Endoscopic clips versus overstitch suturing system device for mucosotomy closure after peroral endoscopic pyloromyotomy (G-POEM): a prospective single-center study.

BACKGROUND AND AIMS: G-POEM is an emerging method for treatment of severe gastroparesis. Safe mucosal closure is necessary to avoid adverse events. The aim of this study was to compare the efficacy of two closure methods: clips and endoscopic suturing (ES) after G-POEM. METHODS: We performed a single center, prospective study. The closure method was assigned at the discretion of an endoscopist prior to the procedure. The main outcome was the proportion of subjects with successful closure. Unsuccessful closure was defined as a need for a rescue method, or a need for an additional intervention or incomplete closure-related adverse events. Secondary outcomes were the easiness of closure (VAS score 1 = very difficult, 10 = easy), closure time, and cost. RESULTS: A total of 40 patients [21 female; mean age, range 47.5; (20-74)] were included; 20 received ES and 20 clips [mean number of clips 6; range (4-19)]. All 20 patients with ES (100%, 95% CI 84-100%) and 18 patients with clips (89%, 95% CI 70-97%) had successful closure (p = 0.49). One patient needed a rescue method (KING closure) and the other patient an additional clipping on POD1. Closure with clips was quicker [mean time 9.8 (range 4-20) min vs. 14.1 (5-21) min; p = 0.007] and cheaper [mean cost 807 USD (± 402) vs. 2353 USD (± 145); p < 0.001]. Endoscopist assessed the easiness of ES and clips as comparable [mean VAS, range 7.5 (3-10) (ES) vs. 6.9 (3-10) (clips); p = 0.3]. CONCLUSIONS: Both ES and clips are effective methods for mucosal closure in patients undergoing G-POEM. However, centres using clips should have a rescue closure method available as clips may fail in some patients. Closure with ES is more costly than with clips.

Portal hypertension is the main driver of liver stiffness in advanced liver cirrhosis.

Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8%), minority of patients were Child-Pugh A (18/81, 22.2%). LS showed the best correlation with HVPG (r=0.719, p< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

Liver transplantation using grafts from donors after circulatory death - the first Czech Republic experience.

INTRODUCTION: Liver transplantation is established as a lifesaving procedure for patients with acute and chronic liver failure, as well as certain selected malignancies. Due to a continuing organ shortage and ever-growing patient waiting lists, donation after cardiac death (DCD) is becoming more frequently utilized in order to close the gap between “supply and demand”. METHODS: A retrospective analysis of DCD and subsequent liver transplantations was performed. RESULTS: From May 2016 to September 2019, a total of 9 DCD liver transplantations were performed in our institution. All cases except one were primary liver transplantations. The recipients comprised 5 (56%) males and 4 (44%) females. The mean DCD donor age was 41±12 (22-57) years, with ventilation duration of 7±1 days and warm ischemia time 19±3 minutes. The average recipient age was 51±22 (4-73) years, with an average cold ischemia 3h:59m±27m and manipulation time of 23±5 minutes. Periprocedural mortality was 1 (11%). Hepatitis C recurrence was documented in 1 (11%) patient. The mean follow-up time was 19±13 (7-37) months. Until now, we have not observed any signs of ischemic cholangiopathy. CONCLUSION: DCD liver transplantation allows us to enlarge the pool of potential liver grafts, thus decreasing the time spent on the liver recipient waiting list. This paper documents the first series of DCD liver transplantations in the Czech Republic.

Per-oral endoscopic pyloromyotomy (g-poem) for the treatment of gastroparesis - a pilot single-centre study with mid-term follow-up.

INTRODUCTION: Endoscopic pyloromyotomy (G-POEM) is an emerging therapeutic method for the treatment of gastroparesis (GP). So far, only limited case-series suggesting its effectivity have been published. The aim of our study was to assess the effectivity of G-POEM in patients with refractory GP. METHODS: Consecutive patients with severe and refractory GP were offered the procedure. An abnormal gastric emptying study (GES) was necessary for inclusion. The main outcome was treatment success defined as a decrease of the total GSCI symptom score by at least 40% from baseline at 3, 6, 12 and 24 months. RESULTS: G-POEM was performed in 9 patients (5 women, mean age 56.3): 5 post-surgical, 2 diabetic, 1 idiopathic and 1 combined post-surgical and diabetic. The median follow-up was 23M (range 12-31). All procedures were successfully completed. One patient experienced delayed bleeding from gastric ulceration, which was successfully treated endoscopically; all remaining patients recovered uneventfully. Treatment success was achieved in 8/9 patients (88.9%) at 3, 6 and 12M and in 3/4 (75%) at 24M. The mean GSCI decreased from 3.16 to 0.86 (p=0.008), 0.74 (p=0.008), 1.07 (p=0.008) and 1.31 (p=0.11) at 3, 6, 12 and 24M after the procedure. The Quality of Life Index improved from the baseline value of 77 (range 48102) to 113 (86-138, p=0.03) and 96 (50-124, p=0.4) at 12 and 24M. In patients with treatment success, no recurrences have occurred so far. GES improved/normalized in all the patients. CONCLUSION: G-POEM was effective in 88.9% of patients with refractory GP and the effect seems to be long-lasting.

Acute Liver Failure due to Amanita phalloides Poisoning: Therapeutic Approach and Outcome.

INTRODUCTION: Amanita phalloides poisoning is a potentially fatal cause of acute liver failure. The aim of this study was to analyze the impact of initial patients' characteristics and different treatment modalities on the outcome of patients with liver failure caused by Amanita poisoning. MATERIAL AND METHODS: We retrospectively evaluated 23 patients admitted to our center between July 2007 and August 2016. RESULTS: Mean time interval between Amanita phalloides ingestion and the onset of gastrointestinal symptoms was 12.48 ± 9.88 hours and the interval between ingestion and hospital admission 26.26 ± 15.14 hours. The treatment was intiated by oral decontamination using activated charcoal followed by intravenous rehydration and high doses of intravenous N-acetylcysteine and silibinin. Fourteen patients (61%) underwent extracorporeal elimination method. Ten patients had plasmapheresis, 1 patient had hemoperfusion, and 5 patients had fractionated plasma separation and adsorption. Seven patients who met King's College Criteria were listed for urgent liver transplantation; one of them died before transplantation. Six patients underwent liver transplantation; the mean waiting time was 6.5 ± 12.0 days (range, 1-31 days). One patient died 2 months afterward. All 16 patients who did not meet King's College Criteria and received conservative treatment survived. CONCLUSION: Our results documented a good prognostic value of standard King's College Criteria for indication of urgent liver transplantation in acute liver failure caused by Amanita phalloides poisoning. Fractionated plasma separation and adsorption may contribute to low mortality on the waiting list. Intensive care and extracorporeal elimination methods seem to be crucial points of the conservative treatment.

Lack of Impact of Hyperchloremia in Brain-Dead Organ Donors on the Onset of Kidney Allograft Function in the Recipients.

BACKGROUND: Hyperchloremia produces renal vasoconstriction and fall in glomerular filtration rate. In 90% of brain-dead organ donors, diabetes insipidus develops, characterized by inappropriate diuresis, hyperosmolality, and hyperchloremia. The aim of this study was to determine the relationship between the serum concentration of chlorides of the donor and the onset of the function of the kidney allograft in the recipient. METHODS: We retrospectively studied 213 donors and kidney allograft recipients. Serum creatinine concentrations and glomerular filtration rates on the 1st, 7th, and 30th days after transplantation of the recipients from hyperchloremic donors were compared with the recipients from normochloremic donors, as well as the incidences of acute tubular necrosis and delayed graft function. RESULTS: On the 1st day, serum creatinine concentrations of the recipients from hyperchloremic and normochloremic donors, respectively, were 448.2 ± 212.1 µmol/L and 502.2 ± 197.8 µmol/L (P = .1), on the 7th day, 168.6 ± 102.6 µmol/L and 196.9 ± 120.6 µmol/L (P = .13), and on the 30th day, 129.4 ± 43.3 µmol/L and 131.8 ± 43.6 µmol/L (P = .73). The differences were statistically significant. The groups also did not differ significantly in glomerular filtration rates and incidences of acute tubular necrosis and delayed graft function. CONCLUSIONS: In this study, no significant correlation between serum chloride concentrations of the organ donors and the onset of the function of kidney allografts in the recipients was found.

Incidental hepatocellular carcinoma: risk factors and long-term outcome after liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) currently represents the treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively known HCC (pkHCC) is diagnosed via imaging methods before OLT or before HCC is found postoperatively in the liver explant, denoted as incidental HCC (iHCC). The aim of this study was a comprehensive analysis of the post-transplantation survival of patients with iHCC and the identification of risk factors of iHCC occurrence in cirrhotic liver. METHODS: We retrospectively reviewed 33 adult cirrhotic patients with incidentally found HCC, comparing them with 606 tumor-free adult cirrhotic patients with end-stage liver disease (group Ci) who underwent OLT in our center from January 1995 to August 2012. Within the same period, a total of 84 patients underwent transplantation for pkHCC. We compared post-transplantation survivals of iHCC, Ci, and pkHCC patients. In the group of cirrhotic patients (Ci + iHCC), we searched for risk factors of iHCC occurrence. RESULTS: There was no difference in sex, Model for End-Stage Liver Disease score, and time spent on the waiting list in either group. In the multivariate analysis we identified age >57 years (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.75-8.14; P < .001), hepatitis C virus or alcoholic liver disease (OR, 3.89; 95% CI, 1.42-10.7; P < .001), and alpha-fetoprotein level >6.4 µg/L (OR, 6.65; 95% CI, 2.82-15.7; P = .002) to be independent predictors of iHCC occurrence. Both the 1-, 3-, and 5-year overall survival (OS) and the 1-, 3- and 5-year recurrence-free survival (RFS) differed in iHCC patients compared with the Ci group (iHCC: OS 79%, 72%, and 68%, respectively; RFS 79%, 72%, and 63%, respectively; vs Ci: OS = RFS: 93%, 94%, and 87%, respectively; P < .001). CONCLUSIONS: The survival of iHCC patients is worse than in tumor-free cirrhotic patients, but similar to pkHCC patients. The independent risk factors for iHCC occurrence in cirrhotic liver are age, hepatitis C virus, or alcoholic liver disease etiology of liver cirrhosis and alpha-fetoprotein level.

Urgent liver transplantation for chemotherapy-induced HBV reactivation: a suitable option in patients recently treated for malignant lymphoma.

BACKGROUND: Hepatitis B (HBV) reactivation induced by chemotherapy is a problem currently encountered in the management of malignancies. HBV reactivation occurs particularly in patients who were not checked for HBV status, and therefore have not undergone antiviral prophylaxis. HBV reactivation may ultimately lead to fulminant liver failure (FLF). Liver transplantation (OLT), the only remaining effective treatment option, is generally denied for subjects with a recent history of malignancy. CASE REPORTS: We described retrospectively three cases of FLF caused by HBV reactivation in two men and one woman undergoing rituximab-containing chemotherapy for malignant lymphomas: follicular, diffuse large B-cell and lymphoplasmacytic types. The two men reactivated after eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and the one woman after 13 cycles of rituximab monotherapy; their hematologic disease was in remission. All three patients were hepatitis B surface antigen (HBsAg)-positive with high HBV DNA levels. Neither man had been screened for HBV before chemotherapy; the woman had been treated with lamivudine (LAM) experiencing an HBV flare-up due to emergence of LAM resistance. All patients fulfilled King's College criteria for urgent OLT upon admission to the transplant center and underwent an urgent OLT. Their hemato-oncologic prognosis was considered to be favorable. All three patients are alive (54, 46, and 37 months post-transplantation), tumor-free and HBsAg negative on a standard HBV prophylaxis regimen: hepatitis B immunoglobulin and LAM + adefovir or tenofovir. CONCLUSIONS: Before chemotherapy appropriate prophylaxis for HBV reactivation should always be administered to at-risk patients. However, if reactivation with FLF occurs, OLT should not be generally denied. The prognosis of the hematologic malignancy should be assessed; OLT should be considered for patients in remission with a favorable long-term prognosis, for our data suggest acceptable survival.

The effect of immunosuppression on manifestations of sepsis in an animal model of cecal ligation and puncture.

OBJECTIVE: The diagnosis of sepsis is difficult in immunocompromised patients owing to their modified response to infection. Our experiment in minipigs was designed to compare responses to sepsis between experimental groups of septic minipigs with and without immunosuppression. METHODS: Minipigs with identical baseline parameters were randomized into 3 groups: Sepsis (n = 10); immunosuppression (n = 11), including cyclosporine, methylprednisolone, and mycophenolate mofetil treatment before surgery, and a sham group (n = 6). Sepsis was induced by cecal ligation and puncture (CLP). We recorded selected clinical and laboratory parameters up to 24 hours postoperatively. RESULTS: All CLP animals developed septic shock with a febrile response, tachycardia, and hypotension requiring noradrenaline administration. The hemodynamic responses to sepsis in septic groups with and without immunosuppression were similar. Noradrenaline infusion was started on average later in the immunosuppression than in the group without immunosuppression; however, the difference was not significant. The kinetics of the plasma levels of most selected cytokines and C-reactive protein were similar in both septic groups. At 10 hours after surgery, the immunosuppression group showed significantly lower interleukin (IL)-6 levels compared with the sepsis group. At 19, 22, and 25 hours after surgery immunosuppressed animals displayed significantly greater increases in IL-10 levels compared with the cohort without immunosuppression. CONCLUSIONS: CLP is a simple, reproducible model of sepsis in minipigs. All CLP animals developed sepsis within 24 hours on average. Significant differences in IL-6 and IL-10 plasma levels were recorded between septic animals with versus without immunosuppression.

The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management.

Prometheus, based on modified fractionated plasma separation and adsorption (FPSA) method, is used in the therapy of acute liver failure as a bridge to liver transplantation. As the therapeutic effect of Prometheus is caused not only by the elimination of terminal metabolites, the aim of the study was to identify the effect of FPSA on the levels of cytokines and markers of inflammation and liver regeneration. Previous studies assessing cytokine levels involved mostly acute-on-chronic liver failure patients. Data concerning markers of inflammation and liver regeneration are not published yet. Eleven patients (three males, eight females) with acute liver failure were investigated. These patients underwent 37 therapeutic sessions on Prometheus device. Before and after each treatment, the plasma levels of selected cytokines, tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), procalcitonin (PCT), hepatocyte growth factor (HGF), and α(1) fetoprotein, were measured, and the kinetics of their plasma concentrations was evaluated. Before the therapy, elevated levels of interleukin (IL)-6, IL-8, IL-10, TNFα, CRP, and PCT were detected. The level of TNFα, CRP, PCT, and α(1) fetoprotein decreased significantly during the therapy. In contrast, an increase of HGF was detected. The decline of IL-6, IL-8, and IL-10 concentrations was not significant. Our results show that Prometheus is highly effective in clearing inflammatory mediators responsible for systemic inflammatory response syndrome and affects the serum levels of inflammatory and regeneration markers important for management of acute liver failure.

[Liver transplantation and peri-operative changes to renal function]. / Transplantace jater a perioperacní zmeny renálních funkcí.

THE AIM OF THE STUDY: Was to analyze in detail perioperative changes of renal function during orthotopic liver transplantation (OLT) and to identify risk factors, that were associated with the need of renal replacement therapy (RRT) during the first week after liver transplantation. METHODS: Prospective study of 50 consecutive patients undergoing OLT was performed. Selected laboratory and clinical parameters were monitored prior to the procedure, after reperfusion, at the end of the procedure, and at 12 hours after the procedure. In the first post-transplant week, necessity to use RRT in the presence of acute kidney injury was monitored and the analysis of risk factors for the need for RRT was performed. Patient survival, graft function, need for dialysis and selected laboratory parameters were assessed at one year post-transplant. RESULTS: During OLT, there was an increase in S(cr) and S(urea), which persisted as late as 12 hours post-transplant. There was a decrease in U(cr) and U(urea) and an increase in S(Na) and S(K). During the procedure any increase in S(cyst) were observed, increase the values were recorded 12 hours after surgery. S(bili) level decreased. There was a rise in the urinary levels of total protein, albumin and beta2-microglobulin. U(prot)/U(cr) increased significantly after reperfusion, with a peak after the procedure. At 12 hours after the procedure, there was a decrease in U(prot)/U(cr), but the values were still many times higher than those seen preoperatively. RRTwas necessary in 14% cases. Risk factors for acute kidney injury requiring RRT included a higher APACHE score, higher BMI, higher preoperative S(cr) and S(urea), hepatorenal syndrome pretransplant, blood loss and intraoperative hemodynamic instability, postoperative complications and dysfunction of the liver graft. One year after OLT, there was no difference in followed laboratory values between patients requiring postoperative RRT and others; no patient was treated with dialysis. CONCLUSION: OLT has a major impact on glomerular and tubular renal functions. Our data suggest that patients surviving acute renal injury treated with RRT in the early postoperative period have a high chance of restoring renal function. A sensitive marker of renal injury during OLT seems to be perioperative proteinuria.

[Biological and non-biological elimination therapy of acute liver failure. Experimental study on large laboratory animal]. / Biologická a nebiologická eliminacní lécba akutního selhání jater experimentální práce na velkém laboratorním zvíreti.

BACKGROUND: Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. METHODS AND RESULTS: Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. CONCLUSIONS: Significant improvement of bilirubin and ICP levels resulting from the treatment with fractionated plasma separation and adsorption (Prometheus) were observed in the case of experimental ALE Except the bilirubin levels, bioartificial liver provided by O. liver Performer with isolated hepatocytes did not bring any significant improvement of laboratory markers, including ICP.

[Living relative donor for liver transplantation in paediatric recipient]. / Transplantace jater dítete od zivého príbuzenského dárce.

Paper refers the first in Czech Republic liver transplantation in a child with the donor being the close living relative - the father. Indication was the chronic liver failure caused by biliary atresia after the Kasai procedures, which enabled the child to survive two years. Liver segments II. -III were transplanted with favourable postoperative development. Within the following twenty months the nutrition status and the psychomotor development of the child significantly improved. Authors discuss present situation and results of the paediatric liver transplantation in the world.

Hemodynamic parameters in a surgical devascularization model of fulminant hepatic failure in the minipig.

Animal models of fulminant hepatic failure (FHF) are important for studying the pathophysiology of this process and for evaluation of the efficacy of artificial and bioartificial liver support systems. In experiments, hemodynamic parameters were monitored in a group of minipigs with FHF induced by surgical devascularization, and compared with those in a control group. During the experiment, animals were analgosedated and were on mechanical lung ventilation. Crystalloid and colloidal solutions were administered and norepinephrine in continuous infusion was applied if mean arterial pressure (MAP) decreased below 60 mm Hg despite adequate intravascular volumes. An increase in heart rate, and decreases in MAP and systemic vascular resistance, compared with the baseline, occurred in the FHF group from 6 h after surgery. A comparison of FHF and control groups revealed no significant differences in systemic vascular resistance and MAP until after 12 h after surgery (systemic vascular resistance index: 953 FHF vs. 1658 controls; p < 0.05; MAP: 58.1 FHF vs. 76 controls; p < 0.05). No significant differences in CI were seen between the FHF group and controls. FHF animals survived for about 13 h after surgery, i.e. a period, which we consider long enough to test a support device. The parameters are believed to be quite adequate, as we were able to maintain satisfactory hemodynamic stability in all experimental animals with induced acute hepatic failure.

[Thromboelastography in liver transplantation, a comparison with conventional laboratory tests]. / Trombelastograf pri transplantaci jater, porovnání s konvencními koagulacními testy.

BACKGROUND: The aim of our study was to compare the results of conventional tests and thromboelastography during liver transplantation and to determine their importance for blood loss. METHODS AND RESULTS: Thromboelastography and conventional laboratory tests were undertaken in 25 patients at the end of the anhepatic phase. Transfusion requirements correlated significantly only with prothrombin time and reaction time, R. These two tests likewise correlated significantly one with the other. CONCLUSIONS: Lowered plasma levels of coagulation factors of the prothrombin complex influenced the blood losses in our patients. While not replacing conventional tests, thromboelastography can serve as an additional test for monitoring acute changes in hemostasis.

[A model of acute hepatic failure in a minipig from the surgical and anesthesia point of view]. / Model akutního selhání jater u miniprasete z hlediska chirurga a anesteziologa.

AIM: The aim of this study was to create an easily reproducible model of the acute hepatic failure (ASJ) in a minipig, which may allow to test supporting eliminating systems. The aim of this report was to describe the surgical technique with the anaesthesiological procedure and to demonstrate the experimental results on a group of the laboratory animals. METHODOLOGY: The ASJ was mocked using surgical devascularization of the liver: a ligature of the a. hepatica propria and v. portae, creating a portocaval anastomosis end-to-side. The animals were analgosedated during the experiment and were on a ventilatory support. Biochemical indicators of the hepatic failure, the ICP and the haemodynamics parameters were monitored. Hypoglycaemia with levels below 3.5 mmol and any increase of the intracranial pressure (ICP) were considered the onset of the hepatic failure. MATERIAL: 20 minipigs weighing 25-30 kg and divided in 3 groups, were included in the experiment: I--10 animals were assigned to the acute hepatic failure (ASJ) group, II--5 animals with the mock acute hepatic failure (ASJ), whose ICP was monitored in conjunction with the standard monitoring and III. 5 animals without the acute hepatic failure (ASJ)--a control group. RESULTS: We proved significant differences in the AST levels (33.44 +/- 39.96 vs. 1.56 +/- 0.50 mmol/l), the lactate levels (2.97 +/- 1.16 vs. 1.18 +/- 0.61 mmol/l), and the ammonium levels (264.3 +/- 93.05 vs. 42.5 +/- 12.98 micromol/l) in the acute hepatic failure (ASJ) group compared with the control group (p < 0.01) 6 hours after the surgery and significant changes in the glycaemia levels and the intracranial pressure (ICP) measurements 4 hours after the surgical procedure. Increase in the pulse frequency, the blood pressure, decrease of the mean arterial pressure (MAP) and decrease in the systemic venous resistence index (SVRI) in the acute hepatic failure (ASJ) group was recorded 6 hours after the procedure compared with the initial findings, with significant differences between the acute hepatic failure (ASJ groups and the control group as late as during the 12th hour following the procedure (SVRI: 953 ASJ vs. 1658 control, p - 0.05, MAP: 58.1 ASJ vs. 76 control, p - 0.05). No statistically significant differences in the heart index between the acute hepatic failure (ASJ) group and the control group were recorded. The animals with the acute hepatic failure (ASJ) survived 13 hours following the surgical procedure, on average.

Devascularization surgical model of acute liver failure in minipigs.

AIM: The study was designed to develop a readily reproducible model of acute liver failure (ALF) in the minipig, to gain an 8-hour therapeutic window to mimic, as closely as possible, acute liver failure in man. METHOD: We used reversible devascularization model of ALF in the minipig involving hepatic artery ligation and establish an end-to-side portocaval anastomosis. Standard laboratory monitoring was complemented with intracranial pressure (ICP) measurement. MATERIAL: Twenty minipigs (weight 25-30 kg) were used for the experiment. The animals were divided into 3 groups: I: 10 animals in an experimental group with ALF; II: 5 animals in an experimental group with ALF and ICP measurement, and III: 5 animals in a control group without ALF. RESULTS: Laboratory testing has shown the significant changes in levels of AST (33.44 +/- 39.96 vs. 1.56 +/- 0.50 mmol/l), lactate (2.97 +/- 1.16 vs. 1.18 +/- 0.61 mmol/l), and ammonia (264.3 +/- 93.05 vs. 42.5 +/- 12.98 mmol/l) between ALF groups and controls (p < 001) 6 h after the operative procedure, and significant changes in hypoglycemia and intracranial pressure were found 4 h after the operative procedure. The difference in Quick values (67.4 +/- 17.03 vs. 75.2 +/- 2.68) was not significant. We assume that the therapeutic window starts 4 h after the beginning of the experiment. CONCLUSION: Our devascularization model of ALF is simple and readily reproducible. The therapeutic window occurring shortly after surgery and persisting for a mean 9 h is suitable to evaluate bioartificial liver devices.