Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very ...important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659)
Background & Aims Primary biliary cirrhosis (PBC) is believed to result from the interaction of genetic and environmental factors. The controlled studies aiming to assess risk factors for PBC are ...still limited. Our aim was to identify risk factors and co-morbidities associated with PBC in a large monocentric cohort. Methods We enrolled 222 patients with PBC and 509 controls matched for age, gender, and residential location. Standardized questionnaire data, including more than 200 questions regarding demographic and anthropometric features, lifestyle, individual and familial medical history, and reproductive history, were prospectively collected and examined. Risk factors with odds ratio (OR) and confidence intervals (CI) were determined using conditional logistic regression analyses. Results Family history of PBC (OR 6.8, 95% CI 2.8–16.4) or autoimmune thyroid disease (AITD) (OR 7.1, 95% CI 3.5–14.5) in first-degree relatives, and individual history of active or passive smoking (OR 3.1, 95% CI 2.0–5.0), recurrent urinary tract infections (UTI) (OR 2.7; 95% CI 2.0–3.7), AITD (OR 7.7, 95% CI 4.8–12.3), Sjögren syndrome (OR 11.9, 95% CI 5.4–26.3), Raynaud syndrome (OR 7.2, 95% CI 4.3–12.1), pruritus during pregnancy (OR 3.9, 95% CI 2.8–5.3), or abortion (OR 2.0, 95% CI 1.6–2.5) were significantly associated with increased risk of PBC, while use of oral contraceptives (OR 0.6; 95% CI 0.5–0.8) was associated with decreased risk. Conclusion This study confirms some of the previously reported risk factors for PBC, namely family history of disease and individual history of smoking, UTI, and autoimmune conditions, and further identifies the use of oral contraceptives as a putative protective factor.
Linked ContentThis article is linked to Jones and Hansen, Cheung et al and Cheung et al papers. To view these articles, visit https://doi.org/10.1111/apt.13507, https://doi.org/10.1111/apt.13519 and ...https://doi.org/10.1111/apt.13465.
Abstract
Context
Liver function abnormalities (LFAs) have been described in patients with Turner syndrome (TS). Although a high risk of cirrhosis has been reported, there is a need to assess the ...severity of liver damage in a large cohort of adult patients with TS.
Objective
Evaluate the types of LFAs and their respective prevalence, search for their risk factors, and evaluate the severity of liver impairment by using a noninvasive fibrosis marker.
Methods
This was a monocentric retrospective cross-sectional study. Data were collected during a day hospital visit. The main outcome measures were liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), FIB-4 score, liver ultrasound imaging, elastography, and liver biopsies, when available.
Results
264 patients with TS were evaluated at a mean age of 31.15 ± 11.48 years. The overall prevalence of LFAs was 42.8%. The risk factors were age, body mass index, insulin resistance, and an X isochromosome (Xq). The mean FIB-4 sore of the entire cohort was 0.67 ± 0.41. Less than 10% of patients were at risk of developing fibrosis. Cirrhosis was observed in 2/19 liver biopsies. There was no significant difference in the prevalence of LFAs between premenopausal patients with natural cycles and those receiving hormone replacement therapy (P = .063). A multivariate analysis adjusted for age showed no statistically significant correlation between hormone replacement therapy and abnormal gamma-glutamyl transferase levels (P = .12).
Conclusion
Patients with TS have a high prevalence of LFA. However, 10% are at high risk of developing fibrosis. The FIB-4 score is useful and should be part of the routine screening strategy. Longitudinal studies and better interactions with hepatologists should improve our knowledge of liver disease in patients with TS.
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