The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials

AbstractA clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.

Download Full-text

Medical therapy for polycystic liver disease

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2016.0023 ◽

2016 ◽

Vol 98 (1) ◽

pp. 18-23 ◽

Cited By ~ 12

Author(s):

S Khan ◽

A Dennison ◽

G Garcea

Keyword(s):

Quality Of Life ◽

Liver Disease ◽

Liver Volume ◽

Somatostatin Analogues ◽

Cochrane Library ◽

Polycystic Liver Disease ◽

Randomised Trials ◽

Polycystic Liver ◽

The Impact

Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE®, PubMed, Embase™ and Cochrane Library search. Search terms included ‘polycystic’, ‘liver’, ‘sirolimus’, ‘everolimus’, ‘PCLD’, ‘somatostatin’, ‘octreotide’, ‘lanreotide’ and ‘rapamycin’. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36®. Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.

Download Full-text

Evaluating health-related quality of life in patients with polycystic liver disease and determining the impact of symptoms and liver volume

Liver International ◽

10.1111/liv.12430 ◽

2014 ◽

Vol 34 (10) ◽

pp. 1578-1583 ◽

Cited By ~ 34

Author(s):

Titus F. M. Wijnands ◽

Myrte K. Neijenhuis ◽

Wietske Kievit ◽

Frederik Nevens ◽

Marie C. Hogan ◽

...

Keyword(s):

Quality Of Life ◽

Liver Disease ◽

Liver Volume ◽

Polycystic Liver Disease ◽

Health Related Quality ◽

Polycystic Liver ◽

Related Quality ◽

Health Related ◽

The Impact

Download Full-text

Impact of liver volume on polycystic liver disease-related symptoms and quality of life

United European Gastroenterology Journal ◽

10.1177/2050640617705577 ◽

2017 ◽

Vol 6 (1) ◽

pp. 81-88 ◽

Cited By ~ 14

Author(s):

Myrte K Neijenhuis ◽

Wietske Kievit ◽

Stef MH Verheesen ◽

Hedwig M D’Agnolo ◽

Tom JG Gevers ◽

...

Keyword(s):

Quality Of Life ◽

Liver Disease ◽

Liver Volume ◽

Symptom Burden ◽

Symptom Assessment ◽

Polycystic Liver Disease ◽

Polycystic Liver ◽

Disease Stages ◽

The Impact

Background Symptoms in polycystic liver disease (PLD) are thought to be caused by compression of organs and structures by the enlarged liver. Aim The aim of this article is to assess the impact of liver volume on symptoms and quality of life (QoL) in PLD. Methods We included PLD patients from two prospective studies that used the PLD-questionnaire (PLD-Q) for symptom assessment. QoL was assessed through SF-36, summarized in a physical (PCS) and mental (MCS) component score. Liver volume was correlated with PLD-Q total scores. Patients were classified based on height-corrected liver volume in mild (<1600 ml), moderate (1600–3200 ml), and severe (>3200 ml) disease. PLD-Q and QoL (PCS and MCS) scores were compared across disease stages. Results We included 82 of 131 patients from the original studies (disease stages; mild n = 26, moderate n = 33, and severe n = 23). Patients with larger liver volume reported higher symptom burden ( r = 0.516, p < 0.001). Symptom scores increased with disease progression, except for abdominal pain ( p = 0.088). PCS decreased with advancing disease ( p < 0.001), in contrast to MCS ( p = 0.055). Moderate ( p = 0.007) and severe ( p < 0.001) PLD patients had lower PCS scores than the general population. Conclusion PLD with larger liver volume is more likely to be symptomatic and is associated with lower QoL.

Download Full-text

Management of cystic liver disease

10.1093/med/9780199592548.003.0311_update_001 ◽

2018 ◽

Author(s):

René M. M. van Aerts ◽

Tom J. G. Gevers ◽

Joost P. H. Drenth

Keyword(s):

Liver Disease ◽

Liver Volume ◽

Somatostatin Analogues ◽

Polycystic Liver Disease ◽

Total Liver Volume ◽

Liver Cysts ◽

Polycystic Liver ◽

Exogenous Oestrogen ◽

Autosomal Dominant Polycystic Kidney ◽

Cystic Liver

In a subset of autosomal dominant polycystic kidney disease patients, hepatic cysts dominate the clinical picture. These patients may develop polycystic liver disease, and enlargement of the liver leads to compression of adjacent abdominal and thoracic organs. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use, multiple pregnancies, and severity of renal disease. Treatment is only indicated in those with symptoms, and choice of treatment depends on total liver volume, size, and location of the liver cysts. Current radiological and surgical therapies include aspiration-sclerotherapy, fenestration, segmental hepatic resection, and liver transplantation. They all are palliative in nature and are partially effective and have non-negligible morbidity and mortality. Somatostatin analogues are still in development for polycystic liver disease.

Download Full-text

Quality of life and liver transplantation in patients with polycystic liver disease

Liver Transplantation ◽

10.1002/lt.20796 ◽

2006 ◽

Vol 12 (8) ◽

pp. 1184-1185 ◽

Cited By ~ 7

Author(s):

Amy A. Dan ◽

Zobair M. Younossi

Keyword(s):

Quality Of Life ◽

Liver Transplantation ◽

Liver Disease ◽

Polycystic Liver Disease ◽

Polycystic Liver

Download Full-text

Liver transplantation improves quality of life in patients with polycystic liver disease

Nature Clinical Practice Gastroenterology &#38 Hepatology ◽

10.1038/ncpgasthep0613 ◽

2006 ◽

Vol 3 (11) ◽

pp. 599-600

Keyword(s):

Quality Of Life ◽

Liver Transplantation ◽

Liver Disease ◽

Polycystic Liver Disease ◽

Polycystic Liver

Download Full-text

1406 POLYCYSTIC LIVER DISEASE PATIENTS HAVE LOW QUALITY OF LIFE WHICH IS ASSOCIATED WITH CONCURRENT ABDOMINAL SYMPTOMS

Journal of Hepatology ◽

10.1016/s0168-8278(13)61405-1 ◽

2013 ◽

Vol 58 ◽

pp. S564

Author(s):

T.F. Wijnands ◽

T.J. Gevers ◽

W. Kievit ◽

J.P. Drenth

Keyword(s):

Quality Of Life ◽

Liver Disease ◽

Polycystic Liver Disease ◽

Abdominal Symptoms ◽

Polycystic Liver

Download Full-text

Drug holiday in patients with polycystic liver disease treated with somatostatin analogues

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818804784 ◽

2018 ◽

Vol 11 ◽

pp. 175628481880478 ◽

Cited By ~ 2

Author(s):

René M. M. van Aerts ◽

Marieke Kolkman ◽

Wietske Kievit ◽

Tom J. G. Gevers ◽

Frederik Nevens ◽

...

Keyword(s):

Liver Disease ◽

Liver Volume ◽

Somatostatin Analogues ◽

Interquartile Range ◽

Drug Holiday ◽

Intermittent Therapy ◽

Polycystic Liver Disease ◽

Total Liver Volume ◽

Polycystic Liver ◽

Cessation Of Treatment

Background: Somatostatin analogues (SAs) reduce liver volume and relief symptoms in polycystic liver disease (PLD). Its effect wears off after continuing therapy suggesting development of SA tolerance in patients on chronic therapy. We postulate that a drug holiday resensitizes the liver to its acute pharmacological effects. Therefore, this study examines the liver volume-reducing effect of SAs after a drug holiday. Methods: Patients were identified from the International PLD Registry and included in our analysis when (1) treated with SAs during two cycles separated by a drug holiday and (2) height-adjusted total liver volume (hTLV) was available at start and end of each cycle. For our primary outcome we compared the effect of SAs (in % per 6 months) on hTLV between the first and second treatment cycle. Results: In 34 patients, initial liver volume-reducing effect was similar to that after rechallenge [−2.6% per 6 months (interquartile range, −3.8–0.8) versus −1.6% per 6 months (interquartile range, −3.1–1.1), p = 0.510]. Cessation of treatment led to a rebound effect, but liver volume remained stable compared with the baseline with intermittent therapy in responders to SA [−0.6% (interquartile range, −7.4–5.7) after 46.5 months]. Conclusions: PLD patients treated with SAs benefit from retreatment after a drug holiday. The significant increase of liver volume after cessation of treatment complicates widespread use of a drug holiday as new treatment strategy. Our results contribute to a better understanding of the pharmacological effect of SAs and help to identify patients who might benefit.

Download Full-text