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Bajaj JS, Pompili E, Caraceni P. The burden of hepatic encephalopathy and the use of albumin as a potential treatment. Ann Hepatol 2024; 30:101751. [PMID: 39631456 DOI: 10.1016/j.aohep.2024.101751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 09/30/2024] [Indexed: 12/07/2024]
Abstract
As a potential sequela of cirrhosis, hepatic encephalopathy (HE) significantly impacts the lives of patients and caregivers and places a substantial burden on the healthcare system. With an increasing incidence over time and a cumulative effect on cognition, HE adversely effects quality of life, morbidity and mortality in patients with cirrhosis. HE can range from minimal or covert (MHE/CHE) to overt and symptomatic (OHE). HE has profound impacts on the health and wellbeing of patients and their families and caregivers. Effective treatments could improve the quality of life for all those affected. In this article, we discuss the existing treatments for HE and focus on the potential role of albumin in the treatment of HE. Currently approved therapies for HE (lactulose and rifaximin) are focused on decreasing the formation of ammonia in the gastrointestinal tract. Among the many agents with alternative mechanisms being investigated for treatment of HE, albumin has been studied in clinical trials with acute (≤ 3 days), short-term (up to 2 weeks) prolonged (> 2 weeks) and long-term administration (months). Current studies indicate that acute or short-term administration of albumin does not provide significant benefit for patients with OHE. However, there is increasing evidence that prolonged or long-term albumin therapy can help improve cognition in OHE and prevent recurrence. Additional studies are needed to substantiate these positive findings for longer term administration of albumin in HE and to increase our comprehension of the pharmacologic basis of the effects of albumin.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Healthcare System, Richmond, Virginia, USA.
| | - Enrico Pompili
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
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Lapenna L, Di Cola S, Merli M. The crucial role of risk factors when dealing with hepatic Encephalopathy. Metab Brain Dis 2024; 40:29. [PMID: 39570425 DOI: 10.1007/s11011-024-01446-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 10/11/2024] [Indexed: 11/22/2024]
Abstract
Hepatic encephalopathy (HE) is a common condition in patients with cirrhosis, representing the second most frequent cause of decompensation. Approximately 30-40% of patients with cirrhosis will experience overt HE during the clinical course of their illness. In most cases, it is possible to identify a precipitating or risk factor for HE. These are distinct concepts that play different roles in the development of this condition. While precipitating factors act acutely, risk factors are generally present over an extended period and contribute to the overall likelihood of developing HE. The two types of factors require different approaches, with risk factors being more susceptible to prevention. The aim of this review is to describe the most important risk factors (such as severity of liver disease, previous episode of HE, minimal/covert HE, spontaneous and iatrogenic shunt, malnutrition, chronic therapies, metabolic diseases) for the development of HE and how to prevent it.
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Affiliation(s)
- Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Simone Di Cola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
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Smith ML, Wade JB, Wolstenholme J, Bajaj JS. Gut microbiome-brain-cirrhosis axis. Hepatology 2024; 80:465-485. [PMID: 36866864 PMCID: PMC10480351 DOI: 10.1097/hep.0000000000000344] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 02/10/2023] [Indexed: 03/04/2023]
Abstract
Cirrhosis is characterized by inflammation, degeneration, and fibrosis of liver tissue. Along with being the most common cause of liver failure and liver transplant, cirrhosis is a significant risk factor for several neuropsychiatric conditions. The most common of these is HE, which is characterized by cognitive and ataxic symptoms, resulting from the buildup of metabolic toxins with liver failure. However, cirrhosis patients also show a significantly increased risk for neurodegenerative diseases such as Alzheimer and Parkinson diseases, and for mood disorders such as anxiety and depression. In recent years, more attention has been played to communication between the ways the gut and liver communicate with each other and with the central nervous system, and the way these organs influence each other's function. This bidirectional communication has come to be known as the gut-liver-brain axis. The gut microbiome has emerged as a key mechanism affecting gut-liver, gut-brain, and brain-liver communication. Clinical studies and animal models have demonstrated the significant patterns of gut dysbiosis when cirrhosis is present, both with or without concomitant alcohol use disorder, and have provided compelling evidence that this dysbiosis also influences the cognitive and mood-related behaviors. In this review, we have summarized the pathophysiological and cognitive effects associated with cirrhosis, links to cirrhosis-associated disruption of the gut microbiome, and the current evidence from clinical and preclinical studies for the modulation of the gut microbiome as a treatment for cirrhosis and associated neuropsychiatric conditions.
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Affiliation(s)
- Maren L Smith
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA
- Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, USA
| | - James B Wade
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Jennifer Wolstenholme
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA
- Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
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Neye RM, Kircheis G, Stratmann D, Hilger N, Lüth S. Assessment of Cirrhotic Patients by the EncephalApp Fails to Predict Low-Grade Hepatic Encephalopathy. Dig Dis 2024; 42:567-575. [PMID: 38865987 DOI: 10.1159/000538924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 04/13/2024] [Indexed: 06/14/2024]
Abstract
INTRODUCTION An early detection of low-grade hepatic encephalopathy (HE) is of high importance. The aim of the study was to compare a neuropsychological with a psychophysical test on the basis of the psychometric hepatic encephalopathy score (PHES) regarding effectiveness in diagnosing minimal HE (MHE). METHODS In our prospective controlled observational study, we examined a total of 103 patients with liver cirrhosis for HE. The PHES, CFF, and EncephalApp were performed in all patients. Graduation was based on the result of the PHES. Patients without evidence for HE 1&2 according to the mental state (West-Haven criteria) with a PHES <-4 value points and no clinical symptoms were defined as having MHE. Patients were considered as HE0 when in the PHES none of the psychometric subtest results was abnormal or with a PHES ≥-4 value points. Patients with clinical symptoms were considered HE 1&2 patients. Different cut-off values were determined, and their specificity and sensitivity were calculated. RESULTS Ninety-six of the involved patients had liver cirrhosis and 25 acted as a healthy control group. The ROC analysis for the classification resulted in an AUC of 0.806, with the highest Youden index for the cut-off time >224 s, for which the sensitivity was 82% and the specificity 75%. Cases of withdrawals were seen in 10.74% of all tested patients. CONCLUSION The EncephalApp distinguishes well between HE0 and MHE but has its limitations in grading higher forms of HE. Diagnosis using only the EncephalApp is not sufficient.
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Affiliation(s)
- Rebecca Maria Neye
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany,
- Department of Otorhinolaryngology, Head and Neck Surgery, Hospital Ernst von Bergmann Potsdam, Potsdam, Germany,
| | - Gerald Kircheis
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
| | - Daria Stratmann
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
| | - Norbert Hilger
- Department of Psychology, University of Bonn, Bonn, Germany
| | - Stefan Lüth
- Department of Gastroenterology, Hepatology and Diabetology, Center of Internal Medicine II, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
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Moreno-Loro A, Giráldez Á, Jiménez F, López-Bueno I, Pérez-Ramírez A, Romero-Gómez M. Novel approaches in the medical management of compensated cirrhosis. Expert Rev Gastroenterol Hepatol 2024; 18:239-256. [PMID: 38785070 DOI: 10.1080/17474124.2024.2358149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 05/17/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics. AREAS COVERED We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms. EXPERT OPINION We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.
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Affiliation(s)
- Antonio Moreno-Loro
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Álvaro Giráldez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Fernando Jiménez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Ignacio López-Bueno
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alberto Pérez-Ramírez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Manuel Romero-Gómez
- Digestive Diseases Department and ciberehd, Virgen del Rocío University Hospital, Institute of Biomedicine (HUVR/CSIC/US), University of Seville, Seville, Spain
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Shetty A, Saab EG, Choi G. Social Impact of Hepatic Encephalopathy. Clin Liver Dis 2024; 28:273-285. [PMID: 38548439 DOI: 10.1016/j.cld.2024.01.011] [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] [Indexed: 04/02/2024]
Abstract
Hepatic encephalopathy is a medical condition that stems from liver dysfunction, leading to the accumulation of toxins in the bloodstream. This can result in cognitive impairments, mood changes, and motor dysfunction. Its social impact includes challenges in employment, relationships, and daily functioning for affected individuals. Stigma and misunderstanding around the condition can further exacerbate the difficulties faced by both patients and their caregivers. Efforts to raise awareness, improve medical management, and provide support systems can help mitigate the social impact of hepatic encephalopathy.
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Affiliation(s)
- Akshay Shetty
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.
| | - Elena G Saab
- School of Medicine, Wake Forest University, Winston Salem, NC, USA
| | - Gina Choi
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
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Fang G, Liu S, Liu B. Preventive and therapeutic effects of rifaximin on hepatic encephalopathy with differential application dosages and strategies: a network meta-analysis. BMC Gastroenterol 2024; 24:94. [PMID: 38439005 PMCID: PMC10910798 DOI: 10.1186/s12876-024-03184-0] [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: 03/26/2023] [Accepted: 02/20/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that affects the prognosis of patients with liver disease and is considered an independent risk factor for hospitalization and death. Rifaximin has been approved for HE treatment. This review will analyze the effect of rifaximin on different stages of HE with differential application dosages and strategies by traditional and network meta-analyses. METHODS We performed a systematic search of PubMed, EmBase, and Cochrane Library databases up to February 26, 2023, to identify randomized controlled trials (RCTs) about rifaximin for the prevention and treatment of HE. The outcomes included incidence of HE and HE progression, HE reversal, mortality, and adverse effects. RESULTS A total of 21 studies were included. In the primary prevention of HE, rifaximin significantly reduced the incidence of HE (OR: 0.66; 95% CI: 0.45, 0.96; p = 0.032). In secondary prevention, rifaximin significantly reduced the risk of recurrence in patients who were in remission (OR: 0.38; 95% CI: 0.28, 0.52; p < 0.001). In the treatment of minimal HE, rifaximin significantly reduced the breakthrough of MHE to OHE (OR: 0.17; 95% CI: 0.04,0.63; p = 0.008). Rifaximin also significantly improved the clinical symptoms of MHE and OHE patients (OR: 3.76; 95% CI: 2.69, 5.25; p < 0.001). However, rifaximin did not reduce mortality at any stage in HE patients (OR: 0.79; 95% CI: 0.58, 1.08; p = 0.133). Additionally, rifaximin did not increase the risk of adverse effects (OR: 0.96; 95% CI: 0.74, 1.24; p = 0.749). In the network meta-analysis, the 400 mg T.I.D. intervention had a relative advantage for HE risks in primary and secondary prevention. In the treatment of MHE, 600 mg b.i.d. was superior in preventing the breakthrough from MHE to OHE. CONCLUSION Rifaximin prevented HE risks and progression and improved clinical symptoms in patients with MHE but did not reduce mortality. For primary and secondary prevention, 400 mg t.i.d. could be considered. 600 mg b.i.d. could be considered in patients with MHE.
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Affiliation(s)
- Guihua Fang
- Department of Infectious Diseases, The Affiliated Hospital of Guangdong Medical University, No.57 Renmin Avenue South, 524000, Xiashan, Zhanjiang, Guangdong, China
| | - Shuna Liu
- Department of Infectious Diseases, The Affiliated Hospital of Guangdong Medical University, No.57 Renmin Avenue South, 524000, Xiashan, Zhanjiang, Guangdong, China
| | - Bin Liu
- Laboratory of Hepatobiliary Surgery, The Affiliated Hospital of Guangdong Medical University, 524000, Zhanjiang, Guangdong, China.
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Brenner J, Olijslagers SHC, Crijnen YS, de Vries JM, Mandarakas MR, Titulaer MJ. Clinical Outcome Assessments in Encephalitis: A Systematic Review. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2024; 11:e200168. [PMID: 38086078 PMCID: PMC10758981 DOI: 10.1212/nxi.0000000000200168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/11/2023] [Indexed: 12/18/2023]
Abstract
BACKGROUND AND OBJECTIVES Most patients with encephalitis experience persisting neurocognitive and neuropsychiatric sequelae in the years following this acute illness. Reported outcomes are often based on generic clinical outcome assessments that rarely capture the patient perspective. This may result in an underestimation of disease-specific sequelae. Disease-specific clinical outcome assessments can improve clinical relevance of reported outcomes and increase the power of research and trials. There are no patient-reported outcome measures (PROMs) developed or validated specifically for patients with encephalitis. The primary objective of this systematic literature review was to identify PROMs that have been developed for or validated in patients with encephalitis. METHODS We performed a systematic review of the literature published from inception until May 2023 in 3 large international databases (MEDLINE, EMBASE and Cochrane libraries). Eligible studies should have developed or validated a PROM in patients with encephalitis or encephalopathy. Methodologic quality was evaluated using the Consensus-based Standards for the selection of health status Measurement Instruments study design checklist for PROMs. RESULTS We identified no disease-specific PROMs developed or validated for patients with encephalitis. We identified one study on the development and validation of a disease-specific PROM for hepatic encephalopathy, although this disease course is substantially different to that of patients with encephalitis. The methodologic quality of the included study was generally rated as "doubtful." We identified 30 PROMs that have been applied in 46 studies on encephalitis or encephalopathy, although not validated in these populations. The most commonly applied PROMs for measuring Health-Related Quality of Life were the Medical Outcomes Study Short Form-36 and the Sickness Impact Profile. Emotional well-being was often assessed with the Beck Depression Inventory (BDI-II). Sporadically, PROMs were applied to address other aspects of outcome including daily functioning and sleep quality. DISCUSSION This systematic review confirms a critical gap in clinical outcome assessments in patients with encephalitis, failing to identify a validated measuring tool for detecting neurocognitive, functional, and health status. It is therefore essential to develop and/or validate disease-specific PROMs for the population with encephalitis to capture relevant information for patient management and clinical trials about the effects of disease that are at risk of being overlooked.
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Affiliation(s)
- Juliette Brenner
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Sammy H C Olijslagers
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Yvette S Crijnen
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Juna M de Vries
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Melissa R Mandarakas
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Maarten J Titulaer
- From the Department of Neurology (J.B., Y.S.C., J.M.V., M.R.M., M.J.T.), Erasmus University Medical Center, Rotterdam; and Department of Neurology (S.H.C.O.), Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
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Hammd M, Elghezewi A, Abdulhadi A, Alabid A, Alabid A, Badi Y, Kamal I, Hesham Gamal M, Mohamed Fisal K, Mujtaba M, Sherif A, Frandah W. Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. Cureus 2024; 16:e53341. [PMID: 38435950 PMCID: PMC10907550 DOI: 10.7759/cureus.53341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2024] [Indexed: 03/05/2024] Open
Abstract
There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.
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Affiliation(s)
- Mohamed Hammd
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Abdelwahap Elghezewi
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Ahmed Abdulhadi
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Abdelwahhab Alabid
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Abdulfatah Alabid
- Internal Medicine, Faculty of Medicine, Tripoli University, Tripoli, LBY
| | - Yasra Badi
- Internal Medicine, All Saints University School of Medicine, Dominica, USA
| | - Ibrahem Kamal
- General Medicine, Al-Azhar University, Alexandria, EGY
| | - Mohamed Hesham Gamal
- Pharmacology and Therapeutics, Faculty of Pharmacy, Tanta University, Banha, EGY
| | - Khalid Mohamed Fisal
- Pharmacology and Therapeutics, Faculty of Pharmacy, Deraya University, Minia, EGY
| | - Mohamed Mujtaba
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Ahmed Sherif
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Wesam Frandah
- Internal Medicine/Gastroenterology, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
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Bellafante D, Gioia S, Faccioli J, Riggio O, Ridola L, Nardelli S. The Management of Hepatic Encephalopathy from Ward to Domiciliary Care: Current Evidence and Gray Areas. J Clin Med 2023; 13:166. [PMID: 38202173 PMCID: PMC10780160 DOI: 10.3390/jcm13010166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/24/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatic encephalopathy (HE) is a common complication of advanced liver disease and acute liver failure. It is a condition that features several neuropsychiatric symptoms that affect mortality, morbidity and the quality of patients' and caregivers' lives. An HE diagnosis is generally an exclusion diagnosis. Once the patient is admitted to the hospital, clinical examination, blood tests and eventually neuroimaging should be performed with the aim of ruling out other causes of acute brain dysfunction. Moreover, HE is recognized using various precipitants that can potentially promote its onset, alone or in combination, and must be identified. Once the diagnostic process is complete, a correct treatment should be started. The anti-HE treatment is based on a combination of the correction of precipitants; non-absorbable antibiotics, such as rifaximin; and non-absorbable disaccharides. Once the patient is discharged from the hospital, specific anti-HE therapy should be maintained in order to prevent other HE episodes.
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Affiliation(s)
| | | | | | | | | | - Silvia Nardelli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, 00185 Rome, Italy; (D.B.)
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Bakulin IG, Ivanova KN, Eremina EY, Marchenko NV. Comparative Analysis of the Efficacy of Different Regimens of 12 Months Rifaximin-Alfa Therapy in Patients with Liver Cirrhosis and Minimal Hepatic Encephalopathy. Diagnostics (Basel) 2023; 13:3239. [PMID: 37892060 PMCID: PMC10606376 DOI: 10.3390/diagnostics13203239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/16/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
It is a matter of current interest which rifaximin-α regimens in patients with liver cirrhosis and minimal hepatic encephalopathy are the most efficient. STUDY OBJECTIVE to evaluate the effect of various rifaximin-α regimens for 12 months on clinical and laboratory parameters and quality of life in patients with liver cirrhosis and minimal hepatic encephalopathy. METHODS It was a multicenter, prospective, open-label, observational study that included 288 patients with liver cirrhosis and minimal hepatic encephalopathy of both sexes over the age of 18 years, who were prescribed a 12-month course of treatment with rifaximin-α in accordance with the product label. Statistical analysis was performed in the population of patients who completed all visits according to the protocol (n = 258). Retrospectively, the patients were divided into two subgroups: subgroup 1 (continuous course)-patients who received the study drug for a year and the number of days of administration was 360 days (n = 41); subgroup 2 (cyclic course)-patients who received the study drug during the year for less than 360 days (n = 217). At each of the 4 visits, the quality of life was assessed using the CLDQ questionnaire, the time to perform the number connection test, the severity of symptoms associated with hepatic encephalopathy, and laboratory parameters. RESULTS During the 12-month observation period, an increase in the total score on the CLDQ quality of life questionnaire in patients with chronic liver diseases was revealed, which indicates an improvement in the quality of life of patients receiving rifaximin-α therapy. When patients were divided into subgroups depending on the duration of therapy, some benefits of continuous rifaximin-α therapy were noted in the more pronounced dynamics of decrease in the time to perform the number connection test, and in decreased severity of the following symptoms associated with hepatic encephalopathy: impaired concentration and memory, cognitive impairment, and decreased performance. Laboratory findings showed positive dynamics in both subgroups. CONCLUSION A continuous rifaximin-α regimen in patients with liver cirrhosis and minimal hepatic encephalopathy for 12 months was superior to cyclic use with a more pronounced effect on the quality of life of patients and on the symptoms associated with hepatic encephalopathy.
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Affiliation(s)
- Igor G. Bakulin
- Department of Propaedeutics of Internal Medicine, Gastroenterology and Dietetics Named after S.M. Ryss «Mechnikov North-Western State Medical University» of the Ministry of Health of Russia, 191015 St. Petersburg, Russia
| | - Kristina N. Ivanova
- Department of Propaedeutics of Internal Medicine, Gastroenterology and Dietetics Named after S.M. Ryss «Mechnikov North-Western State Medical University» of the Ministry of Health of Russia, 191015 St. Petersburg, Russia
| | - Elena Y. Eremina
- Department of Propaedeutics of Internal Diseases, Federal State Budgetary Educational Institution of Higher Education «National Research Mordovian State University Named after. N.P. Ogarev», 430005 Saransk, Russia
| | - Natalya V. Marchenko
- Clinical and Educational Center, Gastroenterology and Hepatology, St. Petersburg State University, 199034 St. Petersburg, Russia
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12
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Testino G, Bottaro LC, Andorno E, Bandini F, Balbinot P, Beltramini S, Bottino S, Caltabellotta M, Caputo F, Caviglia E, Curone P, DI Biagio A, Gagliano C, Gandolfo N, Pestarino L, Rollero A, Romairone E, Sampietro L, Torre E, Zuccarelli S, Pellicano R. Hepatic encephalophathy: management and diagnostic therapeutic assistance path of Ligurian Local Health Company 3 (ASL3). Minerva Med 2023; 114:698-718. [PMID: 36952221 DOI: 10.23736/s0026-4806.22.08408-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2023]
Abstract
Hepatic encephalophathy (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.
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Affiliation(s)
- Gianni Testino
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy -
| | | | - Enzo Andorno
- Liver Transplantation Unit, San Martino Polyclinic Hospital, Genoa, Italy
| | | | - Patrizia Balbinot
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy
| | | | | | | | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Ferrara, Italy
| | | | | | - Antonio DI Biagio
- Department of Health Sciences, Infectious Diseases Clinic, IRCCS San Martino Polyclinic Hospital, University of Genoa, Genoa, Italy
| | | | | | | | | | | | | | - Enrico Torre
- Unit of Endocrinology, Metabolic Diseases and Diabetology, ASL3 Liguria, Genoa, Italy
| | | | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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13
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Fiorillo A, Gallego JJ, Casanova-Ferrer F, Urios A, Ballester MP, San Miguel T, Megías J, Kosenko E, Tosca J, Rios MP, Escudero-García D, Montoliu C. Neurofilament Light Chain Protein in Plasma and Extracellular Vesicles Is Associated with Minimal Hepatic Encephalopathy and Responses to Rifaximin Treatment in Cirrhotic Patients. Int J Mol Sci 2023; 24:14727. [PMID: 37834174 PMCID: PMC10572420 DOI: 10.3390/ijms241914727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/19/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Neurofilament light chain protein (NfL) levels reflect neuronal damage in several neurological diseases and have been proposed as a possible biomarker. Plasma extracellular vesicles (EVs) could play an important role as mediators of the inflammatory changes associated with inducing minimal hepatic encephalopathy (MHE) in cirrhotic patients. This study investigated the association of NfL levels in plasma and EVs with the presence of MHE in cirrhotic patients, and with responses to rifaximin treatment. The NfL levels in plasma and EVs were assessed in 71 patients with liver cirrhosis (40 with MHE and 31 without MHE) and 26 controls. A total of 31 patients with MHE received rifaximin treatment. We examined changes in NfL levels in plasma and EVs before and after 6 months of rifaximin treatment. The NfL measures were correlated with cognitive alterations and plasma inflammatory cytokines. MHE patients showed increased plasma levels of NfL, which were reverted after rifaximin treatment in patients who responded to treatment. The NfL content in EVs also showed a reversal pattern in MHE patients treated with rifaximin. In multivariable analyses, NfL levels were independently associated with the presence of MHE. We also showed that patients with high levels of both ammonia and fractalkine had significantly higher NfL levels than patients with low levels of least one of these parameters. Rifaximin treatment in MHE patients showed promising results in improving axonal damage, suggesting that rifaximin may have therapeutic benefits against disease progression in MHE.
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Affiliation(s)
- Alessandra Fiorillo
- Fundación de Investigación, Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain; (A.F.); (J.J.G.); (F.C.-F.); (A.U.)
| | - Juan José Gallego
- Fundación de Investigación, Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain; (A.F.); (J.J.G.); (F.C.-F.); (A.U.)
| | - Franc Casanova-Ferrer
- Fundación de Investigación, Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain; (A.F.); (J.J.G.); (F.C.-F.); (A.U.)
| | - Amparo Urios
- Fundación de Investigación, Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain; (A.F.); (J.J.G.); (F.C.-F.); (A.U.)
| | - María-Pilar Ballester
- Servicio de Medicina Digestiva, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (M.-P.B.); (J.T.); (D.E.-G.)
| | - Teresa San Miguel
- Departamento de Patología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain; (T.S.M.); (J.M.)
| | - Javier Megías
- Departamento de Patología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain; (T.S.M.); (J.M.)
| | - Elena Kosenko
- Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia;
| | - Joan Tosca
- Servicio de Medicina Digestiva, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (M.-P.B.); (J.T.); (D.E.-G.)
| | - Maria-Pilar Rios
- Servicio de Digestivo, Hospital Arnau de Vilanova, 46015 Valencia, Spain;
| | - Desamparados Escudero-García
- Servicio de Medicina Digestiva, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain; (M.-P.B.); (J.T.); (D.E.-G.)
- Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain
| | - Carmina Montoliu
- Fundación de Investigación, Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain; (A.F.); (J.J.G.); (F.C.-F.); (A.U.)
- Departamento de Patología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain; (T.S.M.); (J.M.)
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14
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Hamzaoui L, Mahmoudi M, Mohamed G, Elloumi H, Laabidi A, Boubaker J, Boudabbous M, Tahri N, Jemni I, Safer L, Jomni T, Douggui H, Trad D, Gargouri D, Ayadi S, Debbeche R, Belhouchet S, Marouani R, Cheikh I, Abdelli MN. EncephalApp Stroop Test for covert hepatic encephalopathy screening in Tunisian cirrhotic patients. F1000Res 2023; 11:686. [PMID: 37767072 PMCID: PMC10521086 DOI: 10.12688/f1000research.121781.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Background: Covert hepatic encephalopathy (CHE) is underdiagnosed and is difficult to detect. The EncephalApp Stroop test is validated for its screening. The aim of the study was to define Tunisian norms for the test based on healthy controls norms and to estimate the prevalence of CHE in cirrhotic Tunisian patients. Methods: A prospective, multicenter, cross-sectional study was conducted. Ambulatory or hospitalized cirrhotic patients aged 40 years and over were recruited at 11 centers. Healthy subjects aged 40 years and over were recruited at 8 centers. We used a translated Arabic version of the streamlined EncephalApp Stroop test. The task has two components: "Off" and "On" state depending on the discordance or concordance of the stimuli. Results: 142 patients were included. The mean age was 57.26 years [40-86]. 40 (28.17%) of cirrhotic patients who were included were diagnosed as having a minimal hepatic encephalopathy or CHE. Among the ineligible patients, 22 had overt hepatic encephalopathy. If we consider these patients, the overall prevalence rate of CHE was around 24.39% in cirrhotic patients. It was more frequent in women (34.21% vs 25.96%), and in patients whose level of school education is between 6 and 13 years. Its prevalence does not appear to be affected by gender, MELD score, etiology of cirrhosis and age group of patients, as these variables were independent with respective p according to the chi-square test 0.413; 0.736; 0.663 and 0.1. The stroop times (On / Off and On + Off) correlated significantly with each other, are associated significantly and positively with age (respective Pearson coefficients: 0.578; 0.567 and 0.6). The more the age increases, the more the stroop response times increases (p > 10 -3). Conclusions: EncephalApp Stroop test was an efficient screening tool for CHE in Tunisian cirrhotic patients.
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Affiliation(s)
- Lamine Hamzaoui
- Gastroenterology, Mohamed Taher Maamouri Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Nabeul, Tunisia
| | - Moufida Mahmoudi
- Gastroenterology, Mohamed Taher Maamouri Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Nabeul, Tunisia
| | - Ghanem Mohamed
- Gastroenterology, Military Hospital of Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Hanene Elloumi
- Gastroenterology, Habib Bougatfa Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Bizerte, Tunisia
| | - Asma Laabidi
- Gastroenterology, La Rabta Hospital A, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Jalel Boubaker
- Gastroenterology, La Rabta Hospital A, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Mona Boudabbous
- Gastroenterology, Hedi Chaker Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Nabil Tahri
- Gastroenterology, Hedi Chaker Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Imen Jemni
- Gastroenterology, Fattouma Bourguiba University Hospital, Monastir, Monastir, Tunisia
| | - Leila Safer
- Gastroenterology, Fattouma Bourguiba University Hospital, Monastir, Monastir, Tunisia
| | - Taieb Jomni
- Gastroenterology, La Marsa Internal Security Forces Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Hedi Douggui
- Gastroenterology, La Marsa Internal Security Forces Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Dorra Trad
- Gastroenterology, Habib Thameur Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Dalila Gargouri
- Gastroenterology, Habib Thameur Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Shema Ayadi
- Gastroenterology, Hospital Charles Nicolle, Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Radhouane Debbeche
- Gastroenterology, Hospital Charles Nicolle, Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
| | | | - Ridha Marouani
- Gastroenterology, Kasserine Hospital, Kasserine, Tunisia
| | - Imed Cheikh
- Gastroenterology, Habib Bougatfa Hospital, Tunis El Manar University, Faculty of Medicine of Tunis, Bizerte, Tunisia
| | - Mohamed Nabil Abdelli
- Gastroenterology, Military Hospital of Tunis, Tunis El Manar University, Faculty of Medicine of Tunis, Tunis, Tunisia
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15
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Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev 2023; 7:CD011585. [PMID: 37467180 PMCID: PMC10360160 DOI: 10.1002/14651858.cd011585.pub2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
BACKGROUND Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia. OBJECTIVES To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023. SELECTION CRITERIA We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non-absorbable disaccharide, versus placebo/no intervention, or a non-absorbable disaccharide alone. DATA COLLECTION AND ANALYSIS Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health-related quality of life, hepatic encephalopathy, non-serious adverse events, blood ammonia, Number Connection Test-A, and length of hospital stay. MAIN RESULTS We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non-absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non-absorbable disaccharide versus a non-absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non-mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I2 = 0%; 13 trials, 1007 participants; moderate-certainty evidence), and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I2 = 0%; 10 trials, 786 participants; low-certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I2 = 0%; 14 trials, 1946 participants; moderate-certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I2 = 0%; 9 trials, 801 participants; moderate-certainty evidence) and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I2 = 0%; 8 trials, 681 participants; low-certainty evidence). However, there was very low-certainty evidence that use of rifaximin plus a non-absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non-absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I2 = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health-related quality of life when compared to placebo/no intervention (mean difference (MD) -1.43, 95% CI -2.87 to 0.02; P = 0.05, I2 = 81%; 4 trials, 214 participants; moderate-certainty evidence), and may benefit health-related quality of life in people with minimal hepatic encephalopathy (MD -2.07, 95% CI -2.79 to -1.35; P < 0.001, I2 = 0%; 3 trials, 176 participants). The overall effect on health-related quality of life when comparing rifaximin to non-absorbable disaccharides is very uncertain (MD -0.33, 95% CI -1.65 to 0.98; P = 0.62, I2 = 0%; 2 trials, 249 participants; very low-certainty evidence). None of the combined rifaximin/non-absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I2 = 68%; 13 trials, 1009 participants; moderate-certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I2 = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I2 = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non-absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I2 = 0%; 13 trials, 921 participants; low-certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I2 = 62%; 17 trials, 2332 participants; low-certainty evidence). AUTHORS' CONCLUSIONS Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.
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Affiliation(s)
- Harry D Zacharias
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Fady Kamel
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Jaclyn Tan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Nina Kimer
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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16
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Gairing SJ, Schleicher EM, Galle PR, Labenz C. Prediction and prevention of the first episode of overt hepatic encephalopathy in patients with cirrhosis. Hepatol Commun 2023; 7:02009842-202304010-00007. [PMID: 36930868 PMCID: PMC10027066 DOI: 10.1097/hc9.0000000000000096] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 12/13/2022] [Indexed: 03/19/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the most important complications of patients with liver cirrhosis. In addition, HE is associated with a dismal prognosis and has detrimental effects on patients' quality of life. Thus, it is of pivotal importance to identify patients at high risk for overt HE (OHE) in whom primary prophylaxis may be justified. In this narrative review, we aim to provide insight into predictors and prediction tools for a first-time episode of OHE and to scrutinize the current level of evidence of primary prophylaxis. In recent decades, several cognitive tests, composite scores, and blood-based biomarkers have been demonstrated to be predictive of a first-time episode of OHE. Among the best validated are the established tests for minimal HE, such as the Psychometric Hepatic Encephalopathy Score, determination of the critical flicker frequency, Stroop EncephalApp, or the Animal Naming Test. Individualized risk stratification using blood-based biomarkers and cross-sectional imaging (sarcopenia and spontaneous portosystemic shunts) is coming to the fore, but validation in larger multicenter cohorts is often lacking. On the basis of current evidence, a recommendation for primary prophylaxis of a first episode of OHE cannot be made in general. Only 2 studies have investigated the prevention of a first-time OHE episode as the primary endpoint. In this narrative review, we provide a concise overview of the current evidence levels on prediction tools and pharmacological prevention of a first episode of OHE. In addition, we give an outlook on future research targets to improve knowledge on this important topic.
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Affiliation(s)
- Simon J Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Eva M Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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17
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Moon AM, Kim HP, Jiang Y, Lupu G, Bissram JS, Barritt AS, Tapper EB. Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy. Am J Gastroenterol 2023; 118:284-293. [PMID: 36730910 PMCID: PMC9904367 DOI: 10.14309/ajg.0000000000002008] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/09/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). METHODS We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. RESULTS We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. DISCUSSION Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.
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Affiliation(s)
- Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Hannah P Kim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Yue Jiang
- Department of Statistical Science, Duke University, Durham, North Carolina, USA
| | - Gabriel Lupu
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jennifer S Bissram
- Health Sciences Library, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
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Abstract
Hepatic encephalopathy (HE) is brain dysfunction secondary to liver insufficiency or portosystemic shunting. HE is a major burden on patients and caregivers, impairs quality of life and is associated with higher mortality. Overt HE is a clinical diagnosis while Covert HE, needs specialized diagnostic strategies. Mainstay of treatment of HE is nonabsorbable disaccharides such as lactulose as well as rifaximin; however, investigational therapies are discussed in this review. Better tools are needed to prognosticate which patients will go on to develop HE but microbiome and metabolomic-driven strategies are promising. Here we review methods to prevent the HE development and admissions.
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Minimal Hepatic Encephalopathy Affects Daily Life of Cirrhotic Patients: A Viewpoint on Clinical Consequences and Therapeutic Opportunities. J Clin Med 2022; 11:jcm11237246. [PMID: 36498820 PMCID: PMC9736966 DOI: 10.3390/jcm11237246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/21/2022] [Accepted: 11/27/2022] [Indexed: 12/12/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a frequent complication of hepatic encephalopathy (HE) and can affect up to 80% of patients with liver cirrhosis. It is characterized by the lack of obvious clinical signs and the presence of alterations detectable using psychometric or electrophysiological testing focused on attention, working memory, psychomotor speed and visuospatial ability. Ideally, each patient should be tested for this condition because, despite the absence of symptoms, it has severe repercussions on daily life activities. It may be responsible for an inability to drive, sleep disturbances, risk of falls and inability to work. Some studies have highlighted its prognostically unfavorable role on mortality and risk of "overt" HE (OHE). Finally, MHE severely affects the lives of patients and caregivers, altering their quality of life and their socioeconomic status. Several treatments have been proposed for MHE treatment, including non-absorbable disaccharides, poorly absorbable antibiotics, such as rifaximin, probiotics and branched-chain amino acids, with promising results. For this reason, early diagnosis and intervention with appropriate measures is essential, with the aim of improving both performance on psychometric tests, as well as clinical aspects related to this condition.
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Vidal-Cevallos P, Chávez-Tapia NC, Uribe M. Current approaches to hepatic encephalopathy. Ann Hepatol 2022; 27:100757. [PMID: 36115576 DOI: 10.1016/j.aohep.2022.100757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/07/2022] [Indexed: 02/04/2023]
Abstract
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.
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Affiliation(s)
- Paulina Vidal-Cevallos
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Norberto C Chávez-Tapia
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Misael Uribe
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico.
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21
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Efficacy of rifaximin against covert hepatic encephalopathy and hyperammonemia in Japanese patients. PLoS One 2022; 17:e0270786. [PMID: 35776720 PMCID: PMC9249214 DOI: 10.1371/journal.pone.0270786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 06/20/2022] [Indexed: 11/23/2022] Open
Abstract
Covert hepatic encephalopathy (CHE) impairs patient quality of life and occurs in approximately 30% of liver cirrhosis (LC) cases. Japanese clinical practice guidelines recommend rifaximin to treat overt HE (OHE). However, the usefulness of rifaximin against CHE is not thoroughly investigated in Japanese patients. We aimed to investigate the efficacy of rifaximin against hyperammonemia and CHE in Japan. We observed 102 patients with HE showing hyperammonemia secondary to LC and examined various biochemical and behavioral parameters following rifaximin treatment. CHE was diagnosed when the patients exhibited two or more abnormal neuropsychological test (NPT) scores but did not indicate OHE symptoms. In the 102 cases, a significant therapeutic effect of rifaximin on hyperammonemia was observed from 2 to 48 weeks after starting treatment. Excluding 10 patients diagnosed with OHE upon starting rifaximin treatment, 12 of the 92 remaining patients (11.8%) transitioned to OHE within 1 year. The 1 year cumulative OHE transition rate was 14.5%. Among the 24 patients with CHE diagnosed by the NPT for whom NPT results could be evaluated at 4 and 12 weeks after starting treatment, 10 (41.6%) had recovered from CHE at 12 weeks. When the factors contributing to recovery from CHE were examined by multivariate analysis, an ammonia level <129 μg/dL was a significant factor. Rifaximin was thus significantly effective against both hyperammonemia and CHE in Japanese patients.
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22
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Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers 2022; 8:43. [PMID: 35739133 DOI: 10.1038/s41572-022-00366-6] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 01/18/2023]
Abstract
Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging.
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Affiliation(s)
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Radha K Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (Uttar Pradesh), India
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain
| | - Boris Görg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Rajiv Jalan
- Liver Failure Group ILDH, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Gerald Kircheis
- Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg an der Havel, Brandenburg Medical School, Brandenburg an der Havel, Germany
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma - Sapienza, Roma, Italy
| | | | - Manuel Romero-Gomez
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, UK
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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23
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Serper M, Kaplan DE, Lin M, Taddei TH, Parikh ND, Werner RM, Tapper EB. Inpatient Gastroenterology Consultation and Outcomes of Cirrhosis-Related Hospitalizations in Two Large National Cohorts. Dig Dis Sci 2022; 67:2094-2104. [PMID: 34374917 PMCID: PMC10849043 DOI: 10.1007/s10620-021-07150-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 04/10/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Little is known about use of specialty care among patients admitted with cirrhosis complications. AIMS We sought to characterize the use and impact of gastroenterology/hepatology (GI/HEP) consultations in hospitalized patients with cirrhosis. We studied two national cohorts-the Veterans Affairs Costs and Outcomes in Liver Disease (VOCAL) and a nationally representative database of commercially insured patients (Optum Clinformatics™ DataMart). METHODS Cirrhosis-related admissions were classified by ICD9/10 codes for ascites, hepatic encephalopathy, alcohol-associated hepatitis, spontaneous bacterial peritonitis, or infection related. We included 20,287/222,166 index admissions from VOCAL/Optum from 2010 to 2016. Propensity-matched analyses were conducted to balance clinical characteristics. Mortality and readmission were evaluated using competing risk regression (subhazard ratios, sHR), and length of stay (LOS) was assessed using negative binomial regression. RESULTS GI/HEP consultations were completed among 37% and 42% patients in VOCAL and Optum, respectively. In propensity-matched analyses for VOCAL, GI/HEP consultation was associated with adjusted estimates of increased LOS (1.55 + 1.03 additional days), 90-day mortality (sHR 1.23, 95% CI 1.14-1.36), and lower 30-day readmissions (sHR 0.82, 95% CI 0.75-0.89). In Optum, inpatient consultation was associated with higher LOS (1.13 + 1.01 additional days), higher 90-day mortality (sHR 1.57, 95% CI 1.43-1.72), and higher 30-day readmission risk (sHR 1.04, 95% CI 1.02-1.05). Post-discharge primary and specialty care was higher among admissions receiving GI/HEP consultation in both cohorts. CONCLUSIONS Use of GI/HEP consultation for cirrhosis-related admissions was low. Patients who received consultation had higher disease severity, and consultation was not associated with lower mortality but was associated with lower 30-day readmissions in the VA cohort only.
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Affiliation(s)
- Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Spruce St, 2 Dulles, Philadelphia, PA, USA.
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA.
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Spruce St, 2 Dulles, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
| | - Menghan Lin
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Tamar H Taddei
- VA Connecticut Healthcare System, West Haven, CT, USA
- Division of Gastroenterology, Yale University School of Medicine, New Haven, CT, USA
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Rachel M Werner
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA
- Division of General Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
- Gastroenterology Section, Ann Arbor Healthcare System, Ann Arbor, VA, USA
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Ballester MP, Gallego JJ, Fiorillo A, Casanova-Ferrer F, Giménez-Garzó C, Escudero-García D, Tosca J, Ríos MP, Montón C, Durbán L, Ballester J, Benlloch S, Urios A, San-Miguel T, Kosenko E, Serra MÁ, Felipo V, Montoliu C. Metabolic syndrome is associated with poor response to rifaximin in minimal hepatic encephalopathy. Sci Rep 2022; 12:2463. [PMID: 35165326 PMCID: PMC8844048 DOI: 10.1038/s41598-022-06416-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 01/18/2022] [Indexed: 12/13/2022] Open
Abstract
AbstractPatients with cirrhosis may show minimal hepatic encephalopathy (MHE), for which rifaximin is effective. Metabolic syndrome may be associated with cognitive impairment. Our aims were to evaluate the influence of metabolic syndrome features on response to rifaximin for neurological and inflammatory alterations in MHE. A prospective cohort study was conducted in 63 cirrhotic patients and 30 controls from two tertiary centres recruited between 2015 and 2019. Metabolic syndrome was defined according to the Adult Treatment Panel-III. Patients were classified into 31 without and 32 with MHE according to the Psychometric Hepatic Encephalopathy Score (PHES). All participants performed specific psychometric tests, and inflammatory parameters were studied. Patients with MHE received rifaximin (400 mg/8 h). Response was evaluated by PHES at 3 and 6 months. Response according to metabolic syndrome manifestations was compared. The response rate was 66%. Older age (p = 0.012) and all metabolic syndrome diseases (p < 0.05) were associated with non-response, plus an increase in risk as the number of manifestations rose (p < 0.001). Patients with metabolic manifestations exhibited worse processing speed (p = 0.011), working memory (p = 0.005), visual coordination (p = 0.013) and lower proportion of activated CD4+ lymphocytes (p = 0.039) at baseline, as well as worse concentration (p = 0.030), bimanual coordination (p = 0.004) and higher levels of intermediate monocytes (p = 0.026), CX3CL1 (p < 0.05), IL-17 (p = 0.022), AHR (p = 0.010) and IgG (p < 0.05) at 3 and/or 6 months of rifaximin. Patients with clinical signs of metabolic syndrome have poor response to rifaximin for MHE, with a higher proportion of neurological alterations associated with a pro-inflammatory environment.
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25
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Mohamed AS, Elmeteini MA, Mohamed GAE, Elserafy DM, Elmadani AA, Hashem RE. Cognitive impairment in recipients of liver transplantation and relation to hepatic encephalopathy. MIDDLE EAST CURRENT PSYCHIATRY 2022. [DOI: 10.1186/s43045-022-00175-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Liver transplantation (LT) helped to save the life of end stage liver disease (ESLD) patients; however, there is a debate on the persistence of cognitive impairment. The study aimed to evaluate cognitive functions in patients with ESLD before and after liver transplantation and to assess its relation to hepatic encephalopathy (HE). Thirty recipients 47.6 ± 11 years undergone living donor liver transplantation at the transplantation center of both Ain Shams Center for Organ Transplant and Egypt air organ transplant unit were prospectively assessed by Trail Making Test, Wechsler Memory Scale–Revised, Benton Visual Retention—for the evaluation of cognitive functions before and 3 months after transplantation.
Results
The mean age of the patients was 47.6 ± 11 years, 17 males and 13 females. Eight out of 30 (26.7%) had past history of hepatic encephalopathy. The study reported significant improvement in the post-operative 3 months scores of Trail Making Test part (A), the digit span forward test, digit span backward test and the correct score difference of the Benton Visual Retention, as p value was (0.02), (0.01) (0.02), and (0.01) respectively, compared to the pre-operative scores. However, there was no difference in the scores of part (B), verbal association I, II, information subtest of WMS. Cognitive performance showed no significant difference between patients with or without history of HE.
Conclusions
Patients with ESLD have significant cognitive impairment that showed improvement after LT; HE did not correlate with cognitive function. Hence, transplantation has a favorable outcome on the cognitive impairment.
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Minimal hepatic encephalopathy - diagnosis and treatment. GASTROENTEROLOGY REVIEW 2022; 16:311-317. [PMID: 34976238 PMCID: PMC8690948 DOI: 10.5114/pg.2021.111389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 02/18/2021] [Indexed: 11/22/2022]
Abstract
Hepatic encephalopathy is a dysfunction of the central nervous system caused by chronic and acute liver disease. It presents a wide spectrum of symptoms from undetectable in a standard clinical examination to hepatic coma. The mildest form of hepatic encephalopathy is minimal hepatic encephalopathy. It significantly influences the quality of life, prognosis, and the incidence of complications. A wide range of psychometric and neurophysiological tests are used in the diagnostics. Treatment is based on the same principles as in overt encephalopathy. The most commonly used drugs include rifaximin, ornithine aspartate, and LOLA.
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Faccioli J, Gioia S, Nardelli S, Riggio O, Ridola L. Lactulose in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:223-240. [DOI: 10.1007/978-981-19-2615-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sahney A, Wadhawan M. Encephalopathy in Cirrhosis: Prevention and Management. J Clin Exp Hepatol 2022; 12:927-936. [PMID: 35677508 PMCID: PMC9168742 DOI: 10.1016/j.jceh.2021.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/09/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatic encephalopathy (HE) is a major neuropsychiatric complication of cirrhosis. The clinical manifestations of HE ranges from mild confusion, disorientation to altered behaviour and coma in advanced stages. HE is an important cause of recurrent admissions in liver cirrhosis patients. HE is the most common cause of altered mentation in a patient of liver cirrhosis. Lactulose and rifaximin are approved treatment options for the treatment of HE. In patients who have localised neurological signs or are not improving with lactulose and rifaximin should be investigated for other causes of altered sensorium.
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Affiliation(s)
| | - Manav Wadhawan
- Address for correspondence: Manav Wadhawan, Institute of Digestive & Liver Diseases, BLK Superspeciality Hospital, Delhi, India.
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Cheng J, Chen Y, Cao W, Zuo G. Is rifaximin better than nonabsorbable disaccharides in hepatic encephalopathy?: A meta-analysis. Medicine (Baltimore) 2021; 100:e28232. [PMID: 34941089 PMCID: PMC8701975 DOI: 10.1097/md.0000000000028232] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/16/2021] [Accepted: 11/24/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The purpose of the present meta-analysis was to compare the efficacy of rifaximin and nonabsorbable disaccharides (NADs) in hepatic encephalopathy (HE). METHODS After the registration of the present meta-analysis on INPLASY, all procedures were performed according to PRISMA 2020. Relevant literature was retrieved on PubMed, Embase, and the Cochrane Library up to September 5, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the enrolled studies, and Review Manager software (version 5.3) was used to analyze the clinical efficacy, blood ammonia and adverse effects. RESULTS Six studies with 559 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. Analysis of the complete resolution of HE showed that rifaximin was better than NADs (risk ratio [RR] = 1.87, 95% confidence interval [CI] = 1.03-3.39, P = .04). However, there were no significant differences in mental status (RR = 1.04, 95% CI = 0.92-1.18, P = .53), blood ammonia level (standard mean difference = -0.02, 95% CI = -0.40-0.02, P = .08), or drug adverse drug effects (OR = 0.43, 95% CI = 0.10-1.77, I2 = 56%, P = .24) between the rifaximin and NADs treatment groups. CONCLUSION Rifaximin is not superior to NADs in the treatment of HE.
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Affiliation(s)
- Junxiong Cheng
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, PR China
| | - Yafang Chen
- College of Pharmaceutical Sclences and Chinese Medicine, Southwest University, Chongqing, PR China
| | - Wenfu Cao
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, PR China
| | - Guoqing Zuo
- Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, PR China
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Bloom PP, Tapper EB, Young VB, Lok AS. Microbiome therapeutics for hepatic encephalopathy. J Hepatol 2021; 75:1452-1464. [PMID: 34453966 PMCID: PMC10471317 DOI: 10.1016/j.jhep.2021.08.004] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/20/2021] [Accepted: 08/02/2021] [Indexed: 12/13/2022]
Abstract
Hepatic encephalopathy (HE) is a complication of cirrhosis characterised by neuropsychiatric and motor dysfunction. Microbiota-host interactions play an important role in HE pathogenesis. Therapies targeting microbial community composition and function have been explored for the treatment of HE. Prebiotics, probiotics and faecal microbiota transplant (FMT) have been used with the aim of increasing the abundance of potentially beneficial taxa, while antibiotics have been used to decrease the abundance of potentially harmful taxa. Other microbiome therapeutics, including postbiotics and absorbents, have been used to target microbial products. Microbiome-targeted therapies for HE have had some success, notably lactulose and rifaximin, with probiotics and FMT also showing promise. However, there remain several challenges to the effective application of microbiome therapeutics in HE, including the resilience of the microbiome to sustainable change and unpredictable clinical outcomes from microbiota alterations. Future work in this space should focus on rigorous trial design, microbiome therapy selection, and a personalised approach to HE.
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Affiliation(s)
- Patricia P Bloom
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, USA.
| | - Elliot B Tapper
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, USA
| | - Vincent B Young
- Department of Internal Medicine, Division of Infectious Disease, University of Michigan, USA; Department of Microbiology and Immunology, University of Michigan, USA
| | - Anna S Lok
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, USA
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Hasan LZ, Wu GY. Novel Agents in the Management of Hepatic Encephalopathy: A Review. J Clin Transl Hepatol 2021; 9:749-759. [PMID: 34722190 PMCID: PMC8516841 DOI: 10.14218/jcth.2021.00102] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/28/2021] [Accepted: 06/01/2021] [Indexed: 12/15/2022] Open
Abstract
Hepatic encephalopathy is an often devastating complication of chronic liver disease, associated with high mortality and increased burden on patients and healthcare systems. Current agents (such as nonabsorbable disaccharides and oral antibiotics) are often only partially effective and associated with unpleasant side effects. With our improved understanding of the pathophysiology of hepatic encephalopathy, multiple treatment modalities have emerged with promising results when used alone or as an adjunct to standard medications. The mechanisms of these agents vary greatly, and include the manipulation of gut microbial composition, reduction of oxidative stress, inhibition of inflammatory mediators, protection of endothelial integrity, modulation of neurotransmitter release and function, and other novel methods to reduce blood ammonia and neurotoxins. Despite their promising results, the studies assessing these treatment modalities are often limited by study design, sample size, outcome assessment heterogeneity, and paucity of data regarding their safety profiles. In this article, we discuss these novel agents in depth and provide the best evidence supporting their use, along with a critical look at their limitations and future directions.
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Affiliation(s)
- Leen Z. Hasan
- Correspondence to: Leen Z. Hasan, Department of Medicine, Internal Medicine Residency Program, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-1235, USA. ORCID: https://orcid.org/0000-0003-3852-8591. Tel: +1-617-283-6633, Fax: +1-860-679-4613, E-mail: ,
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Han X, Luo Z, Wang W, Zheng P, Li T, Mei Z, Wang J. Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy. Front Pharmacol 2021; 12:696065. [PMID: 34690751 PMCID: PMC8533823 DOI: 10.3389/fphar.2021.696065] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02-1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12-2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18-1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54-1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54-0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.
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Affiliation(s)
- Xianghui Han
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhanyang Luo
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Institute of Digestive Diseases, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Jianyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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33
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Caraceni P, Vargas V, Solà E, Alessandria C, de Wit K, Trebicka J, Angeli P, Mookerjee RP, Durand F, Pose E, Krag A, Bajaj JS, Beuers U, Ginès P, Napoleone L, Carol M, Avitabile E, Thu AM, Cervera M, Pérez M, Belén Rubio‐Garcia A, Ardiaca A, Vives A, Pich J, Fabrellas N, Zaccherini G, Chiappa MT, Jiménez C, Palacio E, Campion D, Lanzillotti T, Piano S, Nicolao G, Uschner F, Graf_Dirmeier S, Francoz C, Roux O, Esnault V, Helder J, Aban M, Kazankov K, Korenjak M, Kamath P, Abraldes JG, Watson H. The Use of Rifaximin in Patients With Cirrhosis. Hepatology 2021; 74:1660-1673. [PMID: 33421158 PMCID: PMC8518409 DOI: 10.1002/hep.31708] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 12/12/2022]
Abstract
Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.
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Affiliation(s)
- Paolo Caraceni
- University of BolognaUniversity Hospital S. Orsola‐Malpighi di BolognaBolognaItaly
| | - Victor Vargas
- Hospital Vall d’HebronUniversitat Autònoma de BarcelonaCIEREHDBarcelonaCataloniaSpain
| | - Elsa Solà
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
| | - Carlo Alessandria
- Division of Gastroenterology and HepatologyCittà della Salute e della Scienza HospitalUniversity of TorinoTurinItaly
| | - Koos de Wit
- Amsterdam University Medical CentersAmsterdamthe Netherlands
| | - Jonel Trebicka
- Goethe‐University ‐ Frankfurt am MainFrankfurt am MainGermany,EF‐CLIFBarcelonaCataloniaSpain
| | | | | | | | - Elisa Pose
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
| | - Aleksander Krag
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark,Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
| | | | - Ulrich Beuers
- Amsterdam University Medical CentersAmsterdamthe Netherlands
| | - Pere Ginès
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
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34
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol 2021; 56:593-619. [PMID: 34231046 PMCID: PMC8280040 DOI: 10.1007/s00535-021-01788-x] [Citation(s) in RCA: 189] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Gastroenterology, Nara Medical University, Shijo-cho 840, Kashihara, Nara, 634-8522, Japan.
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuaki Chayama
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tetsuo Takehara
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis", The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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35
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Yoshiji H, Nagoshi S, Akahane T, Asaoka Y, Ueno Y, Ogawa K, Kawaguchi T, Kurosaki M, Sakaida I, Shimizu M, Taniai M, Terai S, Nishikawa H, Hiasa Y, Hidaka H, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res 2021; 51:725-749. [PMID: 34231046 DOI: 10.1111/hepr.13678] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 05/26/2021] [Indexed: 12/14/2022]
Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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Affiliation(s)
- Hitoshi Yoshiji
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan.,Department of Gastroenterology, Nara Medical University, Nara, Japan
| | - Sumiko Nagoshi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takemi Akahane
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshinari Asaoka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoshiyuki Ueno
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Koji Ogawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Takumi Kawaguchi
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masayuki Kurosaki
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Isao Sakaida
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Masahito Shimizu
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Makiko Taniai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Shuji Terai
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroki Nishikawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Yoichi Hiasa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hisashi Hidaka
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
| | | | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis, The Japanese Society of Gastroenterology/the Japan Society of hepatology, Tokyo, Japan
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36
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Moran S, López-Sánchez M, Milke-García MDP, Rodríguez-Leal G. Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis. World J Gastroenterol 2021; 27:3050-3063. [PMID: 34168407 PMCID: PMC8192295 DOI: 10.3748/wjg.v27.i22.3050] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/01/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.
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Affiliation(s)
- Segundo Moran
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | - Marlene López-Sánchez
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
| | | | - Gustavo Rodríguez-Leal
- Laboratory of Hepatology Research, Centro Médico Nacional, Siglo XXI, Mexican Institute of Social Security, Mexico City 06720, Mexico
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37
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Miwa T, Hanai T, Toshihide M, Ogiso Y, Imai K, Suetsugu A, Takai K, Shiraki M, Katsumura N, Shimizu M. Zinc deficiency predicts overt hepatic encephalopathy and mortality in liver cirrhosis patients with minimal hepatic encephalopathy. Hepatol Res 2021; 51:662-673. [PMID: 33242359 DOI: 10.1111/hepr.13601] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 11/07/2020] [Accepted: 11/15/2021] [Indexed: 12/13/2022]
Abstract
AIM Minimal hepatic encephalopathy (MHE) is associated with poor outcomes and the development of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis (LC). Zinc plays a key role in the detoxification of ammonia, a risk factor of hepatic encephalopathy. This study aimed to investigate whether zinc deficiency predicts OHE occurrence and mortality in LC patients with MHE. METHOD This retrospective study included 100 LC patients with MHE. MHE was diagnosed using a computer-aided neuropsychiatric test. Predictors associated with the development of OHE were analyzed using the Fine-Gray competing risk regression model. Cox proportional hazards regression analysis was carried out to evaluate the risk factors of mortality. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS Of the 100 LC patients with MHE, 41% had zinc deficiency (<60 μg/dl). Zinc deficiency was observed more frequently in the patients with reduced liver function reserve. During the median follow-up period of 9.9 months, 16% of the patients with MHE developed OHE. The patients with zinc deficiency had a higher risk of OHE than those without zinc deficiency (p = 0.03). Zinc deficiency was also associated with poor survival (p = 0.004). Multivariate analyses showed that zinc predicts the development of OHE (subdistribution hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.92-0.99; p = 0.008) and mortality (HR, 0.96; 95% CI, 0.93-0.99; p = 0.02), independently of liver function reserves. CONCLUSION Zinc deficiency is likely to be a predictor of both OHE development and mortality in LC patients with MHE.
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Affiliation(s)
- Takao Miwa
- Department of Gastroenterology, Chuno Kosei Hospital, Seki, Japan.,Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.,Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Maeda Toshihide
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yui Ogiso
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kenji Imai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.,Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Makoto Shiraki
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Naoki Katsumura
- Department of Gastroenterology, Chuno Kosei Hospital, Seki, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
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38
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Rudler M, Weiss N, Bouzbib C, Thabut D. Diagnosis and Management of Hepatic Encephalopathy. Clin Liver Dis 2021; 25:393-417. [PMID: 33838857 DOI: 10.1016/j.cld.2021.01.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatic encephalopathy (HE) is a severe complication of cirrhosis. The prevalence of overt HE (OHE) ranges from 30% to 45%, whereas the prevalence of minimal HE (MHE) is as high as 85% in some case series. Widespread use of transjugular intrahepatic portosystemic shunt to control complications related to portal hypertension is associated with an increase in HE incidence. If the diagnosis of OHE remains simple in most cases, then the diagnosis of MHE is less codified because of many differential diagnoses with different therapeutic implications. This review analyzes current knowledge about the pathophysiology, diagnosis, and different therapeutic options of HE.
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Affiliation(s)
- Marika Rudler
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Nicolas Weiss
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Neurological Intensive Care Unit, Neurology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France
| | - Charlotte Bouzbib
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Dominique Thabut
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France.
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Kc M, Olson APJ, Wang Q, Lim N. Unexpected clinical outcomes following the implementation of a standardised order set for hepatic encephalopathy. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000621. [PMID: 33866310 PMCID: PMC8055129 DOI: 10.1136/bmjgast-2021-000621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/14/2021] [Accepted: 03/27/2021] [Indexed: 11/08/2022] Open
Abstract
Objective We evaluated the effect on clinical outcomes of implementing a standardised inpatient order set for patients admitted with hepatic encephalopathy (HE). Methods A retrospective review of patients with cirrhosis admitted with HE. Hospital admissions for HE for which the electronic health record (EHR) order set was used were compared with admissions where the order set was not used. Primary outcome was length of hospital stay (LOS). Secondary outcomes were 30-day readmissions, in-hospital complications, in-hospital and 90-day mortality. Results There were 341 patients with 980 admissions over the study period: 263 patients with 736 admissions where the order set was implemented, and 78 patients with 244 admissions where the order set was not implemented. Median LOS was 4 days (IQR 3–8) in the order set group compared with 3 days (IQR 2–7) (p<0.001); incidence rate ratio 1.37 (95% CI 1.20 to 1.57), p<0.001. 30-day readmissions rate was 56% in the order set group compared with 40%, p=0.01; OR for readmission was 1.88 (95% CI 1.04 to 3.43), p=0.04. Hypokalaemia occurred in 46% of admissions with order set use compared with 36%, when the order set was not used; p=0.003, OR 1.72 (95% CI 1.22 to 2.43), p=0.002. No significant differences were seen for in-hospital mortality and 90-day mortality. Conclusion Implementation of an inpatient EHR order set for use in patients with HE was associated with unexpected clinical outcomes including increased LOS and readmissions. The convenience and advantages of standardisation of patient care should be balanced with a degree of individualisation, particularly in the care of medically complex patients. Furthermore, standardised processes should be evaluated frequently after implementation to assess for unintended consequences.
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Affiliation(s)
- Mandip Kc
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Andrew P J Olson
- Department of Medicine, Division of General Internal Medicine, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.,Department of Pediatrics, Division of Pediatric Hospital Medicine, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Qi Wang
- Clinical and Translational Science Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
| | - Nicholas Lim
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
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Abstract
Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis. In its subclinical form, called “minimal hepatic encephalopathy (MHE), only psychometric tests or electrophysiological evaluation can reveal alterations in attention, working memory, psychomotor speed and visuospatial ability, while clinical neurological signs are lacking. The term “covert” (CHE) has been recently used to unify MHE and Grade I HE in order to refer to a condition that is not unapparent but also non overt. “Overt” HE (OHE) is characterized by personality changes, progressive disorientation in time and space, acute confusional state, stupor and coma. Based on its time course, OHE can be divided in Episodic, Recurrent or Persistent. Episodic HE is generally triggered by one or more precipitant factors that should be found and treated. Unlike MHE, clinical examination and clinical decision are crucial for OHE diagnosis and West Haven criteria are widely used to assess the severity of neurological dysfunction. Primary prophylaxis of OHE is indicated only in the patient with gastrointestinal bleeding using non-absorbable antibiotics (Rifaximin) or non-absorbable disaccharides (Lactulose). Treatment of OHE is based on the identification and correction of precipitating factors and starting empirical ammonia-lowering treatment with Rifaximin and Lactulose (per os and enemas). The latter should be used for secondary prophylaxis, adding Rifaximin if HE becomes recurrent. In recurrent/persistent HE, the treatment options include fecal transplantation, TIPS revision and closure of eventual splenorenal shunts. Treatment of MHE should be individualized on a case-by-case basis.
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de Wit K, Schaapman JJ, Nevens F, Verbeek J, Coenen S, Cuperus FJC, Kramer M, Tjwa ETTL, Mostafavi N, Dijkgraaf MGW, van Delden OM, Beuers UHW, Coenraad MJ, Takkenberg RB. Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial). BMJ Open Gastroenterol 2020; 7:e000531. [PMID: 33372103 PMCID: PMC7783616 DOI: 10.1136/bmjgast-2020-000531] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/12/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking. METHODS AND ANALYSIS The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium. ETHICS AND DISSEMINATION This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS ClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).
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Affiliation(s)
- K de Wit
- Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - J J Schaapman
- Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - F Nevens
- Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - J Verbeek
- Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - S Coenen
- Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - F J C Cuperus
- Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - M Kramer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - E T T L Tjwa
- Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - N Mostafavi
- Biostatistics Unit, Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - M G W Dijkgraaf
- Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - O M van Delden
- Interventional Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - U H W Beuers
- Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - M J Coenraad
- Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - R B Takkenberg
- Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
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Parker R. Early identification of hepatic encephalopathy improves outcomes. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2020; 29:S10-S13. [PMID: 32976023 DOI: 10.12968/bjon.2020.29.sup17.s10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Early identification and prompt treatment of hepatic encephalopathy can help reduce its progression into its overt form. As the initial signs and symptoms of this complication can be extremely subtle, diagnosis can be difficult, particularly for non-specialists. This article describes how the use of simple and widely available tests can help facilitate this.
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Affiliation(s)
- Richard Parker
- Consultant Hepatologist, Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Sweeney E, Richardson P. Overt hepatic encephalopathy: management and prevention of recurrence. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2020; 29:S14-S17. [PMID: 32976024 DOI: 10.12968/bjon.2020.29.sup17.s14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Most patients with overt hepatic encephalopathy are managed in an acute hospital setting. The mainstays of treatment are non-absorbable disaccharides, To prevent a recurrence, and thus further hospital admission, the focus is on identifying and avoiding precipitants, optimising nutrition and prescribing medication including rifaximin-α*†.
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Affiliation(s)
- Elizabeth Sweeney
- Gastroenterology Specialist Registrar, Royal Liverpool University Hospital
| | - Paul Richardson
- Consultant Hepatologist, Royal Liverpool University Hospital
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Nishikawa H, Enomoto H, Nishiguchi S, Iijima H. Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis. Int J Mol Sci 2020; 21:E5254. [PMID: 32722100 PMCID: PMC7432211 DOI: 10.3390/ijms21155254] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/15/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya 6638136, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
| | | | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
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Stawicka A, Jaroszewicz J, Zbrzeźniak J, Sołowianowicz N, Woszczenko A, Świderska M, Flisiak R. Clinical Usefulness of the Inhibitory Control Test (ICT) in the Diagnosis of Minimal Hepatic Encephalopathy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E3645. [PMID: 32455895 PMCID: PMC7277853 DOI: 10.3390/ijerph17103645] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 12/21/2022]
Abstract
Background: Minimal hepatic encephalopathy (MHE) refers to a number of neuropsychiatric and neurophysiological disorders in patients with cirrhosis who do not show abnormalities on physical examination or in clinical tests. The aim of this study was to determine the prevalence, risk factors, and predictive value of minimal hepatic encephalopathy and the usefulness of the inhibitory control test (ICT) in the diagnosis. Methods: Seventy patients (mean age 53 years, range 24-77) with liver cirrhosis were enrolled in the study. MHE was diagnosed based on PHES (psychometric hepatic encephalopathy score) and ICT. PHES and ICT were validated in a group of 56 control subjects. Results: Minimal hepatic encephalopathy was diagnosed using PHES in 21 patients (30%). ICT diagnosed MHE in 30 patients (42%), and the test had a sensitivity of 65% and a specificity of 57% compared to PHES. The ICT score (lures/target accuracy rate) correlated with the age of subjects (R = 0.35, p = 0.002) and only slightly with education (education in years R = -0.22, p = 0.06). MHE diagnosed with PHES or ICT was associated with a significantly higher model of end-stage liver disease (MELD) score in the follow-up. MHE diagnosed with ICT was correlated with a significantly higher incidence of symptoms of decompensated cirrhosis (p = 0.02) in the follow-up. Conclusions: ICT had moderate sensitivity and specificity in diagnosing MHE compared to PHES. Importantly, MHE detected with PHES or ICT was associated with poorer survival and a more severe progression of the disease.
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Affiliation(s)
- Agnieszka Stawicka
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland
| | - Justyna Zbrzeźniak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
| | - Natalia Sołowianowicz
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
| | - Aleksandra Woszczenko
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
| | - Magdalena Świderska
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland; (J.J.); (J.Z.); (N.S.); (A.W.); (M.Ś.); (R.F.)
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KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol 2020; 26:83-127. [PMID: 31918536 PMCID: PMC7160350 DOI: 10.3350/cmh.2019.0010n] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023] Open
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Dhiman RK, Thumburu KK, Verma N, Chopra M, Rathi S, Dutta U, Singal AK, Taneja S, Duseja A, Singh M. Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. Clin Gastroenterol Hepatol 2020; 18:800-812.e25. [PMID: 31476436 DOI: 10.1016/j.cgh.2019.08.047] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to synthesize evidence for most effective treatments for minimal hepatic encephalopathy (HE) and prevention of overt HE in patients with cirrhosis. METHODS We performed a systematic search of the PubMed, EMBASE, OvidSP, and Cochrane Central Register of Controlled Trials databases through July 26, 2018, for randomized controlled trials evaluating treatments for minimal HE in patients with cirrhosis, with primary outcomes of reversal of minimal HE or prevention of overt HE. We conducted a meta-analysis and then used network meta-analysis and surface under cumulated ranking (SUCRA) to pool the direct and indirect estimates and rank the different treatments. We appraised study quality using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS Our meta-analysis and network meta-analysis included 25 trials, comprising 1563 participants. Agents found to be effective in reversing minimal HE compared with placebo or no treatment included rifaximin (odds ratio [OR], 7.53; 95% predictive interval [PrI], 4.45-12.73; SUCRA, 89.2%; moderate quality), lactulose (OR, 5.39; 95% PrI, 3.60-8.0; SUCRA, 67.2%; moderate quality), the combination of probiotics and lactulose (OR, 4.66; 95% PrI, 1.90-11.39; SUCRA, 52.4%; low quality), L-ornithine L-aspartate (OR, 4.45; 95% PrI, 2.67-7.42; SUCRA, 47.2%; low moderate quality), and probiotics (OR, 3.89; 95% PrI, 2.52-6.02; SUCRA, 34.1%; low quality). Agents found to be effective in preventing episodes of overt HE compared with placebo or no treatment included L-ornithine L-aspartate (OR, 0.19; 95% PrI, 0.04-0.91; SUCRA, 75.1%; high moderate quality), lactulose (OR, 0.22; 95% PrI, 0.09-0.52; SUCRA, 73.9%; moderate quality), and probiotics (OR, 0.27; 95% PrI, 0.11-0.62; SUCRA, 59.6%; low quality). CONCLUSIONS In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis. L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE. Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects. International prospective register of systematic reviews ID: 107003.
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Affiliation(s)
| | | | | | | | | | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | | | | | - Meenu Singh
- Department of Paediatrics, Chandigarh, India
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Coronel-Castillo C, Contreras-Carmona J, Frati-Munari A, Uribe M, Méndez-Sánchez N. Efficacy of rifaximin in the different clinical scenarios of hepatic encephalopathy. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020. [DOI: 10.1016/j.rgmxen.2019.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Coronel-Castillo CE, Contreras-Carmona J, Frati-Munari AC, Uribe M, Méndez-Sánchez N. Efficacy of rifaximin in the different clinical scenarios of hepatic encephalopathy. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:56-68. [PMID: 31836274 DOI: 10.1016/j.rgmx.2019.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 08/21/2019] [Accepted: 09/04/2019] [Indexed: 06/10/2023]
Abstract
Hepatic encephalopathy is a frequent complication in patients with cirrhosis of the liver and is associated with a high mortality rate. Costs attributed to the management of patients with cirrhosis are especially high due to complications, such as hepatic encephalopathy, given that they increase the number of days of hospital stay. Different drugs are currently used to treat hepatic encephalopathy, and the main ones are lactulose, L-ornithine L-aspartate (LOLA), and certain antibiotics, especially rifaximin-α (RFX). Even though many of them have been shown to be effective to greater or lesser degrees, it is important to understand the differences between them, so that every patient receives individualized treatment and the best option is chosen, in accordance with the different clinical scenarios. Thus, the aim of the present study was to analyze the evidence on the advantages and disadvantages of the individual or combined use of the 3 main treatments for hepatic encephalopathy, specifically taking into consideration their different degrees of efficacy, their impact on quality of life, prophylaxis, and cost reduction.
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Affiliation(s)
- C E Coronel-Castillo
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J Contreras-Carmona
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - A C Frati-Munari
- Departamento de Medicina Interna, Fundación Clínica Médica Sur, Ciudad de México, México
| | - M Uribe
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México
| | - N Méndez-Sánchez
- Unidad de Investigación en Hígado, Fundación Clínica Médica Sur, Ciudad de México, México; Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México.
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Pawar VB, Surude RG, Sonthalia N, Zanwar V, Jain S, Contractor Q, Rathi PM. Minimal Hepatic Encephalopathy in Indians: Psychometric Hepatic Encephalopathy Score and Inhibitory Control Test for Diagnosis and Rifaximin or Lactulose for Its Reversal. J Clin Transl Hepatol 2019; 7:304-312. [PMID: 31915599 PMCID: PMC6943207 DOI: 10.14218/jcth.2017.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Revised: 05/28/2018] [Accepted: 02/14/2019] [Indexed: 12/15/2022] Open
Abstract
Background and Aims: Psychometric hepatic encephalopathy score (PHES) is used widely for diagnosis of minimal hepatic encephalopathy (MHE). This prospective study aimed to determine the utility of the inhibitory control test (ICT) for the diagnosis of MHE. Additionally, the efficacy of rifaximin and lactulose for reversal of MHE was evaluated. Methods: A total of 180 eligible cirrhotic patients underwent testing for MHE. When PHES was ≤ -5 and ICT lures were ≥ 14, MHE was diagnosed. The 108 patients with MHE were randomized to three groups for treatment with either lactulose, rifaximin, or placebo. Treatment outcomes were measured at the end of 3 months. Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%. The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients, by abnormal ICT and normal PHES in 37 patients, and by abnormal PHES and normal ICT in 15 patients. For diagnosis of MHE, ICT had sensitivity of 78.87%, specificity of 66.06% with 60.22% positive predictive value and 82.76% negative predictive value. An area under the curve value of 0.724 (95% CI: 0.653-0.788) was obtained for diagnosis of MHE. Reversal of MHE was seen in 71.42%, 70.27% and 11.11% of patients in the rifaximin, lactulose and placebo arms (p < 0.001). Rifaximin showed better tolerability compared to lactulose. Conclusions: For the diagnosis of MHE, ICT is a simple tool but has lower sensitivity and better specificity than PHES. Rifaximin is as efficacious as lactulose in the treatment of MHE and better tolerated.
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Affiliation(s)
- Vinay B. Pawar
- Correspondence to: Vinay B. Pawar, Department of Gastroenterology, Topiwala National Medical College and BYL Ch Hospital, Dr. A.L Nair Road, Mumbai, Maharashtra 400008, India. Tel: +22-23021639, E-mail:
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