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Currently there is a trend to support the use of antiviral therapy as the first line treatment of polyarteritis nodosa (PAN) associated to hepatitis B virus (HBV) infection.1 ,2 A combination of a short course of corticosteroids, plasma exchange, and interferon α (INFα) has been proposed. However, we have doubts about this approach in all cases and circumstances of PAN related to HBV infection. One of these circumstances would be precore mutant HBV infection.
A 37 year old man was diagnosed with PAN. The initial clinical manifestations were mononeuritis multiplex, orchitis, mild renal failure (creatinine: 168 μmol/l, proteinuria of 0.6 g/dl), abdominal pain, and prolonged fever. Leucocytosis (30 000 WBC, 80% neutrophils), serum asparate aminotransferase: 94 U/L, serum alanine aminotransferase: 244U/l, increased erythrocyte sedimentation rate (90 mm/h) and complement consumption were also observed. Histological diagnosis was performed by testicular biopsy. Infection with HBV precore mutant was present (HBsAg +, HBeAg −, Anti HBe Ag +, Anti HBc Ab IgG/M +, HBV DNA 1180 pg/ml). Retrospective sequence analysis of the serum HBV DNA showed the presence of the precore mutant (substitution of G to A at nucleotide 1896). A therapeutic regimen of prednisone 1 mg/kg per day (twice a week) with rapid discontinuation (one week), plasma exchange, and INFα was started. Significant improvement in clinical symptoms and laboratory data, including renal function, with regression of sediment anomalities and normalisation of the creatinine occurred with this treatment. HBV DNA load (measured two weeks after INFα) and transaminases values were similar to previous range. Four weeks later, while receiving this treatment, abdominal pain, prominent leucocytosis, increased erythrocyte sedimentation rate, and decreased complement component 3 were observed again. The patient developed acute pulmonary oedema secondary to myocarditis associated with vasculitis (left ventricular ejection fraction: % EF: 38%; previous EF: 72%); electrocardiography was non-specific and serial creatine kinase measurement was in the normal range. A diagnosis of relapse of PAN with probably secondary myocarditis was made. This situation was controlled with furosemide, digoxin, and intravenous pulses of methylprednisolone 1 g/day, for three days; a pulse of cyclophosphamide 1200 mg intravenously was also administered. INFα and plasma exchange were stopped. Two weeks later the % EF was 45%, and the patient was discharged with oral prednisone and monthly cyclophosphamide pulses. Six months later the patient achieved clinical remission.
We are cautious to recommend antiviral treatment as first line treatment in polyarteritis associated with HBV. The experience with INF in the treatment of polyarteritis is still limited. To our knowledge, this is the first case report of PAN associated with a precore mutant strain of HBV incapable of synthesising HBe antigen; therefore, there is no previous experience with INF. The precore defective HBV is present in one third of patients in the Mediterranean with chronic HBV infection.3 It has been speculated that the absence of HBe Ag in the hepatocyte membrane prevents the elimination of infected cells by immune system stimulated by INF. It is considered a viral infection with few trends to spontaneous remission and more progressive in comparison with the infection caused by the wild type virus. In general, the treatment with INF in the chronic hepatitis produced by this variate is unfavourable. The rates of relapses are very high in patients who have precore mutant compared with wild type HBV infection (40–90% compared with 13%)4-6; and it is recommended to include these patients in multicentric and controlled trials.7 On the other hand, HBV mutant infection has been associated with fatal liver failure after immunosuppressive therapy.8 Precore mutant HBV associated PAN should be considered as an individual entity whose therapeutic approach is complex and not defined at present. It is necessary to perform prospective studies to evaluate the exact role of immunosuppressive and antiviral therapy, including new antiviral agents.