Management of Clinically Significant Itch in Cholestatic Liver Disease

Abstract

Cholestatic liver diseases include primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and progressive familial intrahepatic cholestasis (PFIC). In all of these conditions, cholestatic itch is a major symptom that can severely and chronically impact a person’s quality of life (QoL). At a satellite symposium presented at the 2022 meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C., USA, leading experts discussed the importance of assessing itch in all patients with one of these cholestatic liver diseases. The experts presented patient cases to illustrate the challenges of managing itch in these cholestatic liver diseases. Studies show that many of these patients are not being adequately treated for this important symptom. However, while there are several treatments for itch, although not all are specifically approved medications, finding the right one for each patient may be a process of trial and error. In some cases, for people with severe, chronic, non-treatment-responsive cholestatic itch, a liver transplant may be the only treatment option.

Pruritus in primary biliary cholangitis is under-recorded in patient medical records

“…This suggests that pruritus may be overlooked or under-recorded by physicians, which could be due to several factors. First, physicians may be unfamiliar with available guidelines for recognising and treating pruritus or they may be aware of the lack of clinical evidence supporting the use of the current guideline-recommended therapies,24 which may mean that the condition is not screened for and/or treated by physicians as frequently as required 10. Second, it is possible that the management of PBC in clinical practice is recorded in medical records, but associated conditions such as pruritus/itch are not 15.…”

“…Prior research has found that pruritus in PBC is often difficult to treat: patients need to experiment with different treatments to gain respite as no single drug or therapy exists which effectively eliminates itch 13 28 29. In clinical practice and in clinical trials, it is common to see low numbers of patients responding to the guideline-suggested drugs for pruritus including cholestyramine, rifampicin, naltrexone and sertraline 24 30. While there is evidence supporting the use of fibrates for PBC and pruritus,31–33 the European Association for the Study of the Liver (EASL) 2017 guidelines did not recommend their use as data from phase 3 clinical trials were not published at the time of its release 4.…”

Diseases of bile duct in children

“…Farnesoid x receptor agonists: Farnesoid x receptor (FXR) agonists, which regulate metabolic homeostasis and inhibit bile acid synthesis, are potential therapeutic options for pediatric cholestatic liver diseases[ 98 ].…”

Japanese subgroup analysis of GLIMMER: A global Phase IIb study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis

“…In a Japanese study, the response rate to UDCA was 26.7% in patients diagnosed ≤1999 and 78.4% in patients diagnosed ≥2010 12 . However, UDCA has shown no effect on cholestatic pruritus 23 . In some countries such as the United States, obeticholic acid is also approved for PBC, but this treatment may actually exacerbate pruritus, which is noted as a warning in US prescribing information 24 .…”

“…12 However, UDCA has shown no effect on cholestatic pruritus. 23 In some countries such as the United States, obeticholic acid is also approved for PBC, but this treatment may actually exacerbate pruritus, which is noted as a warning in US prescribing information. 24 The bile acid sequestrant cholestyramine, which is indicated for hypercholesterolemia in Japan, is recommended as an off-label first-line treatment for cholestatic pruritus in Japanese treatment guidelines.…”