Loss of serum HBsAg after interferon-A therapy in liver transplant patients with recurrent hepatitis-B infection.

Reinfection with hepatitis B virus after orthotopic liver transplantation is nearly universal in patients who have not received posttransplant immunoprophylaxis. Recurrence almost invariably leads to chronic liver disease. Interferon has been used both prophylactically and therapeutically but has not been effective. We treated 2 liver transplant patients with recurrent hepatitis B virus (HBV) infection (serum hepatitis B surface antigen [HBsAg] and HBV DNA positive on polymerase chain reaction, and positive liver biopsy result) with interferon, 3 to 6 MU three times weekly for 6 to 22 months. A full response to therapy was manifested in both patients by normalized serum alanine aminotransferase levels and the loss of serum HBsAg and HBV DNA. The effectiveness of interferon in our patients may have been related to coinfection with hepatitis D virus in the first case and the high interferon dose (6 MU, three times weekly) and long treatment period (22 months) in the second. No episodes of rejection were noted during therapy. We conclude that interferon can induce a complete response in liver transplant patients with recurrent HBV infection. Future studies should investigate the use of interferon therapy at higher doses and/or for longer periods.

[Liver allografts from donors older than 60: benefits and risks].

With limited organ resources and an increasing number of candidates for liver transplantation, the world-wide trend is towards using liver allografts from donors older than 60 years. This strategy, however, may be hazardous because of the known correlation between advanced donor age and graft dysfunction. Since January 1996, each of 5 patients received a liver allograft from a donor older than 60 years. Preservation time in these cases was shortened as much as possible and liver allografts were used only if there were no other potential risk factors for primary nonfunction. Mean cold ischemic time was significantly shorter in this donor group (7.8 hrs) than for livers from 28 younger donors (10.2 hour; p < 0.01). 3 of the 5 grafts from older donors had normal function immediately. The other 2 initially had biochemical features of preservation injury, but graft function returned to normal within the first week after transplantation. All 5 patients currently have normal graft function, with follow-up ranging from 3-8 months. There was no difference between the 5 recipients of grafts from older donors and 28 adult recipients of grafts from younger donors in extent of preservation injury and in immediate graft function. We conclude that in countries with limited organ resources, such as Israel, liver allografts from older donors can be used within defined limits and minimal preservation time.

Acute beriberi following liver transplantation.

Patients scheduled for orthotopic liver transplantation (OLT) undergo extensive routine preoperative cardiac assessment. We describe a 32-year-old male who underwent uneventful OLT for endstage liver failure on the basis of chronic hepatitis C and alcoholism. Despite a normal preoperative cardiac workup, the patient developed acute pulmonary edema on the second postoperative day. A diagnosis of beriberi was entertained and confirmed by (1) the thiamine diphosphate effect and (2) the dramatic response to intravenous thiamine. Possible precipitating factors are described. Thiamine, which has no significant toxicity, should probably be routinely supplemented in all patients undergoing OLT, especially those with a previous history of alcohol abuse.

Beneficial effect of lamivudine in recurrent hepatitis B after liver transplantation.

Orthotopic liver transplantation (OLT) in patients infected with hepatitis B virus (HBV) is known to be associated with a high recurrence rate and poor prognosis. Interferon treatment in these patients offers little benefit and may lead to further complications. Lamivudine, the (-)enantiomer of 3'-thiacytidine, a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in patients with chronic HBV infection. Three HBV-positive OLT patients were administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks, in an open, compassionate-use basis. All three patients were HBV DNA-negative before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9 months) after OLT, in spite of adequate immunoprophylaxis. All three patients had high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and histologic evidence of recurrent HBV infection of the grafted liver, and HBV DNA was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV DNA disappeared from the serum of all patients (detected by hybridization); by the 10th week, HBV DNA was also negative by polymerase chain reaction in two out of three patients. Interestingly, the one patient who was HBV DNA positive by polymerase chain reaction still has mildly elevated ALT levels, whereas the other two patients have normal ALT levels. We also noted that on the 5th week there was a transient elevation of serum ALT levels in two patients. No adverse effects or rejection episodes were noted. In conclusion, lamivudine is a beneficial and well-tolerated therapy in OLT patients with recurrent HBV infection. We are studying the effect of lamivudine in other patients and for a longer period of time.

Gallopamil reduces the post-transplantation acute tubular necrosis in kidneys from aged donors.

Due to a shortage of suitable kidneys for transplantation there has been an increase in the use of kidneys taken from old and marginal donors, which has led to a high incidence of acute tubular necrosis. Several reports suggest that the administration of calcium channel blockers improves the initial function after renal transplantation. We conducted a randomized, double-blind placebo-controlled trial to study the effect of the calcium channel blocker gallopamil on the incidence and course of acute tubular necrosis following cadaveric renal transplantation. A trend developed showing a decrease in episodes of acute tubular necrosis in gallopamil versus placebo, and became statistically significant when the outcome of kidneys from donors older than 50 years was analyzed separately [gallopamil 6/14 (42%) vs. placebo 10/11 (91%), P <0.01 corrected chi2]. We conclude that pre-transplantation renal graft perfusion and post-transplantation recipient treatment with gallopamil reduces the incidence of post-transplantation acute tubular necrosis, particularly in kidney taken from older donors.