M. Lamy

Patterns of hepatitis delta virus reinfection and disease in liver transplantation.

Twenty-seven carriers of the hepatitis B surface antigen who underwent liver transplantation in Italy and Belgium for terminal Hepatitis delta virus (HDV) cirrhosis were investigated. In 22 of the patients, HDV infection recurred. Two patients died of coexisting HDV and hepatitis B virus (HBV) reactivation. Four patients who died of unrelated causes were found to have HDV without signs of HBV reactivation. Five patients (18%) cleared both HBV and HDV after transplantation with no evidence of hepatitis (mean follow-up, 29 months). In many surviving patients. HDV infection recurred early without signs of HBV reactivation. Disease returned in the 11 HDV-infected patients in whom HBV also recurred. Histological hepatitis did not recur during an interim of 12-33 months in the 5 HDV-infected patients in whom HBV did not return. The overall medium-term survival in patients with HDV who underwent transplantation was 77.7%. Liver transplantation offers patients with HDV a hope of cure from disease despite a high risk of reinfection. In the transplantation setting. HDV can cause subclinical infections without any apparent assistance from HBV; these infections become symptomatic only if and when HBV reactivates. Thus, HDV may not be in itself pathogenic but requires cooperation from HBV to cause the appearance of the disease.

Acute adenovirus hepatitis in liver transplant recipients.

An acute or fulminant adenovirus hepatitis developed in 5 of 224 pediatric patients who were recipients of orthotopic liver transplants. All had received prednisolone, azathioprine, and cyclosporine as basal immunosuppression, and four received monoclonal (OKT3) or polyclonal (antithymocyte globulin) antibodies for steroid-resistant rejection episodes. These patients initially had high fever and a worsening condition for a mean of 73 days after transplantation (range 44 to 140 days). Results of biochemical tests showed very high serum levels of lactate dehydrogenase. Aspartate aminotransferase values were always markedly more elevated than those of alanine aminotransferase. Two patients had severe leukopenia. Results of histologic studies of the liver showed extensive areas of confluent necrosis and targetlike hepatocyte nuclei. Typical intranuclear viral inclusions were observed on electron microscopy. Adenovirus was cultured in all patients and in two relatives. Two patients died of liver failure; others recovered after cessation of immunosuppression. We conclude that adenovirus hepatitis can be fatal in liver transplant recipients. There is no specific treatment, and immunosuppression must be discontinued.

Epstein-Barr virus infection in 59 orthotopic liver transplant patients.

Fifty-nine orthotopic liver transplant (OLT) patients were studied after transplantation to detect Epstein-Barr virus (EBV) primoinfection and reactivation. Nineteen, all children under 10 years, were EBV seronegative. Seroconversion occurred in 12 (63.3%) of the seronegative patients. Most of these patients (10/12) seroconverted 2 or 3 months after transplantation; 11 out of the 12 demonstrated clinical signs at the time of seroconversion. From 9 primoinfected patients tested for EBV excretion, 8 were found to be positive. Serological evidence of reactivation was found in 9 out 40 (22.5%) seropositive patients and EBV was isolated from 5 (56%). Eleven pediatrie OLT patients with primoinfection showed high and persistent titers of anti-EA antibodies (from 1∶32 to > 1∶256), when tested at least 3 months after serovonversion; however, anti-EBNA antibodies failed to develop in 5 patients and remained persistently low in 4. These patients with high EA and with negative or low EBNA titers constitute an “at risk” group for EBV-related lymphoproliferative syndrome (LpS). At presently, after a period of follow-up ranging from 3 months to 3 years, none of our 12 primoinfected patients have developed any lymphoproliferative evolution. However, in 1, during the acute phase, lymphoblasts and lymphoproliferation were observed in a tonsil biopsy.

Requirements for diagnosis of prenatal cytomegalovirus infection by amniotic fluid culture

BACKGROUNDnAmniotic fluid culture is considered to be the best method for the detection of antenatal cytomegalovirus (CMV) infection and prediction of congenital CMV infection. Recently, however, some false-negative results have been reported.nnnOBJECTIVESnPrediction of congenital CMV infection by amniotic fluid culture with emphasis on false-negative results.nnnSTUDY DESIGNnRetrospective study of 42 pregnant women with primary CMV infection. First, estimation of seroconversion related to the gestational age was established. Afterwards, results of amniotic fluid culture were compared either with CMV isolation from biopsies from aborted fetuses, or with viral culture of newborns urine.nnnRESULTSnIn 18 cases (43%), amniotic fluid culture gave negative results which coincided with 18 uninfected newborns. In 18 other cases (43%), amniotic fluid culture was positive for CMV: 7 newborns with CMV viruria and 11 terminations of pregnancy with CMV isolated from fetal biopsies. In the remaining 6 cases, amniotic fluid culture gave negative results, whereas the 6 newborns were all infected.nnnCONCLUSIONnAmniotic fluid culture remains an accurate method for the diagnosis of CMV antenatal infection. However, in order to avoid false-negative results, the importance of a correct estimation of the gestational age of seroconversion and of a sufficient interval between primary infection and amniocentesis are stressed.

Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a long-term follow-up study

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by positivity for hepatitis B e antigen and hepatitis B virus DNA, with increased DNA polymerase levels for more than 6 months, were entered into a prospective trial of low-dose recombinant human alpha-interferon therapy. All patients were treated with 5 million units of recombinant interferon alfa-2b given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNA polymerase levels (p less than or equal to 0.001), which reached normal values in ten (48%). After 10 months mean follow up, seven patients (33%) were hepatitis B e antigen negative and five (24%) subsequently became positive for antibodies to e antigen. By 27 months, nine patients (43%) were both hepatitis B e antigen negative and e antibody positive. Only one patient became permanently negative for hepatitis B surface antigen. One patient relapsed during the second year of follow up. Side effects necessitated withdrawal of therapy in two patients: one due to worsening thrombocytopenia after two doses of interferon (data omitted from the study results) and one due to a local reaction at the injection sites. Our data indicate that small doses of recombinant interferon alfa-2b given during a 12-week period induce a significant reduction in viral replication and approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.

Specific IgE detected by ELISA and immunoblot after human cytomegalovirus infection (HCMV) in renal transplant (RT) recipients.

BACKGROUNDnSpecific HCMV IgE response has been reported by some authors, and was proposed as a valuable virologic marker of CMV infection.nnnOBJECTIVESnwe evaluated specific HCMV IgE in renal transplant patients with active (primary and secondary) HCMV infection with special interest to symptomatic infections.nnnSTUDY DESIGNnSpecific IgE was tested retrospectively by ELISA and immunoblot (IB) on sera of 55 RT patients who were followed before and after transplantation with virologic markers of CMV infection.nnnRESULTSnTotal serum IgE levels were similar in control group and in patients with primary and secondary HCMV infections. Anti-CMV specific IgE response by ELISA was more frequently found in patients with primary infection (76.9%) than in patients with secondary infection (47.1%). These specific IgE reacted on immunoblot with a 150 kDa protein in 84.6% of patients with primary infection and 94.1% with secondary infections; and reacted with rp52 (pUL44) in 76.9% of primary infection and 47.1% of secondary infection.nnnCONCLUSIONSnAnti-CMV specific IgE tested by immunoblot and ELISA is a marker of CMV infection. It was clearly detected in cases of active infection (primary and secondary) and was present in cases with severe CMV clinical manifestations. In contrast, anti-CMV specific IgE, was consistently negative among healthy blood donors. This is the first report of CMV proteins detected by IgE immunoblot.