Imre Fehérvári

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.

Outcome of liver transplantation based on donor graft quality and recipient status.

BACKGROUND 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. OBJECTIVE To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation. MATERIALS AND METHODS 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]. RESULTS 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. CONCLUSION 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.

Relationship Between Hepatitis C Virus Recurrence and De Novo Diabetes After Liver Transplantation: The Hungarian Experience

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively (P=.011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P=.017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P=.039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P=.019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.

New-onset diabetes mellitus after liver transplantation

A de novo diabetes mellitus a majatultetes gyakori szovődmenye. Celkitűzes: A de novo diabetes gyakorisagat, jelentőseget es a kockazati tenyezők szerepet vizsgaltuk. Modszer: 1995 es 2009 kozott 310 majatultetett beteg adatait dolgoztuk fel retrospektiv modszerrel. De novo diabetest allapitottunk meg, ha az ehomi vercukor a 3. posztoperativ honapon tul ismetelten >6,8 mmol/l volt, es/vagy a majatultetes utan tartos, a 3. posztoperativ honapot meghaladoan is fenntartott antidiabetikus terapia indult. Eredmenyek: De novo diabetes a betegek 20%-anal (63 beteg) alakult ki. A de novo es a kontrollcsoport kozott az alabbiakban talaltunk kulonbseget. Donor-testtomegindex (24±3 vs. 22,4±3,6 kg/m 2 , p = 0,003), ferfi nem (58% vs. 33%, p = 0,002). Recipienseletkor (47,6±7,2 vs. 38,3±14,6 ev, p<0,001), -testtomegindex (26,7±3,8 vs. 23,3±5,6 kg/m 2 , p<0,001), ferfi nem (60% vs. 44%, p = 0,031). A de novo diabetesesek csoportjaban a betegek 66%-at HCV talajan kialakult cirrhosis miatt transzplantaltak, a kontrollcs...UNLABELLED New-onset diabetes is a common complication after liver transplantation. AIM We aimed to analyze the incidence and rate of known risk factors and the impact of new-onset diabetes mellitus on postoperative outcome. METHODS We retrospectively evaluated the files of 310 patients who underwent liver transplantation between 1995 and 2009. Definition of new-onset diabetes included: repeated fasting serum glucose >6.8 mmol/l and/or sustained antidiabetic therapy that was present 3 months after transplantation. RESULTS New-onset diabetes occurred in 63 patients (20%). Differences between the new-onset and the control group were the donor body mass index (24+/-3 vs. 22.4+/-3.6 kg/m 2 , p = 0.003), donor male gender (58% vs. 33%, p = 0.002), and recipient age (47.6+/-7.2 vs. 38.3+/-14.6 year, p<0.001), body mass index (26.7+/-3.8 vs. 23.3+/-5.6 kg/m 2 , p<0.001), male gender (60% vs. 44%, p = 0.031). The 66% of patients with new-onset diabetes were transplanted with cirrhosis caused by hepatitis C virus infection, while in the control group the rate was 23% (p<0.001). Cumulative patient survival rates at 1, 3, 5 and 8 year were 95%, 90.6%, 88% and 88% in the control group, and 87%, 79%, 79% and 64% in the de novo group, respectively (p = 0.011). Cumulative graft survival rates at 1, 3, 5 and 8 year in the control group were 92%, 87%, 86% and 79%, in the de novo diabetes group the rates were 87%, 79%, 79%, 65%, respectively (p = NS). In case of early recurrence (in 6 months), majority of patients developed new-onset diabetes (74% vs. control 26%, p = 0.03). More patients had more than 10 times higher increase of the postoperative virus titer correlate to the preoperative titer in the de novo diabetes group (53% vs. 20%, p = 0.028). Mean fibrosis score was higher in new-onset group one year after the beginning of antiviral therapy (2.05+/-1.53 vs. 1.00+/-1.08, p = 0.039). CONCLUSIONS Risk factors for new-onset diabetes after transplantation are older age, obesity, male gender and cirrhosis due to hepatitis C infection. The early recurrence, viremia and more severe fibrosis after antiviral therapy have an impact on the occurrence of new-onset diabetes in hepatitis C positive patients.

Short report: octreotide in the treatment of external pancreatic fistulas

The efficacy of the long‐lasting somatostatin analogue, octreotide, in the treatment of high‐output pancreatic fistulas was investigated in this prospective, open study. Sixteen patients with post‐operative pancreatic fistulas were treated with subcutaneous injections of octreotide 0.1 mg b.d. The output of the fistulas before the somatostatin therapy ranged between 190 and 5 70 ml/day. The therapy was begun on average 17 days following the appearance of the fistula (range 4 to 35 days). The decrease in volume one day after initiation of therapy ranged from 26% to 69%. By the third day of treatment the fistula volume decreased to 0–45% of the initial output. The treatment resulted in the closure of 14 of the 16 fistulas; the time to closure ranging from 3 to 15 days. The results suggest that octreotide is a useful adjuvant agent in the treatment of an external pancreatic fistula.

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

Surgical aspects of pediatric liver transplantation. Living donor liver transplant program in Hungary

Because of the long waiting time for pediatric liver transplantation, new techniques of liver transplantation were invented. Split and living-donor related liver transplantation are common today and the Kaplan-Meier (3 years) overall survival is over 80%. By splitting the liver, two recipients can be transplanted. In general, the left lobe is used for the pediatric, the right lobe for the adult recipient. There are a lot of combinations depending on the donor and recipient weight. The accepted liver volume is approx. 1% of the recipient body weight. The results of the Hungarian pediatric program improve, 27 transplantations were done using 14 partial liver grafts and living donor program was started. Using strict protocols and improving surgical skills, the overall pediatric survival was over 80% in the last 5 years.

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