90:646-58. [PMID: 25865476 DOI: 10.1016/j.mayocp.2015.03.003] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 02/27/2015] [Accepted: 03/03/2015] [Indexed: 12/12/2022]
Abstract
Hepatic encephalopathy (HE) is one of the most important complications of cirrhosis and portal hypertension. Although the etiology is incompletely understood, it has been linked to ammonia directly and indirectly. Our goal is to review for the clinician the mechanisms behind hyperammonemia and the pathogenesis of HE to explain the rationale for its therapy. We reviewed articles collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar between October 1, 1948, and December 8, 2014, and by a manual search of citations within retrieved articles. Search terms included hepatic encephalopathy, ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic shunt, ammonia and lactulose, rifaximin, zinc, and nutrition. Ammonia homeostatsis is a multiorgan process involving the liver, brain, kidneys, and muscle as well as the gastrointestinal tract. Indeed, hyperammonemia may be the first clue to poor functional reserves, malnutrition, and impending multiorgan dysfunction. Furthermore, the neuropathology of ammonia is critically linked to states of systemic inflammation and endotoxemia. Given the complex interplay among ammonia, inflammation, and other factors, ammonia levels have questionable utility in the staging of HE. The use of nonabsorbable disaccharides, antibiotics, and probiotics reduces gut ammoniagenesis and, in the case of antibiotics and probiotics, systemic inflammation. Nutritional support preserves urea cycle function and prevents wasting of skeletal muscle, a significant site of ammonia metabolism. Correction of hypokalemia, hypovolemia, and acidosis further assists in the reduction of ammonia production in the kidney. Finally, early and aggressive treatment of infection, avoidance of sedatives, and modification of portosystemic shunts are also helpful in reducing the neurocognitive effects of hyperammonemia. Refining the ammonia hypothesis to account for these other factors instructs a solid foundation for the effective treatment and prevention of hepatic encephalopathy.
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Affiliation(s)
- Elliot B Tapper
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA.
| | - Z Gordon Jiang
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Vilas R Patwardhan
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
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Rai R, Saraswat VA, Dhiman RK. Gut microbiota: its role in hepatic encephalopathy. J Clin Exp Hepatol 2015; 5:S29-36. [PMID: 26041954 PMCID: PMC4442863 DOI: 10.1016/j.jceh.2014.12.003] [Citation(s) in RCA: 123] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 12/09/2014] [Indexed: 02/08/2023] Open
Abstract
Ammonia, a key factor in the pathogenesis of hepatic encephalopathy (HE), is predominantly derived from urea breakdown by urease producing large intestinal bacteria and from small intestine and kidneys, where the enzyme glutaminases releases ammonia from circulating glutamine. Non-culture techniques like pyrosequencing of bacterial 16S ribosomal ribonucleic acid are used to characterize fecal microbiota. Fecal microbiota in patients with cirrhosis have been shown to alter with increasing Child-Turcotte-Pugh (CTP) and Model for End stage Liver Disease (MELD) scores, and with development of covert or overt HE. Cirrhosis dysbiosis ratio (CDR), the ratio of autochthonous/good bacteria (e.g. Lachnospiraceae, Ruminococcaceae and Clostridiales) to non-autochthonous/pathogenic bacteria (e.g. Enterobacteriaceae and Streptococcaceae), is significantly higher in controls and patients with compensated cirrhosis than patients with decompensated cirrhosis. Although their stool microbiota do not differ, sigmoid colonic mucosal microbiota in liver cirrhosis patients with and without HE, are different. Linkage of pathogenic colonic mucosal bacteria with poor cognition and inflammation suggests that important processes at the mucosal interface, such as bacterial translocation and immune dysfunction, are involved in the pathogenesis of HE. Fecal microbiome composition does not change significantly when HE is treated with lactulose or when HE recurs after lactulose withdrawal. Despite improving cognition and endotoxemia as well as shifting positive correlation of pathogenic bacteria with metabolites, linked to ammonia, aromatic amino acids and oxidative stress, to a negative correlation, rifaximin changes gut microbiome composition only modestly. These observations suggest that the beneficial effects of lactulose and rifaximin could be associated with a change in microbial metabolic function as well as an improvement in dysbiosis.
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Key Words
- CDR, cirrhosis dysbiosis ratio
- HE, hepatic encephalopathy
- IL, interleukin
- LGG, Lactobacillus GG strain
- LPO, left parietal operculum
- MELD, model for end stage liver disease
- MHE, minimal hepatic encephalopathy
- MRS, magnetic resonance spectroscopy
- PAMPs, pathogen-associated molecular patterns
- PCR, polymerase chain reaction
- RCT, randomized controlled trial
- RNA, ribonucleic acid
- SBP, spontaneous bacterial peritonitis
- SIBO, small intestinal bacterial overgrowth
- SIRS, systemic inflammatory response syndrome
- TNF, tumor necrosis factor
- cirrhosis
- dysbiosis
- fMRI, functional MRI
- gut microbiome
- inflammation
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Affiliation(s)
- Rahul Rai
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India,Address for correspondence: Radha K. Dhiman, Tel.: +91 9914209337; fax: +91 1722744401.
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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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17
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Wang R, Song MY, Li XW, Du P, Yang L. Alterations in intestinal flora and hepatic fibrosis. Shijie Huaren Xiaohua Zazhi 2014; 22:3937-3940. [DOI: 10.11569/wcjd.v22.i26.3937] [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
The normal intestinal flora plays an important role in the maintenance of human health. When the internal and external environment of the body changes and there exists intestinal flora imbalance, a variety of diseases may develop, especially liver diseases. The existence of hepatic fibrosis can cause or aggravate intestinal flora imbalance. The status of the body's intestinal flora is closely related to liver fibrosis, and they can influence each other. This review mainly discusses the relationship between alterations in intestinal flora and hepatic fibrosis to provide new clues to the therapy of this disease in clinical practice.
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Seo YS, Shah VH. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. Clin Mol Hepatol 2012; 18:337-46. [PMID: 23323248 PMCID: PMC3540369 DOI: 10.3350/cmh.2012.18.4.337] [Citation(s) in RCA: 109] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2012] [Revised: 10/03/2012] [Accepted: 10/17/2012] [Indexed: 12/12/2022] Open
Abstract
Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.
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Affiliation(s)
- Yeon Seok Seo
- Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55905, USA
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Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A. Prevention and treatment of hepatic encephalopathy: focusing on gut microbiota. World J Gastroenterol 2012; 18:6693-6700. [PMID: 23239905 PMCID: PMC3520156 DOI: 10.3748/wjg.v18.i46.6693] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Revised: 07/30/2012] [Accepted: 08/04/2012] [Indexed: 02/06/2023] Open
Abstract
The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.
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20
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Chao PW, Ou SM, Chen YT, Lee YJ, Wang FM, Liu CJ, Yang WC, Chen TJ, Chen TW, Li SY. Acute appendicitis in patients with end-stage renal disease. J Gastrointest Surg 2012; 16:1940-6. [PMID: 22777056 DOI: 10.1007/s11605-012-1961-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 06/28/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge. Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis modalities. METHODS This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard model was used to identify risk factors. RESULTS Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p = 0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient outcomes. CONCLUSIONS ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important to prevent delayed surgery.
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Affiliation(s)
- Pei-Wen Chao
- Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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Lunia MK, Sharma BC, Sachdeva S. Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy. Hepatol Int 2012. [PMID: 26201641 DOI: 10.1007/s12072-012-9360-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Gut-derived nitrogenous substances play a role in pathogenesis of HE. The present study was conducted to assess small intestinal bacterial overgrowth (SIBO) and prolonged orocecal transit time (OCTT) in cirrhosis and low-grade HE. METHODS In cross-sectional prospective study, 75 patients were divided into 3 groups: group 1 (no HE, n = 31), group 2 (minimal HE, n = 29), and group 3 (early/grade 1 HE, n = 15). Minimal HE (MHE) was diagnosed when psychometric hepatic encephalopathy score (PHES) was ≤5. Early HE was diagnosed, according to West Haven criteria. All patients underwent glucose hydrogen breath test (GHBT) for SIBO and lactulose hydrogen breath test (LHBT) for OCTT. RESULTS A total of 29 patients (38.67 %) had MHE and 15 (20 %) had early HE. Prevalence of MHE in Child-Turcotte-Pugh (CTP) class A, B, and C was 33.3, 38.71, and 45 %, respectively, while SIBO was detected in 26 (34.67 %). Prevalence of SIBO was 12.5 % in CTP class A, 41.94 % in CTP class B, and 50 % in CTP class C. Five (16.13 %) patients in no HE group had SIBO as compared to 14 (48.28 %) in MHE group and 7 (46.67 %) in early HE group (p = 0.018). OCTT was 111.13 ± 13.95 min in patients with no HE as compared to 137.59 ± 14.80 min in patients with MHE and 150 ± 15.12 min in patients with early HE (p < 0.001). OCTT was significantly prolonged in patients with SIBO (145 ± 17.49 min) than in those without SIBO (120.71 ± 18.3 min) (p < 0.001). CONCLUSION SIBO and delayed OCTT are more common with MHE and early HE in patients with cirrhosis.
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Affiliation(s)
- Manish Kumar Lunia
- Department of Gastroenterology, G B Pant Hospital, 203, Academic Block, New Delhi, 110002, India
| | - Barjesh Chander Sharma
- Department of Gastroenterology, G B Pant Hospital, 203, Academic Block, New Delhi, 110002, India.
| | - Sanjeev Sachdeva
- Department of Gastroenterology, G B Pant Hospital, 203, Academic Block, New Delhi, 110002, India
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Sharma P, Agrawal A, Sharma BC, Sarin SK. Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized controlled trial of lactulose versus no lactulose. J Gastroenterol Hepatol 2011; 26:996-1003. [PMID: 21129028 DOI: 10.1111/j.1440-1746.2010.06596.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIMS Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB. METHODS Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group-L) or no lactulose (Group-P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization. RESULTS Seventy patients were randomized into group-L (Gp-L, n = 35) and group-P (Gp-P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp-L vs Gp-P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp-L and 14 patients (40%) in Gp-P, P = 0.03. The median grade of HE was 2 (range 2-4) and median time interval of development of HE after randomization was 2 days (range 1-4). Nine patients (13%) died; three (8.5%) patients in Gp-L and six (17%) patients in Gp-P, P = 0.23. Patients who developed HE had significantly higher baseline Child-Turcotte-Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10,505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE. CONCLUSIONS Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology, G. B. Pant Hospital, New Delhi, India
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Gupta A, Dhiman RK, Kumari S, Rana S, Agarwal R, Duseja A, Chawla Y. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol 2010; 53:849-55. [PMID: 20675008 DOI: 10.1016/j.jhep.2010.05.017] [Citation(s) in RCA: 152] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Revised: 04/22/2010] [Accepted: 05/17/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy. This cross-sectional study was carried out to elucidate the role of bacterial overgrowth of the small intestine and delayed intestinal transit among patients with MHE. METHODS Two-hundred-thirty patients with cirrhosis were screened; 102 patients (44.4%) who met the eligibility criteria were included in the study. MHE was diagnosed when the psychometric hepatic encephalopathy score was ≤-5. All patients underwent a glucose breath test for small intestinal bacterial overgrowth (SIBO) and lactulose breath test for oro-cecal transit time (OCTT). RESULTS Fifty-seven (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22 (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients who had SIBO than in those who did not have SIBO (p<0.0001). Univariate analysis demonstrated that increased age, female gender, low educational status, low albumin, presence of SIBO, and prolonged OCTT were associated with the presence of MHE. Multivariate analysis demonstrated SIBO as the only factor associated with MHE. CONCLUSIONS Our study conclusively demonstrates high prevalence of SIBO in patients with cirrhosis with MHE. This study gives the rationale of treatment directed against SIBO and gut dysmotility, which may include non-absorbable antibiotics such as rifaximin, probiotics, and prokinetics.
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Affiliation(s)
- Ankur Gupta
- Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India
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Kasicka-Jonderko A, Krusiec-Swidergoł B, Jonderko K, Musialik J, Gonciarz M, Błońska-Fajfrowska B, Gonciarz Z. Gastric myoelectrical activity in patients with primary biliary cirrhosis. J Gastroenterol 2009; 44:346-52. [PMID: 19271110 DOI: 10.1007/s00535-009-0009-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2008] [Accepted: 10/27/2008] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To examine gastric myoelectrical activity in patients with primary biliary cirrhosis (PBC). MATERIALS AND METHODS The study comprised 11 female PBC patients (average age 53.4 years, range 43-70) and two aged-matched control groups: 11 (53.4 years, range 37-78) healthy women, and 10 female patients with chronic hepatitis C, CHC (53.9 years, range 35-66), who were examined prior to administration of an antiviral therapy. Every subject underwent an electrogastrographic recording comprising a 30-min interdigestive and a 120-min postprandial period. RESULTS Abnormal electrogastrograms, containing prolonged epochs of tachygastria in the postprandial phase were found in 2 out of 11 (18.2%) patients having both stage IV of the Scheuer's PBC classification, as well as in 1 patient out of 10 (10%) with CHC at stage F2 according to the METAVIR fibrosis score. CONCLUSION Electrogastrographic abnormalities do not seem to be pathognomonic for the PBC as a disease, but rather would be considered an unspecific sequel of a morbid liver affection.
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Affiliation(s)
- Anna Kasicka-Jonderko
- Department of Basic Biomedical Science, School of Pharmacy, Medical University of Silesia, Kasztanowa Street 3, 41-205, Sosnowiec, Poland
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Kalaitzakis E, Simrén M, Abrahamsson H, Björnsson E. Role of gastric sensorimotor dysfunction in gastrointestinal symptoms and energy intake in liver cirrhosis. Scand J Gastroenterol 2007; 42:237-46. [PMID: 17327944 DOI: 10.1080/00365520600880898] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Altered gastric sensorimotor function is related to the symptomatology in several gastrointestinal diseases. Gastrointestinal symptoms in patients with cirrhosis may result in low energy intake contributing to malnutrition and increased morbidity. The aim of this study was to investigate gastric accommodation to a meal and sensitivity to gastric distension with reference to energy intake, nutritional status and gastrointestinal symptoms in liver cirrhosis. MATERIAL AND METHODS Sixteen patients with cirrhosis and 15 healthy controls underwent a gastric barostat study to assess gastric accommodation to a meal and sensory thresholds for first perception and discomfort. The patients also underwent a slow caloric satiety drinking test. Food intake and nutritional status were also evaluated and gastrointestinal symptoms were assessed by means of a questionnaire. RESULTS Compared with controls, patients with cirrhosis had enhanced gastric accommodation (p<0.05) but lower daily energy intake (p<0.05). Patients with versus those without compromised nutritional status had enhanced gastric accommodation (p<0.05). Gastric accommodation was correlated to daily energy intake in controls (r=0.67, p<0.05) but not in cirrhotic patients (p>0.4). The end-point of the satiety test was inversely related to gastric volumes in cirrhotic patients. Mean post-meal balloon volumes were positively correlated to the Model for End Stage Liver Disease (MELD) score (r=0.53, p<0.05). Sensory thresholds did not differ between patients and controls but were related to gastrointestinal symptom severity and cirrhosis severity scores in the patients. CONCLUSIONS Gastric accommodation is increased in cirrhotic patients but there seems to be some disturbance in its relation to energy intake. The satiety drinking test is not a good surrogate marker of accommodation in cirrhotic patients. In cirrhosis the severity of gastrointestinal symptoms is related to gastric sensitivity.
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Affiliation(s)
- Evangelos Kalaitzakis
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Maheshwari A, Thuluvath PJ. Autonomic neuropathy may be associated with delayed orocaecal transit time in patients with cirrhosis. Auton Neurosci 2005; 118:135-9. [PMID: 15795187 DOI: 10.1016/j.autneu.2005.02.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2004] [Revised: 02/02/2005] [Accepted: 02/08/2005] [Indexed: 12/13/2022]
Abstract
UNLABELLED Orocaecal transit (OCT) time is delayed in patients with cirrhosis, but the reasons for this remain unclear. We hypothesized that autonomic neuropathy (AN) may explain the delay in OCT. METHODS We determined OCT and autonomic function tests (AFT) in 48 patients (Child A-15, B-27, C-6) with cirrhosis of various aetiologies. AFT were categorized as normal, borderline, or abnormal. OCT was measured using the lactulose hydrogen (H2) breath test. OCT was defined as the time from baseline when there was a rise in H2 levels of >20 ppm over baseline or >10 ppm over baseline sustained over 2 consecutive time points. RESULTS Based on OCT, patients were separated into those with delayed OCT (>90 min, group I) and normal OCT (< or = 90 min, group II). Mean OCT time of patients in group I was 169.7+/-49.7 min vs. 84.4+/-12.1 min in group II. Baseline clinical characteristics of patients with and without AN, and those with normal and delayed OCT were similar. Presence of mild encephalopathy did not have an effect on OCT. AN was seen more frequently in group I than group II [16/32 (50%) vs. 3/16 (19%), p=0.03]. Logistic regression analysis showed that the presence of AN was the only independent variable associated with delayed OCT (OR 7.3, CI 1.3-39.4, p=0.02). CONCLUSION Our study showed that the presence of AN was associated with delayed OCT in patients with cirrhosis.
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Affiliation(s)
- Anurag Maheshwari
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, 1830 E. Monument Street, suite 430, Baltimore, MD 21205, USA
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Bouin M, Vincent C, Bouhier K, Debruyne D, Fatome A, Piquet MA, Verwaerde JC, Dao T. Increased oro-cecal transit time in grade I or II hepatic encephalopathy. ACTA ACUST UNITED AC 2005; 28:1240-4. [PMID: 15671935 DOI: 10.1016/s0399-8320(04)95217-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
UNLABELLED The pathogenic mechanisms of hepatic encephalopathy remain to be elucidated. It has been suggested that a digestive motor disorder could promote the absorption of toxins produced within the lumen and thus enhance hepatic encephalopathy. AIM To evaluate oro-cecal transit time in cirrhotic patients with and without hepatic encephalopathy. METHODS Hospitalized patients with alcoholic cirrhosis without encephalopathy and with spontaneous grade I and II encephalopathy were included. Severity of hepatic encephalopathy was assessed clinically and the Child-Pugh score was used to describe cirrhosis severity. Nine healthy volunteers constituted a control group. Oro-cecal transit time was measured with the sulfasalazine test. RESULTS Twenty-eight patients (mean age 62.5 +/- 8.5 years) were included. Ten had hepatic encephalopathy of unknown cause and 18 were free of hepatic encephalopathy. Oro-cecal transit time was significantly longer in patients with hepatic encephalopathy (641 +/- 350 min) compared to patients without hepatic encephalopathy (298 +/- 96; P<0.05) and to controls (354 +/- 90; P<0.05). Oro-cecal transit time was comparable for each Child-Pugh score and was not different between the two grades of hepatic encephalopathy. CONCLUSION Oro-cecal transit time is longer in alcoholic cirrhosis patients with hepatic encephalopathy. This digestive motor disorder provides a partial explanation of hepatic encephalopathy of unknown etiology.
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Affiliation(s)
- Mickael Bouin
- Service d'hépato-gastroentérologie, CHU Côte de Nacre, 14033 Caen Cedex.
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Madoff DC, Wallace MJ, Ahrar K, Saxon RR. TIPS-related hepatic encephalopathy: management options with novel endovascular techniques. Radiographics 2004; 24:21-36; discussion 36-7. [PMID: 14730033 DOI: 10.1148/rg.241035028] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatic encephalopathy is a common complication that develops after creation of a transjugular intrahepatic portosystemic shunt (TIPS). Although most patients respond well to conservative medical therapy (ie, protein-restricted diet, nonabsorbable disaccharides, nonabsorbable antibiotics), a small percentage of patients (3%-7%) do not benefit from these methods and require more invasive therapeutic approaches. One option is emergent liver transplantation, but the majority of patients are not suitable candidates. Recently, various percutaneous techniques have been described that alter the hemodynamics through the shunt by occluding it with coils or balloons or by reducing its diameter by inserting constrained stents or stent-grafts. Other techniques have been used for patients with TIPS-related hepatic encephalopathy in whom spontaneous splenorenal shunts are present. In many patients with refractory hepatic encephalopathy, these percutaneous techniques have produced symptomatic improvement, with either a complete resolution or a substantial reduction in hepatic encephalopathy symptoms that can be controlled with medical therapy. Unfortunately, despite all attempts, some patients remain incapacitated and ultimately die. Further research is necessary to improve our understanding of TIPS-related hepatic encephalopathy so that newer, less invasive and safer procedures can be developed to treat this difficult clinical problem.
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Affiliation(s)
- David C Madoff
- Division of Diagnostic Imaging, Section of Vascular and Interventional Radiology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 325, Houston, TX 77030-4009, USA.
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Gunnarsdottir SA, Sadik R, Shev S, Simrén M, Sjövall H, Stotzer PO, Abrahamsson H, Olsson R, Björnsson ES. Small intestinal motility disturbances and bacterial overgrowth in patients with liver cirrhosis and portal hypertension. Am J Gastroenterol 2003; 98:1362-70. [PMID: 12818282 DOI: 10.1111/j.1572-0241.2003.07475.x] [Citation(s) in RCA: 143] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Altered small bowel motility and a high prevalence of small intestinal bacterial overgrowth (SIBO) has been observed in patients with liver cirrhosis. Our aim was to explore the relationship between motility abnormalities, portal hypertension, and SIBO. METHODS Twenty-four patients with liver cirrhosis were included. Twelve had portal hypertension (PH) and 12 had liver cirrhosis (LC) alone. Child-Pugh score was the same in the groups. Antroduodenojejunal pressure recordings were performed, and noninvasive variceal pressure measurements were undertaken. Thirty-two healthy volunteers served as a reference group. Bacterial cultures were obtained from jejunal aspirates. RESULTS The PH group had a higher proportion of individual pressure waves that were retrograde in the proximal duodenum during phase II (52% vs 13% vs 8% of propagated contractions; p < 0.001) as well as postprandially (49% vs 18% vs 13%; p < 0.01) compared with LC and controls, respectively. Long clusters were more common in PH than in controls (9.1 +/- 2.1 vs 4.9 +/- 0.8; p < 0.05), and a higher motility index in phase III in the proximal and distal duodenum was seen in the PH as compared with the other groups. The mean variceal pressure was 21 +/- 1 mm Hg. Motor abnormalities were not correlated to the level of variceal pressure. Thirty-three percent of the patients in the PH group but none in the LC group had SIBO. CONCLUSIONS Abnormal small bowel motility and SIBO is common in patients with liver cirrhosis with concomitant portal hypertension. Portal hypertension per se might be significantly related to small bowel abnormalities observed in patients with liver cirrhosis.
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Affiliation(s)
- Steingerdur Anna Gunnarsdottir
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Göteborg, Sweden
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Chen CY, Lu CL, Chang FY, Lih-Jiun K, Luo JC, Lu RH, Lee SD. Delayed gastrointestinal transit in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2002; 17:1254-9. [PMID: 12423268 DOI: 10.1046/j.1440-1746.2002.02877.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM Disturbed gastrointestinal (GI) motility exists in cirrhotic patients; however, less is known about the character of GI transit in hepatocellular carcinoma (HCC) patients. It is interesting to study the GI transit in HCC patients and to explore the patient factors modulating GI transit. METHODS A non-invasive hydrogen breath test, which measured the orocecal transit time (OCTT), was used to study GI transit in 40 HCC patients, 20 cirrhotics and 40 age- and sex-matched healthy volunteers with normal bowel habits. Meanwhile, their clinical manifestations and various blood parameters, such as platelet count, prothrombin time, erythrocyte sedimentation rate etc. were collected. The plasma endothelin-1 and nitrate/nitrite levels were also measured. RESULTS The OCTT were delayed in HCC and cirrhotic patients compared with controls (116.3 +/- 7.8 and 104.5 +/- 10.6 vs 75.3 +/- 5.1 min, P < 0.05). Neither the severity of liver damage, presence of ascites, tumor size, portal hypertension, nor various blood parameters, such as nitrate/nitrite, endothelin-1, platelet count etc., had any influence on GI transit. Only serum alpha-fetoprotein levels exhibited a trend toward positive correlation with the OCTT (r = 0.271, P = 0.091). CONCLUSIONS Hepatocellular carcinoma patients have delayed GI transit. The confounding factor responsible for the disturbance of GI transit in HCC patients needs further exploration.
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Affiliation(s)
- Chih-Yen Chen
- Division of Gastroenterology, Taipei Veterans General Hospital, Taiwan
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Abstract
OBJECTIVES Hepatitis C virus is a common chronic infection that is widely associated with symptoms of fatigue and pain in the right upper quadrant. Nausea may be an underrecognized symptom. This study was designed to study the frequency of nausea in patients with hepatitis C virus infection compared to controls. METHODS A cross-sectional study design with consecutive outpatients was used. Three groups were administered a dyspepsia and a previously validated Nausea Profile questionnaire. Univariate and multivariate analysis was performed. RESULTS A total of 64 hepatitis C virus (HCV) patients, 53 liver disease controls (LC), and 64 normal controls (NC) were studied. An increased period prevalence of nausea was found in HCV patients 43% versus 29.7% in NC and 18.9% in LC (p = 0.009). There was an increased frequency of fatigue and abdominal pain in HCV patients over 1 month compared to LC and NC combined (p = 0.0001 and 0.0065 respectively). The Nausea Profile score revealed statistically higher total scores and higher subscale scores in the HCV group compared to controls. The total NP score expressed as a percentage of the maximum was 27% in HCV versus 12.7% for LC and 9.2% for NC (p = 0.0005). The odds of nausea using logistic regression were 2.1 CI (1.0-4.5) in HCV patients compared to controls (p = 0.05). Using linear regression, higher Nausea Profile scores were found to be independently associated with the diagnosis of HCV (.0005), fatigue (p = 0.0003), and abdominal pain (p = 0.0001). CONCLUSIONS HCV infection is associated with an increased risk for nausea. The strong association between abdominal pain and nausea may be a clue to the etiology of nausea in these patients. Further etiological studies are needed.
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Affiliation(s)
- T R Riley
- Department of Medicine and Health Evaluation Sciences, The Pennsylvania State University-The Hershey Medical Center, 17033, USA
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Abstract
1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in patients with deep encephalopathy should be considered. A nasogastric tube is placed for patients in deep encephalopathy. Avoid sedatives whenever possible. Correction of the precipitating factor is the most important measure. B. SPECIFIC MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day. ii. Lactulose is administered via enema or nasogastric tube in deep encephalopathy. The oral route is optimized by dosing every hour until stool evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil may be used in selected cases of suspected benzodiazepine use. 2. Chronic Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors, including the institution of prophylactic measures. ii. Nutrition. Improve protein intake by feeding dairy products and vegetable-based diets. Oral branched-chain amino acids can be considered for individuals intolerant of all protein. iii. Lactulose. Dosing aims at two to three soft bowel movements per day. Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring. iv. Refer for liver transplantation in appropriate candidates. For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion. In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases. The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60). Although these may impact the ability to perform daily activities, many subjects can compensate for these defects. Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62). In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried. Benzodiazepines should not be used for patients with sleep difficulties.
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Affiliation(s)
- A T Blei
- Department of Medicine, Lakeside VA Medical Center and Northwestern University, Chicago, Illinois 60611, USA
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Madrid AM, Hurtado C, Venegas M, Cumsille F, Defilippi C. Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am J Gastroenterol 2001; 96:1251-5. [PMID: 11316178 DOI: 10.1111/j.1572-0241.2001.03636.x] [Citation(s) in RCA: 104] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis. These changes might be related to the progressive course and poor prognosis of the disease. We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and some parameters of liver function. METHODS Thirty-four patients with liver cirrhosis of different etiology entered in the study. They were randomly allocated to receive cisapride (12), an alternating regimen of norfloxacin and neomycin (12), or placebo (10) during a period of 6 months. At entry and at 3 and 6 months, a stationary small-intestinal manometry was performed, and orocecal transit time and small-intestinal bacterial overgrowth were also investigated using the H2 breath test. Liver function was estimated with clinical and laboratory measurements (Child-Pugh score). RESULTS After 6 months, both cisapride and antibiotics significantly improved fasting cyclic activity, reduced the duration of orocecal transit time, and decreased small-intestinal bacterial overgrowth. Cisapride administration was followed also by an increase in the amplitude of contractions. No statistically significant variations in these parameters were observed with placebo. An improvement of liver function was observed at 3 and 6 months with both cisapride and antibiotics. CONCLUSIONS Long-term treatment with cisapride or antibiotics reversed altered small-intestinal motility and bacterial overgrowth in patients with liver cirrhosis. These findings suggest a possible role for prokinetics and antibiotics as a modality of treatment in selected cases of decompensated cirrhosis.
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Affiliation(s)
- A M Madrid
- Gastrointestinal Section, University Hospital, University of Chile, Santiago
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Koga H, Aoyagi K, Matsumoto T, Iida M, Fujishima M. Experimental enteropathy in athymic and euthymic rats: synergistic role of lipopolysaccharide and indomethacin. THE AMERICAN JOURNAL OF PHYSIOLOGY 1999; 276:G576-82. [PMID: 10070032 DOI: 10.1152/ajpgi.1999.276.3.g576] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
The aim of this study was to investigate the immunologic and microbiological bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen-free (SPF) rats were reared under conventional or SPF conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously described ulcer index and tissue myeloperoxidase activity. Both euthymic and athymic nude rats developed intestinal ulcers to the same degree under conventional conditions but no or minimal ulcer under SPF conditions. Pretreatment of conventional rats with intragastric kanamycin sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a dose-dependent fashion. Interestingly, when lipopolysaccharide was injected intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in these rats in a dose-dependent manner. We confirmed that kanamycin decreased the number of gram-negative bacteria and endotoxin concentration of the small intestine in a dose-dependent fashion. These results indicate that indomethacin enteropathy is bacteria dependent and does not require a T cell function. Synergy between indomethacin and bacterial lipopolysaccharide may play a major role in this enteropathy.
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Affiliation(s)
- H Koga
- Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan
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Abstract
Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction resulting from underlying liver disease or portal-systemic shunting. HE can present as one of four syndromes, depending on the rapidity of onset of hepatic failure and the presence or absence of preexisting liver disease. The precise pathogenesis is unknown but likely involves impaired hepatic detoxification of ammonia as well as alterations in brain transport and metabolism of amino acids and amines. The etiology of malnutrition in hepatic failure is multifactorial. Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or both. Nutritional support in HE is directed toward reducing morbidity related to underlying malnutrition and concurrent disease. However, reaching nutritional goals is often complicated by protein and carbohydrate intolerance. The use of protein restriction in HE is controversial. Modified formulas that are supplemented in branched chain amino acids may be of value in patients who exhibit protein intolerance with standard feeding solutions or in patients who present with advanced degrees of encephalopathy.
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Affiliation(s)
- B A Mizock
- Division of Critical Care Medicine, Cook County Hospital, Chicago, Illinois, USA
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Quigley EM. Gastrointestinal dysfunction in liver disease and portal hypertension. Gut-liver interactions revisited. Dig Dis Sci 1996; 41:557-61. [PMID: 8617136 DOI: 10.1007/bf02282341] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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