Orthotopic liver transplantation for fulminant hepatic failure

This paper presents the results of liver transplantation for fulminant hepatic failure in 31 patients qualified as UNOS-1 class (extra-urgent indication for transplantation), operated from January 1989 to April 2005. Twenty-one patients (61.8%) survived the 3-month postoperative period. Three-year survival rate with good liver graft function was 52.9% (18 patients). Before the transplantation, eight patients (23.5%) underwent hepatic dialysis using Fractionated Plasma Separation and Adsorption (FPSA) with the use of a Prometheus 4008H System. Liver transplantation remains the only life-saving procedure for the treatment of fulminant liver failure, regardless of its cause.     

Living donor liver transplantation for fulminant hepatic failure

BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated only for elective cases of pediatric patients with end-stage liver disease. In Japan, however, where liver transplantation from brain-dead donor is performed very rarely, this indication has been expanded to emergency cases such as fulminant hepatic failure (FHF). METHODS: Thirty-eight patients with FHF were treated between May 1992 and April 1999. Causes of acute liver failure were non-A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one each. RESULTS: Four patients did not undergo LDLT because of severe brain damage or combined multiple organ failure. The remaining 34 patients underwent a total of 36 LDLTs, including two retransplantations; 16 children received transplants of 17 lateral segments, three children and eight adults transplants of 11 left lobes, and seven adults transplants of eight right lobes. A total of 15 recipients died, four of primary graft dysfunction, three of refractory acute rejection, two of pneumonia, and one each of ductopenic rejection, sepsis, aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ failure by chrome poisoning, and unknown hepatic failure. Primary graft dysfunction developed in adult recipients with small-for-size graft transplants, whereas refractory acute rejection and ductopenic rejection occurred in six grafts each of children with non-A, non-B FHF. CONCLUSIONS: LDLT can be safely expanded to cases of FHF in adult patients. Primary graft dysfunction in adult recipients with small-for-size left lobe grafts can be overcome by using right lobes. However, refractory acute rejection and ductopenic rejection in children remain a major problem.     

Intracranial pressure during liver transplantation for fulminant hepatic failure

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion.     

Bridge therapy to liver transplantation in fulminant hepatic failure

The management of patients with fulminant hepatic failure is a major clinical endeavor. Early intensive care at an institution able to perform liver transplantation is essential. It is recognized that therapy focused solely on attempts at preventing/reversing increased intracranial pressure, and the treatment of other failing organs as they occur falls well short of ideal. This review covers the non-biological and biological techniques utilized in efforts to support liver function. The goal is to foster recovery, or to buy enough time for successful liver transplantation. Prospective, controlled trials are beginning to acknowledge subgroups of fulminant hepatic failure and properly randomize therapy. Our understanding of the essential elements of liver support is improving, but no single device has yet proved indispensable.     

肝移植治疗暴发性肝衰肝性脑病的临床研究

目的 总结肝移植治疗暴发性肝衰肝性脑病的临床经验。方法 回顾性分析４例暴发性肝衰肝性病病人行肝移植手术治疗的临床资料。结果 肝移植治疗暴发性肝衰肝性脑病１个月存活率７５％（３／４）,超过３个月存活率为５０％（２／４）。结论 肝移植是治疗暴发性肝衰肝性脑病的一种有效方法,暴发性肝衰肝性脑病不是肝移植手术的禁忌证。     

Arterial ketone body ratio as a parameter of hepatic mitochondrial redox state during and after hemorrhagic shock

This study was aimed at clarifying the usefulness of the arterial ketone body ratio (AKBR), which reflects hepatic mitochondrial redox state and closely correlates with hepatic energy production, for understanding the degree of hepatic mitochondrial damage and the extent of the deterioration in hepatic energy metabolism during of shortly after hemorrhagic shock. Changes in the AKBR of 33 trauma victims who were admitted to our institute in hemorrhagic shock with a systolic pressure lower than 70 mmHg were measured until the patient recovered with the restoration of AKBR to the normal range ( 1.0) or until the patient died. During hemorrhagic shock the AKBRs were highly decreased, indicating deteriorated hepatic function. With successive fluid resuscitation the AKBR quickly recovered in 15 surviving patients from an initial value of 0.26±0.03 toward normal within hours, indicating that hepatic mitochondria are functioning normally. The AKBR recovered to a normal value of 1.10±0.06 on day 2 (p<0.001). In 18 expired patients, AKBR did not recover to normal range, even though some of the patients recovered from the shock state. On the other hand, AST, ALT, LDH, and prothrombin time on day 2 were not significantly different from the values on admission, and the changes during the interval were not unidirectional even in the surviving patients, providing no information on the current functional state of the liver. Measurement of AKBR during and shortly after hemorrhagic shock provides timely and accurate information about liver function.

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Resumen El presente estudio está orientado a definir la utilidad de la relación de cuerpos cetónicos (arterial ketone body ratio, AKBR), la cual refleja el estado redox de la mitocondria hepática y se correlaciona íntimamente con la producción hepática de energía, para la comprensión del grado de lesión mitocóndrica hepática y de la gravedad del deterioro en el metabolismo energético hepático durante, o poco después del shock hemorrágico. Se determinaron los cambios en la AKBR en 33 pacientes de trauma hospitalizados en estado de shock hemorrágico con presiones sistólicas menores de 75 mmHg hasta su recuperación con restablecimiento de la AKBR a niveles normales (>-1.0), o hasta la muerte. En el curso del shock hemorrágico, la AKBR apareció notoriamente disminuida, hallazgo indicativo de función hepática deteriorada. Con la resucitación con líquidos parenterales, la AKBR rápidamente se recuperó en 15 sobrevivientes, desde su valor inicial de 0.26±0.03 hasta el valor normal en el curso de horas, lo cual indicaba que las mitocondrias hepáticas se hallaban functionando normalmente. La AKBR se recuperó al valor normal de 1.10±0.06 en el día dos (p<0.001). Por el contrario, en 18 pacientes que expiraron, la AKBR no retornó a valores normales aunque algunos de ellos en algún momento se recuperaron del estado de shock. Por otra parte, en el día dos la AST, ALT, LDH y el tiempo de protrombina no se encontraron significativamente diferentes de los valores registrados en la admisión y lo cambios ocurridos en el intervalo no fueron unidireccionales aún en los sobrevivientes, lo cual no aportó información sobre el estado funcional del hígado. La medición de ASKBR durante, o poco después del shock hemorrágico, provee información oportuna y certera de la función hepática.

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Résumé Le but de cette étude a été de clarifier l'utilité du taux des corps cétoniques dans le sang artériel (CCA). Le CCA est considéré comme un reflet fidèle de l'état rédox des mitochondries hépatiques et est étroitement corrélé avec la production d'énergie hépatique, et permet de préciser l'étendue des lésions des mitochondries hépatiques et l'importance de la dégradadation du métabolisme pendant ou après le choc hémorragique. On a mesuré le CCA chez 33 patients ayant un choc hémorragique caractérisé par une pression systolique inféricure à 75 mm Hg, depuis Farrivée jusqu'à ce que le CCA se normalise ( 1.0) ou que le patient dècède. Lors du choc, le CCA était très diminué, témoignant d'une détérioration de la fonction hépatique. Chez les 15 patients survivants, après remplissage, les valeurs de CCA augmentaient à partir des valeurs initiales de 0.26±0.03 vers des valeurs normales, en quelques heures seulement, passant à 1.10±0.06 au J2 (p<0.001), indiquant que les mitochondrie hépatiques étaient intactes. Chez les 18 patients décédés, cependant, le CCA n'a pas atteint les valeurs normales, même lorsque le patient n'était plus en état de choc. En revanche, les valeurs des transaminases AST, ALT, des LDII et du taux de prothrombine à J2 ne différaient pas beaucoup des valeurs à l'admission. Les changements pendant l'intervalle n'était pas unidirectionnels même chez les patients survivants, sans que l'on sache très bien l'état fonctionnel du foie. Mesurer les valeurs de CCA pendant et après un choc hémorragique procure des enseignements importants et précis sur la fonction hépatique.

     

暴发性肝功能衰竭的原位肝移植

目的：探讨原位肝移植治疗暴发性肝功能衰竭的效果。方法：为一暴发性肝功能衰竭的Wilson's病患儿急症实施背驮式原位全肝移植术。结果：患者术后曾发生胆道梗阻并发症，经放射介入下胆道冲选和胆道取石术后缓解，已生存8月余，现生活质量良好。结论：原位肝移值是治疗暴发性肝功能衰竭的有效方法。     

The clinical significance of the arterial ketone body ratio as an early indicator of graft viability in human liver transplantation

Arterial ketone body ratio (AKBR) was measured sequentially in 84 liver transplantations (OLTx). These transplantation procedures were classified into 3 groups with respect to graft survival and patient condition at the end of the first month (Group A, the grafts survived longer than 1 month with satisfactory patient condition; Group B, the grafts survived longer than 1 month but the patients were ICU-bound; Group C, the grafts were lost and the patients died or underwent re-OLTx). In Group A, the AKBR was elevated to above 1.0 by the second postoperative day. In Group B, the AKBR was elevated to above 0.7 but stayed below 1.0 during this period. In Group C, the AKBR remained below 0.7 longer than 2 days after operation. Although conventional liver function tests showed significant increases in Groups B and C as compared with Group A, they were less specific in predicting ultimate graft survival.     

肝移植治疗暴发性肝功能衰竭

fulminant liver failure(FLF)is a rapid onset life-threatening emerency in which liver dysfunction,liver failure and hepatic encephalopathy occur within 8 weeks in previouslv norillal person.It has been confirmed by available clinical experience and literatures during the past decades that FLF patients are ideal recipients of liver transplantation.However,the prognosis of the FLF patients who accepted liver transplantation differed greatly according to the available reports because of the differences of supportive treatment during waiting period,the criterion for recipient assessment,the determination of operation chance,the use of critical techniques during operation and postoperative management between different transplantation centers.We probe the standardized clinical use of the aspects above mentioned in liver transplantation for FLF,particularly discuss the treatment of complications resulting from coagulopathy,determination of operation chance,significance of standardized etiological treatment and the indication of the use of veno-venous bypass technique during transplantation to provide better treatment strategy and improve the prognosis of FLF patients.     

Significance of arterial ketone body ratio measurement in human liver transplantation

Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation.     

Acute phase response after liver transplantation for fulminant hepatic failure and cirrhosis

The hepatic acute phase response after orthotopic transplantation (OLT) was studied in patients with fulminant hepatic failure (FHF) and with cirrhosis, in relation to the pre-existing disease. Plasma levels of C-reactive protein (CRP) increased significantly on day 1 after OLT in both the FHF (=58 /ml) and cirrhosis (=94 /ml) groups and reached a peak 4–5 days post surgery. ₁-Antitrypsin reached normal levels on day 1 post-transplant and fibrinogen reached normal levels on the 3rd day. The main stimulator of acute phase protein synthesis IL-6 was significantly increased pre-OLT in plasma in both FHF (median 54 pg/ml) and cirrhosis (median 8.7 pg/ml) patients compared to controls (2.35 pg/ml, P<0.05). After OLT, IL-6 decreased rapidly in patients with FHF, indicating either removal of the source of IL-6 or clearance by the transplanted liver. In patients with cirrhosis, plasma IL-6 remained low, except in three patients who developed infection/rejection and whose IL-6 levels rose above 100 pg/ml. In conclusion, there is a marked acute phase response in the liver graft after transplantation, irrespective of the aetiology of the liver disease for which the transplant was performed.