Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis

Corpechot, Christophe; Abenavoli, Ludovico; Rabahi, N.; Chrétien, Yves; Andréani, Tony; Johanet, Catherine; Chazouillères, Olivier; Poupon, Raoul

doi:10.1002/hep.22428

Cited by 569 publications

(581 citation statements)

References 29 publications

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“…Of those who had received UDCA for at least a year 79% (63% of the whole patient population) met the Paris criteria for adequate treatment response. 21 Response to UDCA was age-related, with younger presenting and male patients less likely to respond. 16 Younger patients experienced more fatigue and pruritus, whereas male patients experienced less.…”

Section: Resultsmentioning

confidence: 99%

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

et al. 2013

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,4 and the UK-PBC Consortium Primary biliary cirrhosis (PBC) has a complex clinical phenotype, with debate about the extent and specificity of frequently described systemic symptoms such as fatigue. The aim of this study was to use a national patient cohort of 2,353 patients recruited from all clinical centers in the UK to explore the impact of disease on perceived life quality. Clinical data regarding diagnosis, therapy, and biochemical status were collected and have been reported previously. Detailed symptom phenotyping using recognized and validated symptom assessment tools including the PBC-40 was also undertaken and is reported here. Perception of poor quality of life and impaired health status was common in PBC patients (35% and 46%, respectively) and more common than in an age-matched and sex-matched community control group (6% and 15%, P < 0.0001 for both). Fatigue and symptoms of social dysfunction were associated with impaired perceived quality of life using multivariate analysis. Fatigue was the symptom with the greatest impact. Depression was a significant factor, but appeared to be a manifestation of complex symptom burden rather than a primary event. Fatigue had its greatest impact on perceived quality of life when accompanied by symptoms of social dysfunction, suggesting that maintenance of social networks is critical for minimizing the impact of fatigue. Conclusion: The symptom burden in PBC, which is unrelated to disease severity or ursodeoxycholic acid response, is significant and complex and results in significant quality of life deficit. The complexity of symptom burden, and its lack of relation to disease severity and treatment response, suggest that specific approaches to symptom management are warranted that address both symptom biology and social impact. (HEPATOLOGY 2013;58:273-283)

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Section: Resultsmentioning

confidence: 99%

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

et al. 2013

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“…However, around 25% of patients are unresponsive to this drug (Imam and Lindor 2014;Carey et al 2015). Treatment failure can result in bile duct injury and liver cirrhosis, necessitating liver transplant (Corpechot et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

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Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-β), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-β levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

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“…They estimate the risk of LT or death (overall death for the GLOBE score and liver‐related death for the UK‐PBC risk score) in patients with PBC at specific time points. Both scores outperformed previous response criteria7, 8, 9, 10, 11, 13, 14 in terms of prognostic utility and could potentially help physicians identify patients at high risk of disease progression and in need of second‐line therapy. They have also been validated in patients not treated with UDCA, strongly suggesting that such scoring systems reflect disease activity and stage expressed by the laboratory investigations, regardless of treatment.…”

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confidence: 94%

“…These patients experience progressive liver disease that may eventually lead to liver failure or hepatocellular carcinoma 6. It is well established that the liver biochemistry on treatment with UDCA strongly predicts long‐term outcomes in PBC 7, 8, 9, 10, 11. The response to treatment with UDCA (so‐called UDCA response) may therefore be defined in terms of the liver biochemistry measured at a specific time (usually 12 months) after starting treatment.…”

mentioning

confidence: 99%

“…The response to treatment with UDCA (so‐called UDCA response) may therefore be defined in terms of the liver biochemistry measured at a specific time (usually 12 months) after starting treatment. Several definitions of the UDCA response have been proposed 7, 8, 9, 10, 11. One of these definitions was the Toronto criteria, and a composite of Toronto along with other criteria were used to define treatment response criteria for POISE, a phase 3 trial of treatment with obeticholic acid (OCA) reported by Nevens et al12 By these criteria, response was defined as alkaline phosphatase (ALP) <1.67 × the upper limit of normal (ULN), ≥15% reduction in ALP, and total bilirubin ≤ULN.…”

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confidence: 99%

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Clinical application of the GLOBE and United Kingdom‐primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis

Carbone

Harms

Lammers

et al. 2018

Hepatology Communications

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The GLOBAL Primary Biliary Cholangitis (PBC) Study Group and United Kingdom‐PBC (UK‐PBC) Consortium have demonstrated that dichotomous response criteria are not as accurate as continuous equations at predicting mortality or liver transplantation in PBC. The aim of this analysis was to assess the clinical utility of the GLOBE and UK‐PBC risk scores using data from POISE, a phase 3 trial investigating obeticholic acid (OCA) in patients with PBC. Data (N = 216) at baseline and month 12 were used to calculate the GLOBE and UK‐PBC risk scores to assess the projected change in risk with OCA versus placebo. Additionally, the benefit of OCA was assessed in patients not meeting the POISE primary endpoint. Both the GLOBE and UK‐PBC risk scores predicted a significant reduction in long‐term risk of death and liver transplantation after OCA treatment (P < 0.0001). The differences in the relative risk reduction from baseline in the 10‐year event risk after 1 year for OCA 10 mg versus placebo was 26% (GLOBE) and 37% (UK‐PBC). The scores also predicted a significantly decreased risk in patients treated with OCA who did not meet POISE response criteria after 1 year of treatment compared to an increased risk with placebo (P < 0.0001). Conclusion: This analysis demonstrates the use of the GLOBE and UK‐PBC risk scores to assess risk reduction of a cohort treated with OCA. While validation of this risk reduction in studies with clinical outcomes is needed, this study highlights the potential use of these scores in individualizing risk prediction in PBC both in clinical practice and therapeutic trials. (Hepatology Communications 2018;2:683‐692)

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Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis

Cited by 569 publications

References 29 publications

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

Impact of primary biliary cirrhosis on perceived quality of life: The UK-PBC national study

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Clinical application of the GLOBE and United Kingdom‐primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis

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