Complications, symptoms, quality of life and pregnancy in cholestatic liver disease

Abstract

Cholestatic liver diseases (CLDs) encompass a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury and ultimately end-stage liver disease. Many patients with CLD are diagnosed between the ages of 20-50 years, a particularly productive period of life professionally, biologically and in other respects; it is not surprising, thus, that CLD is often associated with impaired health-related quality of life (HRQOL) and uncertainty regarding implications for and outcomes of pregnancy. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most prominent CLDs, both having considerable morbidity and mortality and representing major indications for liver transplantation. These disorders, as a consequence of their complications (eg ascites, hepatic osteodystrophy), associated conditions (eg inflammatory bowel disease) and symptoms (eg pruritus and fatigue), can significantly impair an array of domains of HRQOL. Here we review these impactful clinical aspects of PSC and PBC as well as the topics of fertility and pregnancy.

Primary sclerosing cholangitis: A review and update

“…, fat-soluble vitamin (A, D, E, K) and other micronutrient and mineral ( e.g. , vitamin B12, zinc) deficiency, hepatic osteodystrophy, and pruritus, 39,131 and (ii) cirrhosis, e.g. , portal hypertension, varices, ascites, and hepatocellular carcinoma, which are managed similarly to patients with non-PSC related cirrhosis.…”

Primary Sclerosing Cholangitis and Psychological Wellbeing: A Scoping Review

“…Although prevalence may not differ from the expected in the background population, those who have a diagnosis of PSC tend to reveal a greater number of depressive symptoms and a lower level of wellbeing, with suicide attempts also occurring. 16,17 The presence of such symptoms has been linked to the stage of liver disease experienced by the individual. 14 Severe depression was particularly prevalent in those who have a comorbid diagnosis of inflammatory bowel disease (IBD).…”

“…Fear of malignancies associated with PSC (colorectal cancers, cholangiocarcinomas, and other hepatobiliary malignancies) and possible mortality as a consequence is frequently reported. 16,21 Lower feelings of self-control regarding the illness and the future appeared in the narratives of those with PSC and comorbid anxiety. 11 This may, in part, be due to fears regarding liver transplantation including whether they will be able to receive a suitable donor organ, fear and anguish of causing the donor harm, and fear regarding financial costs.…”

NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A nebulous matter

“…[1][2][3] It is an idiopathic disorder which lacks medical therapy and consequently continues to result in life-alternating and lethal consequences in a considerable proportion of patients. [3][4][5][6][7] Through ongoing efforts across the research spectrum, our knowledge and awareness of PSC are greater now than ever before, yet it is difficult to controvert that fundamental understanding of PSC remains, from essentially every perspective, incomplete. It is perhaps on this basis that PSC has been regarded as the ''black box" of liver disease.…”

“…Fourth, in terms of patient reported outcomes, these were seemingly not measured as study endpoints, but based on adverse event reporting, NGM282 did not worsen pruritus or fatigue; it would be interesting to know if the putative antifibrotic and other therapeutic effects could lessen symptoms of PSC or otherwise improve quality of life. 4 Lastly, cholangiographic changes were not assessed as a study endpoint; given these (or histologic changes in the case of small duct PSC) represent a hallmark of disease diagnosis and progression, the evaluation of a potential therapeutic intervention should include biliary imaging and/or histopathology.…”