C. Cornu

Acute parvovirus B19 infection associated with fulminant hepatitis of favourable prognosis in young children

BACKGROUNDnThe cause of fulminant hepatitis (FH) in children is unexplained in up to 50% of cases. We report parvovirus B19 as an agent associated with FH in children and compare clinical characteristics of these patients with those of age-matched patients with FH of other origin.nnnMETHODSn45 patients presented with FH. No cause was apparent in 21 patients. Parvovirus B19 genome was retrospectively sought by PCR in serum collected at admission in 41 patients.nnnFINDINGSnParvovirus B19 genome was detected in serum from four of 21 patients with unexplained FH (four of 11 younger than 5 years). No B19 DNA was detected in serum from patients with other types of FH or from 82 patients with biliary atresia. Parvovirus B19 IgM was detected in one of the four patients. Patients with parvovirus B19 infection had significantly lower bilirubin concentrations than age-matched patients with FH due to hepatitis A (nine) or other causes (nine) (poisoning with amanita excluded). All patients with parvovirus B19 survived without orthotopic liver transplantation, with restoration of normal liver function within 17 days.nnnINTERPRETATIONnIn patients younger than 5 years with FH of unexplained origin, evidence of acute parvovirus B19 was associated with a distinct clinical pattern. In particular, low bilirubin concentrations and rapid recovery of liver function without transplantation were distinctive features.

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.

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

BACKGROUND/AIMSnThe 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.nnnMETHODSnFifty-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.nnnRESULTSnFive-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).nnnCONCLUSIONSnDelta 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.

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.

Fulminant hepatitis B in an infant born to a hepatitis Be antibody positive, DNA negative carrier.

A boy was born to a mother who was a chronic hepatitis B virus (HBV) carrier. She was hepatitis Be (HBe) antibody positive and HBe antigen and HBV-DNA negative. The boy had not received hepatitis B vaccine and died from fulminant hepatitis at 3 months of age. This case demonstrates the need to vaccinate babies of HBe antibody positive, HBe antigen negative carriers.

Non-A, Non-B Hepatitis in Dialysis Patients: Diagnosis, Prevention and Treatment

The concept of non-A, non-B hepatitis (NANBH) developed as accurate serologic tools became available to recognize various etiologic agents of hepatitis such as the hepatitis A and B viruses, the Epstein Barr virus and the cytomegalovirus (1). NANBH was recognized in the 80’s as the most common type of post-transfusion hepatitis (2). In hemodialysis patients, it emerged as the main cause of liver dysfunction once the spread of hepatitis B in dialysis units was controlled (3, 4).

Anti-HCV Seroconversion in Multitransfused and Immunocompromised Patients A Long-Term Longitudinal Study

In a series of 6 multitransfused, immunocompromised patients, the diagnosis of posttransfusion hepatitis C was based upon the analysis of long‐term follow‐up serum samples. The HCV RNA was detected by a nested PCR assay using primers located in the 5′ noncoding region (5′NCR), and anti‐HCV antibodies were assayed with third‐generation tests. The interval between the first rise in alanine aminotransferase and seroconversion varied from less than 5 months to more than 38 months. Five out of 6 patients seroconverted after 14 months or later. In most cases, the anti‐NS3 and anti‐NS4 antibodies appeared first. In such patients, the etiology of chronic liver disease may thus be overlooked for 1 or more years, a definitive diagnosis requiring the detection of HCV RNA.