Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis.
OBJECTIVE
Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during somatostatin analogue therapy.


METHODS
We pooled the individual patient data of four trials that evaluated long-acting somatostatin analogues (120 mg lanreotide or 40 mg octreotide) for 6-12 months in polycystic liver disease patients. We performed uni- and multivariate linear regression analysis with preselected patient, disease and drug variables to identify independent predictors of response, defined as per cent change in liver or kidney volume (in ADPKD subgroup). All analyses were adjusted for baseline liver volume and centre.


RESULTS
We included 153 polycystic liver disease patients (86% female, median liver volume 4974 ml) from three international centres, all treated with octreotide (n = 70) or lanreotide (n = 83). Mean reduction in liver volume was 4.4% (range -31.6 to +9.4%). Multivariate linear regression revealed that elevated baseline alkaline phosphatase was associated with increased liver volume reduction during therapy (-2.7%, 95% CI -5.1 to -0.2%, P = 0.04), independently of baseline liver volume. Somatostatin analogue type, underlying diagnosis and eGFR did not affect response. In our ADPKD subpopulation (n = 100), elevated alkaline phosphatase predicted liver volume reduction (-3.2%, P = 0.03) but did not predict kidney volume reduction (+0.1%, P = 0.97). Total gastro-intestinal symptom severity decreased with therapy in a subgroup analysis (n = 95; P < 0.001).


CONCLUSIONS
Alkaline phosphatase is a liver-specific, independent predictor of response in polycystic liver disease during somatostatin analogue therapy.
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Tom J G
TJ
Gevers
Department of Gastroenterology and Hepatology, Gasthuis Leuven, Leuven, Belgium.
Frederik
F
Nevens
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Vicente E
VE
Torres
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Marie C
MC
Hogan
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Joost P H
JP
Drenth
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D003560:Cysts / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology; D008107:Liver Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015282:Octreotide / Q000627:therapeutic use*; D009929:Organ Size; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D015415:Biomarkers; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D000469:Alkaline Phosphatase; D015282:Octreotide
ADPKD; ADPLD; alkaline phosphatase; drug therapy; hepatic cyst; somatostatin