Zsuzsa Gerlei

Analysis of differences in outcome of two European liver transplant centers

Authors analyzed the differences in the outcome of two European liver transplant centers differing in case volume and experience. The first was the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the second the University Medical Center Groningen, Groningen, The Netherlands (UMCG). We investigated if such differences could be explained. The 1‐, 3‐ and 5‐year patient survival in the UMCG was 86%, 80%, and 77% compared with 65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%, and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were present regarding the donor and recipient age, diagnosis mix, disease severity and operation variables, per‐operative transfusion rate, vascular complications, postoperative infection rate, and need for renal replacement. To determine factors correlating with survival, a separate uni‐ and multivariate analysis was performed in each center individually, between study parameters and patient survival. In both centers, peri‐operative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. The difference in blood loss can be explained by different operation techniques and shorter operation time in SEB, with consequently less time spent on hemostasis. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity.

Biliary complications following orthotopic liver transplantation. The Hungarian experience

INTRODUCTION The authors summarize the characteristics of biliary complications following liver transplantation in the Hungarian liver transplant program. Aims were to analyze the frequency and the types of biliary complications as well as their effect on the patient and graft survival. The authors observed the known risk factors in the Hungarian practice, and they also try to find unknown risk factors for biliary complications. They review the therapy of biliary complications. METHOD In the retrospective study, patients were divided into two groups, with and without biliary complication after liver transplantation. These two groups were compared with many factors, and with the survivals. The biliary complication group was divided into two parts: those who had an early and those with a late biliary complication. These two new groups were also compared with the controls. The results are summarized in tables and statistical figures. Categorical variables are evaluated by chi 2 -test, continuous ones are with Levine Test (for homogenicity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis. RESULTS Biliary complication appeared in 25% of the patients. The most frequent complications were stenosis (18%), biliary leakage (9%), biliary necrosis (6%), and ischaemic type of biliary lesions (3%). The 5-year survival is worse when biliary complications were diagnosed (55%) than without such a complication (66%). In the biliary complication group the retransplantation rate was higher (15%). The most frequent treatments were interventional radiologic methods (69%), surgical methods (17%), and the ERCP. CONCLUSIONS The rate of biliary complications met the international reviews. Risk factors for biliary complications were cholangitis, hepatic artery thrombosis and stenosis, high rate of intraoperative blood transfusions, and acute rejection. Biliary complications frequently associated with the initial poor function of the transplanted graft. Early biliary complications have a negative impact on patient survival, while late complications influence a decreased quality of life. Biliary complications were treated mostly by interventional radiologic procedures.

The recurrence of hepatitis C virus after liver transplantation

A hazai majatultetesi programban magas a hepatitis C-virus (HCV) okozta vegstadiumu majbetegseg miatt vegzett majatultetesek aranya. Celkituzes: A szerzok dolgozatukban elemzik a C-hepatitis miatt majatultetesen atesett betegek adatait. Modszer: Az 1995 ota vegzett 295 primer majatultetes adatainak retrospektiv elemzese: donor- es recipiens-, valamint perioperativ es tulelesi adatok, szerumvirus-RNS-titer, percutan majbiopsziak szovettani eredmenyei. Eredmenyek: A mutet 111 betegnel tortent HCV-fertozes miatt, ez az elvegzett majatultetesek 37,6%-a. A vizsgalt 111 beteg kozul 22 beteg (20%) a posztoperativ idoszakban, a virus kiujulasanak eszlelese elott, egyeb okbol meghalt. A 89 beteg kozul 16 esetben (18%) a virus visszatereset meg nem eszleltek, 73 betegnel (82%) azonban a virus kiujulasa szovettanilag igazolhato volt. Negyven betegnel (56%) a C-virus okozta hepatitis kiujulasat egy even belul eszleltek, kozuluk 28 esetben (39%) 6 honapon belul, 12 esetben hat honapon tul, de 1 even belul (17%), es 32 betegnel (44%) egy even tul. A vegstadiumu C-cirrhosis miatt majatultetett betegek kumulativ 1, 3, 5 es 10 eves tulelese 73%, 67%, 56% es 49% volt. A HCV-negativ, majatultetett betegeknel ezek az ertekek 80%, 74%, 70% es 70%, a kulonbseg szignifikans. A majgraft kumulativ tulelese HCV-pozitiv betegeknel 72%, 66%, 56% es 49% volt, mig HCV-negativ betegeknel 76%, 72%, 68% es 68%, itt nem szignifikans a kulonbseg. Korai kiujulas eseten szignifikansan magasabb szerumvirus-RNS-titert mertek az elso 6 honapban majatultetes utan. A majatultetes utan 6 honappal vett protokollbiopszia korai kiujulas eseten magasabb Knodell-pontszamot eredmenyezett, mint kesoi kiujulaskor. A fibrosisindex eseteben ez forditva volt. A majatultetestol az elso antiviralis kezelesig eltelt ido 1995–2002 kozott atlagosan 20 honap volt, 2003 ota 8 honap. Kovetkeztetesek: Az idosebb donorokbol szarmazo, marginalis majgraftok magasabb vertranszfuzio-igeny mellett torteno beultetese elorevetiti a hamarabb bekovetkezo virusrekurrenciat. Ezt a tendenciat erositi a posztoperativ akut rejectio es az emiatt adott szteroid boluskezeles. A kombinalt antiviralis kezeles protokollja kulonbozik az altalanosan alkalmazottol: az un. „stopszabaly” nem ervenyes. Virusnegativva a betegek csak kevesebb mint 10%-a valik, melynek a fenntartott immunszuppresszio az oka. A majatultetes utan koran, akar fel even belul elkezdett antiviralis kezeles a beteg- es grafttulelest pozitivan befolyasolja, es feltehetoen csokkenti a HCV-reinfekcio miatti retranszplantaciok szamat. A masodik majatultetesnel akkor varhatok jo eredmenyek, ha idoben tortenik, a recipiens meg megfelelo fizikai allapota mellett. Ennek megiteleseben a MELD-score segit. Kulcsszavak: majatultetes, hepatitis C-virus, interferon, rekurrencia, retranszplantacio, tuleles The recurrence of hepatitis C virus after liver transplantation. The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. Aim: Authors present the results of liver transplantations performed due to HCV infection. Method: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. Results: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recur

Hepatitis B and liver transplantation

The authors overview the results of liver transplantations of HBV patients in Hungary. The special needs of pre- and postoperative period of HBV infected patients in the treatment are discussed. 4 patients were transplanted because of HBV cirrhosis. 1 patient died in the early postoperative period, 3 patients are well and active. The authors also overview the de novo HBV infections in transplanted patients, found in 6 cases.

Hepatitis C-vírus kiújulása májátültetés után

A hazai majatultetesi programban magas a hepatitis C-virus (HCV) okozta vegstadiumu majbetegseg miatt vegzett majatultetesek aranya. Celkituzes: A szerzok dolgozatukban elemzik a C-hepatitis miatt majatultetesen atesett betegek adatait. Modszer: Az 1995 ota vegzett 295 primer majatultetes adatainak retrospektiv elemzese: donor- es recipiens-, valamint perioperativ es tulelesi adatok, szerumvirus-RNS-titer, percutan majbiopsziak szovettani eredmenyei. Eredmenyek: A mutet 111 betegnel tortent HCV-fertozes miatt, ez az elvegzett majatultetesek 37,6%-a. A vizsgalt 111 beteg kozul 22 beteg (20%) a posztoperativ idoszakban, a virus kiujulasanak eszlelese elott, egyeb okbol meghalt. A 89 beteg kozul 16 esetben (18%) a virus visszatereset meg nem eszleltek, 73 betegnel (82%) azonban a virus kiujulasa szovettanilag igazolhato volt. Negyven betegnel (56%) a C-virus okozta hepatitis kiujulasat egy even belul eszleltek, kozuluk 28 esetben (39%) 6 honapon belul, 12 esetben hat honapon tul, de 1 even belul (17%), es 32 betegnel (44%) egy even tul. A vegstadiumu C-cirrhosis miatt majatultetett betegek kumulativ 1, 3, 5 es 10 eves tulelese 73%, 67%, 56% es 49% volt. A HCV-negativ, majatultetett betegeknel ezek az ertekek 80%, 74%, 70% es 70%, a kulonbseg szignifikans. A majgraft kumulativ tulelese HCV-pozitiv betegeknel 72%, 66%, 56% es 49% volt, mig HCV-negativ betegeknel 76%, 72%, 68% es 68%, itt nem szignifikans a kulonbseg. Korai kiujulas eseten szignifikansan magasabb szerumvirus-RNS-titert mertek az elso 6 honapban majatultetes utan. A majatultetes utan 6 honappal vett protokollbiopszia korai kiujulas eseten magasabb Knodell-pontszamot eredmenyezett, mint kesoi kiujulaskor. A fibrosisindex eseteben ez forditva volt. A majatultetestol az elso antiviralis kezelesig eltelt ido 1995–2002 kozott atlagosan 20 honap volt, 2003 ota 8 honap. Kovetkeztetesek: Az idosebb donorokbol szarmazo, marginalis majgraftok magasabb vertranszfuzio-igeny mellett torteno beultetese elorevetiti a hamarabb bekovetkezo virusrekurrenciat. Ezt a tendenciat erositi a posztoperativ akut rejectio es az emiatt adott szteroid boluskezeles. A kombinalt antiviralis kezeles protokollja kulonbozik az altalanosan alkalmazottol: az un. „stopszabaly” nem ervenyes. Virusnegativva a betegek csak kevesebb mint 10%-a valik, melynek a fenntartott immunszuppresszio az oka. A majatultetes utan koran, akar fel even belul elkezdett antiviralis kezeles a beteg- es grafttulelest pozitivan befolyasolja, es feltehetoen csokkenti a HCV-reinfekcio miatti retranszplantaciok szamat. A masodik majatultetesnel akkor varhatok jo eredmenyek, ha idoben tortenik, a recipiens meg megfelelo fizikai allapota mellett. Ennek megiteleseben a MELD-score segit. Kulcsszavak: majatultetes, hepatitis C-virus, interferon, rekurrencia, retranszplantacio, tuleles The recurrence of hepatitis C virus after liver transplantation. The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C. Aim: Authors present the results of liver transplantations performed due to HCV infection. Method: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report. Results: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recur

The role of marginal donors in liver transplantation. The Hungarian experience

UNLABELLED Availability of suitable donor organs has always limited liver transplantations. Use of marginal donors (Extended Donor Criteria) for liver transplantation is an alternative to overcome the organ shortage. The aim of this study was to analyze the characteristics of organ donation in Hungary with special regard to marginal donors. METHODS We reviewed data from donors and recipients between January 2003 and December 2008 retrospectively. Extended donor criteria were adopted from international recommendations. RESULTS During this period, 1078 donors were reported to the clinic. 835 (77.4%) donors were excluded from liver transplantation and 243 (22.6%) were implanted. From the 243 transplantations 40 recipients (16%) received marginal graft, 203 (84%) received non-marginal graft. Extended Donor Criteria status had no negative impact on the patient and graft survival, postoperative graft dysfunction, and other complications. Recurrence of Hepatitis C occurred earlier in those patients who received marginal graft. CONCLUSION There is an increasing number of patients waiting for liver transplantation in Hungary. There is no significant difference in morbidity and mortality of patients receiving marginal or non-marginal graft. Use of marginal grafts should be avoided in Hepatitis C virus positive recipients. Acceptance of older donors for liver transplantation should be considered.

Kidney function and liver transplantation

INTRODUCTION In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. AIM The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. METHOD Retrospective data analysis was performed after primary liver transplantations (n = 319). RESULTS impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). CONCLUSIONS Selection of personalized immunosuppressive medication has a positive effect on renal function.

Percutaneous transhepatic metallic stent placement for the treatment of post-transplantation portal vein stenosis

UNLABELLED Liver transplantation is a routinely used therapeutic choice in the treatment of end stage liver disease. Portal vein stenosis is a rare vascular complication after liver transplantation. We report the interventional radiological management of three cases of portal vein stenosis. AIM The surgical management of portal vein stenosis can be hazardous for the patient and the transplanted liver in the early post-transplantation period. In general, interventional radiological methods are tolerable for patients and can be safely performed with high success rate. The aim of this report is to analyze the feasibility, the risks and the efficacy of the percutaneous transhepatic self expanding metallic stent placement into the portal vein. METHOD Three of the 396 liver transplantations cases in Budapest developed significant portal vein stenosis. In these cases, ultrasound guided percutaneous transhepatic portal vein puncture with fine needle was performed. The tract was dilated with a coaxial dilator set, and an adequately sized sheath introducer was inserted into the liver parenchyma. Two nitinol and one stainless steel self expanding metallic stent were implanted at the stenotic portal vein anastomoses. The tract was embolized with gelfoam particles (1 case), or coils (1 case). In the third patient no tract embolization was performed. RESULT All treatments were technically successful, without minor or major complications. In two cases the amount of free abdominal fluid decreased significantly, and in the third case the esophageal varicosity regressed. The morphological success was documented with ultrasound and computed tomography examination. Two patients are alive and well after 10 and 39 months of follow up, while the third patient died after one month in multi organ failure. CONCLUSION Percutaneous transhepatic metallic stent placement for the treatment of post-transplantation portal vein stenosis is a safe and effective method.

Investigation of redox homeostasis in liver and renal transplant recipients

The time course of free radical reactions is evaluated by the authors. Within pretransplant patients as of their poorly functioning metabolism free radical overproduction may be observed, hence their antioxidant capacity decreases. When the graft is functioning well, the free radical-antioxidant balance of homeostasis is reestablished. During the early postoperative period, when symptoms (acute rejection, infection, acute tubular necrosis, cholestasis) appear, free radical reactions increase. The authors demonstrate, this is strengthened by the fact that the mediator [interleukin-6 (IL-6), C-reactive protein, serum amyloid-A], and enzyme levels that take part in the free radical processes rise. The monitoring of these parameters during the early postoperative period is a good early indicator for acute rejection and for the effect of therapy. During acute rejection just as during infection most of these parameters increased significantly compared to the healthy control. They show the activation of the immune system but they are not useful for differential diagnosis, with the exception of IL-6 which we measured in larger quantities during bacterial infection but not so in acute rejection. For the prediction of early renal graft function we used urinary enzyme levels (dipeptidyl-aminopeptidase, glutathione-S-transferase). Tissue damage is followed by enzyme increasing and antioxidant capacity depletion. With choosing of adequate tests, the perioperative redox homeostasis of the transplanted patients can be monitored and with dosing the antioxidants the uncontrolled forming of reactive oxygen metabolites can also be decreased and checked.

Special considerations in generic substitution of immunosuppressive drugs in transplantation

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payers presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers.