ročník 3,1995 č.1-2

Editorial

  1. Liver transplantation. Development, clinical experience and present status

Abstrakta

  1. Poznámky k indikaci transplantace jater u dospělých
  2. Energetický výdej (EE) a substrátová utilizace (SU) v perioperačním období orthotopické transplantace jater (OLTx)
  3. Indikace k transjugulárnímu intrahepatálnímu zkratu (TIPS)
  4. Poznámka ke standardizaci odběru jaterního štěpu

Editorial

Liver transplantation. Development, clinical experience and present status

Neuhaus,P., Lüsebrink,R.
Virchow Clinical Center, Clinic for General-, Visceral - and Transplantation Surgery, Humboldt University Berlin

Introduction

Liver transplantation today has evolved into an established form of treatment for acute, chronic and life-threatening liver disease. The history of clinical liver transplantation goes back to 1963, when Starzl performed the first liver transplantation in America (27). Until 1995 more than 50 000 liver transplants have been performed worldwide and experience has grown meanwhile in many transplant center especially in Europe and the United States. But only 15 years ago, before the advent of ciclosporine A the one-year-success-rate worldwide was below 30 %. Since 1988 according to the European Liver Transplant Registry (ELTR) success rates in experienced liver transplant centers have reached 70 - 80 %. In Germany there are about 6OO liver transplants each year of which about 20 % are performed in Berlin. The number of liver transplants could be even higher because of a rising demand, if public acceptance of organ donation and organ procurement in general would be improved. This general problem also applies to the situation in kidney and heart transplantation.
Intensive research and dramatic progress in some fields has made the afore mentioned doubling in success rates over the last 10 years possible. Since most deaths occured during the first three postoperative months after liver transplantation, especially aspects of organ procurement, operative technique and anesthesia, intensive care management and immunosuppression were the fields of research to improve survival figures (16). On the other hand the question of recurrence of the underlying disease has to be addressed in patient with tumor and with posthepatitic cirrhosis caused by hepatitis B and C.
Undoubtedly all singular aspects are connected as for instance immunosuppression influences reappearance of tumor and viral hepatitis, but in general it may be allowed to conclude that progress in liver transplantation and a success rate of 90 % overall one-year-survival in our center have established liver transplantation as a standard treatment for endstage liver disease.

Indications and contraindications

In principal all kinds of liver disease are acceptable, if no other form of treatment exists and the disease will lead to death in a foreseeable time, sometimes also if severe comlications and problems of other diseases may be cured by liver transplantation - like in inborn errors of metabolism, e.g. giant polycystic liver and kidney disease or hyperoxalurea who is imminent kidney failure.
Contraindications are active sepsis outside the liver e.g. osteomylitis but not secondary biliary cirrhosis and cholangitis with recurrent septic episodes. Extrahepatic manifestation of tumor disease, positive HIV-status and sometimes severe cardiopulmonary disease are also contraindications. Since these are very cases, the problem is not so much to distinguish between indications and contraindications but to establish the right time for transplantation in chronic and acute liver disease.
For some diseases like primary biliary cirrhosis (PBC) prognosis parameters and so-called prognostic indices exist which allow an individual prognosis for each patient on simple, clinical and laboratory parameters like ascites, edema, bilirubin, albumin and some others. On the other hand posthepatitic and toxic cirrhosis which are most common in our own patients do not follow a steady course like PBC for instance but are not characterized by stable periods in change with life-threatening periods of decompensation.
Concerning acute liver failure (AFL) several specific treatment protocols have been established like for paracetamol intoxication. In other ALF it is of crucial importance to define point of no return, where treatment by medical means or spontaneous regeneration capacity are of no more hope and transplantation becomes the only life-saving option.
Laboratory parameters, also liver function tests in these cases do not permit the individual exact prognosis and only long-term follow-up by an experienced hepatologist allows to establish an indication for liver transplantation at a time where operative and postoperative risks are not prohibitively high. Today not only survival but also quality of life ability to work and an individual discussion of pros and cons with the patient are of incresing importance in decision making.
Objective laboratory parameters are serum bilirubin, serum albumin and clotting factors. Of clinical importance are ascites, encephalopathy and general status including bodymass and skinfold thickness. This parameters are not far away from the Child classification for severe liver cirrhosis. Severe complications of any liver cirrhosis like refractory ascites and peripheral edemas, recurrent esophageal bleeding with small liver size (contraindication for shunt or TIPSS), recurrent spontaneous bacterial peritonitis and also something bothering are severe itching together with osteoporosis in PBC-patients can constitute an indication for liver transplantation in spite of still sufficient synthetic function of the liver. Liver function tests like ICG-,MGX- and aminopyrine-bresth-test as leading objective parameters have failed to establish the exact time for liver transplantation in our view, although they use useful tools in the context with other parameters.

Organ donation and organ preservation

Organ donation may be termed the "Achilles heel" of organ transplantation in North America and Europe nowadays. The increasing demand is confronted with old and new obstacles like insufficient education of people, sometimes lack of adequate legislation and sometimes also lack of interest in organ donation in hospitals where transplantation is not performed. Progress on the other hand is visible on the field of organ preservation, which today allows also to use organs of donors more than 60 years old or donor with severe prefinal cardiovascular pulmonary or other complications. This way mainly due to the development of a new preservation solution, the so-called University of Wisconsin solution (10), witch was developed on the basis of colloidal impermeable substances, while so-called Eurocollins-solution was based mainly on the osmolarity of glucosein the high concentrations, which by anaerobic glycolysis during cold ischemie led to a negative accumulations of intracellural metabolites. With the use of UW-solution liver preservation can be extended up to 24 hours. Improved microcirculation after reperfusion and less edema and therefore also a significantly improved cellular function early after transplantantion are seen (Figure 1).


Fig.1 - Liver preservation with Eurocollins-solution (left): swelling, edema, patchy and inhomogeneous perfusion. Rightside: liver preserved with UW-solution shows homogeneous perfusion on the whole surface, normal size and no swelling, normal color, excellent perfusion of peripheral acini.

Other pharmacological agents designed for endothelial and membrane protection (prostaglandins) as radical scavangers and antitoxicants (gluthation, superoxide, dismutase, allopurinol), calcium antagonists (Diltiazem) as well as many others fully understood substances (Silibinin, Alpha-Tocopherol, vitamin C and N-Acetylacystein) have been use experimentally for organ protection. Some of these substances have already been used in many centers in clinical preservation, others have at least improved our knowledges of preservation and reperfusion injuries. Nevertheless the surgical expertise an skills during organ procurement are of predominant importance, because impairment of anatomical structures like arteries and bile duct and severe disturbances of mocrocirculation by rough handling can be determinal to the graft and lethal to the recipient.

Operative technique and anesthesina during liver transplantation

Often the most difficult surgical part of liver transplantation is the removal of the recipient disease liver. Portal collateral with numerous thin-walled veins under high pressure, completely collateralized adhesion after precedent operation in the right abdominal quadrant and usually severe clotting abnormalities are the dominant problems for surgeon and anesthesiologist. Arteriovanous shunts and hyperdynamic cardiovascular problems, secondary heart, lung and kidney problems as well as neurological disturbances can make the choice ot anesthetic agents and anesthesia in general difficult, especially during the extremly critical anhepatic and reperfusion phase. This is a big challange for the knowledge and the experince of the anesthesiologists involved (5). Special technique achieve hemostasis with infrared light contact coagulation, electrocoaguation and the use of fibrin glue on one side as well as prevention of fibrinolysis after reperfusion through continuons administration of the proteinase inhibitor appronitine have led to significant decrease in intraoperative and postoperative bleeding and coagulation problem (1). The general use of extracorporel bypass between inferior V.cava and portal vein on one side and the axillary vein on the other side during the anhepatic phase reduces stasis and hypertension for small intestine and kidney. The detrimental effect of toxic metabolite from the lower half of the body after reopening of the V.cava in thus avoided. Possibly also the complete avoidance of halogenated anesthetic agents during liver transplantation bears a posivite influence.
Surgical anastomosis of the vascular supply to the liver always follows the same scheme. Supra- and infrahepatic V.cava are anastomosed first, then hepatic artery and portal vein are anastomosed before the blood-flow through the liver is re-established. In experienced hands this takes about 50 - 60 minutes and should not cause any problems and this time artery and portal vein are opened and 500 ml of cold and acidotic perfusate as well as blood are allowed to escape from the intrahepatic V.cava, before the clamps are released altogether. Vascular complications like arterial and portal vein thrombosis have been reduced from former 8 - 10 % of now less to 2 % in our own experience (11).
The main technical problem leading to severe and sometimes lethal complications after liver transplantation is the bile duct anastomosis. According to the literature end-to-end bile duct anastomosis is followed by 10 - 20 % complications (7,8, 14). Breakdown and stenosis which in a substantial number lead to severe comlications and make difficult re-operation necessary are still to common. Therefore we developed the so-called side-to-side choledochocholedochostomy and applied this successfully in pig and monkey experiments. With the use of this anastomosis the number of anastomosis complications in Berlin has gone down to 1 % (17), none of our patient died following biliary complications (Figure 2).


Fig.2 - Postoperative X-ray of biliary tract anastomosis with side-to-side choledochocholedochostomy

Interestingly we now see another type of biliary tracts lesions, which in literature amounts to 5 - 8 %. Here is destruction of the intra- and extrahepatic bile duct is dependent or ischemia during preservation (ischemic type biliary lesion = ITBL), which obviously results from an insufficient perfusion and preservation of bile duct system and its arterial plexus (Figure 3).


Fig.3 - Rarification and destruction of intrahepatic biliary ducts in case of ischemic type biliary lesion (ITBL) caused by preservation injury

We have studied this problem in another animal model and thereafter changed all preservation and perfusion technique. Since then these ITBL changes have not been encountered (2).

Immunosuppression

Before the advent of ciclosporine A one-year-survival probability in liver transplanted patients was 30 % (21,25, 28). With the use of ciclosporine A as an specific immunosuppressant which inhibits interleukin-2 dependent proliferation of lymphocytes, success rates could be improved to 70 % (3,26, 29). Research over the last 10 years has brought up many new interesting substances, some of which can already be used in the clinic.
Especially the new substance FK 506 (Tacrolimus, PROGRAF) with a similar mechanism of action as ciclosporine A has shown an improved efficacy compared to ciclosporine A in two international prospective randomized studies in the United States and in Europe. Altough patient survival in FK 506 - treated patients was not significancy better than in ciclosporine A-treated patients, the number and severity of acute and chronic rejections was lower in FK 506 - treated patients than in ciclosporine-treated patients. Moreover the number of severe infection, sepsis, pneumonia and cytomegaly virus infection seems to be significancy lower in FK - than in ciclosporine - treated patients. It remains to be seen whether FK 506 will replace ciclosporine A as the standard immunosuppressant after liver transplantation or whether both substances will find a specific spectrum of indications.
Another promising direction of research aims at inhibition of immunological reactions with monoclonal antibodies against T-cell receptors. Such an antibody against interleukin-2 receptors has been used in Berlin, Heidelberg and Hanover in more than 100 patients (12,15,19,20). Different from cytotoxic antilymphocyt antibodies with quite a spectrum of severe side effects these blocking IL-2 receptor antibodies are virtually without toxicity. IL-2 receptor antibodies in combinations with ciclosporine A lead to a significantly lower number of rejection episodes after liver transplantation and therefore provide a better graft function in this early phase. In our experience rejection frequency during the first 30 days after liver transplantation was reduced from former 30 % to about 10 %. Interestingly the number of so-called chronic and late rejection after liver transplantation is almost zero with the use of Tacrolimus (PROGRAF). These rejections which occur with the frequency of 6 - 8 % under ciclosporine - treatment can in most cases be treated by so-called "FK 506 rescue therapy", if the therapy is instituted in an early phase (4,6,13,30).
Already in clinical trials or rating clinical trials are other substances like microphenolicmorfetil, nephlunomyte and propramycin. Altogether important progress in immunosuppression can be expected in the next years.

Progress in intensive care

Intensive care treatement after liver transplantation is of course closely connected to the quality of organ harvesting and preservation, surgical technique, immunosuppression and rejection episodes and secondary organ problems due to surgery, anesthesia and toxicity of drugs. In the early phase anesthesia, cardiovascular, lung, kidney and cerebral function are of major importance. These have to be carefully monitored, supported and guided to normality by experienced intensive care experts. The causual relationship between intraoperative problems and postoperative course for exemple is demonstrated by the transfusion requirements. With the use of aprotitnin transfusion reqiurement in Berlin could be lowered to 7.6 units of pack red blood cells (1), while in the literature much higher requirements of intraoperative blood transfusions were reported (Omaha 1989 14.3, Pittsburgh 1985 42.8 units of blood). Of similar importance and connected to the operative trauma is an early extubation which we try to achieve in the 6 - 8 hours after transplantation. More than 80 % of our patients can be extubated in this period (23), and the known negative infuence of artificial ventilation on splanchnic perfusion and hemodynamic of the liver can thus be avoided.
Another important aspects of intensive care management is the number of infectious complications. In order to avoid infectious complications all our patients are treated with so-called selective bowel decontamination (SBD) which consists of colistin sulphate, tobramycin and amphotericin B as an oral preparation which eliminantes gram-negative bacteria like E coli, Pseudomonas and Klebsiella pneumoniae as well as fungi. From the intestinal tract the effectiveness of this regimen can be shown in a regular bacterial monitoring with oral and anal swabs (22). The underlying assumption is that the reticuloendothelial system in the liver is severely damaged after liver transplantation and the mucosal barriere of the gastrointestinal tract for bacterial translocation is lowered. By these machanisms the risk of gram-negative sepsis and pneumonia after liver transplantation is significantly incresed. SBD lowers infectious risk with gram-negative bacteria by significantly reducing these bacteria in the blood and therefore we mainly encounter entercocci as infectious agents which can be treated comparatively easy. In 350 liver transplants in our unit we saw 49 pneumonias, 29 (59 %) of which were caused by atypial micro-organisms. It has to be mentioned that 21 of these 29 pneumonias were lifethreatening, and occourred usually late after liver transplantation with severaly impaired graft fuction, repeated rejection episodes and secondary organ disturbances neccessitating artificial ventilation, dialysis, ect.

Recurrence of underlying disease

Altogether only 3 % of our patients died in the first 3 months after liver transplantation, compared to more than 20 % in the European Transplant Registry. This can be explained by a comparatively low number of initial non-function of the graft, by a lower incidence of techical complications (biliary), the use of highly potent new immunosuppressants and the afore mentioned improvements in intensive care and in prophylaxis of infections. From 3 - 12 month after liver transplantation patients died mainly from recurrence of primary disease, especially viral hepatitis and tumor. An overview of the indications for liver transplantation in the Virchow Transplant Center Berlin is shown on Table 1.
End-stage-liver-disease n %
Cholestatic liver diseases 91 15
- primary biliary cirrhosis 35
- primary sclerosing cirrhosis 30
- secondary sclerosing cirrhosis 6
Postnecrotic liver disease * 340 57
- hepatitis B 99
- hepatitis NANB + C 106
- alcohol-toxic cirrhosis 91
- auto-immune hepatitis 17
- cryptogenic cirrhosis 27
Acute liver failure 39 7
- hepatitis B 10
- hepatitis NANB 10
- others 19
Metabolism disorders 20 3
Liver tumors* 41 7
- hepatocellular carcinoma 13
- central bile duct carcinoma 14
- others 13
Retransplantation 47 8
Others 13 2
Total 591 100

*(hepatocellular carcinoma in cirrhosis n=23)

Table 1 - Indications for liver transplantation at the University Hospital Rudolf Virchow, Berlin (591 transplantations in 544 patients 9/88 - 3/95)

About 60 % of all transplant were performed for postnecrotic cirrhosis mainly from viral or alcohol-toxic origin. About 10 % of our patients were transplanted with tumors. The survival curve of tumor patients is obviously less favourable than survival of patients with non-malignant disease .
We therefore have restricted the indication for liver transplantation in patients with hepatocellular carcinomas and have only transplanted for small tumors less than 5 cm in diameter in cirrhosis.
Small liver tumors without cirrhosis are always resectable and only oncologically unfavourable tumors remain as unresectable liver transplantation with the main indication big tumor, both excluded from our series. These tumors with an extremely high probability of extrahepatic micrometastasis show usually early and explosive recurrence under the condition of immunosuppression. On the other hand radical resection of small hepacellular carcinomas in cirrhosis induced by viral hepatitis can only seldomly be cured by resection alone becauce viral induced genetic changes in the liver cell lead to tumor occurrence at other side. In this situation only the total removal of the diseased organ by transplantation carries a real chance of cure.
All other tumor entitis, especially metastases, cholangiocellular carcinomas and central bile duct carcinomas can at this moment not be accepted as a established indication for liver transplantation because these tumors regulary recur after short times. Transplantations for these indications should only be carried out in controlled clinical trial and with individual decision making.

Recurrence of hepatitis

Recurrence of underlying disease is especially threatening for patients posthepatitic cirrhosis. Without immunoprophylaxis almost 100 % of hepatitis B and C-infected patients show infection of their transplanted liver 2 - 3 months after transplantation. To date there is no vaccination against hepatitis C available, but hepatitis C-reccurence after liver transplantation usually shows a mild course under immunosuppression. Although the early development of cirrhosis in the transplanted liver or fulminant liver failure cannot be excluded completely, both are uncommon. On the other hand differentiation between graft hepatitis and rejection is often a problem. This may sometimes lead to over immunosuppression with adverse effects, especially infectious comlications.
Completely different is the situation in patients with hepetitis B. Prophylaxis with immunoglobulins starting during operation in the anhepatic phase should be life-long persued in order to avoid infection of the transplanted liver with virus coming from polymorphonuclear cells and other organs. The high risk of re-infection without immunoglobulin prophylaxis and fulminant hepatitis and liver failure after transplantation has led to the opinion in the United States that hepatitis B-positive patients should only be transplanted in exceptional cases, some centers regard hepatitis B as a contradiction. In Berlin with the use of immunoprophylaxis one-year-survival in 100 HBsAg-positive patients is 91 % which is identical with other indications.
Despite immunoprophylaxis the reinfection rate in HBV-DNA-positive patients is 60 %, whereas re-infection rate in DNA-negative patients is only 30 % (9, 18). These HBV-DNA-negative patients and all patients who remain postoperatively HBsAg-negative have an exellent total survival. Preoperatively HBV-DNA-positive patients with re-infection after liver transplantation od the other hand have only 50 % survival. Since this subgroup is not identifiable before operation, possibly in this group there might be a higher number of precore mutants, and since there is no other chance of treatement for these patients in our view the option of liver transplantation should not be withheld for HBV-DNA-positive patients today. Possibly the use of new antiviral substance like ganciclovir before and after transplantation can modify the course of the viral hepatitis so that re-infection might not be lethal in these cases either.

Alcoholic cirrhosis

A special often controversely discussed group of patients suffers from alcoholic liver cirrhosis. If alcoholism is considered as a disease than these patients can of course not be excluded from a life-saving therapeutic option. If on the other hand the underlying psychic instability and other problems, which inducted alcoholism, are not successfully treated or eliminated compliance and also overall success after liver transplantation will be questionable. Therefore candidates with this diagnosis must be evaluated very carefully by hepatologists, psychiatrists, anesthesiologists and transplant surgeons. Because of a very strict selection process for patients with alcohol-toxic liver cirrhosis we have reached a five-year-survival od 86 % in this which accounts for 15 % of our programme.
Since only 15 - 20 % of all patients dark again after transplantation and most of our patients have gone back to work the result can in principal be viewed positively.

Conclusion

Liver transplantation has developed into an established and accepted form of treatment for endstage liver disease of different origin. Risk and success rate can be esential for individual patients and sometimes be calculated from clinical and laboratory parameters like in PBC. Long-term survival figures are still scarce but 5- and 10-years-figure available today are promising. The problem of organ donation and the high cost of liver transplantation in Germany (approximately DM 250.000,- in the first year) must be weight against the individual benefit for the patient. A more general gain in experience, knowledge and insight on the side of the involved clinicians will also severe for the benefit of other patients.

Literature

  1. Bechstein,W.O., Reiss,H., Neuhaus,P. et al.: The effect of aprotinin on blood product requirements during orthotopic liver transplantation. Chir.Transplant.,5,1991,422-426.
  2. Blumhardt,G., Lemmens,H.P., Topalidis,T. et al.: Increased flow rate of prevention in the hepatic artery during organ prevention can improve postischemic liver function. Transplant.Proc.,25,1993,2540-2542.
  3. Calne,R.Y., Roller,K., White,D.J.G. et al.: Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organ: 32 kidney,2 pancreas and 2 liver. Lancet 1979, 2,1033.
  4. D°Alessandro,A.M., Kalayoglu,M., Pirsch,J.D., et al: FK 506 rescue therapy for resistant rejection episodes in liver transplant recipients. Transplant.Proc.,23,1991,2987-2988.
  5. Gerlach,H., Rossaint,R., Slama,K. et al.: No requirement for cryoprecipitate or platelet transfusion during liver transplantation. Transplant.Proc.,25,1993,1813-1816.
  6. Gibbs,J.F., Husberg,B.S., Klintmalm,G.B., et al: Outcome analysis of FK 506 therapy for acute and chronic rejection. Transplant.Proc.,25,1993,622-623.
  7. Hiatt,J.R., Quinones-Baldrich,W.J., Ramming,K.P. et al.: Operations upon the biliary tract during transplantation of the liver. SGO,165,1987,89-93.
  8. Hollis,R.R., Wood,R.P., Shaw,B.W: Biliary tract reconstruction in orthotopic liver transplantation. Transplant.Proc.,20,1988,543-545.
  9. Hopf,U., Neuhaus,P., König,V., et al.: Orthotope Lebertransplantation bei hepatiticher Zirrhose: Zur Problematik der Infektion des Transplatates mit persistierenden Hepatitisviren. Z.Gastroenterol.,30,1992,576-582.
  10. Kalayoglu,M., Stratta,R.J., Sollinger,H.W., et al.: Clinical results in liver transplantation using UW solution for extended preservation. Transplant.Proc.,21,1989,1342-1343.
  11. Lemmens,H.P., Blumhardt,G., Neuhaus,P. et al.: Technique of arterial anastomosis in liver transplantation, surgical management in routine situation and anatomical variation. Transpl.Int.,5,1992,198.
  12. Lemmens,H.P., Blumhardt,G., Steffen,R., et al.: Erste klinische Erfahrungen mit dem IL-2-Rezeptor Antikörper in der Quardrupel-Immunsupression nach Lebertransplantation. Z. Transplantationmedizin 3,1991,132-133.
  13. Lewis,W.D., Jenkins,R.L., Burke,P.A., et al.: FK 506 rescue therapy in liver transplant recipients with drug-resistant rejection. Transplant.Proc.,23,1991,2989-2991.
  14. Maggi,U., Rossi,G., Colledan,M. et al.: Major surgical complications after 73 consecutive liver transplantation. Ann.Surg.45,1991,6,476-479.
  15. Neuhaus,P., Bechstein,W.O., Blumhardt,G. et al.: Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody. Transplantation 5,1993,1320-1327.
  16. Neuhaus,P., Blumhardt,G., Bechtsein,W.O. et al.:96. Fortschritte im Bereich der Lebertransplantation in den letzten 10 Jahren. Langenbecks Arch.Chir.Kogressbericht 1992,209-216.
  17. Neuhaus,P., Blumhardt,G., Bechstein,W.O. et al.: Side to side anastomosis of the common bile duct is the method of choice for biliary tract reconstruction after liver transplantation. Transplant.Proc.,22,1990,1571-1573.
  18. Neuhaus,P., Steffen,R., Blumhardt,G. et al.: Experience with immunoprophylaxis and interferon therapy after liver transplantation in HBsAg positive patients. Transplant.Proc., 23,1991,1522-1524.
  19. Otto,G.,Theis,J.,Kabelitz,D.,et al.: Anti-CD25 monoclonal antibody prevents early rejection in liver transplantation - a pilot study. Transplant.Proc.,23,1991,1387.
  20. Otto,G., Theis,J., Manner,M. et al.: Monoclonal antibody to interleukin 2 receptor in liver graft rejetion. Lancet 335, 1990,1596.
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  23. Rossaint,R.,Slama,K.,Jaeger,M. et al.: Fluid restriction and early extubation for successful liver transplantation. Transplat.Proc.,22,1990,1533-1534.
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  25. Starzl,T.E., Koep,L.J., Halgrimson,C.G. et al.: Fifteen years of clinical liver transplantation. Gastroenterology 77, 1979,375-388.
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Address correspondence to:
Prof.Dr.med.P.Neuhaus
Virchow Clinical Center
Clinic for General-, Visceral- and Transplantation Surgery
Humboldt-University Berlin
Augustenburger Platz 1
D-13353 Berlin/Germany

Abstrakta

Poznámky k indikaci transplantace jater u dospělých

Trunečka,P.
Klinika diabetologie a hepatogastroenterologie
Institutu klinické a experimentální medicíny, Praha
Přednosta: Doc.MUDr.Špičák,J.,CSc.

Souhrn

Autor podává základní koncept indikační rozvahy nad nemocným zvažovaným k transplantaci jater z důvodu jaterního selhání a nádorů jater. Indikace k jaterní transplantaci je dána především stupněm funkční poruchy a ne nozologickou jednotkou, která k jaternímu selhání vedla. Jednotlivé nosologické jednotky však implikují specifické kontraindikace a přežívání nemocných po transplantaci. Autor podává přehled diagnóz u dospělého nejčastěji indikovaných k transplantaci jater a jejich průměrné přežití. Je diskutována otázka správného načasování jaterní transplantace.
Klíčová slova: transplantace jater - indikace

Summary

Author presents a basic concept of indication process for patients with chronic liver failure and hepatic tumor referred for liver transplantation. Degree of the hepatic failure is more important factor for a decision whether proceed with transplantation or not than the diagnosis of disease leading to hepatic failure but disease specific factors imply survival rate and contraindications. Author lists the most frequent diagnoses indicated for liver transplantation and theirs corresponding survival. The timing of liver transplantation is discussed.
Key words: liver transplantation - indications

Energetický výdej (EE) a substrátová utilizace (SU) v perioperačním období orthotopické transplantace jater (OLTx)


J.Bonaventura*, G.Pittoni+, F.Michielan+, P.Feltracco+,
G.Davia°+, U.Tedeschi++, U.Cillo++, D.F.D°Amico++, P.Burra+++, E.Baldi+++, G.P.Giron+, Táborská,D*
* ARK nemocnice u sv.Anny, Brno
přednosta: doc.MUDr.J.Vomela, CSc.
+ Istituto dell°Anestesiologia e Rianimazione
++ Clinica Chirurgica I
+++ Istituto della Gastroenterologia
Universita° degli Studi di Padova, Italia

Souhrn

V období květen 1993 - leden 1994 jsme pomocí indirektní kalorimetrie vyšetřili 25 pacientů s terminálním onemocněním jater předoperačně a v průběhu OLTx. Metoda indirektní kalorimetrie umožnila detekovat metabolickou závažnost "end-stage-liver-disease" (ESLD) u jednotlivých pacientů, jejich reaktivitu na chirurgicky indukovaný stres a reakci organismu na reperfuzi, která je odrazem kvality dárcovského graftu, doby trvání anhepatické fáze a individuálních vlivů příjemce.
Klíčová slova: orthotopická transplantace jater - indirektní kalorimetrie

Summary

Energy expenditure(EE) and substrate utilization(SU) in the perioperative and postoperative periods in orthotopic liver transplantation (OLTx)
J.Bonaventura* G.Pittoni+,,F.Michielan+,P.Feltracco+,G.Davia°+,
U.Tedeschi++,U.Cillo++,D.F.D°Amico++,P.Burra+++,Baldi E.+++,
G.P.Giron+ D.Táborská*
Indirect calorimetry is a useful non invasive method to measure VO2 and VCO2 and to calculate EE and SU.We investigated this method of metabolic measure during anaesthesia for OLTx to verify its practical usefulness to provide informations about the reaction of patients with end-stage-liver-diseases (ESLD) to surgical stress.
PREE : VO2 was 133.7+-7.96ml/min/m2 BSA,VCO2 was 99.72+-5.12ml/min/m2) BSA a EE was 121.75+-7.99% resp. to calculated values using H.B. formula (Harris Benedict). After induction of anesthesia and in the subsequent phases of surgical intervention VO2 markedly reduced.The VO2 value in ANEE drops to 77.84+-9.9ml/min/m2 BSA (p lass than 0.001 respect to PREE VO2),
VCO2 drops to 76.69+-3.40ml/min/m2 BSA (p less than 0.05 respect to PREE VCO2), RQ values increases from 0.72+-0.02 to 0.98+-0.11 (p less than 0.05). SU indicated an increased glucose and aminoacid utilization coupled with high nitrogen catabolism (from 0.09+-0.02 gN/kg/dayPREE to 0.23+-0.06gN/kg/day-ANEE). The contributon of glucose to energy production PREE v.ANEE changes from 2.05+-7.52 to 59.83+-++.02 and therefore lipid percentage contribution reduced from 90.45+-7.99/ to 5.83+-8.36% This metabolic pattern is maintained through the subsequent phahes until the end of anheptic phase (APEE) without significant changes. When anhepatic phase is prolonged over 100 minutes the increase of aminoacids utilization is twice augmented and glucose utilization is also augmented. When liver graft is reperfused we observed a prompt increase of VO2 from72.37+-9.88 to100.32+-13.13ml /min/m2BSA, (respect to APEE)VCO2 from 83.78+-5.82 to105.65+-8.15ml/ min/m2BSA and EE increases from 71.72+-6.75% to 87.23+-8.39%(p less than 0.05 in all differences). This new pattern is thereafter maintained till end of the surgical intervention. SU during RPEE shows increase of glucose utilization and remains during the watching period. Aminoacids utilization shows peak after 20 minutes after reperfusion.
Key words: orthotopic liver transplantation - indirect calorimetry

Indikace k transjugulárnímu intrahepatálnímu zkratu (TIPS)

Hůlek,P.,Krajina,A.
I.Interní klinika FN, Hradec Králové
Přednosta: Prof.MUDr.J.Kvasnička,CSc.
Radiodiagnostická klinika FN, Hradec Králové
Přednosta: MUDr.P.Eliáš,CSc.

Souhrn

K TIPS (trasnsjugulární intrahepatická portosystémová spojka stentem) jsou indikováni nemocní se symptomickou portální hypertenzí, obvykle při jaterní cirhóze. První skupinu tvoří nemocní po krvácení z jícnových varixů, kteří jsou metodou TIPS léčeni v rámci prevence recidivy krvácení. Druhou skupinu tvoří nemocní s probíhajícím krvácením, které nelze zastavit standardní léčbou. Ve třetí skupině jsou nemocní s refrakterním ascitem. Existují i méně obvyklé indikace. Za 33 měsíců bylo metodou TIPS léčeno 91 nemocných. 71% z nich v rámci prevence opakovaného krvácení, 6,6% při probíhajícím krvácení a 17% pro refrakterní ascites. 6% nemocných bylo zařazeno do Childovy klasifikační skupiny A, 44,5% do skupiny B a 47,3% do skupiny C. U 91% nemocných byl použit spirální Z stent.
Klíčová slova: Portální hypertenze - jaterní cirhóza - portosystémový zkrat.

Summary

Patients with symptomatic portal hypertension due to liver cirrhosis are indicated for TIPS procedure (transjugular intrahepatic portosystemic stent shunt) .Patients after bleeding from esophageal varices belong into the first group. The second group consist from the patients with continual bleeding which is not possible to stop endoscopically and the third group consist from the patients with refractory asctites. There are also less usual indications. During 33 months period 91 patients has been treated by TIPS procedure. 71% of patients has been treated as prevention of variceal hemorrhage, 6,6% during continual bleeding and 17% for refractory ascites. 6% of patients has been classified as Child`s group A, 44,5% as Child`s B and 47,3% as Child`s C. Spiral Z stent has been used in 91% of patients.
Key words: Portal hypertension - liver cirrhosis - portosystemic shunt.

Poznámka ke standardizaci odběru jaterního štěpu

Ryska,M., Bělina,F., Adamec,M., Kučera,M., +Gintelová,J., +Pokorná,E.
Klinika kardiovaskulární a transplantační chirurgie
Institut klinické a experimentální medicíny (IKEM), Praha
přednosta: MUDr.J.Pirk,DrSc.
+ Transplantcentrum IKEM, Praha
ředitel: MUDr.S.Vítko

Souhrn

Jedním z důležitých faktorů, které ovlivňují výsledky transplantace jater, je kvalitní jaterní štěp. Kvalita odebraného orgánu je dána celkovým stavem dárce, správným posouzením jeho kvality při odběru, technicky dobře provedeným odběrem a kvalitní perfuzí. Jaterní štěp může být odebrán odběrovým týmem, který následně neprovádí vlastní transplantaci. Je proto vhodné, aby byl odběr jater prováděn standardně tak, aby ho bylo možné použít v kterémkoliv transplantačním centru.
Autoři odebrali od prosinec 1994 do května 1995 36 jaterních štěpů. V jednom případě nebyl štěp pro pochybnosti o kvalitě perfuze použit a jednou jsme zaznamenali primární afunkci štěpu.
Klíčová slova: transplantace jater - odběr jaterního štěpu

Summary

The contribution to standardization of liver graft
Ryska,M.,Bělina,F.,Adamec,M. et al.
One of the most important aspect influencing to the results of liver transplant is available graft. The quality of organ is depends on the status of donor and judgement of organ quality by donor surgeon. The procurement should be performed without technical mistakes with good perfusion. Liver harvesting can be performed by donor team which does not transplant this graft. It is available to standard the process of the graft harvesting at certain way that is suitable for transplantation in any transplant center.
Within the period of 6 months (December 94 - May 95) 36 liver grafts were harvested by authors. Because of the doubt of the quality of liver perfusion one liver graft was not transplanted. Primary graft non - function we noted in 1 case.
Key words: liver transplantation - the harvesting of liver graft