We read with great interest the article by McNally et al.,1 who reported the involvement of a seasonally varying environmental agent in the etiology of primary biliary cirrhosis (PBC), and who have reported previously that a transient environmental agent may be involved in the etiology using a space-time clustering method among cases of PBC in a defined geographical population of northeast England.2
A combination of genetic predisposition and environmental factors are thought to contribute the etiology of PBC.3 As environmental factors, certain bacterial and viral infections, including Escherichia coli, mycobacteria, and a retrovirus, are reported to be involved.4 To date, however, no specific virus has been implicated in the pathogenesis, although cases of PBC tend to cluster within areas.
Herpes simplex virus (HSV) is a hepatotropic virus, but it is an uncommon cause of hepatitis in immunocompetent adults. HSV hepatitis occurs in neonatal infections, pregnancy, and immunosuppressed patients. Recently, we frequently detected immunoglobulin M (IgM) anti-HSV antibody in patients with PBC. Twenty-two (55%) of 40 patients were positive (cutoff index >1.2) for IgM anti-HSV, 13 (33%) were negative (<0.8), and five (12%) were undetermined (0.8-1.2) (Fig. 1). Nineteen of 22 patients with positive IgM anti-HSV were positive for immunoglobulin G (IgG) anti-HSV, and three were negative. Nine of 13 patients with negative IgM anti-HSV were positive for IgG anti-HSV, and four were negative. Four of five undetermined patients were positive for IgG anti-HSV, and one was negative.
Nakamura et al.5 reported that two different progression types exist in PBC and that positive anti-gp210 (antinuclear membrane) and positive anticentromere antibodies represent the hepatic failure type and portal hypertension type, respectively. All five patients with antinuclear membrane antibodies showed strong positivity (Fig. 1, arrows). Five of 13 patients with anticentromere antibodies showed weak positivity (Fig. 1, arrowheads).
Our results support environmental factors involved in the etiology of PBC, although further studies should be done to evaluate whether HSV is an infectious agent or whether IgM anti-HSV is the result of a response to cross-reactive cellular proteins.