Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1 year later: evaluation of prognostic value

Vries, Elisabeth M.G. de; Wang, Junfeng; Leeflang, Mariska; Boonstra, Kirsten; Weersma, Rinse K.; Beuers, Ulrich; Geskus, Ronald B.; Ponsioen, Cyriel Y.

doi:10.1111/liv.13110

Cited by 76 publications

(70 citation statements)

References 23 publications

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“…Endpoints were PSC‐related death or LT. Using a systematic approach to distinguish patients with a more favorable versus poor outcome yielded a positive association between level of ALP both at diagnosis and at 1 year, and the hazard of reaching an endpoint was around 2.5 × ULN . A larger decrease in ALP in the first year after diagnosis decreased the event rate.…”

Section: Potential Biomarkersmentioning

confidence: 99%

Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

et al. 2018

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Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for which there is no effective therapy. Interest has grown in developing treatments for this condition, with several agents proposed as potential therapies. However, there is a lack of clarity about how to measure clinical benefit in trials involving patients with this complex and rare disease. This article reviews regulatory information, the available literature on natural history, as well as potential candidate clinical and surrogate endpoints for PSC. (Hepatology 2018; 00:000-000).

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Section: Potential Biomarkersmentioning

confidence: 99%

Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

et al. 2018

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“…For example, SAP was lower in those with ED PSC and tended to remain <1.5× the ULN years after the initial diagnosis. A lower SAP has been associated with an improved prognosis . In addition, their MELD score was significantly lower at the time of diagnosis.…”

Section: Discussionmentioning

confidence: 97%

Variations in primary sclerosing cholangitis across the age spectrum

Eaton

McCauley

Atkinson

et al. 2017

J of Gastro and Hepatol

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Background & Aim Primary sclerosing cholangitis (PSC) typically develops in middle-age adults. Little is known about phenotypic differences when PSC is diagnosed at various ages. Therefore, we sought to compare the clinical characteristics of a large PSC cohort based on the age when PSC was diagnosed. Methods We performed a multicenter retrospective review to compare the features of PSC among those diagnosed between 1–19 years (yrs) (n=95), 20–59 yrs (n=662), and 60–79 yrs (n=102). Results Those with an early diagnosis (ED) PSC were more likely to have small duct PSC (13%) versus those with a middle age diagnosis (MD) (5%) and late diagnosis (LD) groups (2%), p<0.01 and appeared to have a decrease risk of hepatobiliary malignancies: ED vs. MD: HR, 0.25; 95% CI 0.06–1.03 and ED vs LD: HR, 0.07; 95% CI 0.01–0.62. Cholangiocarcinoma (CCA) was diagnosed in 78 subjects (ED n=0; MD n=66, LD n=12) and was more likely to be diagnosed within a year after the PSC diagnosis among those found to have PSC late in life: ED 0% (0/95), MD 2% (14/662), LD 6% (6/102), p=0.02. Similarly, hepatic decompensation was more common among those with LD PSC versus younger individuals: LD vs. MD: HR,1.64; 95% CI 0.98–2.70 and LD vs ED: HR, 2.26; 95% CI 1.02–5.05. Conclusions Those diagnosed with PSC early in life are more likely to have small duct PSC and less likely to have disease related complications. Clinicians should be vigilant for underlying CCA among those with PSC diagnosed late in life.

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“…Four to fourteen percent of patients with PSC will have overlapping autoimmune hepatitis (AIH) (4, 6, 26). There remains controversy and a lack of consensus on the criteria that should be used to define PSC-AIH overlap, which may appear simultaneously or PSC may appear following a diagnosis of AIH.…”

Section: Introductionmentioning

confidence: 99%

“…The elevated laboratory values may decrease after the diagnosis, as one study with over 300 patients showed that the average alkaline phosphatase, aspartate transaminase, alanine transaminase, and total bilirubin decreased from 1.99, 1.45, 2.11, 0.81 x the upper limit of normal to 1.22, 0.88, 1.00, and 0.65 x the upper limits of normal in one year (26). In fact, up to 40% of patients may experience normalized alkaline phosphatase levels in 1 year, and these patients have a higher rate of liver transplant-free survival (26, 38). Hepatomegaly and splenomegaly are present in 43.6% and 29.3% of patients, respectively, at presentation (9).…”

Section: Introductionmentioning

confidence: 99%

The evolution of natural history of primary sclerosing cholangitis

Takakura

Tabibian

Bowlus

2017

Current Opinion in Gastroenterology

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Purpose of review Primary sclerosing cholangitis (PSC) is a rare, idiopathic biliary disease often with an insidious onset, variable disease course, and premature death related to benign and malignant PSC-related sequelae. This review aims to discuss the epidemiology, clinical variants, and natural history of PSC, incorporating data from recent population-based studies. Recent findings PSC naturally leads to cirrhosis, cholangiocarcinoma, other hepatobiliary malignancies, dominant strictures, hepatic osteodystrophy and bacterial cholangitis. The incidence of PSC appears to be increasing, the reasons for which are unclear. The time from diagnosis to liver transplant appears to be longer in more recent studies compared to earlier studies which, suggesting a better overall prognosis than previously believed. In addition, with an increasing number of patients undergoing liver transplantation for PSC, the frequency of death due to liver failure has decreased while cancer-related deaths have increased among patients with PSC. Summary PSC is a heterogeneous disease with a variety of clinical outcomes, both fatal and non-fatal. The progression of liver fibrosis in an individual patient is difficult to predict and may vary from a relatively benign, non-progressive form to a rapidly progressive form with the need for liver transplantation.

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Alkaline phosphatase at diagnosis of primary sclerosing cholangitis and 1 year later: evaluation of prognostic value

Abstract: ALP can be used to discriminate between PSC patients with a good and a poor prognosis. These findings indicate that ALP can serve as stratifier, and potentially as surrogate endpoint for clinical trials in PSC.

Cited by 76 publications

References 23 publications

Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

Variations in primary sclerosing cholangitis across the age spectrum

The evolution of natural history of primary sclerosing cholangitis

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