Effect of genotype on the severity and volume progression of polycystic liver disease in autosomal dominant polycystic kidney disease

Chebib, Fouad T.; Jung, Yeonsoon; Heyer, Christina M.; Irazabal, María V.; Hogan, Marie C.; Harris, Peter C.; Torres, Vicente E.; El-Zoghby, Ziad M.

doi:10.1093/ndt/gfw008

Cited by 59 publications

(83 citation statements)

References 33 publications

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“…In our population, the proportion of patients who are symptomatic (Qian Grade 4) is equal between ADPKD and ADPLD, even as the distribution between mild, moderate and severe disease which supports the homogeneous composition of this cohort. Compared with other ADPKD cohorts in which the appearance of PLD is no inclusion criteria, the proportion of females in our ADPKD population is higher . This corresponds with the results of our study and previous literature as females are more at risk to develop severe hepatomegaly and therefore are more often tertiary referred because of symptomatic PLD compared with males.…”

Section: Discussionsupporting

confidence: 87%

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Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Aerts

Kievit

Jong

et al. 2018

Liver International

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Section: Discussionsupporting

confidence: 87%

“…An important finding is that in female patients, liver volume is 6.9% smaller per decade of age. This contrasts with a recent study that suggested that hTLV increased with 10.0% per decade in female APDKD patient . These conflicting conclusions can be attributed to differences in disease populations.…”

Section: Discussioncontrasting

confidence: 83%

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Aerts

Kievit

Jong

et al. 2018

Liver International

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“…Recent studies have shown a substantial reduction in the rate of growth or even a reduction in LV in female patients after menopause. 13,14 Therefore, young premenopausal women and men with severe PLD might have a higher risk for sustained and faster enlargement of the liver after PHCF. Perioperative complications associated with PHCF were common but manageable in most cases.…”

Section: Discussionmentioning

confidence: 99%

Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease

Chebib

Harmon

Irazabal

et al. 2016

Journal of the American College of Surgeons

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BACKGROUND Partial hepatectomy and cyst fenestration (PHCF) selectively provides clinical benefit in highly symptomatic patients with polycystic liver disease (PLD). This study aims to ascertain whether the reduction in liver volume (LV) achieved by PHCF is sustained long term. STUDY DESIGN Clinical data were retrieved from the electronic records of all patients with PLD who underwent PHCF between 1985 and 2014. Preoperative LVs (LV1), postoperative LVs (LV2), and late follow-up LVs (LV3) were measured from magnetic resonance or CT images. RESULTS Among 186 patients who underwent PHCF, 91% were Caucasian women with autosomal dominant polycystic kidney disease with a mean age of 49 years. Major perioperative complications (Clavien III/IV) occurred in 21% of the patients. Operative mortality (<90 days) was 2.7%. Eleven patients had liver failure develop, received liver transplants, or had liver-related deaths. Overall survival was 95.7%, 93.3%, 85.6%, and 77.7% at 1, 5, 10, and 15 years respectively. Imaging records for volumetry were unavailable in 32 patients. Of the remaining 154 patients, 34 had imaging for 1 LV, 64 for 2 LVs, and 55 for all 3 LVs. Median LV was 6,781 mL (interquartile range 4,903 to 8,341 mL) preoperatively and 2,502 mL (interquartile range 2,089 to 3,136 mL) after PHCF, leading to a median postoperative LV reduction of 61%. At follow-up (mean 8 years), median LV was 2,519 mL (interquartile range 2,083 to 3,752 mL). Interestingly, 33 of 62 patients with available LV2 and LV3 showed additional regression in LV at follow-up (median –14.1%), and the rest showed mild growth of 9.9%. Overall volumetric comparison of preoperative with follow-up liver imaging showed sustained LV reduction (median 61%). CONCLUSIONS Sustained long-term reductions in LV after PHCF can be achieved in selected patients with severe, highly symptomatic PLD. In our experience, liver-related death and subsequent liver transplantation are infrequent after PHCF.

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“…11 In contrast, the severity of polycystic liver disease seems similar in patients with PKD1 and PKD2 mutations. 17 …”

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confidence: 99%

PKD2 -Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

Gall

Audrézet

Renaudineau

et al. 2017

American Journal of Kidney Diseases

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Background PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. Study Design Case series, January 2010 to March 2016. Settings & Participants Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. Outcomes Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. Results The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54–0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10–3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%–14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%–81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n = 36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. Limitations Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. Conclusions Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.

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Effect of genotype on the severity and volume progression of polycystic liver disease in autosomal dominant polycystic kidney disease

Abstract: In contrast to the renal phenotype, the ADPKD genotype was not associated with the severity or growth rate of PLD in ADKPD patients. This finding, along with gender influence, indicates that modifiers beyond the disease gene significantly influence the liver phenotype.

Cited by 59 publications

References 33 publications

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Outcomes and Durability of Hepatic Reduction after Combined Partial Hepatectomy and Cyst Fenestration for Massive Polycystic Liver Disease

PKD2 -Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

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