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Maiwall R, Kulkarni AV, Arab JP, Piano S. Acute liver failure. Lancet 2024; 404:789-802. [PMID: 39098320 DOI: 10.1016/s0140-6736(24)00693-7] [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: 09/12/2023] [Revised: 03/13/2024] [Accepted: 04/03/2024] [Indexed: 08/06/2024]
Abstract
Acute liver failure (ALF) is a life-threatening disorder characterised by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease. The cause of ALF varies across the world. Common causes of ALF in adults include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis. The cause of liver failure affects the management and prognosis, and therefore extensive investigation for cause is strongly suggested. Sepsis with multiorgan failure and cerebral oedema remain the leading causes of death in patients with ALF and early identification and appropriate management can alter the course of ALF. Liver transplantation is the best current therapy, although the role of artificial liver support systems, particularly therapeutic plasma exchange, can be useful for patients with ALF, especially in non-transplant centres. In this Seminar, we discuss the cause, prognostic models, and management of ALF.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Juan Pablo Arab
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
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2
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Agumava LU, Gulyaev VA, Lutsyk KN, Olisov OD, Akhmetshin RB, Magomedov KM, Kazymov BI, Akhmedov AR, Alekberov KF, Yaremin BI, Novruzbekov MS. Issues of intensive care and liver transplantation tactics in fulminant liver failure. BULLETIN OF THE MEDICAL INSTITUTE "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH) 2023. [DOI: 10.20340/vmi-rvz.2023.1.tx.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.
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Affiliation(s)
- L. U. Agumava
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - V. A. Gulyaev
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. N. Lutsyk
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - O. D. Olisov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - R. B. Akhmetshin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. M. Magomedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Kazymov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - A. R. Akhmedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. F. Alekberov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Yaremin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - M. S. Novruzbekov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
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Kim JD. [Acute Liver Failure: Current Updates and Management]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:17-28. [PMID: 36695063 DOI: 10.4166/kjg.2022.148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 12/25/2022] [Accepted: 12/29/2022] [Indexed: 01/26/2023]
Abstract
Acute liver failure (ALF) is a rare disease condition with a dynamic clinical course and catastrophic outcomes. Several etiologies are involved in ALF. Hepatitis A and B infections and indiscriminate use of untested herbs or supplemental agents are the most common causes of ALF in Korea. Noninvasive neurological monitoring tools have been used in patients with ALF in recent times. Ongoing improvements in intensive care, including continuous renal replacement therapy, therapeutic plasma exchange, vasopressor, and extracorporeal membrane oxygenation, have reduced the mortality rate of patients with ALF. However, liver transplantation is still the most effective treatment for patients with intractable ALF. There is a need for further research in the areas of better prognostication and precise selection of patients for emergency transplantation.
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Affiliation(s)
- Jin Dong Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
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Chhonker SK, Rawat D, Koiri RK. Repurposing PDE5 inhibitor tadalafil and sildenafil as anticancer agent against hepatocellular carcinoma via targeting key events of glucose metabolism and multidrug resistance. J Biochem Mol Toxicol 2022; 36:e23100. [PMID: 35608386 DOI: 10.1002/jbt.23100] [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: 08/21/2021] [Revised: 02/28/2022] [Accepted: 05/11/2022] [Indexed: 11/12/2022]
Abstract
Hepatocellular carcinoma (HCC) has emerged as one of the most common and lethal cancers worldwide and is caused due to contamination of diets with aflatoxin B1 and chronic viral hepatitis. Recent reports suggest that phosphodiesterase-5 inhibitor (PDE5i) exhibits anticancer properties against several forms of cancer but till now has not been evaluated against HCC. We aimed to evaluate the anticancer property of phosphodiesterase-5 inhibitors (PDE5i) tadalafil and sildenafil against aflatoxin B1 HCC. Rats of HCC group were fed with 5% alcohol via drinking water for 3 weeks, followed by administration of AFB1 (1 mg/kg/bw, i.p.) at an interval of two subsequent days. PDE5i (tadalafil and sildenafil, 10 mg/kg bw) was administered along with drinking water after 6 weeks of treatment with AFB1 for 2 weeks. In the present investigation, in HCC elevation in the level of SGOT, SGPT, ALP, and urea vis-à-vis activity of key glycolytic enzyme LDH and mRNA expression of c-myc, Akt, LDH-A, and PFKFB3 was noted. Similarly, the level of multidrug resistance protein (MDR) and breast cancer resistance protein (BCRP/ABCG2) was elevated along with increased expression of angiogenesis marker (HIF-1α, VEGF, and TGF-β1) in HCC. Post-treatment with PDE5 inhibitor (tadalafil and sildenafil) downregulated and brought back the above parameters towards normal and out of two PDE5i (tadalafil and sildenafil), sildenafil effect was more potent as compared to tadalafil. Our findings demonstrate for the first time that PDE5 inhibitors tadalafil and sildenafil are able to prohibit the development and progression of aflatoxin B1 induced HCC.
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Affiliation(s)
- Saurabh Kumar Chhonker
- Biochemistry Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India
| | - Divya Rawat
- Biochemistry Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India
| | - Raj Kumar Koiri
- Biochemistry Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, India
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Abstract
Liver failure in the context of acute (ALF) and acute on chronic liver failure (ACLF) is associated with high mortality in the absence of a liver transplant. For decades, therapeutic plasma exchange (TPE) is performed for the management of immune-mediated diseases. TPE has emerged as an attractive extracorporeal blood purification technique in patients with ALF and ACLF. The basic premise of using TPE is to remove the toxic substances which would allow recovery of native liver functions by facilitating liver regeneration. In recent years, encouraging data have emerged, suggesting the benefits of TPE in patients with liver failure. TPE has emerged as an attractive liver support device for the failing liver until liver transplantation or clinical recovery. The data in patients with ALF suggest routine use of high-volume TPE, while the data for such a strategy are less robust for patients with ACLF.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Affiliation(s)
- O. Detry
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, University of Liège, Sart Tilman B35, B-4000 Liège, Belgium
| | - P. Honoré
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, University of Liège, Sart Tilman B35, B-4000 Liège, Belgium
| | - M. Meurisse
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, University of Liège, Sart Tilman B35, B-4000 Liège, Belgium
| | - N. Jacquet
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, University of Liège, Sart Tilman B35, B-4000 Liège, Belgium
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Wang YM, Li K, Dou XG, Bai H, Zhao XP, Ma X, Li LJ, Chen ZS, Huang YC. Treatment of AECHB and Severe Hepatitis (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498915 DOI: 10.1007/978-94-024-1603-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the general treatment and immune principles and internal management for AECHB and HBV ACLF, including ICU monitoring, general supportive medications/nutrition/nursing, immune therapy, artificial liver supportive systems, hepatocyte/stem cell, and liver transplant, management for special populations, frequently clinical complications and the utilization of Chinese traditional medicines.
Early clinical indicators of severe hepatitis B include acratia, gastrointestinal symptoms, a daily increase in serum bilirubin >1 mg/dL, toxic intestinal paralysis, bleeding tendency and mild mind anomaly or character change, and the presence of other diseases inducing severe hepatitis. Laboratory indicators include T-Bil, PTA, cholinesterase, pre-albumin and albumin. The roles of immune indicators (such as IL-6, TNF-α, and fgl2), gene polymorphisms, HBV genotypes, and gene mutations as early clinical indicators. Intensive Care Unit monitor patients with severe hepatitis include intracranial pressure, infection, blood dynamics, respiratory function, renal function, blood coagulation function, nutritional status and blood purification process. Nursing care should not only include routine care, but psychological and special care (complications). Nutrition support and nursing care should be maintained throughout treatment for severe hepatitis. Common methods of evaluating nutritional status include direct human body measurement, creatinine height index (CHI) and subject global assessment of nutrition (SGA). Malnourished patients should receive enteral or parenteral nutrition support. Immune therapies for severe hepatitis include promoting hepatocyte regeneration (e.g. with glucagon, hepatocyte growth factor and prostaglandin E1), glucocorticoid suppressive therapy, and targeting molecular blocking. Corticosteroid treatment should be early and sufficient, and adverse drug reactions monitored. Treatments currently being investigated are those targeting Toll-like receptors, NK cell/NK cell receptors, macrophage/immune coagulation system, CTLA-4/PD-1 and stem cell transplantation. In addition to conventional drugs and radioiodine, corticosteroids and artificial liver treatment can also be considered for severe hepatitis patients with hyperthyreosis. Patients with gestational severe hepatitis require preventive therapy for fetal growth restriction, and it is necessary to choose the timing and method of fetal delivery. For patients with both diabetes and severe hepatitis, insulin is preferred to oral antidiabetic agents to control blood glucose concentration. Liver toxicity of corticosteroids and immune suppressors should be monitored during treatment for severe hepatitis in patients with connective tissue diseases including SLE, RA and sicca syndrome. Patient with connective tissue diseases should preferably be started after the antiviral treatment with nucleos(t)ide analogues. An artificial liver can improve patients’ liver function; remove endotoxins, blood ammonia and other toxins; correct amino acid metabolism and coagulation disorders; and reverse internal environment imbalances. Non-bioartificial livers are suitable for patients with early and middle stage severe hepatitis; for late-stage patients waiting for liver transplantation; and for transplanted patients with rejection reaction or transplant failure. The type of artificial liver should be determined by each patient’s condition and previous treatment purpose, and patients should be closely monitored for adverse reactions and complications. Bio- and hybrid artificial livers are still under development. MELD score is the international standard for choosing liver transplantation. Surgical methods mainly include the in situ classic type and the piggyback type; transplantation includes no liver prophase, no liver phase or new liver phase. Preoperative preparation, management of intraoperative and postoperative complications and postoperative long-term treatment are keys to success. Severe hepatitis belongs to the categories of “acute jaundice”, “scourge jaundice”, and “hot liver” in traditional Chinese medicine. Treatment methods include Chinese traditional medicines, acupuncture and acupoint injection, external application of drugs, umbilical compress therapy, drip, blow nose therapy, earpins, and clysis. Dietary care is also an important part of traditional Chinese medicine treatment.
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Putignano A, Figorilli F, Alabsawy E, Agarwal B, Jalan R. Long-term outcome in patients with acute liver failure. Liver Int 2018; 38:2228-2238. [PMID: 29927051 DOI: 10.1111/liv.13914] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 06/09/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Acute liver failure patients who meet poor prognostic criteria have high early mortality without emergency liver transplantation. A recent study however, reported that patients that survive spontaneously have a poorer outcome compared with patients undergoing transplantation. In this single centre study, we aimed to confirm or refute this observation. METHODS Early survivors (acute liver failure patients who survived 90 days after the ICU admission) were assessed for long-term outcomes in four distinctive cohorts, incorporating aetiology (Acetaminophen overdose or non-Acetaminophen overdose), and management strategy (conservative or liver transplantation). Chi Squared or Fisher test were used to compare outcomes among the four cohorts (P < 0.05) and Kaplan-Meier curve (Log Rank test) to represent cumulative survival. RESULTS Two hundred consecutive acute liver failure patients between 1990 and 2014 were included; mean age 38.3, ±12.8, male 70, 35%. 124/200 (62%) early survivors were identified; 13/124 (10.5%) acetaminophen patients underwent transplantation and 48/124 (38.7%) survived spontaneously; 36/124 (29.0%) non-acetaminophen underwent transplantation and 27/124 (21.8%) survived spontaneously. A total of 11/124 (8.9%) died subsequently (median survival 5.3± IQR 9.1), three spontaneous survivors and eight transplanted patients (P = 0.025); of the eight transplanted patients, six died of transplant related complications and two of suicide. CONCLUSION The results of this study suggest that although liver transplantation is a life-saving procedure for acute liver failure patients, they have a worse long-term outcome compared with spontaneous survivors. Novel therapies to increase the percentage of spontaneous survivors are urgently needed.
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Affiliation(s)
- Antonella Putignano
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, UK.,Intensive Care Unit, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Francesco Figorilli
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, UK
| | - Eman Alabsawy
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, UK
| | - Banwari Agarwal
- Intensive Care Unit, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, UK
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Abstract
Drug-induced acute liver failure (ALF) disproportionately affects women and nonwhites. It is most frequently caused by antimicrobials and to a lesser extent by complementary and alternative medications, antiepileptics, antimetabolites, nonsteroidals, and statins. Most drug-induced liver injury ALF patients have hepatocellular injury pattern. Cerebral edema and intracranial hypertension are the most serious complications of ALF. Other complications include coagulopathy, sepsis, metabolic derangements, and renal, circulatory, and respiratory dysfunction. Although advances in intensive care have improved outcome, ALF has significant mortality without liver transplantation. Liver-assist devices may provide a bridge to transplant or to spontaneous recovery.
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Affiliation(s)
- Shahid Habib
- Department of Medicine, Southern Arizona Veterans Affairs Healthcare System 3601 S 6th Avenue, Tucson, AZ 85723 USA
| | - Obaid S Shaikh
- Section of Gastroenterology, Department of Medicine, Veterans Affairs Pittsburgh Healthcare System, University Drive C, FU #112, Pittsburgh, PA 15240, USA; Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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Davenport A. Anticoagulation in Patients With Acute Renal Failure Treated With Continuous Renal Replacement Therapies. ACTA ACUST UNITED AC 2016; 2:41-59. [DOI: 10.1111/hdi.1998.2.1.41] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Kim Y, Kim CK, Jung S, Ko SB. Brain Oxygen Monitoring via Jugular Venous Oxygen Saturation in a Patient with Fulminant Hepatic Failure. Korean J Crit Care Med 2016. [DOI: 10.4266/kjccm.2016.00143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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12
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[Blood pressure monitoring - Status quo and future : A contribution to the personalized medicine]. Med Klin Intensivmed Notfmed 2016; 111:610-618. [PMID: 27405940 DOI: 10.1007/s00063-016-0171-y] [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: 01/29/2016] [Accepted: 03/02/2016] [Indexed: 10/21/2022]
Abstract
Sustainment of life demands that the heart create sufficient pressure to maintain enough flow to keep the body healthy and oxygenated. Blood pressures can be easily measured, while volume measurements required additional invasive procedures. In analogy to volumetrically determined ejection fraction, a pressure ejection fraction EF(P) may be calculated. When standardized to heart rate and body surface area, a new, effective performance metric may be defined. These metrics enable the long-term monitoring of the critically ill patient. When presented in a performance diagram, the metrics contain prognostic implications and enable a real-time evaluation of the efficacy of therapeutic measures. Until now, pressure-related prognostic statements were based on statistical averages, which by definition apply to groups. With this new analytical approach, we have the ability to provide patient-specific therapeutics in an area of medicine that requires individualized treatment. Here, we show preliminary results of applying a mathematical risk analysis to blood pressure metrics to assess therapeutic risk.
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Molecular studies of the immunological effects of the sevoflurane preconditioning in the liver and lung in a rat model of liver ischemia/reperfusion injury. Mol Immunol 2016; 72:1-8. [DOI: 10.1016/j.molimm.2016.02.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 02/11/2016] [Accepted: 02/14/2016] [Indexed: 12/20/2022]
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Weingarten MA, Sande AA. Acute liver failure in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2015; 25:455-73. [PMID: 25882813 DOI: 10.1111/vec.12304] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 01/26/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To define acute liver failure (ALF), review the human and veterinary literature, and discuss the etiologies and current concepts in diagnostic and treatment options for ALF in veterinary and human medicine. ETIOLOGY In veterinary medicine ALF is most commonly caused by hepatotoxin exposure, infectious agents, inflammatory diseases, trauma, and hypoxic injury. DIAGNOSIS A patient may be deemed to be in ALF when there is a progression of acute liver injury with no known previous hepatic disease, the development of hepatic encephalopathy of any grade that occurs within 8 weeks after the onset of hyperbilirubinemia (defined as plasma bilirubin >50 μM/L [>2.9 mg/dL]), and the presence of a coagulopathy. Diagnostic testing to more specifically characterize liver dysfunction or pathology is usually required. THERAPY Supportive care to aid the failing liver and compensate for the lost functions of the liver remains the cornerstone of care of patients with ALF. Advanced therapeutic options such as extracorporeal liver assist devices and transplantation are currently available in human medicine. PROGNOSIS The prognosis for ALF depends upon the etiology, the degree of liver damage, and the response to therapy. In veterinary medicine, the prognosis is generally poor.
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15
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Albumin dialysis in artificial liver support systems: open-loop or closed-loop dialysis mode? ASAIO J 2015; 61:324-31. [PMID: 25650810 DOI: 10.1097/mat.0000000000000198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
In artificial liver support systems, the open-loop albumin dialysis mode (OLM) is usually used to remove protein-bound toxins from the blood of patients with liver failure. However, there is still interest in the closed-loop albumin dialysis mode (CLM) because this mode may enable not only the regeneration and reuse of albumin but also the miniaturization of artificial liver systems. In this article, we compared the two modes under a fixed amount of albumin in dialysate experimentally and theoretically. The results show that according to the detoxification efficiency in the 3 hour dialysis for removing albumin-bound bilirubin, CLM is better than OLM. The usage efficiency of albumin in CLM is also higher. Moreover, the advantage of CLM is more significant when the concentration of bilirubin in blood is lower. Under a given amount of albumin in dialysate, if the concentration of bilirubin in blood is high, one may further increase the performance of CLM by means of increasing the flow rate of the albumin dialysate or using the highly concentrated albumin dialysate.
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Bhat S, Kenchetty KP. N-acetyl cysteine in the management of rodenticide consumption - life saving? J Clin Diagn Res 2015; 9:OC10-3. [PMID: 25738016 DOI: 10.7860/jcdr/2015/11484.5455] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Accepted: 11/25/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND AIM OF STUDY Rodenticide is a commonly ingested poison in India. Many rodenticides contain hepatotoxic agents and can cause acute liver failure (ALF). There is no antidote for rodenticide poison, and consumption is often fatal. The Role of N acetyl cysteine (NAC) in acetaminophen induced ALF is well established. Additionally some studies have shown that it may be useful in non-acetaminophen induced ALF also. Cases with ALF secondary to suicidal rodenticide consumption have been reported, and some reports show that NAC is beneficial in these cases. Our study was a retrospective analysis of patients admitted with rodenticide consumption, comparing outcomes in those receiving standard of care management and those who were treated with NAC also. MATERIALS AND METHODS Case sheets of all inpatients of a tertiary medical college hospital between January 2010 and December 2012 admitted with an alleged history of rodenticide consumption were surveyed and data was extracted and analysed. STATISTICAL ANALYSIS Patients were analysed with respect to age, sex, mode of presentation, interval between consumption of rodenticide and starting NAC; the outcome in patients treated with acetylcysteine was compared to outcomes in those not treated with acetylcysteine RESULTS A total of 100 patients were studied out of which 18 died. Sixteen of the deaths were in patients who had not been treated with NAC. We found that patients who had received NAC had lower mortality, lower peak values of AST/ALT, and shorter hospital stay. CONCLUSION NAC may have a role in the management of ALF associated with rodenticide consumption.
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Affiliation(s)
- Smitha Bhat
- Professor, Department of Medicine, Father Muller Medical College , Mangalore, India
| | - Kumar P Kenchetty
- Post Graduate Resident, Department of Medicine, Father Muller Medical College , Mangalore, India
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Abstract
OBJECTIVES High-volume hemofiltration has shown beneficial effects in severe sepsis and multiple organ failure, improving hemodynamics and fluid balance. Recent studies suggest that acute liver failure shares many pathophysiologic similarities with sepsis. Therefore, we assessed the systemic effects of high-volume hemofiltration in children with acute liver failure. DESIGN Retrospective observational cohort study. PATIENTS Twenty-two children. SETTING Forty-two-bed multidisciplinary pediatric and neonatal ICUs in a tertiary university hospital. INTERVENTION We evaluated high-volume hemofiltration therapy as part of standard management of 22 children admitted in our unit for acute liver failure. Fifteen patients had fulminant hepatic failure, three had acute-on-chronic liver disease, and four had primary nonfunction. High-volume hemofiltration was initiated in patients requiring emergency liver transplantation and when hepatic encephalopathy grade higher than 2 and/or hemodynamic instability requiring vasopressors occurred. High-volume hemofiltration was defined by a flow of ultrafiltrate of more than 80 mL/kg/hr. Clinical and biological variables were assessed before and 24 and 48 hours after initiation of high-volume hemofiltration therapy. MEASUREMENTS AND MAIN RESULTS High-volume hemofiltration was initiated with a median grade III of hepatic encephalopathy. The median flow of ultrafiltrate was 119 mL/kg/hr (range, 80-384). After 24 hours of high-volume hemofiltration treatment, we observed an increase in mean arterial pressure (p = 0.0002) and a decrease in serum creatinine (p = 0.0002). In half of the patients, the encephalopathy grade decreased. After 48 hours of treatment, mean arterial pressure (p = 0.0005), grade of hepatic encephalopathy (p = 0.04), and serum creatinine (p = 0.0002) improved. Overall mortality was 45.4% (n = 10). Emergency liver transplantation was performed in eight children. Five patients spontaneously recovered liver function. CONCLUSIONS High-volume hemofiltration therapy significantly improves hemodynamic stability and neurological status in children with acute liver failure awaiting for emergency liver transplantation.
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Li J, Yu Z, Wang Q, Li D, Jia B, Zhou Y, Ye Y, Shen S, Wang Y, Li S, Bai L, Kan Q. Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway. BMC Gastroenterol 2014; 14:151. [PMID: 25145683 PMCID: PMC4236522 DOI: 10.1186/1471-230x-14-151] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Accepted: 08/15/2014] [Indexed: 02/06/2023] Open
Abstract
Background Numerous pathological processes that affect liver function in patients with liver failure have been identified. Among them, hyperammonia is one of the most common phenomena.The purpose of this study was to determine whether hyperammonia could induced specific liver injury. Methods Hyperammonemic cells were established using NH4Cl. The cells were assessed by MTT, ELISA, and flow cytometric analyses. The expression levels of selected genes and proteins were confirmed by quantitative RT-PCR and western blot analyses. Results The effects of 20 mM NH4Cl pretreatment on the cell proliferation and apoptosis of primary hepatocytes and other cells were performed by MTT assays and flow cytometric analyses. Significant increasing in cytotoxicity and apoptosis were only observed in hepatocytes. The cell damage was reduced after adding BAPTA-AM but unchanged after adding EGTA. The expression levels of caspase-3, cytochrome C, calmodulin, and inducible nitric oxide synthase were increased and that of bcl-2 was reduced. The Na+-K+-ATPase activities in hyperammonia liver cells was no signiaficant difference compaired with the control group, but was decreased in astrocytes. NH4Cl pretreatment of primary hepatocytes promoted the activation of mitochondrial permeability transition pores and the mitochondria swelled irregularly. Conclusions Hyperammonia induces specific liver injury through an intrinsic Ca2+-independent apoptosis pathway.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Quancheng Kan
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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19
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Whitehouse T, Wendon J. Acute liver failure. Best Pract Res Clin Gastroenterol 2013; 27:757-69. [PMID: 24160932 DOI: 10.1016/j.bpg.2013.08.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Revised: 08/01/2013] [Accepted: 08/11/2013] [Indexed: 01/31/2023]
Abstract
Untreated acute liver failure (ALF) has a poor outcome and so rapid diagnosis and management is vital if the patient is to survive. ALF has such profound and widespread physiological consequences that whenever possible, patients with ALF should be managed in an intensive care unit. Management is to support the physiology and treat the underlying cause. Advice should be sought from a centre capable of performing liver transplantation. Should recovery seem unlikely, liver transplantation is a viable treatment option in some cases.
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Affiliation(s)
- Tony Whitehouse
- University Hospital Birmingham, Edgbaston, Birmingham B15 2WB, UK.
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20
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Al-Chalabi A, Matevossian E, V Thaden AK, Luppa P, Neiss A, Schuster T, Yang Z, Schreiber C, Schimmel P, Nairz E, Perren A, Radermacher P, Huber W, Schmid RM, Kreymann B. Evaluation of the Hepa Wash® treatment in pigs with acute liver failure. BMC Gastroenterol 2013; 13:83. [PMID: 23668774 PMCID: PMC3659067 DOI: 10.1186/1471-230x-13-83] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2012] [Accepted: 05/10/2013] [Indexed: 12/12/2022] Open
Abstract
Background Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. Methods In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. Results All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. Conclusions Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.
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Affiliation(s)
- Ahmed Al-Chalabi
- II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, München 81675, Gremany.
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Siciliano M, Parlati L, Maldarelli F, Rossi M, Ginanni Corradini S. Liver transplantation in adults: Choosing the appropriate timing. World J Gastrointest Pharmacol Ther 2012; 3:49-61. [PMID: 22966483 PMCID: PMC3437446 DOI: 10.4292/wjgpt.v3.i4.49] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 06/27/2012] [Accepted: 07/08/2012] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation.
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Affiliation(s)
- Maria Siciliano
- Maria Siciliano, Lucia Parlati, Federica Maldarelli, Stefano Ginanni Corradini, Department of Clinical Medicine, Division of Gastroenterology, Sapienza University of Rome, 00185 Rome, Italy
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22
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Vaquero J. Therapeutic hypothermia in the management of acute liver failure. Neurochem Int 2012; 60:723-35. [DOI: 10.1016/j.neuint.2011.09.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Revised: 09/13/2011] [Accepted: 09/13/2011] [Indexed: 02/07/2023]
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23
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Kamat P, Kunde S, Vos M, Vats A, Gupta N, Heffron T, Romero R, Fortenberry JD. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure. Pediatr Crit Care Med 2012; 13:e33-8. [PMID: 21263362 PMCID: PMC3108011 DOI: 10.1097/pcc.0b013e31820ac08f] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVE Pediatric acute liver failure is often accompanied by hepatic encephalopathy, cerebral edema, and raised intracranial pressure. Elevated intracranial pressure can be managed more effectively with intracranial monitoring, but acute-liver-failure-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early intracranial pressure monitoring in acute liver failure in children listed for liver transplantation. DESIGN AND PATIENTS Retrospective review of all intubated pediatric acute liver failure patients with grade III and grade IV encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant who were identified from an institutional liver transplant patient database from 1999 to 2009. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 14 patients were identified who met the inclusion criteria. Their ages ranged from 7 months to 20 yrs. Diagnoses of acute liver failure were infectious (three), drug-induced (seven), autoimmune hepatitis (two), and indeterminate (two). Grade III and IV encephalopathy was seen in ten (71%) and four (29%) patients, respectively. Computed tomography scans before intracranial pressure monitor placement showed cerebral edema in five (35.7%) patients. Before intracranial pressure monitor placement, fresh frozen plasma, vitamin K, and activated recombinant factor VIIa were given to all 14 patients, with significant improvement in coagulopathy (p < .04). The initial intracranial pressure ranged from 5 to 50 cm H2O; the intracranial pressure was significantly higher in patients with cerebral edema by computed tomography (p < .05). Eleven of 14 (78%) patients received hypertonic saline, and three (22%) received mannitol for elevated intracranial pressure. Eight of 14 (56%) monitored patients were managed to liver transplant, with 100% surviving neurologically intact. Four of 14 (28%) patients had spontaneous recovery without liver transplant. Two of 14 (14%) patients died due to multiple organ failure before transplant. One patient had a small 9-mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. CONCLUSIONS In our series of patients, intracranial pressure monitoring had a low complication rate and was associated with a high survival rate despite severe hepatic encephalopathy and cerebral edema in the setting of pediatric acute liver failure. In our experience, monitoring of intracranial pressure allowed interventions to treat increased intracranial pressure and provided additional information regarding central nervous system injury before liver transplant. Further study is warranted to confirm if monitoring allows more directed intracranial pressure therapy and improves survival in pediatric acute liver failure.
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Affiliation(s)
- Pradip Kamat
- Division of Critical Care, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
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Baine AMT, Hori T, Chen F, Gardner LB, Uemoto S, Nguyen JH. Fulminant liver failure models with subsequent encephalopathy in the mouse. Hepatobiliary Pancreat Dis Int 2011; 10:611-619. [PMID: 22146625 DOI: 10.1016/s1499-3872(11)60104-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND A reliable model of fulminant liver failure (FLF) is urgently required in this research field. This study aimed to develop a murine FLF model. METHODS We used three groups of male C57BL/6 mice: control, with azoxymethane treatment (AOM group), and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-alpha group). The effects of body temperature (BT) control on survival in all three groups were investigated. Using BT control, we compared the survival, histopathological findings and biochemical/coagulation profiles between the two experimental groups. The effects of hydration on international normalized ratios of prothrombin time (PT-INRs) were also checked. Dose-dependent survival curves were constructed for both experimental groups. Neurological behavior was assessed using a coma scale. RESULTS No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNF-alpha group, showed a significant difference in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs, and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups. There were significant differences between FLF models in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. CONCLUSIONS AOM provides a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on the research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.
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Affiliation(s)
- Ann-Marie T Baine
- Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA
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25
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Quantitative Color Mapping of the Arterial Enhancement Fraction in Patients With Diffuse Liver Disease. AJR Am J Roentgenol 2011; 197:876-83. [DOI: 10.2214/ajr.10.5943] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Wright G, Chattree A, Jalan R. Management of hepatic encephalopathy. Int J Hepatol 2011; 2011:841407. [PMID: 21994873 PMCID: PMC3177461 DOI: 10.4061/2011/841407] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Accepted: 06/08/2011] [Indexed: 12/11/2022] Open
Abstract
Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease.
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Affiliation(s)
- G. Wright
- University College London Institute of Hepatology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK
| | - A. Chattree
- Department of Gastroenterology, King Georges Hospital, Barley Lane, Goodmayes, Ilford, Essex IG3 8YB, UK
| | - R. Jalan
- University College London Institute of Hepatology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK
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Aspinall RJ, Weis SM, Barnes L, Lutu-Fuga K, Bylund DJ, Pockros PJ, Cheresh DA. A Src family kinase inhibitor improves survival in experimental acute liver failure associated with elevated cerebral and circulating vascular endothelial growth factor levels. Liver Int 2011; 31:1222-30. [PMID: 21745297 PMCID: PMC3337519 DOI: 10.1111/j.1478-3231.2011.02554.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIMS Acute liver failure (ALF) is frequently complicated by cerebral oedema, systemic inflammation and multiorgan dysfunction. Vascular endothelial growth factor (VEGF) may stimulate liver regeneration but it can also be pro-inflammatory, activating endothelial cells and increasing permeability, actions mediated through Src kinase signalling. We therefore examined whether a Src inhibitor could have therapeutic potential in ALF. METHODS Murine ALF was induced with azoxymethane. Liver pathology was graded by a blinded examiner and apoptosis quantified by immunohistochemistry. Cerebral VEGF expression was imaged using VEGF-green fluorescent protein transgenic mice. Circulating and macrophage-secreted VEGF levels were measured. Experimental animals received a Src inhibitor or vehicle controls. RESULTS VEGF was undetectable in normal plasma but reached a mean of 835 pg/ml at grade III encephalopathy (P<0.001). Ammonia, lipopolysaccharide and interferon-gamma acted synergistically to enhance VEGF secretion by macrophages. Production of VEGF by cerebral cortical astrocytes increased with disease progression. Late treatment with inhibitors of Src or VEGF did not improve liver histology, encephalopathy or survival. However, early use of a Src kinase inhibitor significantly reduced hepatic injury, delayed encephalopathy and allowed 25% of mice to survive an otherwise lethal insult. CONCLUSION Systemic and cerebral VEGF levels are significantly elevated during experimental ALF and may be exacerbated by hyperammonemia and macrophage activation. Early use of a Src inhibitor reduced hepatocellular injury and enabled survival, indicating such agents may have some promise in the treatment of ALF.
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Affiliation(s)
- Richard J. Aspinall
- Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA 92037, USA,Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA,Current address for correspondence: Dr Richard J. Aspinall, Department of Gastroenterology & Hepatology, Queen Alexandra Hospital, Portsmouth, PO6 3LY, United Kingdom, , Tel (+44) 2392 286255, Fax (+44) 2392 286822
| | - Sara M. Weis
- Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Leo Barnes
- Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - Kimberly Lutu-Fuga
- Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
| | - David J. Bylund
- Department of Pathology, Scripps Clinic, La Jolla, CA 92037, USA
| | - Paul J. Pockros
- Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA 92037, USA
| | - David A. Cheresh
- Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
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Sundaram V, Shaikh OS. Acute liver failure: current practice and recent advances. Gastroenterol Clin North Am 2011; 40:523-39. [PMID: 21893272 DOI: 10.1016/j.gtc.2011.06.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
ALF is an important cause of liver-related morbidity and mortality. Advances in the management of ICH and SIRS, and cardiorespiratory, metabolic, and renal support have improved the outlook of such patients. Early transfer to a liver transplant center is essential. Routine use of NAC is recommended for patients with early hepatic encephalopathy, irrespective of the etiology. The role of hypothermia remains to be determined. Liver transplantation plays a critical role, particularly for those with advanced encephalopathy. Several detoxification and BAL support systems have been developed to serve as a bridge to transplantation or to spontaneous recovery. However, such systems lack sufficient reliability and efficacy to be applied routinely in clinical practice. Hepatocyte and stem cell transplantation may provide valuable adjunctive therapy in the future.
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Affiliation(s)
- Vinay Sundaram
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
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Arora R, Kathuria S, Jalandhara N. Acute renal dysfunction in patients with alcoholic hepatitis. World J Hepatol 2011; 3:121-4. [PMID: 21731905 PMCID: PMC3124879 DOI: 10.4254/wjh.v3.i5.121] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 03/06/2011] [Accepted: 03/13/2011] [Indexed: 02/06/2023] Open
Abstract
Acute renal dysfunction is common in patients with alcoholic hepatitis (AH). Its presence leads to higher mortality in these patients. Despite advances in medical care, the outcome has changed little over the past decades. Studies using Pentoxifylline and molecular adsorbent recirculation system have shown encouraging data in small studies. Further larger well designed studies are needed to assess these modalities of treatment for the treatment of AH.
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Affiliation(s)
- Robin Arora
- Robin Arora, Nishant Jalandhara, Division of Nephrology, Department of Internal Medicine, Tulane University, New Orleans, LA 70118, United States
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Ford RM, Sakaria SS, Subramanian RM. Critical care management of patients before liver transplantation. Transplant Rev (Orlando) 2010; 24:190-206. [PMID: 20688502 DOI: 10.1016/j.trre.2010.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2010] [Revised: 05/26/2010] [Accepted: 05/28/2010] [Indexed: 02/07/2023]
Abstract
The critical care management of patients before liver transplantation is aimed at optimizing hepatic and extrahepatic organ function before the transplant operation, with a goal to favorably influence perioperative and postoperative graft and patient outcomes. Critical illness in liver disease can present in the context of acute liver failure or acute on chronic liver failure. The differing pathophysiologic processes underlying these 2 types of liver failure necessitate specific approaches to their intensive care management. In their extreme presentations, both types of liver failure present as multiorgan system failure; and therefore, the critical care management of these entities requires a systematic multiorgan system approach to address hepatic and extrahepatic organ dysfunction. This review provides a multiorgan system-based description of critical care management of acute liver failure and acute on chronic liver failure before liver transplantation.
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Affiliation(s)
- Ryan M Ford
- Division of Gastroenterology and Hepatology, Emory University School of Medicine, Atlanta, GA, USA
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31
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Atienza Merino G. [Evaluation of extracorporeal liver support systems in the treatment of liver failure. A systematic review]. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:352-62. [PMID: 20363534 DOI: 10.1016/j.gastrohep.2010.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 11/11/2009] [Revised: 01/11/2010] [Accepted: 01/21/2010] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To evaluate the safety and efficacy of the MARS and Prometheus extracorporeal liver support systems in the treatment of liver failure. DESIGN We performed a systematic review of the literature from January 1999 to June 2009 in the Medline, Embase, HTA, DARE, NHSEED, Cochrane Library Plus, Clinical Trials Registry and HSRPROJ databases. Study selection was based on a series of previously established inclusion criteria related to the study design, population, type of intervention, language, and outcome measures. PATIENTS AND INTERVENTIONS Patients with acute liver failure or acute exacerbations of chronic liver failure treated with the MARS or Prometheus systems. OUTCOME MEASURES Data on safety, long-term survival, clinical effects and biochemical and hemodynamic variables. RESULTS We selected 22 studies evaluating the safety and efficacy of the MARS and Prometheus systems. Adequate evaluation of these techniques was hampered by the heterogeneity of the studies and their methodological limitations. CONCLUSIONS Extracorporeal liver support systems are able to purify both hydrosoluble and protein-bound substances. However, current data show that only the MARS system reduces mortality in acute liver failure and in acute exacerbations of chronic liver failure, although this reduction is non-significant. These techniques can be considered safe, with adverse effects similar to those of the control group. Their main indication is severe liver failure, for short periods while the liver recovers or a liver transplant becomes available.
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Affiliation(s)
- Gerardo Atienza Merino
- Agencia de Evaluación de Tecnologías Sanitarias de Galicia, Consellería de Sanidade, Xunta de Galicia, Galicia, España.
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Mumtaz K, Azam Z, Hamid S, Abid S, Memon S, Ali Shah H, Jafri W. Role of N-acetylcysteine in adults with non-acetaminophen-induced acute liver failure in a center without the facility of liver transplantation. Hepatol Int 2009; 3:563-570. [PMID: 19727985 PMCID: PMC2790590 DOI: 10.1007/s12072-009-9151-0] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2009] [Revised: 07/20/2009] [Accepted: 08/17/2009] [Indexed: 01/06/2023]
Abstract
PURPOSE We aimed to study the role of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). METHODS A total of 47 adult patients were prospectively enrolled with NAI-ALF (group 1 or NAC group) and oral NAC was given. The primary outcome was reduction in mortality with the use of NAC in NAI-ALF. The secondary outcomes were to evaluate safety of NAC and to assess factors predicting mortality. We compared these results with records of NAI-ALF patients admitted in our hospital from 2000 to 2003 (n = 44) who were not given NAC (group 2 or historical controls). RESULTS The two groups were comparable for the etiology of ALF, prothrombin time (PT), alanine aminotransferase, creatinine, albumin, etc. The mean age in group 1 was 27.7 ± 11.8 years and in group 2 37.5 ± 18.8 years (P = 0.004). Bilirubin was 20.63 ± 11.03 and 14.36 ± 8.90 mg/dl in groups 1 and 2, respectively (P = 0.004). There were 8 (17%) and 1 (2.3%) pregnant ALF women with acute hepatitis E virus (HEV) infection in groups 1 and 2, respectively (P = 0.031). All patients were given supportive care, including mechanical ventilation. A total of 34 (37.36%) patients survived; 22 (47%) in group 1 (NAC group) and 12 (27%) in group 2 (controls) (P = 0.05). On multivariable regression analysis, patients not given NAC (odds ratio [OR] = 10.3, 95% confidence interval [CI] = 1.6-65.7), along with age older than 40 years (OR = 10.3, 95% CI = 2.0-52.5), PT more than 50 s (OR = 15.4, 95% CI = 3.8-62.2), patients requiring mechanical ventilation (OR = 20.1, 95% CI = 3.1-130.2), and interval between jaundice and hepatic encephalopathy (OR = 5.0, 95% CI = 1.3-19.1) were independent predictors of mortality. CONCLUSIONS The use of NAC causes reduction in NAI-ALF mortality and its use was safe.
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Affiliation(s)
- Khalid Mumtaz
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Zahid Azam
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Saeed Hamid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Shahab Abid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Sadik Memon
- Isra University Hospital, Hyderabad, Pakistan
| | - Hasnain Ali Shah
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
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Filho JAR, Nani RS, Carmona MJC, Ballesteros MV, D'Albuquerque LAC. Anestesia para trasplante hepático en hepatitis fulminante. COLOMBIAN JOURNAL OF ANESTHESIOLOGY 2009. [DOI: 10.1016/s0120-3347(09)74010-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
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Kitzberger R, Funk GC, Holzinger U, Miehsler W, Kramer L, Kaider A, Ferenci P, Madl C. Severity of organ failure is an independent predictor of intracranial hypertension in acute liver failure. Clin Gastroenterol Hepatol 2009; 7:1000-1006. [PMID: 19465152 DOI: 10.1016/j.cgh.2009.05.019] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2008] [Revised: 04/05/2009] [Accepted: 05/13/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Ionized ammonia (NH(3)) and partial pressure of the gaseous ammonia (pNH(3)) are associated with hepatic encephalopathy and intracranial hypertension in patients with acute liver failure; NH(3) is also believed to contribute to extrahepatic organ failure. We investigated whether the severity of organ failure was associated with intracranial hypertension and evaluated the correlation between NH(3) and pNH(3) and grade of hepatic encephalopathy. METHODS In 87 patients with acute liver failure admitted to the intensive care unit, we simultaneously evaluated arterial ammonia, pNH(3), clinical grade of hepatic encephalopathy, the sequential organ failure assessment score (SOFA score), and evidence of intracranial hypertension. RESULTS In comparing patients with intracranial hypertension (n = 37) with patients without intracranial hypertension (n = 50), the highest NH(3) and pNH(3) levels and SOFA scores before onset of intracranial hypertension were independent predictors of intracranial hypertension (P < .001). Among patients with NH(3) levels less than 146 mumol/L, those with intracranial hypertension had a higher SOFA score than those without intracranial hypertension (median, 10 vs 5.5; P = .004), despite the patients' similar levels of NH(3). NH(3) (r = 0.68, P < .0001) and pNH(3) (r = 0.78, P < .0001) both correlated with grade of hepatic encephalopathy. However, in multiple regression analysis, only pNH(3) (P < .0001) was shown to be a significant independent parameter for predicting grade of hepatic encephalopathy (P = .27). CONCLUSIONS SOFA score and ammonia levels are independent predictors of intracranial hypertension. In patients with acute liver failure admitted to the intensive care unit, pNH(3) level is a better predictor of clinical grade of hepatic encephalopathy than arterial NH(3) level.
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Affiliation(s)
- Reinhard Kitzberger
- Department of Gastroenterology, Hepatology and Medical Intensive Care Medicine, Medical University Hospital Vienna, Vienna, Austria.
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35
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Tsai MH, Chen YC, Lien JM, Tian YC, Peng YS, Fang JT, Yang C, Tang JH, Chu YY, Chen PC, Wu CS. Hemodynamics and metabolic studies on septic shock in patients with acute liver failure. J Crit Care 2009; 23:468-72. [PMID: 19056008 DOI: 10.1016/j.jcrc.2008.04.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2007] [Revised: 01/30/2008] [Accepted: 04/07/2008] [Indexed: 01/09/2023]
Abstract
BACKGROUND Acute liver failure is often accompanied by hyperdynamic circulation, which is also a characteristic of septic shock. Pre-existing acute liver failure may worsen the hemodynamic impairment and prognosis in sepsis. AIMS To evaluate the hemodynamic and metabolic characteristics and clinical outcomes of septic shock in patients with acute liver failure. METHODS Twenty patients with acute liver failure and 19 patients without preexisting liver disease were evaluated. Systemic hemodynamics, arterial and mixed vein blood gases, arterial lactate levels, plasma renin activity, and plasma aldosterone levels were checked during the early phase of septic shock. RESULTS In acute liver failure group, cardiac index (4.92 +/- 1.13 vs 3.69 +/- 1.06 L/min per square meter, P < .001) and oxygen delivery (604.7 +/- 139.7 vs 485.4 +/- 137.3 mL/min per square meter, P = .011) were significantly higher than those without preexisting liver diseases, while systemic vascular resistance index (1041.2 +/- 503.3 vs 1409 +/- 505.25 dyne.s/cm(5).m(2)), oxygen consumption (119.1 +/- 29.2 vs 162.4 +/- 49.4 mL/min per square meter) and oxygen extraction ratio (20% +/- 6% vs. 32% +/- 8%) were significantly higher in the latter group. Furthermore, the patients with acute liver failure had higher arterial lactate (P = .026), plasma renin activity (P = .03), plasma aldosterone levels (P < .001), and intensive care unit as well as hospital mortality rates (P = .005, and 0.02 respectively). CONCLUSIONS In patients with acute liver failure, septic shock was characterized by an accentuated hyperdynamic circulation, hyperlactatemia and an augmented renin-angiotensin-aldosterone system activity. Pre-existing liver failure has a significant impact on the disease severity of septic shock and portends a grave prognosis.
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Affiliation(s)
- Ming-Hung Tsai
- Division of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Taipei 105, Taiwan
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Kumar A, Das K, Sharma P, Mehta V, Sharma BC, Sarin SK. Hemodynamic studies in acute-on-chronic liver failure. Dig Dis Sci 2009; 54:869-78. [PMID: 18688717 DOI: 10.1007/s10620-008-0421-9] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2007] [Accepted: 06/25/2008] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with decompensated cirrhosis and acute liver failure have circulatory dysfunctions leading to high portal pressure and cardiac output (CO) and low systemic vascular resistance (SVR). Circulatory changes in acute-on-chronic liver failure (ACLF) patients have not been studied. We studied the portal, systemic, and pulmonary hemodynamics in patients with ACLF and compared them with compensated and decompensated cirrhotics. PATIENTS AND METHODS Clinical features and hemodynamic profile were studied in patients with ACLF and compared with age- and sex-matched compensated and decompensated cirrhotics with portal hypertension. RESULTS The study cohort comprised 144 patients categorized into one of three groups (ACLF, compensated cirrhosis, and decompensated cirrhosis), with 48 (33%) patients in each group. All values are given as the mean +/- standard deviation, except for frequencies (%). The mean arterial pressure (MAP) and SVR were lower in the ACLF than the compensated group and were similar to those of the decompensated group (MAP 90 +/- 16 vs. 99 +/- 15 vs. 96 +/- 16 mmHg; SVR 912 +/- 435 vs. 1350 +/- 449 vs. 891 +/- 333 dyn s/cm(5)). The mean CO of the ACLF patients was higher than that of the compensated group and similar to that of the decompensated group (CO 8.9 +/- 3.5 vs. 6.1 +/- 1.7 vs. 9.0 +/- 3.0 l/min). The pulmonary vascular resistance (PVR) and pulmonary capillary wedge pressures (PCWP) were similar in all the three groups (PVR 78 +/- 48 vs. 109 +/- 70 vs. 61 +/- 47 dyn s/cm(5); PCWP 8 +/- 4 vs. 8 +/- 4 vs. 10 +/- 5 mmHg). The mean hepatic venous pressure gradient (HVPG) in the ACLF group was 15.1 +/- 6.3 mmHg, which was significantly higher than that of the compensated group (11.7 +/- 6.3 mmHg), but lower than that of the decompensated cirrhosis group (20.2 +/- 6.0 mmHg). When patients of ACLF were categorized on the basis of their variceal size, the mean HVPG in ACLF patients with small varices was similar to that of compensated cirrhotics (13.7 +/- 5.7 vs. 11.7 +/- 6.3 mmHg; P = 0.146), while in the ACLF patients with large varices, the HVPG was comparable to that of the decompensated cirrhotics (18.7 +/- 6.6 vs. 20.2 +/- 6.0 mmHg; P = 0.442). CONCLUSIONS The systemic hemodynamics in patients with ACLF is similar to that in decompensated cirrhotics. The portal pressure in these patients is higher than that in the compensated cirrhotics, and in the subgroup with large varices, it becomes similar to that of decompensated cirrhotics.
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Affiliation(s)
- Ashish Kumar
- Department of Gastroenterology, G B Pant Hospital, New Delhi, India.
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Bjerring PN, Eefsen M, Hansen BA, Larsen FS. The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema. Metab Brain Dis 2009; 24:5-14. [PMID: 19050999 DOI: 10.1007/s11011-008-9116-3] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2008] [Accepted: 10/28/2008] [Indexed: 12/01/2022]
Abstract
Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has been extensively studied and although the development of cerebral edema and ICH is of a complex and multifactorial nature, it is well established that ammonia plays a pivotal role. This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress, inflammation and regulation of cerebral blood flow. Finally, potential therapeutic targets and future perspectives are briefly discussed.
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Affiliation(s)
- Peter Nissen Bjerring
- Dept. Hepatology, section A-2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
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38
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Gerlach JC, Zeilinger K, Patzer II JF. Bioartificial liver systems: why, what, whither? Regen Med 2008; 3:575-95. [DOI: 10.2217/17460751.3.4.575] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Acute liver disease is a life-threatening condition for which liver transplantation is the only recognized effective therapy. While etiology varies considerably, the clinical course of acute liver failure is common among the etiologies: encephalopathy progressing toward coma and multiple organ failure. Detoxification processes, such as molecular adsorbent recirculating system (MARS®) and Prometheus, have had limited success in altering blood chemistries positively in clinical evaluations, but have not been shown to be clinically effective with regard to patient survival or other clinical outcomes in any Phase III prospective, randomized trial. Bioartificial liver systems, which use liver cells (hepatocytes) to provide metabolic support as well as detoxification, have shown promising results in early clinical evaluations, but again have not demonstrated clinical significance in any Phase III prospective, randomized trial. Cell transplantation therapy has had limited success but is not practicable for wide use owing to a lack of cells (whole-organ transplantation has priority). New approaches in regenerative medicine for treatment of liver disease need to be directed toward providing a functional cell source, expandable in large quantities, for use in various applications. To this end, a novel bioreactor design is described that closely mimics the native liver cell environment and is easily scaled from microscopic (<1 ml cells) to clinical (∼600 ml cells) size, while maintaining the same local cell environment throughout the bioreactor. The bioreactor is used for study of primary liver cell isolates, liver-derived cell lines and stem/progenitor cells.
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Affiliation(s)
- Jörg C Gerlach
- Departments of Surgery & Bioengineering, McGowan Institute for Regenerative Medicine, Bridgeside Point Bldg., 100 Technology Drive, Suite 225, Pittsburgh, PA 15219-3130, USA
- Charite - Campus Virchow, Humboldt University Berlin, Germany
| | | | - John F Patzer II
- Departments of Bioengineering, Chemical Engineering & Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA
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Pugliese F, Novelli G, Poli L, Levi Sandri GB, Di Folco G, Ferretti S, Morabito V, Ruberto F, Berloco PB. Hemodynamic improvement as an additional parameter to evaluate the safety and tolerability of the molecular adsorbent recirculating system in liver failure patients. Transplant Proc 2008; 40:1925-1928. [PMID: 18675091 DOI: 10.1016/j.transproceed.2008.05.077] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND The molecular adsorbent recirculating system (MARS) is an extracorporeal acute liver failure (ALF) support system method using albumin-enriched dialysate to remove albumin-bound toxins. PATIENTS AND METHODS Since 1999 we performed 2027 MARS treatments in 191 patients: 39 fulminant hepatic failure (FHF), 16 primary nonfunction (PNF), 21 delayed function (DF), 94 acute-on-chronic liver failure (AoCHF), 7 post-hepatic resection, and 14 intractable pruritus. RESULTS We divided the complications by the AoCHF versus the ALF populations. Among 83 ALF patients, we observed worsening of hemodynamic parameters in 16 patients: 3 with PNF, 2 with DF without retransplantation, 9 with FHF, and 2 after hepatic resection. Among 94 AoCHF patients, 42 showed hemodynamic instability requiring intensive care unit support. Our study did not note significant adverse effects (1.8%), except for infections and hemorrhage from the central venous catheter not due to MARS treatment. The thrombocytopenia was controlled through administration of platelets before the start of treatment when a patient showed a level under 30,000 mm(3). CONCLUSION Our results confirmed that nonbiological hepatic support by MARS was safe and tolerable.
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Affiliation(s)
- F Pugliese
- Scienze Anestesiologiche, Medicina Critica e Terapia del Dolore, La Sapienza Università di Roma, Rome, Italy
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40
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Novelli G, Rossi M, Morabito V, Pugliese F, Ruberto F, Perrella SM, Novelli S, Spoletini G, Ferretti G, Mennini G, Berloco PB. Pediatric acute liver failure with molecular adsorbent recirculating system treatment. Transplant Proc 2008; 40:1921-1924. [PMID: 18675090 DOI: 10.1016/j.transproceed.2008.05.075] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND The prognosis of pediatric acute liver failure (PALF) has been significantly improved by emergency orthotopic liver transplantation (OLT). Since 2004, the molecular adsorbent recirculating system (MARS) has been proposed as a bridging procedure. The aim of our study was to assess its efficacy in children with PALF. PATIENTS AND METHODS Since 1999 we performed treatment of 39 fulminant hepatic failure (FHF) cases with MARS. Since September 2004 we treated 6 pediatric patients with FHF who were of mean age 10.6 years (range, 3-15 years) including 4 females and 2 males. In 3 cases the cause of FHF was unknown; in 2 cases, it was induced by paracetamol overdose; and in 1, by acute hepatitis B virus. Inclusion criteria were: bilirubin >15 mg/dL; creatinine >or=2 mg/dL; encephalopathy grade >II; and International normalized ratio (INR) >2.5. Other estimated parameters were: AST and ALT serum levels, lactate, and urine volume. Neurological status was monitored using the Glasgow Coma Scale (GCS). Continuous MARS treatment was performed in all patients with a kit change every 8 hours. Intensive care unit (ICU) treatment was applied to optimize regeneration and to prevent cardiovascular complications. RESULTS We observed a significant improvement among levels of bilirubin (P< .009), ammonia (P< .005), creatinine (P< .02), GCS (P< .002), and predictive criteria and as Sequential Organ Failure Assessment (SOFA) and Pediatric End-Stage Liver Disease (PELD). Three children underwent OLT: 1 died after 5 days due to primary nonfunction and 2 children are alive after a median follow-up of 14 months. In 2 children the MARS treatment led to resolution of clinical status without liver transplantation. One child died before OLT due to sepsis and multiorgan failure. CONCLUSIONS We concluded that application of the MARS liver support device in combination with experienced ICU management contributed to improve the clinical status in children with PALF awaiting liver transplantation.
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Affiliation(s)
- G Novelli
- Dipartimento Paride Stefanini Unità di Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Rome, Italy.
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41
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42
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Lautrette A, Liotier J, Deteix P, Souweine B. [Hepatorenal syndrome]. Nephrol Ther 2008; 5:150-6. [PMID: 18514053 DOI: 10.1016/j.nephro.2008.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The hepatorenal syndrome (HRS) is an acute functional renal failure due to renal arterial vasoconstriction occurring in cirrhotic patients with vascular dysfunction. The renal arterial vasoconstriction is the result of diffuse arteriole vasodilatation. There are two types of HRS, which can be differentiated according to the course and the stage of the renal failure; they have a different prognosis. Liver transplantation remains the standard treatment. Maintenance medical therapy is mainly based on vasopressin analogues. The interest of both dialysis and portosystemic intrahepatic shunt techniques remains to be determined. The prognosis of HRS is poor and in the absence of treatment, onset is usually followed by rapid fatal outcome.
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Affiliation(s)
- A Lautrette
- Service de néphrologie et de réanimation médicale, hôpital Gabriel-Montpied, B.P. 69, 63003 Clermont-Ferrand cedex 1, France
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Kantola T, Koivusalo AM, Höckerstedt K, Isoniemi H. The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients. Transpl Int 2008; 21:857-66. [PMID: 18510596 DOI: 10.1111/j.1432-2277.2008.00698.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Acute liver failure (ALF) is a medical emergency. Molecular adsorbent recirculating system (MARS), an artificial liver support system, can partly compensate for the detoxifying function of the liver by removing toxins from blood. To analyze the efficacy of MARS treatment, the outcomes of 113 ALF patients, treated with MARS between 2001 and 2007, were compared with a historical control group of 46 ALF patients treated without MARS between 1995 and 2001. Overall survival of transplanted patients was 94% in the MARS group and 77% in the control group (P=0.06). Without transplantation, survival was 66% and 40% (P=0.03), respectively. However, the etiological distribution of ALF differed significantly between the groups. In ALF patients with unknown etiology, groups were comparable at baseline; 91% and 69% of transplanted patients survived the MARS and control groups and the native liver recovered in 20% and 8% of the patients, respectively. Of the originally nonencephalopathic patients of unknown etiology, 36% underwent liver transplantation in the MARS group compared to 100% in the control group. Interpretation of the results was difficult in toxic etiology patients on account of differing baseline statuses. MARS treatment might partly explain the trend toward increased survival of ALF patients with unknown etiology.
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Affiliation(s)
- Taru Kantola
- Department of Anaesthesiology and Intensive Care Medicine, Surgical Hospital of Helsinki, Helsinki University Hospital, Finland.
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44
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Diagnosis and Management of Liver Failure in the Adult. Crit Care Med 2008. [DOI: 10.1016/b978-032304841-5.50078-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Abstract
Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.
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46
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Eefsen M, Dethloff T, Frederiksen HJ, Hauerberg J, Hansen BA, Larsen FS. Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support. J Hepatol 2007; 47:381-6. [PMID: 17599633 DOI: 10.1016/j.jhep.2007.04.015] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2007] [Revised: 03/27/2007] [Accepted: 04/14/2007] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS Volume expansion and inotropic support with catecholamines are sometimes insufficient to ensure adequate blood pressure and cerebral perfusion in acute liver failure (ALF). The aim of this study was to determine if terlipressin increases cerebral perfusion, cerebral concentration of lactate and intracranial pressure (ICP), and to compare the effect with that of noradrenalin (NA). METHODS Ten patients (median age 42.5 yr; range 15-66; 5 women) who needed inotropic support and had an ICP and a cerebral microdialysis catheter placed had concomitant recording of cerebral perfusion pressure (CPP), cerebral perfusion (using transcranial Doppler sonography (V(mean))) and ICP. Also cerebral extracellular concentration of lactate ([lactate]ec) and pyruvate ([pyruvate]ec) was collected before and after an increase in the NA infusion rate and/or i.v.-injection of 1mg terlipressin. RESULTS Both NA and terlipressin increased CPP and V(mean) (p<0.01). Also ICP increased during NA infusion (p<0.01) but not after terlipressin. The cerebral [lactate]ec decreased after terlipressin injection from 2.34 (1.52-8.38) to 1.99 (0.03-4.83)mmol/l (p=0.027) but not during NA infusion (2.83 (1.53-7.11)mmol/l). The [lactate]ec to [pyruvate]ec ratio remained unchanged in both the NA group (20.7 (13.2-40.0)) and terlipressin group (22.2 (10.5-30.0)). CONCLUSIONS This study shows that terlipressin increases CPP and cerebral perfusion with little influence upon ICP and cerebral [lactate]ec in ALF patients. These findings indicate that terlipressin may be valuable, as an additive treatment to NA infusion to secure brain viability.
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Affiliation(s)
- Martin Eefsen
- Department of Hepatology, A-2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
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Rossi M, Mennini G, Lai Q, Ginanni Corradini S, Drudi F, Pugliese F, Berloco P. Liver transplantation(). J Ultrasound 2007; 10:28-45. [PMID: 23396075 PMCID: PMC3478701 DOI: 10.1016/j.jus.2007.02.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease.The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza).The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center.
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Affiliation(s)
- M. Rossi
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - G. Mennini
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - Q. Lai
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
| | - S. Ginanni Corradini
- Department of Clinical Medicine, Division of Gastroenterology, University “La Sapienza”, Rome, Italy
| | - F.M. Drudi
- Department of Radiology, University “La Sapienza”, Rome, Italy
| | - F. Pugliese
- Department of Anesthesiology, Critical Care Medicine, and the Treatment of Pain, University “La Sapienza”, Rome, Italy
| | - P.B. Berloco
- Department of General Surgery and Transplantation “P. Stefanini”, University “La Sapienza”, Rome, Italy
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48
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Ekse S, Clapp LH, Revhaug A, Ytrebø LM. Endothelium-derived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure. Scand J Gastroenterol 2007; 42:356-65. [PMID: 17354116 DOI: 10.1080/00365520600930636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Acute liver failure (ALF) is hemodynamically characterized by hyperdynamic circulation, but the pathophysiologic mechanisms underlying these disturbances are not known. The purposes of the present experiments were: to study systemic and peripheral hemodynamics in vivo, to measure changes in vascular reactivity in vitro, and to determine the role of endothelium-dependent vasodilator pathways in a well-validated porcine model of ALF. METHODS Landrace pigs (24-29 kg) were allocated to sham operation (n=8) or ALF induced by hepatic devascularization (n=9). Systemic and regional hemodynamics were monitored. Femoral artery rings were prepared for isometric tension recordings 8 h after ALF induction. Contractile responses to phenylephrine were assessed in ring segments of endothelium-intact femoral arteries in the absence or presence of inhibitors of endothelium-derived hyperpolarizing factor, nitric oxide synthase, cyclooxygenase and heme oxygenase pathways. RESULTS Pigs with ALF developed a hyperdynamic circulation. Cardiac index increased (PGT<0.001), while mean arterial pressure (PGT=0.012) and systemic vascular resistance decreased (PGT<0.001) in this group. Femoral artery blood flow decreased in controls, while it remained unchanged in ALF (PGT=0.010). Accordingly, vascular resistance across the hind leg was significantly decreased (PGT<0.001) in ALF. The combination of Ca2+-activated potassium channel inhibitors charybdotoxin and apamin, which block the release of endothelium-derived hyperpolarizing factor, increased the contraction force (ANOVA, PGT=0.05) and Emax (P=0.01) to phenylephrine in ALF. In contrast, inhibitors of nitric oxide synthase, cyclooxygenase and heme oxygenase pathways did not increase isometric contraction force. CONCLUSIONS Endothelium dependent hyperpolarization of vascular smooth muscle contributes to the development of hyperdynamic circulation in ALF.
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MESH Headings
- Analysis of Variance
- Animals
- Apamin/pharmacology
- Biological Factors/metabolism
- Blood Pressure/drug effects
- Cardiac Output/drug effects
- Charybdotoxin/pharmacology
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Endothelium, Vascular/drug effects
- Endothelium, Vascular/metabolism
- Endothelium, Vascular/physiopathology
- Enzyme Inhibitors/pharmacology
- Female
- Femoral Artery/drug effects
- Femoral Artery/metabolism
- Femoral Artery/physiopathology
- Heme Oxygenase (Decyclizing)/drug effects
- Heme Oxygenase (Decyclizing)/metabolism
- Isometric Contraction/drug effects
- Liver Circulation/drug effects
- Liver Failure, Acute/metabolism
- Liver Failure, Acute/physiopathology
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/physiopathology
- Nitric Oxide Synthase/drug effects
- Nitric Oxide Synthase/metabolism
- Phenylephrine/pharmacology
- Potassium Channel Blockers/pharmacology
- Potassium Channels, Calcium-Activated/drug effects
- Potassium Channels, Calcium-Activated/metabolism
- Prostaglandin-Endoperoxide Synthases/drug effects
- Prostaglandin-Endoperoxide Synthases/metabolism
- Swine
- Up-Regulation/drug effects
- Vascular Resistance/drug effects
- Vasoconstriction/drug effects
- Vasoconstrictor Agents/pharmacology
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Affiliation(s)
- Sveinung Ekse
- Department of Anesthesiology and Intensive Care, University of Tromsø, University Hospital Northern Norway, Tromsø, Norway
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Abstract
OBJECTIVE To review the incidence, etiologies, pathophysiology, and treatment of acute liver failure (ALF) in children. Emphasis will be placed on the initial management of the multiple organ system involvement of ALF. METHOD MEDLINE search from 1970 to March 2005 was performed. Search headings were as follows: acute liver failure, fulminant liver failure, pediatric liver failure, hepatic encephalopathy, and liver transplantation. Studies written in English were selected. Pediatric studies were emphasized. Adult studies were referenced if there were no pediatric studies available in regard to a specific aspect of liver failure. CONCLUSIONS Pediatric acute liver failure is a rare but life-threatening disease. The common etiologies differ for given age groups. Management includes treating specific causes and supporting multiple organ system failure. Commonly associated disorders that require initial recognition and treatment include energy production deficiencies (hypoglycemia), coagulation abnormalities, immune system dysfunctions, encephalopathy, and cerebral edema. Criteria used to determine the need for liver transplant are reviewed as well as the difficulties associated with predicting which patients will meet these criteria and how rapidly liver transplant will become the only option. Finally, experimental procedures that may provide additional time for the liver to recover are briefly reported.
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Affiliation(s)
- Joel B Cochran
- Pediatric Department, Medical University of South Carolina, Charleston, SC 29425, USA
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Ytrebø LM, Sen S, Rose C, Davies NA, Nedredal GI, Fuskevaag OM, Ten Have GAM, Prinzen FW, Williams R, Deutz NEP, Jalan R, Revhaug A. Systemic and regional hemodynamics in pigs with acute liver failure and the effect of albumin dialysis. Scand J Gastroenterol 2006; 41:1350-60. [PMID: 17060130 DOI: 10.1080/00365520600714527] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Acute liver failure (ALF) is haemodynamically characterized by a hyperdynamic circulation. The aims of this study were to investigate the systemic and regional haemodynamics in ALF, to measure changes in nitric oxide metabolites (NOx) and to evaluate whether these haemodynamic disturbances could be attenuated with albumin dialysis. MATERIAL AND METHODS Norwegian Landrace pigs (23-30 kg) were randomly allocated to groups as controls (sham-operation, n = 8), ALF (hepatic devascularization, n = 8) and ALF + albumin dialysis (n = 8). Albumin dialysis was started 2 h after ALF induction and continued for 4 h. Systemic and regional haemodynamics were monitored. Creatinine clearance, nitrite/nitrate and catecholamines were measured. A repeated measures ANOVA was used to analyse the data. RESULTS In the ALF group, the cardiac index increased (PGT < 0.0001), while mean arterial pressure (PG = 0.02) and systemic vascular resistance decreased (PGT < 0.0001). Renal resistance (PG = 0.04) and hind-leg resistance (PGT = 0.003) decreased in ALF. There was no difference in jejunal blood flow between the groups. ALF pigs developed renal dysfunction with increased serum creatinine (PGT = 0.002) and decreased creatinine clearance (P = 0.02). Catecholamines were significantly higher in ALF, but NOx levels were not different. Albumin dialysis did not attenuate these haemodynamic or renal disturbances. CONCLUSIONS The haemodynamic disturbances during the early phase of ALF are characterized by progressive systemic vasodilatation with no associated changes in metabolites of NO. Renal vascular resistance decreased and renal dysfunction developed independently of changes in renal blood flow. After 4 h of albumin dialysis there was no attenuation of the haemodynamic or renal disturbances.
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Affiliation(s)
- Lars M Ytrebø
- Department of Digestive Surgery, University Hospital Northern Norway, Tromsø, Norway
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