Cholestasis

BackgroundIntrahepatic cholestasis of pregnancy (ICP) can be a source of significant distress for both pregnant women and the fetus, impairing the quality of life and well-being of pregnant women, leading to psychological disorders among pregnant women with severe or recurrent ICP, and causing life-threatening complications among fetuses. Regrettably, our current understanding of ICP globally is limited, lacking a comprehensive estimation of its incidence. Therefore, in this systematic review and meta-analysis, we aimed to investigate the global and regional incidence of ICP and identify factors that account for its variety across studies.MethodsA comprehensive search strategy was implemented across PubMed, Scopus, and Web of Science databases. To stabilize the variance, the Freeman-Tukey double arcsine transformation was employed. Subgroup analyses were conducted based on continent, publication type, study design and timing, regional classifications, developmental status, and World Bank income grouping. A multivariate meta-regression analysis was performed to estimate the effects of the continuous moderators on the effect size.ResultsA total of 42,972,872 pregnant women were analyzed from 302 studies. The overall pooled incidence [95% confidence interval] of ICP was 2.9% [2.5, 3.3]. Studies with larger sample sizes tended to provide significantly lower estimates of ICP incidence: 1.6% [1.3, 2] vs 4.7% [3.9, 5.5]. Asia had the highest incidence of ICP among the continents, whereas Oceania had the lowest. Countries that were classified as developed and with higher income had a lower incidence of ICP than those classified as developing and low and middle income.ConclusionsThe findings of this study will provide valuable insights into the current knowledge regarding the association of the quality of public health and socioeconomic variations with the incidence of ICP on a global scale.

IntroductionProgressive Familial intrahepatic cholestasis (PFIC) are rare disorders of bile acid (BAs) secretion and transport with a genetic background. PFIC are paediatric manifestations, but the same variants causing PFIC can also cause cholestasis with a later paediatric onset or adult-onset cholestatic disease (AOCD). Pruritus is a symptom of cholestasis that can be so devastating that it requires a liver transplant (LT) in children; some PFIC types have been described as at risk of liver cancer development. Commonly prescribed medications for PFIC symptoms can partially relieve pruritus without changing the natural history of the disease. Recently, a therapy reducing the intestinal resorption of BAs has been approved; it is effective on both pruritus and cholestasis in PFIC, potentially being a disease-modifying intervention.Areas coveredThe clinical and genetic characteristics of different PFIC and AOCD are summarized to provide a common background for geneticists and paediatric and adult hepatologists in diagnosis and management.Expert opinionCollaboration between paediatric and adult hepatologists and geneticists will become crucial for cholestatic disease research and patient treatment. Therefore, adult hepatologists will need to learn more about FIC. This might enable the implementation of individualized surveillance in FIC patients and the evaluation of patient family histories.

Primary Biliary Cholangitis is an autoimmune liver disease distinguished by Anti-mitochondrial Antibodies and chronic non-suppurative lymphocytic microcholangitis. UDCA remains the exclusively recommended initial therapy for PBC. However, 40% of patients experience either incomplete biochemical response or intolerance to UDCA, which represents poorer outcomes and increased mortality. Therefore, early identification of high-risk patients and timely intensive treatments are necessary to delay the progression of PBC and better improve the prognosis. Intensive therapeutic strategies based on more stringent treatment goals and early efficacy assessment criteria are elaborated in this review. To exclude AIH-PBC overlap syndrome, liver biopsy is required for cholestasis patients with negative AMAs or PBC patients who respond inadequately to UDCA, especially those with elevated ALT and IgG. Combined immunosuppressants are considered for patients with moderate-to-severe hepatitis. ALP normalization is considered the improved therapeutic goal for high-risk patients, which has been verified achievable in multiple treatment attempts. The control of pruritus and fatigue constitutes the key therapeutic targets in the symptom management of PBC. Bezafibrate, Seladelpar, and IBAT inhibitors have demonstrated significant therapeutic potential in pruritus. Last but not least, Liver Stiffness Measurement is substantiated as efficient in the fibrotic monitoring of PBC patients. OCA and fibrates are respectively useful for compensated and decompensated fibrotic patients. Moreover, the conventional efficacy assessment procedure, which is the "wait-to-fail" strategy, exhibits suboptimal sensitivity in the timely detection of treatment-responsive patients. Therefore, early prediction and evaluation criteria at baseline and 1-month treatment will help in timely interventions for patients with insufficient efficacy. This improved identification strategy is expected to provide precise and personalized treatment for PBC patients.

Background & aimsPrimary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) go along with reduced health-related quality of life (HRQOL). Variant syndromes, that is, conditions with features of both PBC/PSC and AIH, are associated with higher clinical complexity and worse prognosis. Studies on HRQOL in patients with variant syndromes are lacking. We aimed to provide large-scale evidence addressing this gap.MethodsWe included adult patients with clinical diagnoses of autoimmune liver diseases across nine countries in a cross-sectional study. We descriptively compared demographical, clinical and patient-reported outcomes between the conditions and investigated whether additional AIH contributes to reduced HRQOL compared to the cholestatic liver disease alone. Further, we explored the role of fatigue, cirrhosis and depression severity regarding HRQOL.ResultsN = 1275 patients were included (PBC: n = 342, PBC-AIH: n = 160, PSC: n = 305, PSC-AIH: n = 121, AIH: n = 347). Patients with variant syndromes showed high rates of cirrhosis and increased depressive or anxiety symptoms. Additional AIH was associated with further reduction in physical and mental HRQOL in people with PSC (physical: ΔR2 = 0.012, p = 0.041; mental: ΔR2 = 0.016, p = 0.020), but not with PBC (physical: ΔR2 = 0.008, p = 0.081; mental: ΔR2 = 0.001, p = 0.609). Physical HRQOL was associated with higher age and fatigue, while mental HRQOL was associated with lower age, fatigue, and depression severity.ConclusionsPatients with variant syndromes of autoimmune liver diseases show high physical and mental burden, with fatigue as the main contributor. Particularly PSC-AIH goes along with more severely reduced HRQOL compared to the cholestatic liver disease alone, which is attributable to a higher symptom burden.