Mini review
Pathophysiology and current management of pruritus in liver disease

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Summary

Pruritus is frequently reported by patients with cholestatic hepatobiliary diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and hereditary cholestatic syndromes, but may accompany almost any other liver disease. Increased concentrations of bile salts, histamine, progesterone metabolites or endogenous opioids have been controversially discussed as potential pruritogens in cholestasis in the past. Most recently, novel insights unravelled lysophosphatidic acid (LPA), a potent neuronal activator, as a potential pruritogen in pruritus of cholestasis. Nevertheless, the pathogenesis of pruritus in cholestasis is still not clearly defined and current antipruritic treatment strategies provide relief only in a part of the affected patients. Based on recent experimental and clinical findings, this review outlines the actual insight in pathogenesis of pruritus in cholestasis and summarizes evidence-based and experimental therapeutic interventions for cholestatic patients suffering from itch.

Section snippets

Definition and prevalence

The observation that pruritus accompanies jaundice has already been made by the ancient Greek physician Aretæus the Cappadocian in the 2nd century BC [1]. Today, itch is well known as a frequent and agonizing symptom accompanying many types of liver diseases, particularly those with cholestatic features [2], [3], [4]. In these disorders, cholestasis may be due to:

  • impaired hepatocellular secretion as observed in intrahepatic cholestasis of pregnancy (ICP), benign recurrent intrahepatic

Clinical picture

Although pruritus is frequently undervalued by clinicians, it is often the major burden of the cholestatic patient and can dramatically reduce quality of life. Pruritus may be mild and tolerable, but does, in some patients, limit activities of daily life and cause severe sleep deprivation resulting in lassitude, fatigue, depression and even suicidal sensation. In rare cases, intractable pruritus may become a primary indication for liver transplantation even in the absence of liver failure [4],

Bile salts

Aretæus, the Cappadocian, explained the itchy skin in jaundiced patients by prickly bilious particles [1]. More than two millennia later, his hypothesis is at least partly still valid as the removal of bile from the body either by external biliary diversion [21], [22], [23] or nasobiliary drainage [24], [25], [26] quickly and dramatically alleviates severe cholestatic pruritus. Thus, certain biliary substances contribute either directly or indirectly to the onset of itching. During cholestasis,

Management

Treatment options for pruritus in cholestasis remain limited to a few evidence-based and several experimental medical and interventional therapies. Therapeutic interventions should primarily focus on an adequate therapy of the underlying hepatobiliary disease, as this may result in relief of pruritus.

The rationale for medical and interventional therapeutic approaches is:

  • to remove the pruritogens from the enterohepatic cycle by non-absorbable, anion exchange resins such as cholestyramine,

Conflict of interest statement

The authors have no conflicts of interest that are directly relevant to the content of this review.

Funding: Supported by the Deutsche Forschungsgemeinschaft (KR3618/1-1 to A.E.K.).

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