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Grassin P, Descamps R, Bourgine J, Lubrano J, Fiant AL, Lelong-Boulouard V, Hanouz JL. Safety of perioperative intravenous lidocaine in liver surgery - A pilot study. J Anaesthesiol Clin Pharmacol 2024; 40:242-247. [PMID: 38919445 PMCID: PMC11196064 DOI: 10.4103/joacp.joacp_391_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 05/05/2023] [Accepted: 05/10/2023] [Indexed: 06/27/2024] Open
Abstract
Background and Aims Perioperative lidocaine infusion has many interesting properties such as analgesic effects in the context of enhanced recovery after surgery. However, its use is limited in liver surgery due to its hepatic metabolism. Material and Methods This prospective, monocentric study was conducted from 2020 to 2021. Patients undergoing liver surgery were included. They received a lidocaine infusion protocol until the beginning of hepatic transection (bolus dose of 1.5 mg kg-1, then a continuous infusion of 2 mg kg-1 h-1). Plasma concentrations of lidocaine were measured four times during and after lidocaine infusion. Results Twenty subjects who underwent liver resection were analyzed. There was 35% of preexisting liver disease before tumor diagnosis, and 75% of liver resection was defined as "major hepatectomy." Plasmatic levels of lidocaine were in the therapeutic range. No blood sample showed a concentration above the toxicity threshold: 1.6 (1.3-2.1) μg ml-1 one hour after the start of infusion, 2.5 (1.7-2.8) μg ml-1 at the end of hepatic transection, 1.7 (1.3-2.0) μg ml-1 one hour after the end of infusion, and 1.2 (0.8-1.4) μg ml-1 at the end of surgery. Comparative analysis between the presence of a preexisting liver disease or not and the association of intraoperative vascular clamping or not did not show significant difference concerning lidocaine blood levels. Conclusion Perioperative lidocaine infusion seems safe in the field of liver surgery. Nevertheless, additional prospective studies need to assess the clinical usefulness in terms of analgesia and antitumoral effects.
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Affiliation(s)
- Pierre Grassin
- Department of Anesthesiology and Critical Care, Caen University Hospital, Caen, France
| | - Richard Descamps
- Department of Anesthesiology and Critical Care, Caen University Hospital, Caen, France
| | - Joanna Bourgine
- Department of Pharmacology, Caen University Hospital, Caen, France
| | - Jean Lubrano
- Department of Digestive Surgery, Caen University Hospital, Caen, France
| | - Anne-Lise Fiant
- Department of Anesthesiology and Critical Care, Caen University Hospital, Caen, France
| | | | - Jean-Luc Hanouz
- Department of Anesthesiology and Critical Care, Caen University Hospital, Caen, France
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2
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Jovanović M, Kovačević M, Vezmar-Kovačević S, Palibrk I, Bjelanović J, Miljković B, Vučićević K. Lidocaine clearance as pharmacokinetic parameter of metabolic hepatic activity in patients with impaired liver. J Med Biochem 2023; 42:304-310. [PMID: 36987422 PMCID: PMC10040201 DOI: 10.5937/jomb0-38952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 10/10/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value. METHODS Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters. RESULTS The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after. CONCLUSIONS LID pharmacokinetic parameters consequently changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and volume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery.
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Affiliation(s)
- Marija Jovanović
- University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy, Belgrade
| | - Milena Kovačević
- University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy, Belgrade
| | - Sandra Vezmar-Kovačević
- University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy, Belgrade
| | - Ivan Palibrk
- University Clinical Centre of Serbia, Department for Anesthesia and Reanimation, Section at Clinic for Digestive Surgery, Belgrade
| | - Jasna Bjelanović
- University Clinical Centre of Serbia, Center for Medical Biochemistry, Belgrade
| | - Branislava Miljković
- University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy, Belgrade
| | - Katarina Vučićević
- University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy, Belgrade
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Pooe K, Thulo M, Makumbe H, Akumadu B, Otun O, Aloke C, Achilonu I. Biophysical description of Bromosulfophthalein interaction with the 28-kDa glutathione transferase from Schistosoma japonicum. Mol Biochem Parasitol 2022; 252:111524. [PMID: 36195242 DOI: 10.1016/j.molbiopara.2022.111524] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/12/2022] [Accepted: 09/29/2022] [Indexed: 12/31/2022]
Abstract
Glutathione transferases (GSTs) are major detoxification enzymes vital for the survival and reproduction of schistosomes during infection in humans. Schistosoma encode two GST isoenzymes, the 26- and 28-kDa isoforms, that show different substrate specificities and cellular localisations. Bromosulfophthalein (BSP) has been identified and characterised as a potent 26-kDa Schistosoma japonicum GST (Sj26GST) inhibitor with an anthelmintic potential. This study describes the structure, function, and ligandin properties of the 28-kDa Schistosoma japonicum GST (Sj28GST) towards BSP. Enzyme kinetics show that BSP is a potent enzyme inhibitor, with a specific activity decreases from 60.4 µmol/min/mg to 0.0742 µmol/min/mg and an IC50 in the micromolar range of 0.74 µM. Far-UV circular dichroism confirmed that purified Sj28GST follows a typical GST fold, which is predominantly alpha-helical. Fluorescence spectroscopy suggests that BSP binding occurs at a site distinct from the glutathione-binding site (G-site); however, the binding does not alter the local G-site environment. Isothermal titration calorimetry studies show that the binding of BSP to Sj28GST is exergonic (∆G°= -33 kJ/mol) and enthalpically-driven, with a stoichiometry of one BSP per dimer. The stability of Sj28GST (∆G(H2O) = 4.7 kcal/mol) is notably lower than Sj26GST, owing to differences in the enzyme's dimeric interfaces. We conclude that Sj28GST shares similar biophysical characteristics with Sj26GST based on its kinetic properties and susceptibility to low concentrations of BSP. The study supports the potential benefits of re-purposing BSP as a potential drug or prodrug to mitigate the scourge of schistosomiasis.
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Affiliation(s)
- Kagiso Pooe
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Monare Thulo
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Hattie Makumbe
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Blessing Akumadu
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Oluwatobin Otun
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Chinyere Aloke
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa
| | - Ikechukwu Achilonu
- Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein 2050, Johannesburg, South Africa.
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Devriendt N, Serrano G, Croubels S, Stock E, Vandermeulen E, Paepe D, von Luckner J, de Rooster H. Evaluation of serum lidocaine/monoethylglycylxylidide concentration to assess shunt closure in dogs with extrahepatic portosystemic shunts. J Vet Intern Med 2021; 35:261-268. [PMID: 33432666 PMCID: PMC7848304 DOI: 10.1111/jvim.16030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 12/21/2020] [Accepted: 12/21/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Liver function tests do not always normalize despite successful attenuation of extrahepatic portosystemic shunts (EHPSS). OBJECTIVES Assess the lidocaine/monoethylglycylxylidide (MEGX) test to determine liver perfusion after EHPSS closure. ANIMALS Twenty dogs with EHPSS. METHODS A prospective cohort study was performed and all dogs were tested at diagnosis, 1, 3, and 6 months postoperatively. After collecting a baseline blood sample (T0), 1 mg/kg body weight of lidocaine was injected intravenously. Fifteen (T15) and 30 minutes (T30) later, blood was collected. Plasma concentrations of lidocaine and its metabolites MEGX and glycylxylidide (GX) were determined, using a high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method. Three months postoperatively, transsplenic portal scintigraphy was performed to determine EHPSS closure. RESULTS At T15, median MEGX concentrations were higher in dogs with closed EHPSS compared to diagnosis (33.73 ng/mL [21.11-66.44 ng/mL] vs 13.74 ng/mL [7.25-21.93 ng/mL]; P < .001), but were not different (12.28 ng/mL [10.62-23.17 ng/mL] vs 13.74 ng/mL [7.25-21.93 ng/mL]) in dogs with persistent shunting. Sensitivity to determine shunt closure for MEGX at T15 was 96.2% (95% confidence interval [CI]: 78.4-99.8) and specificity 82.8% (95% CI: 63.5-93.5). CONCLUSIONS AND CLINICAL IMPORTANCE The lidocaine/MEGX test is a promising, rapid, and noninvasive blood test that seems helpful to differentiate dogs with closed EHPSS and dogs with persistent shunting after gradual attenuation.
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Affiliation(s)
- Nausikaa Devriendt
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Gonçalo Serrano
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Siska Croubels
- Laboratory of Pharmacology and Toxicology, Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Emmelie Stock
- Department of Medical Imaging of Domestic Animals and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Eva Vandermeulen
- Department of Medical Imaging of Domestic Animals and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Dominique Paepe
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | | | - Hilde de Rooster
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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Yamamoto Y. Evaluation of Liver Function and the Role of Biliary Drainage before Major Hepatic Resections. Visc Med 2020; 37:10-17. [PMID: 33718480 DOI: 10.1159/000512439] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 10/20/2020] [Indexed: 12/17/2022] Open
Abstract
Background Prevention of posthepatectomy liver failure is a prerequisite for improving the postoperative outcome of perihilar cholangiocarcinoma. From this perspective, appropriate assessment of future liver remnant (FLR) function and the optimized preparation are mandatory. Summary FLR volume ratio using CT volumetry based on 3-dimensional vascular imaging is the current assessment yardstick and is sufficient for assessing a normal liver. However, in a liver with underling parenchymal disease such as fibrosis or prolonged jaundice, weighing up the degree of liver damage against the FLR volume ratio is necessary to know the real FLR function. For this purpose, the indocyanine green (ICG) clearance test, monoethylglycinexylidide (MEGX) test, liver maximum capacity (LiMAX) test, 99mTc-labeled galactosyl human serum albumin (99mTc-GSA) scintigraphy, albumin-bilirubin (ALBI) grade, and ALPlat (albumin × platelets) criterion are used. After the optimization of FLR function by means of portal vein embolization or associating liver partition and PVL (portal vein ligation) for staged hepatectomy (ALPPS), SPECT scintigraphy with either 99mTc-GSA or 99mTc-mebrofenin compensates for misestimation due to the regional heterogeneity of liver function. The role of preoperative biliary drainage has long been debated, with the associated complications having led to a lack of approval. However, the recent establishment of safety and an improvement in success rates of endoscopic biliary drainage seem to be changing the awareness of the importance of biliary drainage. Key Messages Appropriate selection of an assessment method is of prime importance to predict the FLR function according to the preoperative condition of the liver. Preoperative biliary drainage in patients with perihilar cholangiocarcinoma is gaining support due to the increasing safety and success rate, especially in patients who need optimization of their liver function before hepatectomy.
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Affiliation(s)
- Yuzo Yamamoto
- Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, Japan
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Shen YN, Zheng ML, Guo CX, Bai XL, Pan Y, Yao WY, Liang TB. The role of imaging in prediction of post-hepatectomy liver failure. Clin Imaging 2018; 52:137-145. [PMID: 30059953 DOI: 10.1016/j.clinimag.2018.07.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 07/11/2018] [Accepted: 07/23/2018] [Indexed: 02/08/2023]
Abstract
Post-hepatectomy liver failure (PHLF) is not only a leading cause of mortality but also a leading cause of life-threatening complications in patients undergoing liver resection. The ability to accurately detect the emergence of PHLF represents a crucially important step. Currently, PHLF can be predicted by a comprehensive evaluation of biological, clinical, and anatomical parameters. With the development of new technologies, imaging methods including elastography, diffusion-weighted magnetic resonance imaging, and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI play a more significant role in the pre-operative prediction and assessment of PHLF. In this review, we summarize the mainstream studies, with the aim of evaluating the role of imaging and improving the clinical value of existing scoring systems for predicting PHLF.
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Affiliation(s)
- Yi-Nan Shen
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Meng-Lin Zheng
- Department of Ultrasound, Huashan Hospital of Fudan University, Shanghai, China
| | - Cheng-Xiang Guo
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Xue-Li Bai
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Yao Pan
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wei-Yun Yao
- Department of General Surgery, The People's Hospital of Changxing County, Huzhou, China
| | - Ting-Bo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
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Ye F, Zhan H, Shi G. Design of liver functional reserve monitor based on three-wavelength from red light to IR. Technol Health Care 2018; 26:521-529. [PMID: 29758975 PMCID: PMC6004968 DOI: 10.3233/thc-174843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND The preoperative evaluation of liver functional reserve is very important to determine the excision of liver lobe for the patients with liver cancer. There already exist many effective evaluation methods, but these ones have many disadvantages such as large trauma, complicated process and so on. OBJECTIVE Therefore, it is essential to develop a fast, accurate and simple detection method of liver functional reserve for the practical application in the clinical engineering field. METHODS According to the principle of spectrophotometry, this paper proposes a detection method of liver functional reserve based on three-wavelength from red light to infrared light (IR), in which the artery pulse, the vein pulse and the move of tissue are taken into account. RESULTS By using photoelectric sensor technology and excreting experiment of indocyanine green, a minimally invasive, fast and simple testing equipment is designed in this paper. CONCLUSIONS The testing result shows this equipment can greatly reduce the interference from human body and ambient, realize continuous and real-time detection of arterial degree of blood oxygen saturation and liver functional reserve.
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Affiliation(s)
- Fuli Ye
- School of Biomedical Engineering, Hubei University of Science and Technology, Xianning 437100, Hubei, China
| | - Huimiao Zhan
- School of Biomedical Engineering, Hubei University of Science and Technology, Xianning 437100, Hubei, China
| | - Guilian Shi
- School of Biomedical Engineering, Hubei University of Science and Technology, Xianning 437100, Hubei, China
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Abstract
BACKGROUND With the recent advances in oncological hepatic surgery, major liver resections became more widely utilized procedures. The era of modern hepatic surgery witnessed improvements in patients care in preoperative, intraoperative and postoperative aspects. This significantly improved surgical outcomes regarding morbidity and mortality. This review article focuses on the recent advances in oncological hepatic surgery. DATA SOURCES This review includes only data from peer-reviewed articles and journals. PubMed database was utilized as the primary source of the supporting literature to this review article on the latest advances in oncological hepatic surgery. Comprehensive and high sensitivity search strategies were performed to search related studies exhaustively up till June 2016. We critically and independently assessed over 50 recent publications written on this topic according to the selection criteria and quality assessment standard. We paid particular attention to the studies published in high impact journals that address the use of the surgical techniques mentioned in the articles in well-known institutions. RESULTS Among all utilized approaches aiming at the preoperative assessment of the liver function, Child-Turcotte-Pugh classification remains the most reliable tool correlating with survival outcome. Although the primary radiological tools including ultrasonography, computed tomography and magnetic resonance imaging remain on top of the menu of tests utilized in assessment of focal hepatic lesions, intraoperative ultrasonography projects to be a powerful additional tool in terms of sensitivity and specificity compared to the other conventional techniques in assessment of the liver in the operative setting, a procedure that can change the surgical strategy in 27.2% of the cases and consequently improve the oncological surgical outcome. In addition to the conventional surgical techniques of liver resection and portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy "ALPPS" projects to be an alternative option in patients with marginally resectable tumors with an inadequate size of future liver remnant with an accepted surgical oncological outcome. CONCLUSIONS Considering the clinicopathological nature of hepatic lesions, the comprehensive assessment and proper choice of the liver resection technique in highly selected patients is associated with improved surgical oncological outcome. Patients with underlying marginal future liver remnant volumes can now safely benefit from a wider range of surgical intervention, a breakthrough that significantly improved morbidity and mortality in this group of patients.
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Affiliation(s)
- Ahmed I Salem
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue BX7375 CLINICAL SCIENCE CNTR Madison, WI 53792-7375, USA.
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Stravitz RT, Ilan Y. Potential use of metabolic breath tests to assess liver disease and prognosis: has the time arrived for routine use in the clinic? Liver Int 2017; 37:328-336. [PMID: 27718326 DOI: 10.1111/liv.13268] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 09/23/2016] [Indexed: 02/13/2023]
Abstract
The progression of liver disease may be unique among organ system diseases in that progressive fibrosis compromises not only the sufficiency of hepatocyte mass but also impairs blood flow to the liver, resulting in porto-systemic shunting. Although liver biopsy as an assessment of fibrosis has become the key biomarker of and target for new therapies, it is invasive and subject to sampling error, and cannot quantify metabolic function or porto-systemic shunting. Measurement of the hepatic venous pressure gradient accommodates some of the deficiencies of biopsy but requires expertise not widely available and misses minor changes in hepatocellular mass and thereby information about metabolic function. Thus, an unmet need in clinical hepatology remains unfulfilled: a noninvasive biomarker which quantitates both the hepatocellular insufficiency and porto-systemic shunting inherent in progressive hepatic fibrosis. Ideally, such a biomarker should correlate with clinical endpoints including liver-related survival and cirrhotic complications, be performed at the point-of-care, and be affordable and easy to use. This review, an expert opinion, summarizes background and recent data suggesting that metabolic breath tests may now meet these requirements and have a valid place in clinical hepatology to supplant the time-honoured assessment of hepatic fibrosis.
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Affiliation(s)
- R Todd Stravitz
- Section of Hepatology, Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA, USA
| | - Yaron Ilan
- Gastroenterology and liver Units, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
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Postoperative Liver Failure. GI SURGERY ANNUAL 2017. [PMCID: PMC7123164 DOI: 10.1007/978-981-10-2678-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Technical innovations in surgical techniques, anaesthesia, critical care and a spatial understanding of the intra-hepatic anatomy of the liver, have led to an increasing number of liver resections being performed all over the world. However, the number of complications directly attributed to the procedure and leading to inadequate or poor hepatic functional status in the postoperative period remains a matter of concern. There has always been a problem of arriving at a consensus in the definition of the term: postoperative liver failure (PLF). The burgeoning rate of living donor liver transplants, with lives of perfectly healthy donors involved, has mandated a consensual definition, uniform diagnosis and protocol for management of PLF. The absence of a uniform definition has led to poor comparison among various trials. PLF remains a dreaded complication in resection of the liver, with a reported incidence of up to 8 % [1], and mortality rates of up to 30–70 % have been quoted [2]. Several studies have quoted a lower incidence of PLF in eastern countries, but when it occurs the mortality is as high as in the West [3].
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Postoperative day one serum alanine aminotransferase does not predict patient morbidity and mortality after elective liver resection in non-cirrhotic patients. Hepatobiliary Pancreat Dis Int 2016; 15:655-659. [PMID: 27919856 DOI: 10.1016/s1499-3872(16)60090-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Serum aminotransferases have been used as surrogate markers for liver ischemia-reperfusion injury that follows liver surgery. Some studies have suggested that rises in serum alanine aminotransferase (ALT) correlate with patient outcome after liver resection. We assessed whether postoperative day 1 (POD 1) ALT could be used to predict patient morbidity and mortality following liver resection. We reviewed our prospectively held database and included consecutive adult patients undergoing elective liver resection in our institution between January 2013 and December 2014. Primary outcome assessed was correlation of POD 1 ALT with patient's morbidity and mortality. We also assessed whether concurrent radiofrequency ablation, neoadjuvant chemotherapy and use of the Pringle maneuver significantly affected the level of POD 1 ALT. A total of 110 liver resections were included in the study. The overall in-hospital patient morbidity and mortality were 31.8% and 0.9%, respectively. The median level of POD 1 ALT was 275 IU/L. No correlation was found between POD 1 serum ALT levels and patient morbidity after elective liver resection, whilst correlation with mortality was not possible because of the low number of mortalities. Patients undergoing concurrent radiofrequency ablation were noted to have an increased level of POD 1 serum ALT but not those given neoadjuvant chemotherapy and those in whom the Pringle maneuver was used. Our study demonstrates POD 1 serum ALT does not correlate with patient morbidity after elective liver resection.
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Golriz M, Majlesara A, El Sakka S, Ashrafi M, Arwin J, Fard N, Raisi H, Edalatpour A, Mehrabi A. Small for Size and Flow (SFSF) syndrome: An alternative description for posthepatectomy liver failure. Clin Res Hepatol Gastroenterol 2016; 40:267-275. [PMID: 26516057 DOI: 10.1016/j.clinre.2015.06.024] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 05/29/2015] [Accepted: 06/08/2015] [Indexed: 02/07/2023]
Abstract
Small for Size Syndrome (SFSS) syndrome is a recognizable clinical syndrome occurring in the presence of a reduced mass of liver, which is insufficient to maintain normal liver function. A definition has yet to be fully clarified, but it is a common clinical syndrome following partial liver transplantation and extended hepatectomy, which is characterized by postoperative liver dysfunction with prolonged cholestasis and coagulopathy, portal hypertension, and ascites. So far, this syndrome has been discussed with focus on the remnant size of the liver after partial liver transplantation or extended hepatectomy. However, the current viewpoints believe that the excessive flow of portal vein for the volume of the liver parenchyma leads to over-pressure, sinusoidal endothelial damages and haemorrhage. The new hypothesis declares that in both extended hepatectomy and partial liver transplantation, progression of Small for Size Syndrome is not determined only by the "size" of the liver graft or remnant, but by the hemodynamic parameters of the hepatic circulation, especially portal vein flow. Therefore, we suggest the term "Small for Size and Flow (SFSF)" for this syndrome. We believe that it is important for liver surgeons to know the pathogenesis and manifestation of this syndrome to react early enough preventing non-reversible tissue damages.
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Affiliation(s)
- Mohammad Golriz
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ali Majlesara
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Saroa El Sakka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Maryam Ashrafi
- Department of Nephrology, University of Heidelberg, Heidelberg, Germany
| | - Jalal Arwin
- Department of Gynecology, University of Heidelberg, Heidelberg, Germany
| | - Nassim Fard
- Department of Radiology, University of Heidelberg, Heidelberg, Germany
| | - Hanna Raisi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arman Edalatpour
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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Feng YH, Hu XD, Zhai L, Liu JB, Qiu LY, Zu Y, Liang S, Gui Y, Qian LX. Shear wave elastography results correlate with liver fibrosis histology and liver function reserve. World J Gastroenterol 2016; 22:4338-4344. [PMID: 27158202 PMCID: PMC4853691 DOI: 10.3748/wjg.v22.i17.4338] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 01/25/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve.
METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient.
RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032).
CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.
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Saluti G, Giusepponi D, Moretti S, Di Salvo A, Galarini R. Flexible Method for Analysis of Lidocaine and Its Metabolite in Biological Fluids. J Chromatogr Sci 2016; 54:1193-200. [DOI: 10.1093/chromsci/bmw051] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Indexed: 11/14/2022]
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Defining Post Hepatectomy Liver Insufficiency: Where do We stand? J Gastrointest Surg 2015; 19:2079-92. [PMID: 26063080 DOI: 10.1007/s11605-015-2872-6] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 06/02/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) is a major source of morbidity and mortality in patients undergoing liver resection. The aim of this review is to summarize the recent literature available on PHLF including its definition, predictive factors, preoperative risk assessment, severity grading, preventative measures, and management strategies. METHODS A systematic literature search was carried out with the search engines PubMed, Medline, and Cochrane Database using the keywords related to "liver failure", "posthepatectomy", and "hepatic resection". RESULTS Liver resection is a curative treatment of liver tumors. However, it leads to concurrent death and regeneration of the remaining hepatocytes. Factors related to the patient, liver parenchyma and the extent of surgery can inhibit regeneration leading to PHLF. CONCLUSION Given its resistance to treatment and the high postoperative mortality associated with PHLF, great effort has been put in to both accurately identify patients at high risk and to develop strategies that can help prevent its occurrence.
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16
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Abstract
PURPOSE OF REVIEW It is our opinion that there is an unmet need in hepatology for a minimally or noninvasive test of liver function and physiology. Quantitative liver function tests define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high-affinity hepatic transporters exhibit high 'first-pass' hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. RECENT FINDINGS We highlight one quantitative liver function test, the dual cholate test, and introduce the concept of a disease severity index linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. SUMMARY It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.
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Pugalenthi A, Cutter CS, Fong Y. Current treatment for small (< 5 cm) hepatocellular carcinoma: evolving roles for ablation and resection. Adv Surg 2014; 48:97-114. [PMID: 25293610 DOI: 10.1016/j.yasu.2014.05.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Serenari M, Cescon M, Cucchetti A, Pinna AD. Liver function impairment in liver transplantation and after extended hepatectomy. World J Gastroenterol 2013; 19:7922-7929. [PMID: 24307786 PMCID: PMC3848140 DOI: 10.3748/wjg.v19.i44.7922] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 10/03/2013] [Accepted: 10/14/2013] [Indexed: 02/06/2023] Open
Abstract
Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to a pattern of clinical manifestations, namely “post-hepatectomy liver failure” and “small-for-size syndrome” respectively, that can range from mild cholestasis to irreversible organ non-function and death of the patient. Many mechanisms are involved in their occurrence but in the recent past, high portal blood flow through a relatively small liver vascular bed has taken a central role. Therefore, several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation, such as portocaval shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic artery. However, high portal flow is not the only factor responsible, and before major liver resections, preoperative assessment of the residual liver function is necessary. Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume, preventing post-hepatectomy liver failure. More recently, a new surgical procedure, that combines in situ splitting of the liver and portal vein ligation, has gradually come to light, inducing remarkable hypertrophy of the healthy liver in just a few days. Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.
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Abstract
The author draws attention on the importance surgical risk analysis from patient's safety point of view. Recently the development in quality assurance affected surgical practice as well, hence determination and evaluation of surgical risk are more exactly defined. This resulted in a significant decrease in mortality during surgical interventions on the liver despite a wider indication and increased numbers, recently. Importantly, surgical risk is much higher in patients with liver disease compared to patients with normal liver. The risk of surgical interventions for liver diseases (HCC, tumor) in patients with diffuse liver diseases (cirrhosis, chronic hepatitis, ALD) can be expressed numerically. For many years the Child-Turcotte-Pugh stadium could have been determined by using actual laboratory values. Recently the "50-50 rule" or more frequently the MELD score -- originally used in the practice of liver transplantation -- mean objective expression of surgical risk. Treatment optimalisation can reduce surgical risk, selected on the basis of risk analysis in multidisciplinary settings, which focus on the need of liver surgeons.
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Affiliation(s)
- Ferenc Jakab
- Uzsoki Utcai Kórház, 1145 Budapest, Uzsoki u. 29-41.
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20
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Chen X, Zhai J, Cai X, Zhang Y, Wei L, Shi L, Wu D, Shen F, Lau WY, Wu M. Severity of portal hypertension and prediction of postoperative liver failure after liver resection in patients with Child–Pugh grade A cirrhosis. Br J Surg 2012; 99:1701-10. [PMID: 23132418 DOI: 10.1002/bjs.8951] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Abstract
Background
Patients with Child–Pugh grade A cirrhosis and clinical evidence of portal hypertension are likely to develop posthepatectomy liver failure (PHLF). Whether such patients are suitable candidates for partial hepatectomy is controversial. This study explored the impact of portal venous pressure (PVP) on PHLF and the possibility of stratifying patients with Child–Pugh grade A cirrhosis for risk of PHLF using clinical data alone.
Methods
Between April 2009 and May 2011, consecutive patients who underwent partial hepatectomy for hepatocellular carcinoma and intraoperative measurement of PVP were included in this prospective study. Using signs of clinically significant portal hypertension (CSPH), patients with Child–Pugh grade A cirrhosis were subclassified into three groups: no, mild and severe CSPH. Risk factors for PHLF were subjected to univariable and multivariable analysis, and receiver operating characteristic (ROC) curve analysis.
Results
Sixty-seven (35·3 per cent) of 190 patients developed PHLF, which was persistent in 12 patients (6·3 per cent). Four patients (2·1 per cent) died from PHLF within 3 months of surgery. Multivariable analysis showed both PVP and CSPH to be independent predictors of PHLF (P < 0·001). PVP values, incidence of PHLF and persistent PHLF were significantly higher in the severe CSPH group than in the other two groups (P < 0·001). Severe CSPH (odds ratio 27·68, P = 0·005) and a preoperative neutrophil : lymphocyte ratio (NLR) of 2·8 or above (odds ratio 49·75, P = 0·002) were independent factors affecting the incidence of persistent PHLF.
Conclusion
The severity of CSPH, corresponding to different PVP levels, could be used to stratify patients with Child-Pugh grade A cirrhosis and to predict the incidence of PHLF. Patients with severe CSPH or a NLR of 2·8 or above were more likely to develop persistent PHLF after partial hepatectomy.
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Affiliation(s)
- X Chen
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- School of Graduation, Soochow University, Suzhou, Hong Kong, China
| | - J Zhai
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - X Cai
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Y Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - L Wei
- Tumour Immunology and Gene Therapy Centre, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - L Shi
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - D Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - F Shen
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - W-Y Lau
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - M Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- National Scientific Centre for Liver Cancer, Shanghai, China
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21
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Grazi GL. Liver resections: complications and survival outcome. Expert Rev Pharmacoecon Outcomes Res 2012; 7:269-79. [PMID: 20528313 DOI: 10.1586/14737167.7.3.269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Today, liver resection represents one of the most effective therapies in the treatment of defined liver diseases, particularly for hepatocellular carcinomas, liver metastases and tumors originating from the bile ducts. There have been a number of improvements in the technique but the use of kellyclasia associated with meticulous control of hemostasis and biliostasis appears to be more effective and efficient. The procedure is still burdened with some postoperative complications, the more characteristic of which are liver insufficiency, biliary leakage and ascites. Several neoplastic diseases, both primitive and secondary, can benefit from this therapy with substantial improvement of long-term survival, and a notable change in the natural history of the disease. For these situations, a consultation should always be performed by a surgeon experienced in hepatic surgery.
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Affiliation(s)
- Gian Luca Grazi
- Associate Professor of General Surgery, University of Bologna, Liver & Multi Organ Transplant Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy. ; www.liversurgery.info
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Filicori F, Keutgen XM, Zanello M, Ercolani G, Di Saverio S, Sacchetti F, Pinna AD, Grazi GL. Prognostic criteria for postoperative mortality in 170 patients undergoing major right hepatectomy. Hepatobiliary Pancreat Dis Int 2012; 11:507-12. [PMID: 23060396 DOI: 10.1016/s1499-3872(12)60215-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Postoperative hepatic failure is a dreadful complication after major hepatectomy and carries high morbidity and mortality rates. In this study, we assessed the accuracy of the 50/50 criteria (bilirubin >2.9 mg/dL and international normalized ratio >1.7 on postoperative day 5) and the Mullen criteria (bilirubin peak >7 mg/dL on postoperative days 1-7) in predicting death from hepatic failure in patients undergoing right hepatectomy only. In addition, we identified prognostic factors linked to intra-hospital morbidity and mortality in these patients. METHODS One hundred seventy consecutive patients underwent major right hepatectomy at a tertiary medical center from 2000 to 2008. Nineteen (11.2%) patients suffered from liver cirrhosis. Univariate and multivariate analyses were performed to identify predictors of intra-hospital mortality, morbidity and death from hepatic failure. RESULTS The intra-hospital mortality was 6.5% (11/170). Of the six patients who died from hepatic failure, one was positive for the 50/50 criteria, but all six patients were positive for the Mullen criteria. Multivariate analysis showed that male gender, hepatitis C (HCV), hepatocellular carcinoma, postoperative bilirubin >7 mg/dL and ALT<188 U/L on postoperative day 1 were predictive of death from hepatic failure in the postoperative period. Age >65 years, HCV, reoperation, and renal failure were significant predictors of overall intra-hospital mortality on multivariate analysis. CONCLUSIONS The Mullen criteria were more accurate than the 50/50 criteria in predicting death from hepatic failure in patients undergoing right hepatectomy. A bilirubin peak >7 mg/dL in the postoperative period, HCV positivity, hepatocellular carcinoma, and an ALT level <188 U/L on postoperative day 1 were associated with death from hepatic failure in our patient population.
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Affiliation(s)
- Filippo Filicori
- General Surgery and Transplant Unit, Department of General Surgery and Organ Transplantation, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
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Ben Said D, Ben Ali R, Ferchichi H, Salouage I, Ouanes L, Gaïes E, Trabelsi S, Kooli E, Kourda N, Abdelmoula J, Lakhal M, Klouz A. Lidocaïne test for easier and less time consuming assessment of liver function in several hepatic injury models. Hepatol Int 2011; 5:941-8. [PMID: 21484114 DOI: 10.1007/s12072-011-9270-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2010] [Accepted: 03/06/2011] [Indexed: 01/21/2023]
Abstract
PURPOSE In this study, we developed an ex vivo functional assay to assess liver metabolic capacity adapted from the lidocaïne test in rats. METHODS Animals used were subjected to different models of liver injury: hypothermic ischemia (H/I, n = 8), ischemia-reperfusion (I/R, n = 8) and CCl4 induced liver cirrhosis (n = 11), and compared with sham operated rats (n = 5). Livers were then extracted and a fragment of whole tissue was incubated with lidocaïne for 15, 30, 60, 120, 240, 360, and 720 min at which both lidocaïne and its major metabolite monoethylglycinexylidide (MEGX) were measured by high performance liquid chromatography (HPLC). A histological study and biochemical assays (transaminase levels) were also performed to further evaluate and confirm our data. RESULTS Pharmacokinetic profile of lidocaïne metabolism in sham-operated animals revealed that the maximum concentration of MEGX is achieved at 120 min. Both lidocaïne metabolism and MEGX formation levels were significantly altered in all three models of hepatic injury. The extent of hepatic damage was confirmed by increased levels of transaminase levels and alteration of hepatocyte's structure with areas of necrosis. CONCLUSION Our method provides reliable and reproducible results using only a small portion of liver which allows for a fast and easy assessment of liver metabolic capacity. Moreover, our method presents an alternative to the in vivo technique and seems more feasible in a clinical setting.
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Affiliation(s)
- Dorra Ben Said
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia. .,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia.
| | - Ridha Ben Ali
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Henda Ferchichi
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Issam Salouage
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Lobna Ouanes
- Laboratoire de Physiologie, Faculté de Médecine de Tunis, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Emna Gaïes
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Sameh Trabelsi
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Emna Kooli
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia
| | - Nadia Kourda
- Service Anatomo-pathologie, Hopital Charles Nicolle, Tunis, Tunisia
| | | | - Mohamed Lakhal
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
| | - Anis Klouz
- Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia.,Unité d'expérimentation animale, Faculté de Médecine de Tunis, Tunis, Tunisia
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24
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Abstract
Today, the assessment of liver function in patients suffering from acute or chronic liver disease is based on liver biopsy and blood tests including synthetic function, liver enzymes and viral load, most of which provide only circumstantial evidence as to the degree of hepatic impairment. Most of these tests lack the degree of sensitivity to be useful for follow-up of these patients at the frequency that is needed for decision making in clinical hepatology. Accurate assessment of liver function is essential to determine both short- and long-term prognosis, and for making decisions about liver and non-liver surgery, TIPS, chemoembolization or radiofrequency ablation in patients with chronic liver disease. Liver function tests can serve as the basis for accurate decision-making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled (13) C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method for assessing liver function at the point-of-care. The (13) C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision-making. Our recent findings regarding the ability of point-of-care (13) C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders.
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Affiliation(s)
- Yaron Ilan
- Gastroenterology and Liver Units, Deparent of Medicine, Hadassah Hebrew University Medical Center; Jerusalem, Israel
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25
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de Graaf W, Bennink RJ, Veteläinen R, van Gulik TM. Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation. J Nucl Med 2010; 51:742-52. [PMID: 20395336 DOI: 10.2967/jnumed.109.069435] [Citation(s) in RCA: 120] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
This review describes the application of 2 nuclear imaging techniques for assessment of hepatic function in the setting of liver surgery and transplantation. The biochemical and technical background, as well as the clinical applications, of (99m)Tc-labeled diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) scintigraphy and hepatobiliary scintigraphy (HBS) with (99m)Tc-labeled iminodiacetic acid derivates is discussed. (99m)Tc-mebrofenin is considered the most suitable iminodiacetic acid agent for (99m)Tc-HBS. (99m)Tc-GSA scintigraphy and (99m)Tc-mebrofenin HBS are based on 2 different principles. (99m)Tc-GSA scintigraphy is a receptor-mediated technique whereas HBS represents hepatic uptake and excretion function. Both techniques are noninvasive and provide visual and quantitative information on both total and regional liver function. They can be used for preoperative assessment of future remnant liver function, follow-up after preoperative portal vein embolization, and evaluation of postoperative liver regeneration. In liver transplantation, these methods are used to assess graft function and biliary complications.
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Affiliation(s)
- Wilmar de Graaf
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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Delis SG, Bakoyiannis A, Dervenis C, Tassopoulos N. Perioperative risk assessment for hepatocellular carcinoma by using the MELD score. J Gastrointest Surg 2009; 13:2268-75. [PMID: 19662460 DOI: 10.1007/s11605-009-0977-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2009] [Accepted: 07/21/2009] [Indexed: 01/31/2023]
Abstract
BACKGROUND/AIMS The aim of this study was to evaluate the ability of Model for End-Stage Liver Disease (MELD) in predicting post hepatectomy outcome for hepatocellular carcinoma (HCC). METHODS Between 2001 and 2005, 94 cirrhotic patients with HCC underwent hepatectomy and were analyzed retrospectively. MELD score associated with postoperative mortality and morbidity, hospital stay, and 3-year survival. RESULTS Twenty-eight major and 66 minor resections were performed. Thirty-day mortality rate was 6.4%. MELD <or= 9 was associated with no perioperative mortality vs 15.3% when MELD > 9 (p = 0.01). Overall morbidity rate was 32%; 21% when MELD <or= 9 vs 42% when MELD > 9 (p = 0.01). Median hospital stay was 11 days (7 days, when MELD <or= 9 and 14 days when MELD > 9; p = 0.03). Three-year survival reached 48% (63% when MELD <or= 9; 30% when MELD > 9; p < 0.01). In multivariate analysis, MELD > 9 (p = 0.01), clinical tumor symptoms (p = 0.04), and American Society of Anesthesiologists score (p = 0.04) were independent predictors of perioperative mortality; MELD > 9 (p = 0.01), tumor size >5 cm (p = 0.01), presence of tumor symptoms (p = 0.02), high tumor grade (p = 0.01), and absence of tumor capsule (p = 0.01) were independent predictors of decreased long-term survival. CONCLUSION MELD score seems to predict outcome of cirrhotic patients with HCC after hepatectomy.
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Affiliation(s)
- Spiros G Delis
- Division of Liver and GI Transplantation, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
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Delis SG, Bakoyiannis A, Biliatis I, Athanassiou K, Tassopoulos N, Dervenis C. Model for end-stage liver disease (MELD) score, as a prognostic factor for post-operative morbidity and mortality in cirrhotic patients, undergoing hepatectomy for hepatocellular carcinoma. HPB (Oxford) 2009; 11:351-7. [PMID: 19718364 PMCID: PMC2727090 DOI: 10.1111/j.1477-2574.2009.00067.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2009] [Accepted: 04/01/2009] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS To evaluate the ability of the model for end-stage liver disease (MELD) in predicting the post-hepatectomy outcome for hepatocellular carcinoma (HCC). METHODS Between 2001 and 2004, 69 cirrhotic patients with HCC underwent hepatectomy and the results were retrospectively analysed. MELD score was associated with post-operative mortality and morbidity, hospital stay and 3-year survival. RESULTS Seventeen major and 52 minor resections were performed. Thirty-day mortality rate was 7.2%. MELD < or = 9 was associated with no peri-operative mortality vs. 19% when MELD > 9 (P < 0.02). Overall morbidity rate was 36.23%; 48% when MELD > 9 vs. 25% when MELD < or = 9 (P < 0.02). Median hospital stay was 12 days [8.8 days, when MELD < or = 9 and 15.6 days when MELD > 9 (P = 0.037)]. Three-year survival reached 49% (66% when MELD < or = 9; 32% when MELD > 9 (P < 0.01). In multivariate analysis, MELD > 9 (P < 0.01), clinical tumour symptoms (P < 0.05) and American Society of Anesthesiologists (ASA) score (P < 0.05) were independent predictors of peri-operative mortality; MELD > 9 (P < 0.01), tumour size >5 cm (P < 0.01), high tumour grade (P = 0.01) and absence of tumour capsule (P < 0.01) were independent predictors of decreased long-term survival. CONCLUSION MELD score seems to predict outcome of cirrhotic patients with HCC, after hepatectomy.
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Affiliation(s)
- Spiros G Delis
- Division of Liver and GI Transplantation, University of Miami Miller School of MedicineMiami, FL, USA,Liver surgical unit, 1st Surgical Department, Kostantopouleio-‘Agia Olga’ HospitalAthens, Greece
| | - Andreas Bakoyiannis
- Liver surgical unit, 1st Surgical Department, Kostantopouleio-‘Agia Olga’ HospitalAthens, Greece
| | - Ioannis Biliatis
- Liver surgical unit, 1st Surgical Department, Kostantopouleio-‘Agia Olga’ HospitalAthens, Greece
| | - Konstantinos Athanassiou
- Liver surgical unit, 1st Surgical Department, Kostantopouleio-‘Agia Olga’ HospitalAthens, Greece
| | - Nikos Tassopoulos
- First Department of Medicine, Western Attica Gen. HospitalAthens, Greece
| | - Christos Dervenis
- Liver surgical unit, 1st Surgical Department, Kostantopouleio-‘Agia Olga’ HospitalAthens, Greece
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Quantitative assessment of hepatic function and its relevance to the liver surgeon. J Gastrointest Surg 2009; 13:374-85. [PMID: 18622661 DOI: 10.1007/s11605-008-0564-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2008] [Accepted: 06/04/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND Standard evaluation of patients undergoing hepatic surgery has been through radiological and quantitative determination of liver function. As more complex and extensive surgery is now being performed, often in the presence of cirrhosis/fibrosis or following administration of chemotherapy, it is questioned whether additional assessment may be required prior to embarking on such surgery. The aim of this review was to determine the current knowledge base in relation to the performance of quantitative assessment of hepatic function both pre- and post-operatively in patients undergoing hepatic resectional surgery and liver transplantation. METHODS An electronic search was performed of the medical literature using the MEDLINE database to identify relevant articles with cross-referencing of all identified papers to ensure full literature capture. RESULTS AND CONCLUSIONS The review has identified a number of different methods of dynamically assessing hepatic function, the most frequently performed being through the use of indocyanine green clearance. With the recent and further anticipated developments in hepatic resectional surgery, it is likely that quantitative assessment will become more widely practiced in order to reduce post-operative hepatic failure and improve outcome.
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Limquiaco JL, Wong GLH, Wong VWS, Lai PBS, Chan HLY. Evaluation of model for end stage liver disease (MELD)-based systems as prognostic index for hepatocellular carcinoma. J Gastroenterol Hepatol 2009; 24:63-9. [PMID: 19054256 DOI: 10.1111/j.1440-1746.2008.05701.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The Cancer of Liver Italian Program (CLIP) and Japan Integrated Scoring System (JIS) used the Child-Turcotte-Pugh (CTP) score to evaluate the liver function. AIM We aimed to evaluate the performance of Model for End Stage Liver Disease (MELD) based CLIP and JIS to predict the prognosis of hepatocellular carcinoma (HCC). METHODS Consecutive patients with HCC who presented to our Hepatoma Clinic from January 2003 to April 2005 were studied. MELD-based CLIP and JIS were generated by replacing the original CTP score with MELD score at three categories (<10, 10-14 and >14). RESULTS Among 471 HCC patients (85.1% males; aged 58.8 +/- 12.2 years), 73% had chronic hepatitis B, 37.4% had >1 nodule, 84.1% had tumor size >2 cm, 55.0% had Child's B cirrhosis, 12.7% underwent tumor resection and 20.6% received locoregional therapy. The cumulative survival at 3 and 6 months were 67% and 55%, respectively. For 3-month survival, the area under the receiver operating characteristic curves (AUC) of MELD-CLIP (0.69) and MELD-JIS (0.69) were superior to the original systems (0.64, P = 0.004 and 0.64, P = 0.0018, respectively). For 6-month survival, AUC of MELD-CLIP (0.64) and MELD-JIS (0.62) were also superior to the original systems (0.54, P = 0.003 and 0.59, P = 0.002, respectively). The MELD-based systems performed best among patients who received locoregional therapy to HCC. Advanced cirrhosis (hypoalbuminemia, hyperbilirubinemia, ascites, coagulopathy and elevated creatinine), and cancer (portal vein thrombosis, elevated alpha-fetoprotein, large and multiple tumors) were associated with higher mortality. CONCLUSIONS MELD-based systems performed better than Child-Pugh based systems as prognostic indexes for HCC.
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Affiliation(s)
- Jenny L Limquiaco
- Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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31
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Abstract
PURPOSE OF REVIEW This is a review on the techniques for assessing liver function in critically ill patients. RECENT FINDINGS Actually, there is no ideal real-time and bedside technique for assessing liver function in critically ill patients. Though not allowing to differentiate between liver blood flow and cell function, dynamic tests, that is indocyanine green plasma disappearance rate and lidocaine metabolism (monoethylglycinxylidide test), are superior, however, to static tests. Recently, the indocyanine green plasma disappearance rate, which nowadays can be measured reliably by a transcutaneous system in critically ill patients, was confirmed to correlate well with indocyanine green clearance. In general, the indocyanine green plasma disappearance rate is superior to bilirubin, which is still used as a marker of liver function, and comparable or even superior to complex intensive care scoring systems in terms of outcome prediction. Furthermore, indocyanine green plasma disappearance rate is more sensitive than serum enzyme tests for assessing liver dysfunction and early improvement in the indocyanine green plasma disappearance rate after onset of septic shock is associated with better outcome. SUMMARY Since no ideal tool is currently available, dynamic tests such as indocyanine green plasma disappearance rate and monoethylglycinxylidide test may be recommended for assessing liver function in critically ill patients. The indocyanine green plasma disappearance rate has the advantage, however, of being measurable noninvasively at the bedside and providing results within a few minutes.
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Affiliation(s)
- Samir G Sakka
- Department of Anaesthesiology and Intensive Care Medicine, Friedrich-Schiller-University of Jena, Germany.
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32
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Ercolani G, Cucchetti A, Cescon M, Ravaioli M, Grazi GL, Pinna AD. Predictive indices of morbidity and mortality after liver resection. Ann Surg 2006; 244:635-7; author reply 637. [PMID: 16998379 PMCID: PMC1856548 DOI: 10.1097/01.sla.0000239644.28302.16] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Cucchetti A, Ercolani G, Cescon M, Ravaioli M, Zanello M, Del Gaudio M, Lauro A, Vivarelli M, Grazi GL, Pinna AD. Recovery from liver failure after hepatectomy for hepatocellular carcinoma in cirrhosis: meaning of the model for end-stage liver disease. J Am Coll Surg 2006; 203:670-676. [PMID: 17084328 DOI: 10.1016/j.jamcollsurg.2006.06.018] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2006] [Revised: 06/06/2006] [Accepted: 06/20/2006] [Indexed: 12/25/2022]
Abstract
BACKGROUND Hepatectomy for hepatocellular carcinoma in cirrhosis is followed by an impairment of liver function that can lead to patient death. The model for end-stage liver disease (MELD) is considered an index of hepatic functional reserve, and its assessment on postoperative course may properly identify individuals at risk of liver failure. STUDY DESIGN Two hundred hepatectomies for hepatocellular carcinoma in cirrhosis were reviewed. Irreversible postoperative liver failure was defined as an impairment of liver function after hepatectomy that led to patient death or required transplantation. The MELD scores at postoperative days (POD) 1, 3, 5, and 7 were calculated and kinetics of changes investigated with t-test; logistic regression was applied to identify predictive variables of postoperative liver failure. RESULTS Kinetics of postoperative MELD score showed an impairment of liver function between PODs 1 and 3; 185 patients in whom postoperative liver failure did not develop showed a considerable decrease in MELD score between PODs 3 and 5 (11.9+/-2.8 and 10.6+/-2.4, respectively, p<0.001). On the contrary, 15 patients, who experienced the event, showed an increase in MELD score between PODs 3 and 5 (18.2+/-3.9 and 18.3+/-3.6, respectively; p=0.845). Multivariate analysis showed preoperative MELD score (p<0.001), major hepatectomy (p=0.028), and MELD score increase between PODs 3 and 5 (p=0.011) as independent predictors of irreversible postoperative liver failure. Scores are reported as mean+/-SD. CONCLUSIONS Recovery from liver impairment after hepatectomy for hepatocellular carcinoma in cirrhosis starts from POD 3; MELD scores increasing between PODs 3 and 5 may identify patients at risk of liver failure and represents the trigger for beginning intensive treatment or evaluating salvage transplantation.
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Affiliation(s)
- Alessandro Cucchetti
- Department of Surgery and Transplantation, University of Bologna, Policlinico S Orsola-Malpighi, Bologna, Italy
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Cucchetti A, Ercolani G, Vivarelli M, Cescon M, Ravaioli M, La Barba G, Zanello M, Grazi GL, Pinna AD. Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis. Liver Transpl 2006; 12:966-971. [PMID: 16598792 DOI: 10.1002/lt.20761] [Citation(s) in RCA: 185] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The objective of this study was to predict postoperative liver failure and morbidity after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis. The model for end-stage liver disease (MELD) score is currently accepted as a disease severity index of cirrhotic patients awaiting liver transplantation; however, its impact on prognosis after resection of HCC on cirrhosis has never been investigated. One hundred fifty-four cirrhotic patients resected in a tertiary care setting for HCC were retrospectively analyzed. For each patient, the MELD score was calculated and related to postoperative liver failure and complications (morbidity). Hospital stay and 1-year survival was also investigated. MELD accuracy in predicting postoperative liver failure and morbidity of cirrhotic patients was assessed using receiver operating characteristic (ROC) analysis. Eleven patients (7.1%) experienced postoperative liver failure leading to death or transplantation. ROC analysis identified cirrhotic patients with a MELD score equal to or above 11 at high risk for postoperative liver failure (area under the curve [AUC] = 0.92, 95% confidence interval [CI] = 0.87-0.96; sensitivity = 82%; specificity = 89%). Forty-six patients (29.9%) developed at least 1 postoperative complication: ROC analysis identified patients with a MELD score equal to or above 9 at major risk for postoperative complications (AUC = 0.85, 95% CI = 0.78-0.89; sensitivity = 87%; specificity = 63%). Cirrhotic patients with MELD score below 9 had no postoperative liver failure and low morbidity (8.1%). In conclusion, the MELD score can accurately predict postoperative liver failure and morbidity of cirrhotic patients referred for resection of HCC and should be used to select the best candidates for hepatectomy.
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Affiliation(s)
- Alessandro Cucchetti
- Department of Surgery and Transplantation, University of Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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35
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Mullin EJ, Metcalfe MS, Maddern GJ. How much liver resection is too much? Am J Surg 2005; 190:87-97. [PMID: 15972178 DOI: 10.1016/j.amjsurg.2005.01.043] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2004] [Revised: 12/07/2004] [Accepted: 01/11/2005] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatic failure occurring after liver resection carries a poor prognosis and is a complication dreaded by surgeons. Inadequate reserve in the remaining parenchyma leads to a steady decrease in liver function, inability to regenerate, and progression to liver failure. For this reason, many methods to quantify functional hepatic reserve have been developed. METHODS This article reviews the main methods used in the assessment of hepatic reserve in patients undergoing hepatectomy and their use in operative decision making. RESULTS A range of methods to categorically quantify the functional reserve of the liver have been developed, ranging from scoring systems (such as the Child-Pugh classification) to tests assessing complex hepatic metabolic pathways to radiological methods to assess functional reserve. However, no one method has or is ever likely to emerge as a single measure with which to dictate safe limits of resectability. CONCLUSIONS In the future, the role of residual liver function assessment may be of most benefit in the routine stratification of risk, thus enabling both patient consent to be obtained and surgical procedure to be performed, with full information and facts regarding operative risks. However, there is no one single test that remains conclusively superior.
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Affiliation(s)
- Emma J Mullin
- University of Adelaide, Department of Surgery, The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia
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36
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Emond JC, Samstein B, Renz JF. A critical evaluation of hepatic resection in cirrhosis: optimizing patient selection and outcomes. World J Surg 2005; 29:124-30. [PMID: 15654659 DOI: 10.1007/s00268-004-7633-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatic resection has long been the mainstay of treatment of primary liver cancers, particularly hepatocellular carcinoma (HCC). Because of the high incidence of cirrhosis in patients with HCC, the use of resection was initially limited by the ability of the cirrhotic liver to sustain the surgical insult and the mass reduction. Today, hepatectomy in cirrhosis is undergoing a remarkable evolution. Although surgical and anesthetic improvements have increased the safety of this option, the rapid development of alternative therapies has decreased the need for it. Local excision for small HCC is likely to be replaced by image-guided, percutaneous ablative techniques. Furthermore, total replacement of a cirrhotic liver may be a more effective long-term cure than resection. Unquestionably, resection remains the optimal approach for patients with large tumors and healthy underlying liver function. The role of rapidly evolving new approaches will remain the subject of intensive inquiry in the years to come. In this report, we have attempted to clarify current practice with respect to the evaluation, selection, and technique of resection in cirrhosis, and identify areas of active inquiry.
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Affiliation(s)
- Jean C Emond
- Center for Liver Disease and Transplantation, College of Physicians and Surgeons of Columbia University, 622 West 168th St., Room PH-14C, New York, NY, USA.
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37
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Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world, responsible for 500,000 deaths globally every year. Although HCC is a slow-growing tumor, it is often rapidly fatal because it is usually not discovered until the disease is advanced. HCC occurs primarily in individuals with cirrhosis, a condition that increases the risk of performing potentially curative surgical therapy. Over the last 2 decades, however, the safety of surgical resections has greatly improved because of advances in radiologic assessment, patient selection, and perioperative care. As such, the operative mortality rate for hepatectomy has decreased from the 10%-20% level seen in the 1980s to less than 5% today. The ultimate goal of treatment of HCC is to prolong the quality of life by eradicating the malignancy while preserving hepatic function. For treatment with a curative intent, the gold standard remains surgical resection, by either partial hepatectomy or total hepatectomy followed by liver transplantation. Resectability and choice of procedure depend on many factors, including baseline liver function, absence of extrahepatic metastases, size of residual liver, availability of resources including liver graft, and expertise of the surgical team. Patients without cirrhosis can tolerate extensive resections, and partial hepatectomy should be considered first. For Child class B and C patients with a small HCC, liver transplantation offers the best results, whereas partial liver resection is indicated in patients with well-compensated cirrhosis. Living donor liver transplantation should be considered using the same criteria as that used for cadaveric transplantation.
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Affiliation(s)
- Tae-Jin Song
- College of Medicine, Korea University, Seoul, South Korea
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38
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Abstract
Disturbances of some partial liver functions, such as synthesis, excretion, or biotransformation of xenobiotics, are important for prognosis and ultimate survival in patients presenting with multiple organ dysfunction on the intesive care unit (ICU). The incidence of liver dysfunction is underestimated when traditional "static" measures such as serum-transaminases or bilirubin as opposed to "dynamic" tests, such as clearance tests, are used to diagnose liver dysfunction. Similar to the central role of the failing liver in MODS, extrahepatic complications, such as hepatorenal syndrome and brain edema develop in acute or fulminant hepatic failure and determine the prognosis of the patient. This is reflected in the required presence of hepatic encephalopathy in addition to hyperbilirubinemia and coagulopathy for the diagnosis of acute liver failure. In addition to these clinical signs, dynamic tests, such as indocyanine green clearance, which is available at the bed-side, are useful for the monitoring of perfusion and global liver function. In addition to specific and causal therapeutic interventions, e.g. N-acetylcysteine for paracetamol poisoning or termination of pregnancy for the HELLP-syndrome, new therapeutic measures, e.g. terlipressin/albumin or albumin dialysis are likely to improve the poor prognosis of acute-on-chronic liver failure. Nevertheless, liver transplantation remains the treatment of choice for fulminant hepatic failure when the expected survival is <20%.
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Affiliation(s)
- M Bauer
- Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, Homburg/Saar.
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Matsuyama K, Fukuda Y, Miyake H, Yogita S, Tashiro S. Experimental study of the evaluation of liver function on the opposite side during portacaval anastomosis and ligation of the left portal branch. THE JOURNAL OF MEDICAL INVESTIGATION 2004; 51:84-95. [PMID: 15000261 DOI: 10.2152/jmi.51.84] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Hepatocellular carcinoma is likely to accompany liver cirrhosis in which the portal pressure increases with portasystemic shunt. When portal tumor thrombus is present in the primary bifurcation, blood flow differs between the thrombolic lobe and the non-thrombolic lobe. In those cases, it is difficult to evaluate exactly residual liver function by conventional test. Therefore, the following studies were performed. MATERIALS AND METHODS Adult mongrel dogs are divided into a control group (C group), group undergoing ligation of the left portal branch (PL group), group undergoing portacaval anastomosis (PCS group) and group undergoing both ligation of the left portal branch and portacaval anastomosis (PL+PCSgroup)(n=5). ICG-R15 and MEGX15 in peripheral venous blood and right hepatic venous blood were determined. Mitochondrial metabolic capacity (adenosine triphosphate level, energy charge) was measured by high-performance liquid chromatography using liver biopsied specimens. RESULTS The MEGX ratio (right hepatic venous blood MEGX15/peripheral venous blood MEGX 15) positively correlated with energy charge in the right hepatic lobe. CONCLUSIONS In evaluating liver function of the right hepatic lobe during portacaval shunt and the left portal branch ligation, the MEGX ratio may sensitively reflect the mitochondrial function.
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Affiliation(s)
- Kazuo Matsuyama
- Department of Digestive and Pediatric Surgery, The University of Tokushima School of Medicine, Tokushima, Japan
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40
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Petrolati A, Festi D, De Berardinis G, Colaiocco-Ferrante L, Di Paolo D, Tisone G, Angelico M. 13C-methacetin breath test for monitoring hepatic function in cirrhotic patients before and after liver transplantation. Aliment Pharmacol Ther 2003; 18:785-90. [PMID: 14535871 DOI: 10.1046/j.1365-2036.2003.01752.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND In patients with chronic liver disease, the measurement of liver function is critical for monitoring disease progression, predicting the prognosis and choosing therapeutic strategies. The 13C-methacetin breath test is a simple, non-invasive diagnostic tool based on an inexpensive, non-toxic substance, which allows the accurate measurement of liver functional reserve. AIM To investigate the 13C-methacetin breath test as a tool to monitor hepatic function in liver transplant candidates and recipients. METHODS Twenty-eight cirrhotic patients listed for orthotopic liver transplantation and 10 healthy controls were studied. The 13C-methacetin breath test (75 mg per os) was performed at baseline and at 12-week intervals. Intra-operative measurements were obtained during the liver transplantation procedure in nine patients. Results were expressed as the 13C-methacetin cumulative oxidation percentage 45 min after substrate ingestion. RESULTS The mean 13C-methacetin cumulative oxidation at 45 min was 16.4 +/- 3.5% in healthy controls and 5.4 +/- 4.2% in cirrhotic patients at the time of listing. In 11 patients who underwent successful liver transplantation, mean oxidation increased from 3.3 +/- 1.6% before transplantation to 17.0 +/- 5.2% at 6 months of follow-up. Variations in methacetine oxidation were closely related to the recovery of liver function. The mean intra-operative 13C-methacetin cumulative oxidation increased from 0.1% during the anhepatic phase to 3.7 +/- 2.0% 2 h after reperfusion. CONCLUSIONS The 13C-methacetin breath test is a simple and potentially useful tool for monitoring hepatic function in cirrhotic patients listed for liver transplantation, and during the intra-operative and post-operative phases.
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Affiliation(s)
- A Petrolati
- Gastroenterology Unit, Department of Public Health, University of Rome Tor Vergata Medical School, Rome, Italy
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Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 2003. [PMID: 12677151 DOI: 10.1097/00000658-200304000-00016] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To evaluate prognostic factors that could affect disease-free survival and recurrence after liver resection for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA Tumor recurrence is the main cause of poor survival after liver resection for HCC on cirrhosis. METHODS Two hundred twenty-four liver resections for HCC on cirrhosis were retrospectively reviewed. Univariate and multivariate analyses were performed on several clinicopathologic variables to analyze factors affecting long-term outcome and intrahepatic recurrence. The relation between preoperative aminotransferase level and recurrence rate was evaluated in the overall group, and separately in HCV-positive and in HBsAg-positive patients. Median follow-up was 35.6 months. RESULTS The 1-, 3-, and 5-year overall survival rates were 83%, 62.8%, and 42.5%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 70.3%, 43%, and 27.4%, respectively. The 1-, 3-, and 5-year recurrence rates were 20.8%, 38.6%, and 54.4% respectively. Tumor recurrence appeared in 93 patients (41.5%) and was the main cause of death in 51 patients (56%). Number of nodules, tumor capsule, microvascular portal vein thrombosis, and preoperative serum aspartate aminotransferase (AST) level significantly affected disease-free survival and recurrence rates. On multivariate analysis, single nodules and preoperative AST level less than twice normal (2N) were related to a better 5-year disease-free survival and lower tumor recurrence. In particular, among HCV-positive patients the recurrence rate was strongly affected by the preoperative AST level. CONCLUSIONS Child A patients with single nodules are the best candidates for liver resection. Tumor recurrence is strictly linked to the status of the underlying liver disease, and a preoperative AST level equal to 2N seems to be a sensitive cutoff among patients with different risks of recurrence. HCV-positive patients with AST levels above 2N have the highest risk for intrahepatic recurrence and should be monitored carefully or offered alternative treatments.
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Grazi GL, Cescon M, Ravaioli M, Ercolani G, Gardini A, Del Gaudio M, Vetrone G, Cavallari A. Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre. Aliment Pharmacol Ther 2003; 17 Suppl 2:119-29. [PMID: 12786623 DOI: 10.1046/j.1365-2036.17.s2.9.x] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Differences in risk factors for survival and recurrence after liver resection for hepatocellular carcinoma (HCC) in patients with or without cirrhosis are not fully clarified. AIM To review a single-centre experience of curative liver resections for HCC in order to evaluate clinicopathologic features and the long-term outcome of cirrhotic and noncirrhotic patients. METHODS From 1981 to 2002, 308 curative liver resections for HCC on cirrhosis (Group 1) and 135 for HCC without cirrhosis (Group 2) were performed. The main demographic, clinicopathologic and operative parameters, as well as early results were analysed and compared. Overall and disease-free survival were evaluated. Prognostic factors for survival and for tumour recurrence were studied by univariate and multivariate analysis. RESULTS Group 1 had worse preoperative liver function and higher frequency of hepatitis C virus infection. In Group 2, HCC showed larger mean tumour diameter (P < 0.001), poorer differentiation (P < 0.05) and more frequent macrovascular invasion (P < 0.05). Although more extended resections were performed in Group 2 (P < 0.001), there were no differences in blood transfusions, while post-operative complication rate was higher in Group 1 (P < 0.005). After 1992, in-hospital mortality was 2.9% in Group 1 and 1.1% in Group 2 (P = N.S.). The 3- and 5-year overall survival was 63.7% and 42.2% in Group 1, and 67.9% and 51% in Group 2 (P < 0.05). The 3- and 5-year disease-free survival was 49.3% and 27.8% in Group 1, and 58% and 45.6% in Group 2 (P < 0.005). Serum bilirubin level > 1.2 mg/dL, multiple nodules, micro and macrovascular invasion, diaphragm infiltration and blood transfusions independently affected survival in Group 1. Blood replacement was the only negative prognostic factor in Group 2. Independent risk factors for tumour recurrence were satellite nodules and resection performed before 1992 in Group 1, and age < 60 in Group 2. CONCLUSIONS Despite a more aggressive behaviour, HCC without cirrhosis led to better overall and disease-free survival compared to HCC with cirrhosis after curative liver resection. Age and intra-operative blood transfusions are the only predictors of outcome in patients without cirrhosis. The impact of the latter on long-term survival in both our groups outlines the importance of surgical technique on the results of hepatectomies.
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Affiliation(s)
- G L Grazi
- Department of Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M, Varotti G, Cetta F, Cavallari A. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 2003; 237:536-43. [PMID: 12677151 PMCID: PMC1514472 DOI: 10.1097/01.sla.0000059988.22416.f2] [Citation(s) in RCA: 262] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To evaluate prognostic factors that could affect disease-free survival and recurrence after liver resection for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA Tumor recurrence is the main cause of poor survival after liver resection for HCC on cirrhosis. METHODS Two hundred twenty-four liver resections for HCC on cirrhosis were retrospectively reviewed. Univariate and multivariate analyses were performed on several clinicopathologic variables to analyze factors affecting long-term outcome and intrahepatic recurrence. The relation between preoperative aminotransferase level and recurrence rate was evaluated in the overall group, and separately in HCV-positive and in HBsAg-positive patients. Median follow-up was 35.6 months. RESULTS The 1-, 3-, and 5-year overall survival rates were 83%, 62.8%, and 42.5%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 70.3%, 43%, and 27.4%, respectively. The 1-, 3-, and 5-year recurrence rates were 20.8%, 38.6%, and 54.4% respectively. Tumor recurrence appeared in 93 patients (41.5%) and was the main cause of death in 51 patients (56%). Number of nodules, tumor capsule, microvascular portal vein thrombosis, and preoperative serum aspartate aminotransferase (AST) level significantly affected disease-free survival and recurrence rates. On multivariate analysis, single nodules and preoperative AST level less than twice normal (2N) were related to a better 5-year disease-free survival and lower tumor recurrence. In particular, among HCV-positive patients the recurrence rate was strongly affected by the preoperative AST level. CONCLUSIONS Child A patients with single nodules are the best candidates for liver resection. Tumor recurrence is strictly linked to the status of the underlying liver disease, and a preoperative AST level equal to 2N seems to be a sensitive cutoff among patients with different risks of recurrence. HCV-positive patients with AST levels above 2N have the highest risk for intrahepatic recurrence and should be monitored carefully or offered alternative treatments.
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Affiliation(s)
- Giorgio Ercolani
- Department of Surgery and Transplantation, Surgical Unit, S. Orsola Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
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Pea F, Licari M, Baldassarre M, Furlanut M. MEGX disposition in critically-ill trauma patients: subsequent assessments during the first week following trauma. Fundam Clin Pharmacol 2002; 16:519-25. [PMID: 12685511 DOI: 10.1046/j.1472-8206.2002.00108.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The objective of this study was to evaluate MEGX disposition as a surrogate marker in assessing the influence that injury may exert on liver function during the first week after the traumatic event in young vs. elderly patients. The MEGX exposure over time was assessed at 0.25, 0.5, 1, 2, 4 and 6 h after the intravenous administration of a 1 mg/kg lidocaine test dose in 12 young and 7 elderly trauma patients on days 1, 4 and 7 after a severe injury (Apache II score > 10). MEGX plasma concentration-time profiles were consistently different on day 1 in the elderly vs. young, consistent with a statistically significant lower rate of both lidocaine clearance and MEGX formation, and with a considerably longer MEGX elimination in the elderly than in the young. This suggests an impairment of liver blood flow as a result of splanchnic vasoconstriction occurring mainly in elderly trauma patients. A significant improvement in MEGX disposition occurred on days 4 and 7 vs. the day of trauma in most elderly, whereas minor changes were observed in the young. Multiple factors may account for these major changes in the elderly: the more severe status, the major sensitivity to the pathophysiologic changes induced by trauma, and also at least partially the ageing processes. Although referring to a limited number of observations, our findings on MEGX disposition suggest that liver function may be affected by the severity of injury, even if the influence of age should not be underestimated in these patients.
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Affiliation(s)
- Federico Pea
- Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Italy.
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Wojcicki J, Kozlowski K, Drozdzik M, Wojcicki M. Comparison of MEGX (monoethylglycinexylidide) and antipyrine tests in patients with liver cirrhosis. Eur J Drug Metab Pharmacokinet 2002; 27:243-7. [PMID: 12587953 DOI: 10.1007/bf03192334] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The aim of the study was to compare the feasibility of the MEGX (monoethylglycinexylidide) and antipyrine tests in reference to standard biochemical parameters used for liver assessment in cirrhotic patients. The study was carried out in 44 subjects: 14 healthy controls and 30 cirrhotic patients classified according to the Child-Pugh's score to subgroups A (n=11), B (n=12) and C (n=7). All subjects underwent two dynamic liver tests, i.e. MEGX (monoethylglycinexylidide) and antipyrine test in a crossover schedule with at least 5-day interval. For the MEGX, lidocaine was administrated intravenously, at a dose of 1 mg/kg, and blood samples for MEGX assay were collected after 15 minutes. MEGX concentrations were measured by fluorescence polarization immunoassay. The antipyrine concentrations were evaluated following a single oral administration of 1000 mg antipyrine. The blood was sampled for 24 hours after the drug administration, and antipyrine concentrations were measured spectrophotometrically. Standard biochemical parameters used for liver assessment were measured by means of routine laboratory methods. It was concluded that in patients liver with cirrhosis, liver dynamic tests were better predictors of hepatic function. The MEGX test was more feasible in clinical setting, but it was noted that antipyrine test was more sensitive in staging liver cirrhosis.
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Affiliation(s)
- J Wojcicki
- Department of Experimental and Clinical Pharmacology, Pomeranian Academy of Medicine, Szczecin, Poland
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Abstract
The resection of primary and secondary liver tumors has become accepted as the only curative therapy that can be offered to patients with these cancers. Technical advances made over the last two decades have improved the ability of the surgeon to perform these procedures with decreased morbidity. This article reviews hepatic anatomy, the preoperative evaluation of patients and various technical aspects involved in liver resections. The latter includes the role of intraoperative ultrasound and techniques of vascular occlusion and hepatic parenchymal dissection.
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Affiliation(s)
- Ming-Hui Fan
- Division of Surgical Oncology, 3302 Cancer Center, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor 48109, USA
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Abstract
The role of the pathologist in dealing with common problems of liver disease in children is likely to change dramatically as the molecular genetic revolution progresses. For example, microchip arrays for genes involved in bile salt synthesis and transport will pinpoint the specific mutations responsible for infantile cholestasis and similar methods will sort out infectious agents of acute and chronic hepatitis. But even as biochemistry, microbiology, and immunology laboratories already provide essential diagnostic information in such settings, informed histopathologic interpretation will continue to guide investigations of etiology and therapeutics and will remain an important medical necessity [95,96,100,102,104].
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Affiliation(s)
- Milton J Finegold
- Department of Pathology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
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Achilefu S, Dorshow RB. Dynamic and Continuous Monitoring of Renal and Hepatic Functions with Exogenous Markers. Top Curr Chem (Cham) 2002. [DOI: 10.1007/3-540-46009-8_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Grazi GL, Ercolani G, Pierangeli F, Del Gaudio M, Cescon M, Cavallari A, Mazziotti A. Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value. Ann Surg 2001; 234:71-8. [PMID: 11420485 PMCID: PMC1421950 DOI: 10.1097/00000658-200107000-00011] [Citation(s) in RCA: 276] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To review a single-center experience to update the performance indexes of liver resection (LR). SUMMARY BACKGROUND DATA Several therapies have been proposed in the treatment of hepatocellular carcinoma (HCC) on cirrhosis, although LR was the first to be widely applied. METHODS Of 408 patients with cirrhosis admitted for HCC in the period 1983 to 1998, 264 had a LR. Patient selection, surgical technique, 30-day deaths, long-term survival, recurrence rate, and recurrence treatment were reviewed after stratifying patients according to the year of surgery. Mean follow-up was 34.5 +/- 29.1 months. RESULTS The number of Child A patients who underwent surgery after the discovery of the tumor at routine evaluation increased significantly from 64.5% to 87.9% during the study period. Procedures carried out without blood transfusions increased from 31.4% to 76.9%. The overall operative death rate was 4.9%. Actuarial survival rates were 63.1% and 41.1% after 3 and 5 years, respectively; actuarial tumor-free survival rates were 49.3% and 27.9% at the same intervals. After 1992, surgical deaths decreased from 9.3% to 1.3%. Actuarial survival rates increased from 52.9% and 32.3% to 71.7% and 49.4% after 3 and 5 years, respectively. There was no difference in the actuarial recurrence rate between the two periods, but the chance to treat recurrence increased over time from 22.4% to 53.7% with a concomitant, significant improvement in survival. CONCLUSIONS LR represents a well-established therapy for HCC on cirrhosis. It remains one of the fundamentals in the multidisciplinary approach to this tumor and should be considered as the first option for patients with preserved hepatic function and limited disease. Today, LR should offer a surgical death rate of less than 1.5%, a 5-year survival rate of approximately 50%, and a 5-year tumor-free survival rate of 28% when performed in specialized centers.
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Affiliation(s)
- G L Grazi
- Department of Surgery and Transplantation, University of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy.
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Abstract
The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) can complement established static liver function tests if prognostic information is of particular interest. Because of its ease of use and rapid turnaround, the MEGX test has found widespread application for realtime assessment of hepatic function in transplantation, critical care medicine, and various experimental models. Lidocaine is metabolized primarily by the liver cytochrome P450 system through sequential oxidative N-dealkylation, the major initial metabolite in humans being MEGX. Because of the relatively high extraction ratio of lidocaine, this liver function test depends not only on hepatic metabolic capacity but also on hepatic blood flow. For the determination of MEGX in serum, an immunoassay based on the fluorescence polarization immunoassay technique high-performance liquid chromatography and gas liquid chromatography methods have been described. Whereas high-performance liquid chromatography and gas liquid chromatography are specific for MEGX, the fluorescence polarization immunoassay also cross-reacts with 3-OH-MEGX. Although this is not a problem in humans, some species, such as the rat, produce significant amounts of this metabolite. The findings of most studies published so far suggest that the MEGX test is a useful tool that can improve our decision-making process with respect to the selection of transplant candidates. Patients with a MEGX 15- or 30-minute test value <10 microg/L have a particularly poor 1-year survival rate. Serial monitoring of liver graft recipients early after transplantation with the MEGX test may initially alert the clinician to a major change in liver function; if used with other tests, such as serum hyaluronic acid concentrations, it may become more discriminatory. In critically ill patients, several studies have shown that an initially rapid decrease in MEGX test values is associated with an enhanced risk for the development of multiple organ dysfunction syndrome and a poor outcome. Further, this decrease appears to be associated with an enhanced systemic inflammatory response. The MEGX test has potential for investigating the pathogenesis of multiple organ dysfunction syndrome with regard to early hepatic functional impairment in critically ill patients after polytrauma or sepsis.
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Affiliation(s)
- M Oellerich
- Department of Clinical Chemistry, Georg-August University, Göttingen, Germany.
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