Pierre-François Laterre

Liver transplantation and HBsAg-positive postnecrotic cirrhosis : adequate immunoprophylaxis and delta virus co-infection as the significant determinants of long-term prognosis

BACKGROUND/AIMS The place of liver transplantation in hepatitis B viral (HBV)-related diseases remains controversial because of the high rate of reinfection. The aim of this study was to define the determinants of long-term prognosis after transplantation. METHODS Fifty-eight patients were transplanted during the period February 1984-September 1996. Six patients died during the early (< 3 months) posttransplant period from causes unrelated to HBV infection. All 52 long-term (> 3 months) survivors were evaluated in relation to the mode of presentation, viral replication at time of transplantation, absence of hepatocellular cancer at time of transplantation and use of adequate immunoprophylaxis (IP). Adequate immunoprophylaxis, defined as maintenance of anti-HBs levels over 100 mUI/ml, was introduced in December 1989. Intention-to-treat IP analysis compared patients transplanted before and after this date. The median follow-up was 74 months (range 4 to 131). Forty-seven patients (90%) had a minimal follow-up of 3 years. RESULTS Five-year actuarial survival rates of 58 patients and of 52 long-term survivors were 72 +/- 6% and 80 +/- 6%, respectively. Univariate analysis showed that delta co-infection (n = 25) significantly improved survival (p < 0.001) [96 +/- 4% vs 63 +/- 10% in HBV patients (n = 27) at 5 years] as did absence of hepatocellular cancer (n = 36) (p = 0.020) [89 +/- 5% vs 61 +/- 12% in 16 non-cancer patients]. IP, however, significantly influenced 5-year survival in the HBV-patient group (n = 17) (p = 0.001) [85 +/- 10% vs 30 +/- 14% in 10 patients without IP). Multivariate analysis selected delta co-infection (p = 0.002) and IP (p = 0.01) as the significant determinants of prognosis independently influencing survival. Uni- and multivariate analyses showed that survival without reinfection was significantly influenced by IP (p = 0.002) [73 +/- 8% (n = 31) versus 33 +/- 12% in 15 non-treated patients). CONCLUSIONS Delta virus co-infection and immunoprophylaxis are the most important prognostic factors after transplantation for postnecrotic HBsAg-positive cirrhosis. Transplantation can be proposed as a therapeutic tool only if life-long adequate adjuvant therapy can be achieved. Under this condition good results can even be obtained if there is viral replication at the time of transplantation.

The effects of intraoperative intravenous clonidine on fluid requirements, hemodynamic variables, and support during liver transplantation: a prospective, randomized study.

In this prospective, nonblind study, we report the use of clonidine during orthotopic liver transplantation (OLT).Twenty adult patients in a stable medical condition were studied. General anesthesia consisted of isoflurane in air/oxygen and sufentanil. Patients in the clonidine group received a slow IV infusion (15 min) of 4 [micro sign]g/kg clonidine during induction. The other patients were used as controls. IV fluid requirements were determined as follows: albumin (4% solution) was administered to maintain filling pressures to a pulmonary capillary wedge pressure (PCWP) of more than 12 mm Hg. Packed red blood cells were transfused to maintain a hemoglobin level of 8-9 g/dL. Circulatory stability was evaluated using: systolic and diastolic arterial blood pressure and heart rate recorded at 2-min intervals; and the vasopressor/inotropic support required to maintain adequate hemodynamic variables after reperfusion. Intraoperative albumin and packed red blood cell requirements were significantly reduced in patients in the clonidine group (1644 +/- 140 and 50 +/- 50 mL vs 2867 +/- 226 mL and 1350 +/- 443 mL; P < 0.05). Heart rate was significantly slower in patients of the clonidine group. There were no differences in systolic arterial blood pressure. After reperfusion, patients in the control group showed significantly lower diastolic arterial blood pressure, required more vasopressor/inotropic support, and were more acidotic than patients in the clonidine group. We conclude that the administration of 4 [micro sign]g/kg clonidine during induction of OLT significantly reduced the intraoperative requirements of IV fluids and blood products without compromising circulatory stability. Improvement in immediate reperfusion-induced disturbances was observed. Implications: The administration of 4 [micro sign]g/kg clonidine during induction of liver transplantation significantly reduced the intraoperative requirements for IV fluids and blood products without compromising the circulatory stability. Improvement in immediate reperfusion-induced disturbances was also observed. (Anesth Analg 1998;86:468-76)

Liver transplantation and haemophilia A.

Liver transplantation has become the standard treatment for a variety of inherited metabolic disorders. We report on two patients who underwent successful transplantation for posthepatitis viral cirrhosis, which developed following blood factor replacement for haemophilia A. The second patient was transplanted before the occurrence of major complications of either his liver or haemophilic disease. We propose early liver transplantation to achieve metabolic cure of haemophilia.

The effects of intraoperative intravenous clonidine on gastric intramucosal PCO2.

To investigate the effects of clonidine given as an anesthetic adjunct on splanchnic perfusion, we determined intramucosal gastric PCO2 using gastric tonometry in 60 patients scheduled for large intestine surgery.After induction of anesthesia, patients were randomly assigned to four groups. Patients in Group 1 received an IV infusion of sufentanil (0.2 [micro sign]g [center dot] kg-1 [center dot] h-1); patients in Group 2 received an IV infusion of clonidine (4 [micro sign]g/kg in 20 min followed by 2 [micro sign]g [center dot] kg-1 [center dot] h-1); patients in Group 3 received an IV infusion of ketamine (0.5 mg/kg followed by 0.25 mg [center dot] kg-1 [center dot] h-1); patients in Group 4 received an epidural infusion of bupivacaine (7 mL of 0.5% followed by 5 mL/h of 0.25%). Gastric intramucosal PCO2 was assessed immediately before skin incision and every hour during surgery using a nasogastric tube. A last measurement was taken after skin closure. An arterial sample was collected simultaneously to measure arterial PCO (2). Oxygen consumption (VO2/min) was continuously recorded. Gastric intramucosal PCO2 significantly increased during surgery in all groups independent of the anesthetic technique considered (P < 0.01) and was not related to metabolic changes or blood pressure variations. This increase, however, remains in the physiologic range. In conclusion, our results demonstrate that clonidine given as an anesthetic adjutant at the dose used has no deleterious effect on splanchnic perfusion during colonic surgery. Implications: IV clonidine given as an anesthetic adjunct at a dose of 4 [micro sign]g/kg in 20 min, followed by 2 [micro sign]g [center dot] kg-1 [center dot] h-1, has no deleterious effect on splanchnic perfusion during colonic surgery. (Anesth Analg 1998;87:686-90)