Natural history of hepatitis B in perinatally infected carriers

Objectives: To establish natural seroconversion rates and incidence of hepatic pathology in perinatally infected hepatitis B carriers.

Methods: Seventy three perinatally infected hepatitis B carriers identified through maternal screening were evaluated. Fifty three were born to parents from the Indian subcontinent, nine were Oriental, six were Afro-Caribbean, and five were white. Median follow up was 10.24 (range 2.02–20.16) years.

Results: Only three of the children followed up had cleared hepatitis B surface antigen during this period, and 30% of the children had seroconverted to anti-HBe. Seroconversions to anti-HBe were observed in Asian (18/50) and white (4/5) children, but not in Oriental or Afro-Caribbean children. More girls (40%) than boys (23%) had seroconverted, but the difference was not significant. All children were asymptomatic with normal physical examination, growth, and development. Almost half (48%) of the hepatitis B e antigen (HBeAg) positive children had normal hepatic transaminases and liver function. Thirty five liver biopsies were performed in children with active virus replication (HBeAg or hepatitis B virus DNA positive) who were being considered for antiviral treatment as part of a clinical trial and were scored using the Ishak method. Two thirds (62%) of the children had mild hepatitis, 60% had mild fibrosis, and 18% had moderate to severe fibrosis. There was a weak correlation between histological evidence of hepatitis and hepatic transaminase activity, implying that biochemical monitoring of hepatic disease activity may be ineffective.

Conclusions: These asymptomatic hepatitis B virus carrier children remain infectious in the medium to long term with notable liver pathology. They should receive antiviral treatment to reduce infectivity and to prevent further progression of liver disease. Hepatic transaminases alone are not a reliable marker of liver pathology, and liver histology is essential before consideration for antiviral treatment.

The natural history of self-harm from adolescence to young adulthood : a population-based cohort study

Background Knowledge about the natural history of self-harm is scarce, especially during the transition from adolescence to young adulthood, a period characterised by a sharp rise in self-inflicted deaths. From a repeated measures cohort of a representative sample, we describe the course of self-harm from middle adolescence to young adulthood.

Methods A stratified, random sample of 1943 adolescents was recruited from 44 schools across the state of Victoria, Australia, between August, 1992, and January, 2008. We obtained data pertaining to self-harm from questionnaires and telephone interviews at seven waves of follow-up, commencing at mean age 15·9 years (SD 0·49) and ending at mean age 29·0 years (SD 0·59). Summary adolescent measures (waves three to six) were obtained for cannabis use, cigarette smoking, high-risk alcohol use, depression and anxiety, antisocial behaviour and parental separation or divorce.

Findings 1802 participants responded in the adolescent phase, with 149 (8%) reporting self-harm, More girls (95/947 [10%]) than boys (54/855 [6%]) reported self-harm (risk ratio 1·6, 95% CI 1·2–2·2). We recorded a substantial reduction in the frequency of self-harm during late adolescence. 122 of 1652 (7%) participants who reported self-harm during adolescence reported no further self-harm in young adulthood, with a stronger continuity in girls (13/888) than boys (1/764). During adolescence, incident self-harm was independently associated with symptoms of depression and anxiety (HR 3·7, 95% CI 2·4–5·9), antisocial behaviour (1·9, 1·1–3·4), high-risk alcohol use (2·1, 1·2–3·7), cannabis use (2·4, 1·4–4·4), and cigarette smoking (1·8, 1·0–3·1). Adolescent symptoms of depression and anxiety were clearly associated with incident self-harm in young adulthood (5·9, 2·2–16).

Interpretation Most self-harming behaviour in adolescents resolves spontaneously. The early detection and treatment of common mental disorders during adolescence might constitute an important and hitherto unrecognised component of suicide prevention in young adults.

Funding National Health and Medical Research Council, Australia, and operational infrastructure support programme, Government of Victoria, Australia.

Lynch syndrome: natural history and colonoscopic surveillance

Lynch syndrome is the commonest inherited cause of bowel cancer. This thesis explores the natural history and cancer risk in Lynch syndrome and documents the effect of colorectal cancer on fertility. It also demonstrates that colonoscopic surveillance can prevent colorectal cancers and thus improve survival in these subjects.

The natural history of internalizing behaviours from adolescence to emerging adulthood: findings from the Australian Temperament Project

BACKGROUND: The aims of the study were to describe the patterning and persistence of anxiety and depressive symptoms from adolescence to young adulthood and to examine long-term developmental relationships with earlier patterns of internalizing behaviours in childhood. METHOD: We used parallel processes latent growth curve modelling to build trajectories of internalizing from adolescence to adulthood, using seven waves of follow-ups (ages 11-27 years) from 1406 participants of the Australian Temperament Project. We then used latent factors to capture the stability of maternal reported child internalizing symptoms across three waves of early childhood follow-ups (ages 5, 7 and 9 years), and examined relationships among these patterns of symptoms across the three developmental periods, adjusting for gender and socio-economic status. RESULTS: We observed strong continuity in depressive symptoms from adolescence to young adulthood. In contrast, adolescent anxiety was not persistent across the same period, nor was it related to later depressive symptoms. Anxiety was, however, related to non-specific stress in young adulthood, but only moderately so. Although childhood internalizing was related to adolescent and adult profiles, the associations were weak and indirect by adulthood, suggesting that other factors are important in the development of internalizing symptoms. CONCLUSIONS: Once established, adolescent depressive symptoms are not only strongly persistent, but also have the potential to differentiate into anxiety in young adulthood. Relationships with childhood internalizing symptoms are weak, suggesting that early adolescence may be an important period for targeted intervention, but also that further research into the childhood origins of internalizing behaviours is needed.