H. E. Harris

Clinical course of hepatitis C virus during the first decade of infection: cohort study

Abstract Objective: To determine the clinical course of hepatitis C virus in the first decade of infection in a group of patients who acquired their infections on a known date. Design: Cohort study. Setting: Clinical centres throughout the United Kingdom. Participants: 924 transfusion recipients infected with the hepatitis C virus (HCV) traced during the HCV lookback programme and 475 transfusion recipients who tested negative for antibodies to HCV (controls). Main outcome measures: Clinical evidence of liver disease and survival after 10 years of infection. Results: All cause mortality was not significantly different between patients and controls (Coxs hazards ratio 1.41, 95% confidence interval 0.95 to 2.08). Patients were more likely to be certified with a death related to liver disease than were controls (12.84, 1.73 to 95.44), but although the risk of death directly from liver disease was higher in patients than controls this difference was not significant (5.78, 0.72 to 46.70). Forty per cent of the patients who died directly from liver disease were known to have consumed excess alcohol. Clinical follow up of 826 patients showed that liver function was abnormal in 307 (37.2%), and 115 (13.9%) reported physical signs or symptoms of liver disease. Factors associated with developing liver disease were testing positive for HCV ribonucleic acid (odds ratio 6.44, 2.67 to 15.48), having acquired infection when older (at age ≥ 40 years; 1.80, 1.14 to 2.85), and years since transfusion (odds ratio 1.096 per year, 1.00 to 1.20). For patients with severe disease, sex was also significant (odds ratio for women 0.38, 0.17 to 0.88). Of the 362 patients who had undergone liver biopsy, 328 (91%) had abnormal histological results and 35 (10%) of these were cirrhotic. Conclusions: Hepatitis C virus infection did not have a great impact on all cause mortality in the first decade of infection. Infected patients were at increased risk of dying directly from liver disease, particularly if they consumed excess alcohol, but this difference was not statistically significant. What is already known on this topic The clinical course of HCV infection is unclear because most information has come from studies of patients with established chronic liver disease Studies that follow patients from disease onset are rare because most HCV infections are asymptomatic What this study adds HCV infection does not have a great impact on all cause mortality in the first decade of infection Infected patients have an increased risk of dying from a liver related cause, particularly if they consumed excess alcohol

Do the psychosocial and behavioral changes that accompany motherhood influence the impact of pregnancy on long-term weight gain ?

The aim of the present study was to assess whether the psychosocial and behavioral changes that occur during and after pregnancy influence long-term weight gain. The study examined 74 mothers enrolled in the Antenatal Care (ANC) Project (a randomized controlled trial of antenatal care based in South London), all of whom had volunteered to take part in a subsequent follow-up study. Data on body weight at the beginning of pregnancy; lifestyle and behavior during pregnancy; antenatal care and obstetric history; together with measures of postnatal depression and parenting stress following pregnancy were taken from the existing ANC Project database. Additional measurements of height and weight together with information on a variety of lifestyle changes and psychosocial characteristics, were gathered during semi-structured interviews at each mothers home, two and a half years after their children had been born. The results show that pregnancy-related weight gains are not simply the result of retaining weight that is gained during pregnancy, but that they also originate from gaining additional weight in the postpartum period. Mothers who felt they ate more after their children were born, had significantly greater long-term weight gains (2.78 (1.42) kg) than those who felt that they had not increased their food intake (-1.15 (0.76) kg; t = 2.49, p = 0.016). Similarly, mothers who felt they had greater access to food postpartum, had significantly greater long-term weight gains (1.70 (0.87) kg) than those who felt they did not have greater access to food (-1.37 (1.13) kg; t = 2.18, p = 0.032). There was some evidence that the lifestyle changes which accompany pregnancy and motherhood increase some womens vulnerability to eating disorder psychopathology. Mothers who felt they did less exercise after pregnancy than they did before, were also at greater risk of long-term weight gain (p = 0.028), as were mothers with low numbers of supportive individuals (p = 0.033). Neither the stress of parenting nor maternal depression were significantly associated with an increased risk of long-term weight gain (p > 0.05).

The impact of pregnancy on the long-term weight gain of primiparous women in England

OBJECTIVES: To investigate the impact of pregnancy on long-term weight gain of primiparous mothers in England, and to identify potential risk factors for maternal obesity. DESIGN: A retrospective, repeat-pregnancy study which examined the change in maternal body weight from the beginning of the first successful pregnancy to the beginning of the second. SUBJECTS: Two hundred and forty-three mothers, all of whom had been weighed during the first trimester of their first and second pregnancies, and none of whom had fallen pregnant less than 12 months after the birth of their first child. MEASUREMENTS: Sociodemographic, behavioural, medical, obstetric and perinatal data, together with antenatal measurements of maternal body weight and height, were extracted from each mother’s obstetric notes. A comprehensive survey of weighing scales used at all antenatal clinics was undertaken. RESULTS: After accounting for the effect of ageing, there was no significant long-term increase in mean maternal body weight following the first pregnancy (95% Confidence Intervals: −0.82–0.28 kg). While most mothers (70.8%) gained 1.0 kg or less, 24.7% gained more than 1.54 kg. Even after accounting for the maximum error in clinic scales, 14.8% of the mothers gained 1.54 kg or more in association with their first pregnancy. Mothers with higher BMIs at the beginning of their first pregnancy, who gained more weight during pregnancy, gave birth to heavier babies and had longer intervals between their pregnancies, gained significantly more weight from one pregnancy to the next. CONCLUSIONS: Pregnancy has little impact on the mean weight gain of primiparous women from England, who have a low prevalence of obesity (BMI≥26.0, 25.5%). Nevertheless, pregnancy may be associated with a permanent increase in maternal body weight simply because it is a period of positive energy balance during which some women gain excessive weight. Other factors, such as prepregnant BMI, determine whether long-term weight gain actually occurs.

Is there an independent association between parity and maternal weight gain

The independent associations between parity and maternal body mass index (BMI), and between parity and maternal weight gain, were investigated using a combination of cross-sectional and longitudinal analyses based on a retrospective, repeat-pregnancy study that examined the change in maternal body weight from the beginning of one pregnancy to the beginning of the next. A group of 523 multiparous women who had been weighed regularly during pregnancy, and none of whom had fallen pregnant less than 12 months after the birth of their previous child, were examined. Sociodemographic, behavioural, medical, obstetric and perinatal data, together with antenatal measurements of maternal body weight and height, were abstracted from each mothers obstetric notes. Parity was found to be independently associated with maternal BMI (p < 0.001), gestational weight gain (p < 0.001) and interpregnancy weight gain (p = 0.032). Women of different parities were found to be at differential risk of long-term weight gain for two reasons. First, primiparous women are at risk of long-term weight gain because they gain the most weight during pregnancy, and high gestational weight gain is in itself a risk factor for long-term weight gain. Second, women of higher parity (4+) are at risk of long-term weight gain because they gain more weight in association with pregnancy, irrespective of the amount of weight they gain during their pregnancies. For women of parity 3 or less, the association between maternal body weight and parity appears to be the result of cumulative weight gained during successive pregnancies. For women of greater parity, the association between maternal body weight and parity is partly the result of cumulative excess gestational weight gained during successive pregnancies, and partly the result of gaining more weight from the beginning of one pregnancy to the next at later pregnancies.

Practical Approaches for Estimating Prepregnant Body Weight

Measurements of prepregnant body weight have important research and clinical applications. In practice, however, they are not always recorded; even when they are, this information is not always readily available. For this reason, researchers and clinicians have to rely on retrospective estimates of prepregnant weight, which can be estimated using: 1) maternal self-reports, 2) retrospective extrapolation, or 3) standardized estimates that correct for weight gained during early pregnancy. The aim of the present study was to examine the relative merits of these three approaches. Maternal self-reports tend to be unreliable and biased, being influenced by a variety of sociodemographic characteristics that generally underestimate true prepregnant body weight. Estimates of prepregnant weight based on retrospective extrapolation are vulnerable to measurement error, transient fluctuations in body weight, and incorrectly assume that the rate of weight gain is constant throughout pregnancy. Standardized estimates that correct for weight gained during early pregnancy incorrectly presume that there is little interindividual variation in gestational weight gain and that weight gain is similar for each woman in consecutive pregnancies. Because none of these techniques can provide a precise measure of prepregnant weight, researchers have little alternative but to recruit and weigh women before they become pregnant, although measurements of body weight recorded during the first trimester of pregnancy may provide a reasonable indication of prepregnant weight. For clinicians, self-reports of prepregnant weight or measurements recorded early in pregnancy are probably sufficiently accurate for practical purposes whenever recent, accurate measurements of prepregnant weight are unavailable.

The HCV National Register: towards informing the natural history of hepatitis C infection in the UK

The aim of this paper is to describe the development of a national hepatitis C register and the completeness of the data it contains. This is a descriptive report of the structure and function of the register, including case definitions, registration and follow‐up procedures, and methods used to maximize data quality and to obtain comparative data sources. The register contains data on HCV‐infected individuals who acquired their infections on a known date and by a known route; to date all are transfusion recipients identified during the UK lookback exercise, who tested positive or indeterminate for anti‐HCV after receiving ‘infected’ blood issued before the introduction of routine testing of the blood supply for anti‐HCV. By 31 December 1999, 871 (87%) of 996 eligible transfusion recipients had been registered, and 984 (99%) flagged in the NHS Central Registers. Registered patients had been infected for an average of 11.1 years (SEM 0.1); around half were being cared for by clinicians with a specialist interest in liver disease. Except for the information on tobacco use, current alcohol use, and hepatitis B status, data were more than 80% complete, and for most variables, more than 90% complete. The consistency of data abstraction was found to be 98% (SEM 0.5). In conclusion, the Register contains high quality anonymised data on one of the largest cohorts of individuals with HCV infections acquired on a known date and by a known route. It could serve as a model for other chronic disease registers; developers may find the structure, design, and methodological issues addressed useful.

Are overweight women at increased risk of obesity following pregnancy

Longitudinal studies suggest that women who already have a high BMI are at greater risk of maternal obesity than their lighter counterparts. The aim of the present study was to investigate this possibility by examining the relationship between reproductive history and maternal BMI in a community of 627 women from South Africa with a high prevalence of obesity. Standardized questionnaires were used to obtain detailed sociodemographic and behavioural information, while maternal weight and height were both measured at the time of the interview. Analysis of covariance (ANCOVA) showed that maternal age (r2 0.015, P = 0.001), smoking status (r2 0.012, P = 0.036), and social support (r2 0.011, P = 0.006) were all independently associated with maternal BMI. If overweight women were at increased risk of maternal obesity, then the positive relationship between reproductive history and maternal BMI should be enhanced in this relatively obese community, yet the ANCOVA models showed no independent association between gravidity and maternal BMI after controlling for the effects of confounding factors. Although previous longitudinal studies have found a positive association between prepregnant weight and long-term weight gain, this relationship might arise because overweight women gain more weight over a fixed period of time than normal weight women, and therefore they may appear to be at greater risk of pregnancy-related weight gains. Overweight women are at greater risk of weight gain generally, but there is little unequivocal evidence to suggest that they are at any increased risk of maternal obesity, when compared with women of lower BMI.

A national sample of individuals who acquired hepatitis C virus infections in childhood or adolescence: risk factors for advanced disease.

Objectives: To describe hepatitis C virus (HCV)–related liver disease in a national cohort of patients who acquired their infections in childhood or adolescence and to assess risk factors for progressive disease and response to antiviral therapy. Patients and Methods: Demographic, laboratory, and clinical outcome data on 246 individuals who acquired HCV infection before the age of 16 years were extracted from the UK HCV National Register database. Logistic regression analysis was used to investigate the independent effects of sex, age, duration and route of infection, and comorbidity on histological stage of liver disease. Results: Median ages at enrollment and follow-up were 14.0 years (range, 2.2–29.6 years) and 19.2 years (range, 2.3–35.5 years), respectively. Mean duration of infection at enrollment was 8.5 years (standard deviation [SD], 3.3 years), and mean duration of follow-up was 4.5 years (SD, 4.5 years). Fifty-nine (24%) had persistently abnormal liver aminotransferase levels; 22% reported physical signs and symptoms of liver disease. Among 123 individuals with liver biopsies, 117 (95%) had abnormal histological findings. Ninety-eight individuals had biopsies referred for independent blind scoring; median Ishak grade and stage scores were 3 and 1, respectively. Presence of comorbidities (odds ratio [OR], 7.19; 95% CI, 2.00–26.17; P = 0.003) and female sex (OR, 0.31; 95% CI, 0.10–1.00; P = 0.05) were independently associated with histological stage scores greater than the median. A total of 110 individuals received antiviral therapy; 47% achieved a sustained response. Conclusions: HCV-related liver disease in those who acquired the infection in childhood or adolescence was mild for most, although comorbidity and female sex were associated with more advanced disease. Antiviral therapy in childhood or adolescence successfully eradicates the virus for many patients.