Correspondence to the Editor * Clayton D, Schifflers E. Models for temporal variation in cancer rates. I: Age-period and age-cohort models. Stat Med 1987;6:449-67. 3 Clayton D Schifflers E. Models for temporal variation in cancer rates. II: Age-period-cohort models. Stat Med 1987;6:467-810 4 Decarli A, La Vecchia C. Age, period and cohort models: review of knowledge and implementation in GLIM. Riv Statist Appl 1987:20:397-410. 5 La Vecchia C, Negri E, Levi F, Decarli A, Boyle F. Cancer mortality in Europe: effects of age, cohort of birth and period of death. Eur J Cancer 1998;34:118-41. 6 Doll R, Peto R. The causes of cancer: Quantitative estimates of avoid- able risks of cancer in the United States today. J Nat1 Cancer Inst 1981;66:1191-308. ’ La Vecchia C, Lucchini F, Franceschi S, Negri E, Levi F. Trends in mortality from primary liver cancer in Europe. Eur J Cancer 2000;36:909-15. Sir Reduced fertility and amenorrhoea are common clinical mani- festations of autoimmune hepatitis (AIH). From the therapeuti- cal standpoint, it is unclear if steroids and/or azathioprine are safe in women longing for pregnancy or who are pregnant. Preg- nancy in AIH patients appears to be an uncommon event, rarely described and with conflicting outcomes im4. We report here the case of a young woman with type 1 AIH who had two uneventful pregnancies during which the liver disease went into spontaneous remission and relapsed in the post-par- turn period, on both occasions. At a routine examination, this clinically asymptomatic 33-year- old had elevated alanine aminotransferase (ALT) values (100 IU/l, upper normal level: 40), y-globulin and IgG levels (20 g/l and 2250 mg/dl), whereas the other liver function tests were within the normal range and abdominal ultrasound examination was normal. Viral and metabolic causes were ruled out and high titre (1:5 120) anti-smooth muscle antibodies with peritubular pattern (SMA-T) 5, anti-neutrophil cytoplasmic antibodies with perinuclear pattern 6, and XRl reactivity ’ were detected. Liver histology showed mononuclear cell infiltration of the portal tracts and periportal necrosis (Knodell index 9). A diagnosis of “definite” AIH with a cumulative score of 17 was made, ac- cording to the recently revised criteria issued by the Intema- tional Autoimmune Hepatitis Group *. Before beginning any immunosuppressive treatment, the patient became pregnant, thereafter a spontaneous normalization of ALT ensued and persisted throughout pregnancy. Two months after the birth of a healthy baby, serum ALT levels became ab- normal again (231 IU/l) and immunosuppressive therapy with steroids was, therefore, commerced (24 mg methylprednisolone daily) A complete and sustained remission has been maintained with methylprednisolone 4 mg/daily for the following 3 years. The patient then became pregnant again and 8 weeks later she interrupted immunosuppressive therapy “sua sponte”. During pregnancy, serum ALT levels were evaluated every month, and persistently remained within normal values. Two months after the delivery of a second healthy baby, ALT flared up to 383 IU/l. A second liver biopsy showed lymphoplasmacellular infiltration of the portal tracts, periportal necrosis, rosettas and mild fibro- sis (Knodell index 12). Steroid therapy was reinstituted (24 mg methylprednisolone daily) with complete biochemical remis- sion shortly thereafter. The pathogenesis of autoimmune hepatitis is still largely unknown and many factors seem to be involved in the breakdown of tolerance against “self ‘; extrinsic triggering factors (viruses, drugs), abnormal autoantigen presentation, Spontaneous remission of autoimmune hepatitis during pregnancy immune cell activation and genetic predisposition have been considered 9. The cytokine network seems to be involved in the clinical expression of AIH. In active disease, a Thl cytokine profile, characterized by tumour necrosis factor-o and b, interleukin (IL)-1-a and B, IL-2, IL- 12 and interferon-y, predominates, while during remission Th2 cytokines, that include IL-4, IL-5, IL-10 and IL-13 prevail. The cytokine balance is known to change greatly during pregnancy and in the post-pat-turn period lo. Furthermore, pregnancy is characterized by an increased production of steroids and other hormones (corticotropin releasing hormone by placental secretion, cortisol, oestrogen and progesterone), that seem to tilt the balance in favour of a Th2 orientation, whereas, in the post- partum a reduction of these hormones has been noted ‘I. High corticosteroid levels were shown to suppress IL-2 levels ” and exert only a minimal suppressive action on IL-lo, which has a potent anti-inflammatory action. Moreover, progesterone levels especially in the third trimester of pregnancy enhance IL-4 production by T cells 13.On account of their paternal antigens, the foetus and placenta may be considered an allograft in the maternal host. It is tempting to speculate that during pregnancy, the Th2 orien- tation of the immune system response may improve AIH through the increase of tolerance. We suggest that the sponta- neous biochemical improvement observed both during pregnan- cies in our AIH patient was due, at least in part, to the modula- tion of ThlfTh2 cytokine balance. This single report does not allow any definite conclusions to be drawn on the management of AIH during pregnancy. The spon- taneous remission of AIH observed in our patient is in contrast, for example, with the experience of Heneghan et al. 4, who de- scribe ALT flares in 4 out of 16 pregnant AIH patients despite immunosuppressive treatment, and 2 cases of “de nova” AIH di- agnosis during pregnancy. However, pregnancy in AIH patients appears to be safe, but a closer follow-up in this peculiar condi- tion is recommended. list ol abbreviations AIH: autoimmune hepatitis; ALT alanine amlnotransferase; IL: Interleukin; SMA-T anti-smooth muscle antibodies with peritubular pattern. P. Muratori, S. Loffreda, 1. Muratori, R. Ferrari, K. Afandi, F. Cassani, 6. Pappas, M. Lenzi, F.G. Bianchi 608