[Development of immunosuppressant treatment after liver transplant]. / Vývoj imunosupresivní lécby po transplantaci jater.

The history of liver transplants extends over more than 60 years. During the first 10 years the operations were carried out only as experiments and primarily focused on designing complex surgical techniques. In the 1960s the research focused on the development of immunosuppressants and the first clinical operations were performed. However, the outcomes of these interventions were very poor. The subsequent 2 decades witnessed the development of new and very efficient immunosuppressants, significantly improving patient survival rates. The number of operations and sites performing these interventions increased. In the United States in 1983, liver transplants were recognised as a clinical treatment method for liver conditions where all conservative options had failed. In the same year the first successful liver transplant was performed in Czechoslovakia. New surgical techniques bringing significant reduction of blood loss during the operation, reduction of over  extensive grafts, splitting operations -  when one organ may be used for 2 recipients -  and collection of liver lobes from living donors resulted in a further increase in the number of transplants. The development of new immunosuppressive protocols have contributed to further improved survival rates of the patients while the majority of transplant sites achieve the longterm survival of 90%. However, the future of transplants lies in inducing the immunological tolerance of the body towards the transplanted organ with no immunosuppressive treatment administered.

[Interventional radiology options to address certain complications of the orthotopic liver transplant]. / Moznosti intervencní radiologie pri resení ne-kte-rých komplikací ortotopické transplantace jater.

At the clinic of imaging method St. Annas University Hospital solved complications arising after ortotopic liver transplantation. For more than 15 years of cooperation with CKTCH Brno intervention was performed on both the arterial and venous system, but most on the biliary tract. The order was a unit patients, which correlates with other comparable work. In the years 1998- 2013 we conducted one intervention on arterial bed, 3× intervention in hepatic venous system and we solved biliary complications in 7 transplant. .

[Treatment of hepatocellular carcinoma and current situation in the Czech Republic]. / Lécba hepatocelulárního karcinomu a soucasný stav v Ceské republice.

Hepatocelullar carcinoma (HCC) is the commonest primary liver malignacy. Its incidence is increasing worldwide. In the Czech Republic, about 250 new cases are reported per year. The patient's prognosis depends on early diagnosis and initiation of a correct therapeutical procedure. During the decision making process, tumor staging, as well as the chronic liver disease stage, must be considered. Surgery, i.e. liver resection or transplantation, is the only potentially curable method. Other treatment options include chemoembolization, radiofrequency ablation, alcoholization and, currently poorly effective systemic chemotherapy. Current monitoring of the radical procedures in the Czech Republic is unsatisfactory. Although surgical treatment has been performed by many clinics, based on the available data, none of the following could be assessed: the number of surgically managed HCC patients in the Czech Republic per year, disease staging in these patients and their short-term and long-term treatment outcomes. In the Czech Republic, 45 liver transplantations have been performed, data on resection procedures are not available. The aim of the authors is to support the Central HCC Patient Registry, presented at the following website: www.koc.cz.

[Liver transplantation for hepatitis B]. / Transplantace jater pro hepatitidu B.

Up to now the outcomes of liver transplantation in patients with chronic viral hepatitis B have not been very good because the recurrence of viral hepatitis in the graft has been high and resulted in a high early graft failure of liver transplant recipients. However, the administration of a combined therapy with lamivudine and hyperimmune anti-HBs globulin has led to a marked improvement in transplantation results and an increase in the number of liver transplantations for this indication. Four men (aged 47 to 55 years) underwent liver transplantation for cirrhosis, caused by chronic viral hepatitis B, at our centre. All were HBsAg carriers. They were our first patients who received therapy with the combined immunoprophylactic regimen of lamivudine and hyperimmune anti-HBs globulin. HBV DNA negativity was achieved in all patients prior to transplantation; three of them were pretreated with lamivudine. At 4 to 17 months of follow-up, sustained suppression of HBV replication (HBV DNA negativity) was maintained in all four patients. No complications associated with this treatment were observed and no emergence of resistant mutants was detected. The combined therapy for chronic viral hepatitis B administered to liver transplant recipients at our centre showed very good outcomes. However, the development of resistant mutants during this therapy poses a problem, which may hopefully be overcome with the use of new antivirotics, such as adefovir or tenofovir.

[The role of liver transplantation in clinical practice]. / Místo transplantace jater v klinické praxi.

The first succesful liver transplantation was made in USA in 1967. These operations had been made only in few centres in the world until the 80-ies of the last century and the results were not so good. However, along with the development of surgical techniques, immunosuppression and postoperational care the results of these operations significantly improved and their amount increased. The liver transplantation was declared the clinical therapy in USA in 1983. In the same year there was made a succesful liver transplantation in Czech republic too. Nowadays there is annually made approximately 10,000 such operations worldwide. During the last decade it is also in Czech republic where the liver transplantation has become an available therapeutic method. There are two workplaces (CKTCH Brno and IKEM Prague) where 70 such operations are made every year. The results of one-year survival are more than 90% and the long-term results and the quality of life of the patients are also very good. The liver transplantation has experienced a dynamic development in the 90-ies of the 20th century and at the edge of the millenium. There were made significant changes in the field of indications and contraindications for transplantation and immunosuppressive therapy. There developed a brand new surgical techniques making possible to use the organs of the donors who are too big, so-called reduction of the implants. Another option constitute so-called split operations when one implant may be divided into left and right lobes and thus each of them may be used separately for the two donees. Due to the significant regeneration ability of the liver tissue it is possible to make the collection of the parts of the liver from the living donor. According to the statistics of the european countries the optimal need should be 10 transplantations/1 million of inhabitants per year. The difference between the need and the real amount of operations in our country is not given by the disability of the transplantation centres to make these operations but by the fact that many suitable patients are not offered this therapeutic modality at all.

[The results of kidney transplantation from very young paediatric cadaveric donors to adult recipients in Czech Republic in the years 1994-2001 (retrospective study of the Czech transplant centres)]. / Výsledky transplantací ledvin od malých detských kadaverózních dárcu dospelým príjemcum v Ceské republice v letech 1994-2001 (Retrospektivní studie ceských transplantacních center).

The results of kidney transplantation from very young paediatric cadaveric donors up to five years, which were transplanted to adult recipients, are evaluated in the first retrospective study of all Czech transplantcentres. In general, 42 of these transplantations were carried out during 1994-2001. In 28 cases single kidney was transplanted, in 14 cases en bloc graft of both children kidneys was transplanted. The reasons of kidney failure by recipients are usual (in 42.9% glomerulonephritis). An average age of the donors was 34.7 months (median 39 months). An average age of the recipients during transplantation was 42.6 years (median 43.5 years). All the kidneys were placed into retroperitoneum. As long as only single kidney was transplanted, the rules, already propagated by Salvatiera in 1970, were respected. At the transplantation of en bloc graft, Kinne's method with possible vessels elongation of the graft and with uretero-uretero anastomoses (in so called Ostrava modification) was used. The higher occurrence of the primary graft non-function (as 50% losses of all grafts) was confirmed in the study. Its reason was an acute thrombosis of vessels or rotation of graft stem. One-, three- and five-years patients and grafts survival were 97.6-90.5-90.5% and 76.2-73.8-73.8% actually. Patients survival are very good while grafts survival are average, momentarily a bit worse than national data published by the Czech Transplant Society, which determines one-, three- and five-years grafts survival with 90.3-82.9-75.5% and 79.1-71.1-65% actually. The kidney transplantation from paediatric cadaveric donors to adult recipients is acceptable under present allocated criteria, in case that some principles are kept. The study confirms the international experiences about rather higher incidence of surgical complications and primary graft non-function. In conclusion, some general references for reduction of complications, as well as for improvement of these transplantation results are introduced.

Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.

OBJECTIVES: This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids. METHODS: In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months. RESULTS: Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S). CONCLUSION: Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.

[TT virus infection in liver transplant recipients with cryptogennic cirrhosis]. / Infekce TT virem u príjemcu jater transplantovaných pro "kryptogenní cirhózu".

The possible causative role of novel TT virus in liver diseases has been intensively studied in regarding its hepatotrophy, ability to cause persistent infection and worldwide prevalence. The aim of this study was to estimate the prevalence as well as the clinical importance of TTV in a normal healthy population group in the Czech Republic and in a group of liver transplant recipients diagnosed with cryptogenic cirrhosis. Polymerase chain reaction (PCR) detected the DNA of TT virus in 68% (13/19) of samples isolated from peripheral blood leukocytes and in 21% (4/19) of plasma samples in the liver transplant group. The viral DNA was detected only in 11.8% (4/34) of leukocytes and in no plasma sample from the healthy population control group. All patients included in this study had good liver function and had no complications during the postoperative period. The prevalence of TTV DNA detection in healthy control group in Czech republic is similar to the rates reported in European and North American countries. Significant difference was proved between the prevalences of TTV in the groups of healthy controls and liver transplant recipients with cryptogenic cirrhosis. However, no association of TTV infection with possible postoperative complications could be found.

Peri- and post-operative course of cytokines and the metabolic activity of neutrophils in human liver transplantation.

Peri- and post-operative (up to day 7 after surgery) neutrophil chemiluminescence and the plasma concentrations of interleukin 6 (IL-6), IL-8, IL-10 and tumour necrosis factor alpha (TNF-alpha) were evaluated in the blood of patients undergoing liver transplantation. IL-6, IL-8 and IL-10 levels increased during early reperfusion and then returned to normal mostly within the first post-operative day. TNF-alpha was increased during the whole period observed. Spontaneous as well as activated neutrophil chemiluminescence was depressed in early reperfusion and remained low during the whole period followed. Samples collected during early reperfusion provided positive correlation for IL-6 vs IL-8 as well as for IL-6 and IL-8 vs chemiluminescence. The data were also evaluated with respect to the outcome of transplantation. Since IL-8, IL-10 and TNF-alpha levels increased significantly during the first post-operative week, mainly in a group of patients who developed serious complications within the first month after surgery, we proved a connection between peri- and early post-operative induction of cytokine release and the outcome of liver allograft transplantation.

Biliary complications in liver transplantation.

OBJECTIVES: Biliary complications (BC) continue to be a major cause of morbidity among liver transplant recipients. The aim of this study was to analyse the incidence, risk factors and management of biliary tract complications at the Centre for Cardiovascular Surgery and Transplantations in Brno. METHODS: Between January 1992 and December 2000, 118 orthotopic LT were performed in 113 patients. Reconstructions of biliary tract included four methods: end-to-end choledochocholedochostomy with a drain in the retained gallbladder in 15 cases, end-to-end or side-to-side choledochocholedochostomy with a T tube in 29 cases, end-to-end choledochocholedochostomy without a T tube in 67 cases and choledochojejunostomy over the drain in 7 cases. Biliary complications were divided into three groups: stenosis, leaks and cholangitis. RESULTS: Biliary complications occurred after 33 LT (27.9%), affecting 28.3% of the recipients. They occurred most frequently when CCwT or CJ types of reconstruction were used (44.8% and 57.1%, respectively) and least frequently in the CCw/oT group of patients (16.4%). The most common type of biliary complication was stenosis which occurred in 20 patients (in 12 at the anastomotic site, in 5 it was caused by external compression and 3 had nonanastomotic strictures); biliary leaks were in 13 patients and cholangitis in 10 patients. Twenty three biliary complications occurred in the early postoperative period and 12 during the follow-up. Endoscopic treatment was used as primary therapy in 17 patients, primary surgical intervention was used in 12 patients and five patients were treated conservatively. Five patients died due to biliary complications (mortality, 15.1%). CONCLUSIONS: It can be concluded that BC is a common cause of morbidity after LT. In the last few years, its frequency has remained constant. Technical failure or local ischemia are major causes. Biliary leaks predominate in the early posttransplant period. Since end-to-end choledochocholedochostomy without a T tube is associated with the lowest incidence of BC, it is considered to be the method of choice. BC can usually be managed endoscopically, although early leaks frequently require reoperation. Aggressive and early management of BC can reduce mortality in patients after LT.

[The piggyback technique in venous outflow tract reconstruction in liver transplantation]. / Význam piggyback techniky pri rekonstrukci venózního odtoku pri transplantaci jater.

Nowadays, the piggyback technique of venous outflow tract reconstruction has been adopted by an increasing number of transplant teams. From January 1996 to August 2000, we used it in 73 of 84 liver transplantations (86.9%) in our institution. We observed one postoperative complication (1.4%) in direct relation to this technique. The main advantages of the piggyback are 1. maintaining of the haemodynamic stability during the anhepatic phase, 2. avoiding of the veno-venous bypass, 3. diminution of blood loss, 4. easier solution of the graft size mismatch problem, 5. shorter manipulation time and 6. easier retransplantation. Disadvantages of the piggyback technique include 1. more technically demanding recipient's hepatectomy, 2. the potential for venous outflow tract obstruction and 3. possible thrombosis in a blind caval pouch. According to our results and experience in the literature, we consider the piggyback technique as a method of choice for venous outflow tract reconstruction in liver transplantation. It can be used in the majority of patients after gaining some experience.

Hemodynamic measurement in liver transplantation. Piggyback versus conventional techniques.

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Maintaining caval flow during the anhepatic phase with hemodynamic stability is regarded as one of the main advantages of this method. Between November 1994 and November 1998, the piggyback technique was used in 47 patients in our Center. Hemodynamic measurements during the operation showed hyperdynamic circulation with an increase in cardiac output (9.3+/-3.5 L/min) and the calculated cardiac index (5.0+/-1.9 L/min/m2). There was a statistically significant increase in heart rate and a decrease in systolic arterial pressure, cardiac output (CO) and cardiac index (CI) during inferior vena cava clamping ( simulated conventional technique). Only a non-significant decrease in CO and CI was observed during the partial clamp on the inferior vena cava (piggyback technique). Out of those two techniques, piggyback proved to be a safer approach to venous outflow tract reconstruction from the hemodynamic point of view.

[Lipid disorders in liver diseases]. / Poruchy lipidu u jaterních onemocnení.

The liver is the main organ of cholesterol, triglyceride metabolism and lipoprotein synthesis. In diffuse parenchymatous diseases which lead to cirrhosis of the liver a decline of VLDL and HDL particles occurs, as well as a decline of apo-B, apo-E lipoprotein (a). In cholestatic diseases the levels of free cholesterol, phospholipids and sometimes also triglyceride levels rise, in the termonal stage they decline again. A specific marker of cholestasis is the presence of abnormal lipoprotein X, which is formed from non-esterified cholesterol and phsopholipids regurgitating from bile. Primary lipid disorders may then cause liver disease--steatosis. The main risk factors are hypertriglyceridaemias. In the pathogenesis of liver steatosis in particular an increased supply of fatty acids into the liver, is involved, as well as defects in the process of VLDL synthesis and triglyceride release from the liver into the circulation. Hypercholesterolaemia is not a risk factor of steatosis.

[Reconstruction of the venous outflow in liver transplantation using the "piggyback" technique]. / Rekonstrukce venózního odtoku pri transplantaci jater "piggyback" technikou.

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Between November 1994 and November 1997 this technique was used in 29 patients in our institute. Most of the patients were operated on without veno-venous bypass and we observed no complications concerning venous outflow tract reconstruction and no renal failure. Hemodynamic measurements during the operation showed only an insignificant decrease in cardiac index during the partial clamp on the inferior vena cava. The piggyback technique proved to be a convenient and safe approach to the venous outflow tract reconstruction in a majority of liver transplantations and has been used routinely in our institute.

[Kidney transplantation at the Brno Transplantation Center]. / Transplantace ledvin v transplantacním centru Brno.

The transplantation activity in the Brno TC has increased significantly since 1994 and there are now 30 transplantations per 1 million population of the catchment area per year. It is, however, necessary to get more organ donors to attain the national average of 40 renal transplantations per 1 million inhabitants per year, which is also the average value in advanced European countries. With the use of immunosuppression with cyclosporin A the one, five and ten-year survival of grafts increased by 20, 35 and 15% resp., as compared with the period of conventional immunosuppression. The greatest losses of grafts were recorded in the Brno TC during the first year after transplantation and they accounted roughly for 25% during immunosuppression without and immunosuppression with cyclosporin A. The graft losses due to rejection declined from 63 to 21%. However, there was no decline of graft losses for non-immune reasons which accounted during all investigated time intervals for cca 20%. The ratio of graft losses on surgical--urological grounds did not change (before cyclosporin A, 5.9%, and with immunosuppression with cyclosporin A 6.6%). Also graft losses due to the recipient's death declined only insignificantly (14.4% before CyA and 8.4% with CYA). The most frequent causes of death of recipients were infections (40%), followed by cardiac deaths and haemorrhagic conditions (17% in both instances). The high rate of infections is due to aggressive immunosuppressive regimes and large doses of corticoids. Revision of immunosuppressive regimes and protective procedures is necessary. Haemorrhagic conditions such as disseminated coagulopathies remain unexplained so far. The cardiac deaths are associated above all with the rising age of renal transplant recipients and in the majority these deaths could not be prevented (acute myocardial infarctions and sudden deaths at home).

[Fulminant liver failure in poisoning by Lepiota helveolla Bres]. / Fulminantní jaterní selháni po otrave bedlickou chrapácovou.

The authors describe an uncommon and severe intoxication with the mushroom Lepiota Helveolla Bres. which manifested itself by fulminant hepatic failure. The possibility of urgent transplantation of the liver was considered. After conservative treatment the patient recovered, however, completely. In the conclusion the authors' view is discussed as regards indications of urgent transplantation of the liver in intoxications with mushrooms which may cause fulminant hepatic failure.

[Anti-anemia therapy with prophylactic administration of Fe2+ in normal pregnancy and its effect on prepartum hematologic parameters in the mother and neonate]. / Antianemická lécba fyziologických tehotných a její vliv na prepartální hematologické parametry matky a novorozence profylaktickým podáním Fe2+.

Eighty-four non-anaemic pregnant women were treated, starting between the 20th-24th week of Pregnancy, with Actiferrin Compositum--1 capsule per day--from the 36th with 2 capsules per day up to childbirth. The group was compared with the results in 57 non-anaemic not treated pregnant women. Haematological parameters were recorded before the onset of treatment, during the first stage of labour and in neonates on the first day after delivery. By means of the non-paired t-test no significant differences were disclosed between the groups; nevertheless the percentage values of haemoglobin, haematocrit, erythrocytes and serum iron were higher in the treated group, as compared with the non-treated one. Also the ferritin values in neonates of the non-treated group were lower, as compared with the treated group. The paired t-test was highly significant in the Actiferrin treated patients as regards haemoglobin, haematocrit and transferrin values. The results provide evidence that it is indicated to administer as a routine measure Actiferrin Compositum to all pregnant women as prevention of pre-partum anaemia of the mother and low ferritin levels in the neonate.