Orthotopic liver transplantation for acute hepatic failure in children

Abstract Thirty children received 35 liver transplants for fulminant or late-onset liver failure between March 1988 and May 1993. Aetiology included non-A non-B hepatitis in 12, Wilson's disease in 8, drug-induced hepatic failure in 6, hepatitis B in 1, hepatitis A in 1, tyrosinaemia in 1 and congenital haemochromatosis in 1. Three patients were retransplanted, one each for hepatic artery thrombosis, non-A non-B graft reinfection, and chronic rejection. Two of these three patients received a third transplant for chronic rejection and hepatic artery thrombosis. One patient in the retransplant group survived. Overall, graft and patient survival at a mean follow-up of 17 months were 49% and 57%, respectively. Mortality was related to vascular complications in three patients (hepatic venous obstruction, portal vein thrombosis and hepatic artery thrombosis). Two patients died of primary sepsis (cerebral aspergillosis and cytomegalovirus (CMV) pneumonitis in association with graft-versus-host disease). Systemic sepsis and multiorgan failure was documented as a cause of death in four children and sepsis in association with chronic rejection in a further three patients. One child died of respiratory failure 4 weeks after transplantation. Mortality in eight children less than 2 years was 75% and this was significantly greater than for older children ( P < 0.003, Mantel Cox). Earlier referral, even in the absence of a definitive diagnosis and particularly in children under 2 years is advisable and may improve survival.     

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.     

Quality of life after lobectomy for adult liver transplantation

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.     

Liver transplantation for acute hepatic failure

INTRODUCTION: The mortality rate of acute hepatic failure (AHF) with conservative treatment is 40% to 90%, depending on the etiology. Hepatitis B infection is the major cause of AHF in Asia. In this study, we examined the role of liver transplantation for adult patients with AHF. METHODS: Sixteen patients with AHF received liver transplants in the past 6 years. Eight patients received cadaveric donor and another 8 living-related donor grafts. Fifteen patients suffered from hepatitis B-related disease and 1 had drug-induced AHF. Extracorporeal charcoal hemoperfusion was used as a bridge to liver transplantation in the first 2 patients and plasma exchange was used in the following patients. RESULTS: One patient died 1 month after the operation due to primary nonfunction. The other 15 patients are alive with good graft function at 2 months to 6 years follow-up. The success rate is 94%. Postoperative complications included infection in 10 patients (62.5%), acute rejection in 4 patients (25%), and biliary complication in 2 patients (12.5%). No neurological complications were noted. CONCLUSION: Liver transplantation is the most effective treatment for patients with AHF. Living donors may be considered due to the organ shortage and the critical patient disease.     

Risk factors for acute respiratory failure after liver transplantation

OBJECTIVES: To study the risk factors for acute respiratory failure during recovery after liver transplantation. PATIENTS AND METHODS: We prospectively studied 340 consecutive liver transplant operations. Patient data was grouped according to whether acute respiratory failure developed (group I) or not (group II). Acute respiratory failure was defined by the need for mechanical ventilation longer than 5 days after transplantation or by the need for an inspired oxygen fraction of over 50% for 72 hours. We evaluated demographic characteristics, stage of liver disease before the transplant, comorbidity, immunosuppressant treatment administered, and complications during and after surgery. RESULTS: Sixty-six patients were placed in group I and 274 in group II. Univariate analysis showed significant differences between the groups for age, sex, Child-Pugh functional stage, preoperative renal failure, type of immunosuppression, and postoperative complications such as atrial fibrillation, pleural effusion, pulmonary edema, ascites, postoperative acute renal failure, brain dysfunction, early graft dysfunction, and respiratory infection. Multivariate analysis by logistic regression, taking the development or not of acute respiratory failure as the dependent variable, gave a model with 6 variables that accounted for 94% of the cases. The variables entering into the model, with their respective odds ratios (OR) were female sex (OR, 5.5), stage C liver function (OR, 3.9), pulmonary edema (OR, 16.3), postoperative acute renal failure (OR, 9), cerebral dysfunction (OR, 4.5), and respiratory infection (OR, 62). CONCLUSIONS: The development of acute respiratory failure after liver transplantation is affected by the following factors: female sex, Child-Pugh class, pulmonary edema, postoperative acute renal failure, cerebral dysfunction, and respiratory infection.     

Terbinafine-induced hepatic failure requiring liver transplantation.

Drug-induced liver disease accounts for about 50% of acute or subacute liver failure in the United States. United Network of Organ Sharing (UNOS) data suggest 8%-20% of liver transplantation in this country per year is for fulminant liver failure due to drugs. Even though the most common medication implicated in acute liver injury is acetaminophen (75%), there are numerous other drugs that are responsible for acute and chronic liver injury. A variety of antifungal medications are known to cause a wide range of liver injury from a mild hepatocellular-cholestatic injury pattern to acute/subacute liver failure. Terbinafine is one of the antifungals that have been associated with such liver injuries. We report a case of terbinafine-induced severe liver failure requiring liver transplantation.     

肝移植术后急性肝动脉闭塞的介入治疗

目的评价介入医学在诊断和治疗肝移植术后急性肝动脉闭塞中的作用.方法对7例原位肝移植术后急性肝动脉闭塞病例的诊断和介入治疗过程进行了回顾性分析.结果 59例肝移植术后血管造影证实存在肝动脉闭塞7例,其中多普勒超声发现5例;经导管溶栓治疗,7例肝动脉闭塞中5例部分或全部开通,对其中4例进行了血管内支架植入治疗,经1～13个月随访,肝动脉血流通常,避免了再次肝移植.结论血管造影对肝移植后肝动脉并发症的诊断具有重要价值,介入手段是处理肝移植术后急性肝动脉闭塞的有效方法.     

The importance of orthotopic liver transplantation in acute hepatic failure

Selection of patients with acute hepatic failure for liver transplantation remains difficult, and there is no definite proof of a survival effect. We therefore did a retrospective study in 75 consecutive patients referred over a 12-year period. In two-thirds we identified a cause, mostly viruses or drugs. Patients were grouped by the Clichy and King's College criteria. In 20 there was no indication for transplantation. Of the 5 with autoimmune hepatitis, 3 died, significantly differing from the other 15 ( P = 0.009). The remaining 55 met our criteria, except 1. All 9 patients with absolute contraindications died. Of the 46 enlisted, 7 died without transplantation. One-year survival after transplantation was 69%, compared with 58% by "intention to treat." For patients enlisted, transplantation reduced mortality by 78% ( P = 0.069). The Clichy and King's College criteria reliably predict survival without transplantation, except in autoimmune hepatitis. Our study strongly suggests that transplantation improves survival.     

Pediatric liver transplantation for acute liver failure

The only proven therapy for patients unlikely to recover from acute liver failure (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid referral to a transplant center are crucial. We evaluated 12 pediatric patients with ALF who underwent liver transplantation (LT) at our institution during a 3-year period. The reasons for transplantation were hepatitis A (3 patients); non-A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3); Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis with leflunomide treatment (1). Seven of the participants were female and five were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts, one received a whole liver graft, and the remainder received left or left-lateral liver lobe grafts. All patients recovered from hepatic coma the second postoperative day. Two patients died at postoperative days 57 and 71 due to adult respiratory distress syndrome and sepsis with multiorgan failure, respectively. One patient required retransplantation because of chronic rejection 7 months after the initial transplantation. That patient died 10 days after retransplantation because of sepsis. Nine patients were healthy at follow-up (range, 2-46 months). LT is the only treatment option for ALF in patients in countries with low organ-donation rates. In this scenario, donor preparation in a limited time frame is difficult. We have been able to decrease the duration of donor preparation to approximately 4 hours (including biopsy of the donated liver tissue).     

Bullous pemphigoid after liver transplantation for liver failure.

Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants - prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant.     

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.     

Temporary liver transplantation in acute liver failure.

The ability of a heterotopic graft to prolong life in animals dying in hepatic coma due to liver necrosis has never been definitely established. Acute hepatic failure was produced in 15 dogs by an hour of total interruption of the hepatic blood supply. Nine dogs received an intrathoracic hepatic homograft concurrently. Nontransplanted dogs died within 21 hours in hepatic coma, while transplanted dogs survived significantly longer (P less than .001). In all transplanted dogs, biological signs of hepatic failure were corrected in 24 hours. In four animals, the graft was removed on the fifth postoperative day. Two of those survived for 10 and 15 days respectively with normal hepatic function. These results demonstrate that a temporary heterotopic liver transplant is able to support life during the acute, normally lethal phase in dogs with massive liver necrosis.     

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver. Received: 15 September 1997 Received after revision: 4 February 1998 Accepted: 2 March 1998     

Risk factors for development of acute renal failure after liver transplantation

BACKGROUND: Acute renal failure (ARF) is a common complication after liver transplantation (LTx). Identification of risk factors may prevent the development and attenuate the impact of ARF on patients outcome after LTX. METHODS: Retrospective analysis of variables in the pre, intra, and postoperative periods of 92 patients submitted to LTx was performed in order to identify risk factors for development of ARF after LTx. ARF was defined as serum creatinine > or = 2.0 mg/dL in the first 30 days after LTx. Univariate and multivariate analysis by logistic regression were performed. RESULTS: ARF group comprised 56 patients (61%). Preoperative serum creatinine was higher in ARF group. During the intraoperative period, ARF group required more blood transfusions, developed more episodes of hypotension and presented longer anesthesia time. In the postoperative period, ARF group presented higher serum bilirubin and more episodes of hypotension. Dialysis was required in 10 patients (11%). The identifled risk factors for development of ARF were: preoperative serum creatinine > 1.0 mg/dL. more than five blood transfusions in the intraoperative period, hypotension during intra and postoperative periods. The identified mortality risk factors were hypotension in the postoperative period and no recovery of renal function after 30 days. CONCLUSIONS: Several factors are involved in the pathogenesis of ARF after LTx and may influence patients outcome and mortality. Pretransplant renal function and hemodynamic conditions in the operative and postoperative periods were identified as risk factors for development of ARF after LTx. Nonrenal function recovery and postoperative hypotension were identified as mortality risk factors after LTx.     

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.     

Risk factors of acute renal failure after liver transplantation

The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child-Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II-IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.