To predict the change in patient status and differentation of the basic diseases, endogenous thro... more To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (...
Abstract: Malignant diseases are considered as great challenges in clinical transplantation. It i... more Abstract: Malignant diseases are considered as great challenges in clinical transplantation. It is well known that the incidence of malignancy is higher in the transplanted population if compared with the normal population. It is important to distinguish between neoplastic diseases ...
The authors report a case of 47 years patient, who underwent successful combined liver-kidney tra... more The authors report a case of 47 years patient, who underwent successful combined liver-kidney transplantation. The primary cause of cirrhosis was HCV infection combined with membranoproliferative glomerulonephritis, witch resulted end stage kidney and liver disease. One and half year after operation the patient has full rehabilitation. By the case report the authors overview the indications and techniques of combined kidney-liver transplantation.
Although experimental autologous patch or tubular conduit vascular grafts made from the internal ... more Although experimental autologous patch or tubular conduit vascular grafts made from the internal rectus fascia sheath (IRFS) have been reported in the literature, thorough morphological evaluation and verification of the histological arterialisation of such grafts are lacking. Four purpose-bred Beagle dogs were utilised to create eight arterial internal rectus fascia sheath (ARFS) grafts implanted between bisected ends of the external iliac arteries. Four out of the eight ARFS grafts were patent after three months. Haematoxylin-eosin and Azan staining verified that the grafts gained a vessel-like layered structure with the presence of large amounts of collagen fibres. Although the inner surface of the intact IRFS was originally covered with claudin-5-negative and pancytokeratin-positive mesothelial cells in control samples, the internal cells of the ARFS grafts became claudin-5 positive and pancytokeratin negative like in intact arteries. Spindle-shaped cells of the wall of ARFS grafts were α-smooth muscle actin (α-SMA) positive just like the smooth muscle cells of intact arteries, but α-SMA immunoreactivity was negative in the intact IRFS. According to these findings, the fibroblast cells of the ARFS graft have changed into myofibroblast cells. The study has proved that ARFS grafts may be used as an alternative in arterial replacement, since the graft becomes morphologically and functionally similar to the host vessel via arterialisation.
Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in... more Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.
The authors give an overview on the role of drug metabolizing enzymes in the effect and side-effe... more The authors give an overview on the role of drug metabolizing enzymes in the effect and side-effect of drugs. They describe the properties of cytochrome P450 and other phase I enzymes (hydrolases, flavin-monooxygenases), as well as of phase II. enzymes (glucuronyl-, sulfate-, glutathione-, acetyl-, methyltranferases), their polymorphism, inductive and inhibition properties. The possible drug-drug interactions are discussed in detail.
Objectives: Hepatitis C virus (HCV) recurrence after liver transplantation is universal and leads... more Objectives: Hepatitis C virus (HCV) recurrence after liver transplantation is universal and leads to chronic hepatitis and cirrhosis. Combined interferon and ribavirin therapy represents the accepted treatment for recurrent chronic hepatitis C following liver transplantation, according to the literature. Our aim was to assess the efficacy and safety of the recommended combined interferon and ribavirin therapy, and evaluation of the rate of long-term remission under Hungarian circumstances. Methods: 16 patients with chronic recurrent hepatitis C, who had been HCV-PCR positive (genotype 1b), received combined treatment with interferon-alpha-2b (3 MU three times a week) and ribavirin (800-1000 mg daily) for 12 months following transplantation. 12 patients have completed the therapy. Liver biopsies were performed before commencing and after concluding treatment in every patient. Virological responses at completion of the 12-month-long treatment and at the end of the subsequent 6-month-l...
The number of patients suffering from kidney disorders is increasing the need for kidney transpla... more The number of patients suffering from kidney disorders is increasing the need for kidney transplantation. Kidneys originating from living donors (LD) show substantially better results than those originating from cadaveric donors (CD). We performed 3000 kidney transplantations between November 1973 and December 2007, including 154 from LD (5.13%). The early kidney function as measured by the delta creatinine clearance was significantly better among the LD group (P < .001). There was no significant difference in the immunologic data between the LD and the CD groups (P = .047). Four years after transplantation the glomerular filtration rate (GFR) and the serum creatinine level treated to be better among the LD group with tacrolimus versus cyclosporine immunosuppression (P = .089). In the LD group, the acute rejection rate was lower with tacrolimus- versus cyclosporine based immunosuppression (P = .014).
Hypercholesterolemia and xanthomatosis are known complications of chronic cholestasis. This is th... more Hypercholesterolemia and xanthomatosis are known complications of chronic cholestasis. This is the first report on xanthomatosis and severe hypercholesterolemia caused by common bile duct stenosis following laparoscopic cholecystectomy. Laparoscopic cholecystectomy was performed in a 32-year old woman because of numerous tiny gallstones. Bile leakage was observed in the early postoperative period which stopped spontaneously. Six months later itching, progressively increasing serum bilirubin level, cholestasis syndrome, xanthelasma and widespread eruptive xanthomatosis developed in a few months. The cholesterol level was extremely high (92.3 mmol/l), while the triglyceride level was normal. Though the ultrasound and the cholangio-MR did not showed any dilatation of bile ducts, the ERCP verified a 2 mm long, hair's-breadth thin stenosis of choledochus in the level of cystic duct. Primary biliary cirrhosis and primary sclerosing cholangitis were excluded, no evidence for familial h...
New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotop... more New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotopic liver transplantation (OLT). The diabetogenic effect of hepatitis C virus (HCV) infection is well known. The aim of this study was to analyze the glucose homeostasis before and after OLT. The oral glucose tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4) activity was measured. The study period was from 2012 to 2014. We enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients after OLT (group B). Seven patients were monitored continuously both before and after OLT. According to our preoperative OGTT results, 13 patients in group A had newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed (group A/NGT). The calculated homeostasis model assessment insulin resistance (HOMA2-IR) values were both in group A/DM and-IGT higher compared with group A/NGT (2.42 ± 0.81 vs 2 ± 0.98 vs 1.28 ± 0.67; P = .001). In the case of HCV infection (n = 14; 29%) DM and IGT were more frequent. Six patients in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that in patients with all other indications for OLT (15.5 ± 5.2 vs 8.7 ± 3.5; P = .008). We evaluated the same individuals before and after OLT (n = 7), and a decrease in β-cell function was noted. Preoperative OGTT is an important and easy investigation to rule out glucose imbalance before OLT. The HOMA2 calculation can also be useful both in preoperative and postoperative risk assessment. In our results, DPP-4 activity is not specific for the type of glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4 inhibitors can be effective in the therapy of NODAT, especially in HCV-infected patients.
Availability of suitable donor organs has always limited the number of liver transplantations per... more Availability of suitable donor organs has always limited the number of liver transplantations performed. Use of marginal donor organs is an alternative to overcome organ shortage. To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation. Data from 260 whole-liver transplantations performed between January 2003 and September 2009 were analyzed retrospectively. Study groups were established according to donor organ quality (marginal score 0-1 vs 2-5) and recipient status (Model for End-Stage Liver Disease [MELD] score <17 or >17). In patients at low risk, 102 received optimal grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B]. No differences were observed in cumulative patient and graft survival rates; however, total survival differed in the early period after transplantation, that is, within 1 year. There was a higher rate of overall postoperative complications including initial poor graft function, bleeding, infection, and kidney failure in group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) (P = .04). Patients with a high MELD score (G/B and B/B) demonstrated increased risk of postoperative complications. Use of donor organs with marginal score of 2 or higher in patients with high MELD scores increased early patient mortality. In summary, patients with a high MELD score (G/B and B/B) are at an increased risk of post-OLT complications. In contrast, use of marginal grafts (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased the response rate to antiviral therapy. The combination of impaired donor grafts and recipients at high risk should be avoided.
Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with goo... more Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with good graft survival rates. Previous studies have shown beneficial effects of renal replacement therapy in critically ill patients. This observation led us to use intraoperative continuous veno-venous hemofiltration (CVVH) during multiorgan transplantations. We analyzed (CRP) inflammatory response parameters of tumor necrosis factor (TNF)alpha, interleukin(IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) at various stages of the combined transplantations. All patients survived with well-functioning grafts. Mean +/- SD follow-up was 32.8 +/- 14.2 months. During the whole operation we used intraoperative CVVH starting at the beginning and continuing in the intensive care unit (ICU) afterward (mean +/- SD, 11.2 +/- 8.4 hours). Intraoperative TNFalpha, IL-6, CRP, and PCT were measured before surgery, during hepatectomy in the anhepatic phase, before and after liver reperfusion, exactly before kidney reperfusion, after kidney reperfusion, and upon arrival in the ICU. The wash-out of cytokines together with hemodynamic stability gave optimal circumstances for recovery of the transplanted organs. CVVH-based therapy offered stable intraoperative parameters, prevention of fluid overload, correction of metabolic disturbances, and wash-out of cytokines, which gave optimal circumstances for recovery of transplanted organs.
Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We ... more Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The proportion of ALF among the indications for OLT was lower (5.8% vs 9%) and early mortality higher than the European Liver Transplant Registry (1 year cumulative patients survival is 70% in ELTR vs 60% in the HU LT Program). The waiting time for a donor was longer than expected in the Eurotransplant community. Regarding postoperative complications, there was a higher incidence of initial poor function, bacterial infection, sepsis, and multiorgan failure. We conclude that ALF can be managed with reasonable results but requires an extended donor pool with an integrated international network to improve postoperative morbidity and mortality.
There are only few malignant tumours where organ transplantation is the treatment of choice. Tran... more There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapies may help prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The greatest experience with this procedure is in Asia. Despite the favourable results, LT as the treatment of HCC is debated and raises several questions: regarding indication and expectable outcome. Milan criteria seem to answer this questions although they are too strict. The number and size of HCC foci per se is not sufficient predictor of eligibility to transplantation and for prognosis. Majority of the prognostic factors can be evaluated only after transplantation with pathological examination of HCC. Aim of the present research is to find prognostic factors that are characteristic of biological behaviour of HCC, which can be detected before LT in order to select patients who have the greatest benefit from LT. Re-definition of eligibility criteria is an actual question; an international consensus based on additional prospective studies is required for the "new" recommendation.
Magyar Sebészet (Hungarian Journal of Surgery), 2008
Subcapsular hematoma and/or rupture of the graft is uncommon but serious complication of liver tr... more Subcapsular hematoma and/or rupture of the graft is uncommon but serious complication of liver transplantation. It may develop spontaneously or following parenchymal injuries or percutaneous transhepatic invasive procedures. This report describes three cases of subcapsular hematoma and/or rupture of the graft with different courses among 350 liver transplantations. In the first case, the patient died due to graft rupture caused by a pseudoaneurysm after biopsy. In the second case, a small injury of the donor liver resulted in a deep rupture, which required partial resection of the graft. The patient died in sepsis later. The third patient presented with a large subcapsular haematoma during transplantation, which was successfully treated. The authors' strategies developed intraoperatively for the management of hematomas. These involve opening and removing of the haematoma, haemostasis with Argon coagulation, which resulted in an adherent Glisson's capsule to the parenchyma and covering with collagen fleece coated with fibrinogen and thrombin.
Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (M... more Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.
To predict the change in patient status and differentation of the basic diseases, endogenous thro... more To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (...
Abstract: Malignant diseases are considered as great challenges in clinical transplantation. It i... more Abstract: Malignant diseases are considered as great challenges in clinical transplantation. It is well known that the incidence of malignancy is higher in the transplanted population if compared with the normal population. It is important to distinguish between neoplastic diseases ...
The authors report a case of 47 years patient, who underwent successful combined liver-kidney tra... more The authors report a case of 47 years patient, who underwent successful combined liver-kidney transplantation. The primary cause of cirrhosis was HCV infection combined with membranoproliferative glomerulonephritis, witch resulted end stage kidney and liver disease. One and half year after operation the patient has full rehabilitation. By the case report the authors overview the indications and techniques of combined kidney-liver transplantation.
Although experimental autologous patch or tubular conduit vascular grafts made from the internal ... more Although experimental autologous patch or tubular conduit vascular grafts made from the internal rectus fascia sheath (IRFS) have been reported in the literature, thorough morphological evaluation and verification of the histological arterialisation of such grafts are lacking. Four purpose-bred Beagle dogs were utilised to create eight arterial internal rectus fascia sheath (ARFS) grafts implanted between bisected ends of the external iliac arteries. Four out of the eight ARFS grafts were patent after three months. Haematoxylin-eosin and Azan staining verified that the grafts gained a vessel-like layered structure with the presence of large amounts of collagen fibres. Although the inner surface of the intact IRFS was originally covered with claudin-5-negative and pancytokeratin-positive mesothelial cells in control samples, the internal cells of the ARFS grafts became claudin-5 positive and pancytokeratin negative like in intact arteries. Spindle-shaped cells of the wall of ARFS grafts were α-smooth muscle actin (α-SMA) positive just like the smooth muscle cells of intact arteries, but α-SMA immunoreactivity was negative in the intact IRFS. According to these findings, the fibroblast cells of the ARFS graft have changed into myofibroblast cells. The study has proved that ARFS grafts may be used as an alternative in arterial replacement, since the graft becomes morphologically and functionally similar to the host vessel via arterialisation.
Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in... more Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.
The authors give an overview on the role of drug metabolizing enzymes in the effect and side-effe... more The authors give an overview on the role of drug metabolizing enzymes in the effect and side-effect of drugs. They describe the properties of cytochrome P450 and other phase I enzymes (hydrolases, flavin-monooxygenases), as well as of phase II. enzymes (glucuronyl-, sulfate-, glutathione-, acetyl-, methyltranferases), their polymorphism, inductive and inhibition properties. The possible drug-drug interactions are discussed in detail.
Objectives: Hepatitis C virus (HCV) recurrence after liver transplantation is universal and leads... more Objectives: Hepatitis C virus (HCV) recurrence after liver transplantation is universal and leads to chronic hepatitis and cirrhosis. Combined interferon and ribavirin therapy represents the accepted treatment for recurrent chronic hepatitis C following liver transplantation, according to the literature. Our aim was to assess the efficacy and safety of the recommended combined interferon and ribavirin therapy, and evaluation of the rate of long-term remission under Hungarian circumstances. Methods: 16 patients with chronic recurrent hepatitis C, who had been HCV-PCR positive (genotype 1b), received combined treatment with interferon-alpha-2b (3 MU three times a week) and ribavirin (800-1000 mg daily) for 12 months following transplantation. 12 patients have completed the therapy. Liver biopsies were performed before commencing and after concluding treatment in every patient. Virological responses at completion of the 12-month-long treatment and at the end of the subsequent 6-month-l...
The number of patients suffering from kidney disorders is increasing the need for kidney transpla... more The number of patients suffering from kidney disorders is increasing the need for kidney transplantation. Kidneys originating from living donors (LD) show substantially better results than those originating from cadaveric donors (CD). We performed 3000 kidney transplantations between November 1973 and December 2007, including 154 from LD (5.13%). The early kidney function as measured by the delta creatinine clearance was significantly better among the LD group (P < .001). There was no significant difference in the immunologic data between the LD and the CD groups (P = .047). Four years after transplantation the glomerular filtration rate (GFR) and the serum creatinine level treated to be better among the LD group with tacrolimus versus cyclosporine immunosuppression (P = .089). In the LD group, the acute rejection rate was lower with tacrolimus- versus cyclosporine based immunosuppression (P = .014).
Hypercholesterolemia and xanthomatosis are known complications of chronic cholestasis. This is th... more Hypercholesterolemia and xanthomatosis are known complications of chronic cholestasis. This is the first report on xanthomatosis and severe hypercholesterolemia caused by common bile duct stenosis following laparoscopic cholecystectomy. Laparoscopic cholecystectomy was performed in a 32-year old woman because of numerous tiny gallstones. Bile leakage was observed in the early postoperative period which stopped spontaneously. Six months later itching, progressively increasing serum bilirubin level, cholestasis syndrome, xanthelasma and widespread eruptive xanthomatosis developed in a few months. The cholesterol level was extremely high (92.3 mmol/l), while the triglyceride level was normal. Though the ultrasound and the cholangio-MR did not showed any dilatation of bile ducts, the ERCP verified a 2 mm long, hair's-breadth thin stenosis of choledochus in the level of cystic duct. Primary biliary cirrhosis and primary sclerosing cholangitis were excluded, no evidence for familial h...
New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotop... more New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotopic liver transplantation (OLT). The diabetogenic effect of hepatitis C virus (HCV) infection is well known. The aim of this study was to analyze the glucose homeostasis before and after OLT. The oral glucose tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4) activity was measured. The study period was from 2012 to 2014. We enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients after OLT (group B). Seven patients were monitored continuously both before and after OLT. According to our preoperative OGTT results, 13 patients in group A had newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed (group A/NGT). The calculated homeostasis model assessment insulin resistance (HOMA2-IR) values were both in group A/DM and-IGT higher compared with group A/NGT (2.42 ± 0.81 vs 2 ± 0.98 vs 1.28 ± 0.67; P = .001). In the case of HCV infection (n = 14; 29%) DM and IGT were more frequent. Six patients in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that in patients with all other indications for OLT (15.5 ± 5.2 vs 8.7 ± 3.5; P = .008). We evaluated the same individuals before and after OLT (n = 7), and a decrease in β-cell function was noted. Preoperative OGTT is an important and easy investigation to rule out glucose imbalance before OLT. The HOMA2 calculation can also be useful both in preoperative and postoperative risk assessment. In our results, DPP-4 activity is not specific for the type of glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4 inhibitors can be effective in the therapy of NODAT, especially in HCV-infected patients.
Availability of suitable donor organs has always limited the number of liver transplantations per... more Availability of suitable donor organs has always limited the number of liver transplantations performed. Use of marginal donor organs is an alternative to overcome organ shortage. To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation. Data from 260 whole-liver transplantations performed between January 2003 and September 2009 were analyzed retrospectively. Study groups were established according to donor organ quality (marginal score 0-1 vs 2-5) and recipient status (Model for End-Stage Liver Disease [MELD] score <17 or >17). In patients at low risk, 102 received optimal grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B]. No differences were observed in cumulative patient and graft survival rates; however, total survival differed in the early period after transplantation, that is, within 1 year. There was a higher rate of overall postoperative complications including initial poor graft function, bleeding, infection, and kidney failure in group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) (P = .04). Patients with a high MELD score (G/B and B/B) demonstrated increased risk of postoperative complications. Use of donor organs with marginal score of 2 or higher in patients with high MELD scores increased early patient mortality. In summary, patients with a high MELD score (G/B and B/B) are at an increased risk of post-OLT complications. In contrast, use of marginal grafts (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased the response rate to antiviral therapy. The combination of impaired donor grafts and recipients at high risk should be avoided.
Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with goo... more Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with good graft survival rates. Previous studies have shown beneficial effects of renal replacement therapy in critically ill patients. This observation led us to use intraoperative continuous veno-venous hemofiltration (CVVH) during multiorgan transplantations. We analyzed (CRP) inflammatory response parameters of tumor necrosis factor (TNF)alpha, interleukin(IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) at various stages of the combined transplantations. All patients survived with well-functioning grafts. Mean +/- SD follow-up was 32.8 +/- 14.2 months. During the whole operation we used intraoperative CVVH starting at the beginning and continuing in the intensive care unit (ICU) afterward (mean +/- SD, 11.2 +/- 8.4 hours). Intraoperative TNFalpha, IL-6, CRP, and PCT were measured before surgery, during hepatectomy in the anhepatic phase, before and after liver reperfusion, exactly before kidney reperfusion, after kidney reperfusion, and upon arrival in the ICU. The wash-out of cytokines together with hemodynamic stability gave optimal circumstances for recovery of the transplanted organs. CVVH-based therapy offered stable intraoperative parameters, prevention of fluid overload, correction of metabolic disturbances, and wash-out of cytokines, which gave optimal circumstances for recovery of transplanted organs.
Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We ... more Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The proportion of ALF among the indications for OLT was lower (5.8% vs 9%) and early mortality higher than the European Liver Transplant Registry (1 year cumulative patients survival is 70% in ELTR vs 60% in the HU LT Program). The waiting time for a donor was longer than expected in the Eurotransplant community. Regarding postoperative complications, there was a higher incidence of initial poor function, bacterial infection, sepsis, and multiorgan failure. We conclude that ALF can be managed with reasonable results but requires an extended donor pool with an integrated international network to improve postoperative morbidity and mortality.
There are only few malignant tumours where organ transplantation is the treatment of choice. Tran... more There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapies may help prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The greatest experience with this procedure is in Asia. Despite the favourable results, LT as the treatment of HCC is debated and raises several questions: regarding indication and expectable outcome. Milan criteria seem to answer this questions although they are too strict. The number and size of HCC foci per se is not sufficient predictor of eligibility to transplantation and for prognosis. Majority of the prognostic factors can be evaluated only after transplantation with pathological examination of HCC. Aim of the present research is to find prognostic factors that are characteristic of biological behaviour of HCC, which can be detected before LT in order to select patients who have the greatest benefit from LT. Re-definition of eligibility criteria is an actual question; an international consensus based on additional prospective studies is required for the "new" recommendation.
Magyar Sebészet (Hungarian Journal of Surgery), 2008
Subcapsular hematoma and/or rupture of the graft is uncommon but serious complication of liver tr... more Subcapsular hematoma and/or rupture of the graft is uncommon but serious complication of liver transplantation. It may develop spontaneously or following parenchymal injuries or percutaneous transhepatic invasive procedures. This report describes three cases of subcapsular hematoma and/or rupture of the graft with different courses among 350 liver transplantations. In the first case, the patient died due to graft rupture caused by a pseudoaneurysm after biopsy. In the second case, a small injury of the donor liver resulted in a deep rupture, which required partial resection of the graft. The patient died in sepsis later. The third patient presented with a large subcapsular haematoma during transplantation, which was successfully treated. The authors' strategies developed intraoperatively for the management of hematomas. These involve opening and removing of the haematoma, haemostasis with Argon coagulation, which resulted in an adherent Glisson's capsule to the parenchyma and covering with collagen fleece coated with fibrinogen and thrombin.
Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (M... more Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.
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Papers by László Kóbori