Treatment of Polycystic Liver Disease: Impact on Patient-reported Symptom Severity and Health-related Quality of Life

Abstract

Polycystic liver disease (PLD) is a genetic disorder in which patients suffer from progressive development of multiple (>10) hepatic cysts. Most patients remain asymptomatic during the course of their disease. However, a minority of PLD patients suffer from symptoms caused by hepatomegaly leading to serious limitations in daily life. Untreated symptomatic PLD patients score significantly worse on health-related quality of life (HRQoL) compared to age and gender-matched populations. Currently, liver transplantation is the only curative treatment for PLD. The main goal of other available therapies is to strive for symptomatic relief and improvement of HRQoL by suppressing disease progression. In this review, we summarize the effect of PLD treatment on patient-reported outcome measures with a distinction between HRQoL and symptom severity. At present there is heterogeneity in application of questionnaires and no questionnaire is available that measures both HRQoL and PLD symptom severity. Therefore, we recommend the combination of a validated PLD-specific symptom severity questionnaire and a general HRQoL questionnaire to evaluate treatment success as a minimal core set. However, the specific choice of questionnaires depends on treatment choice and/or research question. These questionnaires may serve as a biomarker of treatment response, failure, and adverse events.

FIGURE 1

Schematic overview of the treatment options for polycystic liver disease determined on liver phenotype.

FIGURE 2

Overview of clinical and preclinical investigated therapies. AC5 indicates adenylyl cyclase 5; AMPK, adenosine monophosphate-activated protein kinase; Cdc25A, cell division cycle 25 homolog A; ER, endoplasmic reticulum; GnRH, gonadotropin hormone-releasing hormone; HDAC6, histone deacetylase 6; HSP90, heat shock protein 90; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; PPAR, peroxisome proliferator-activated receptor; TGR5, Takeda G protein-coupled receptor 5; TRPV4, transient receptor potential cation channel subfamily V member 4; UDCA, ursodeoxycholic acid; VEGFR2, vascular endothelial growth factor receptor 2; V2R, vasopressin 2 receptor.