Moexipril for Treatment of Primary Biliary Cirrhosis in Patients with an Incomplete Response to Ursodeoxycholic Acid

Charatcharoenwitthaya, Phunchai; Talwalkar, Jayant A.; Angulo, Paul; Gossard, Andrea A.; Keach, Jill C.; Petz, Janice L.; Jorgensen, Roberta A.; Lindor, Keith D.

doi:10.1007/s10620-009-0744-1

Cited by 12 publications

(10 citation statements)

References 45 publications

(74 reference statements)

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“…Candesartan and ursodeoxycholic acid in combination led to histological improvement in fibrosis compared to ursodeoxycholic acid alone [44]. Both ACEi and ARB decreased portal pressure in cirrhosis in one study, while in others no such effect was demonstrated [45][46][47][48]. Previous data have shown that ACEi have several effects inhibiting HSC activation, decreasing portal hypertension and slowing fibrosis progression by reducing the effect of angiotensin II on the activity and proliferation of hepatic stellate cells [9,45,[49][50][51][52].…”

Section: Discussionmentioning

confidence: 92%

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Stokkeland

Lageborn

Ekbom

et al. 2017

Basic Clin Pharma Tox

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Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver-related mortality and liver-related morbidity in patients with chronic liver disease. We performed a register-based cohort study of all patients with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked. We studied whether the use of statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and antibiotics affected the risk of total mortality, liver-specific mortality and morbidity. We found a reduction in mortality risk for statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32-0.99) for patients with autoimmune hepatitis to 0.84 (95% CI: 0.75-0.95) for patients with alcoholic liver disease. There was a significantly reduced liver-related mortality for patients with alcoholic liver disease who used angiotensin-converting enzyme inhibitors, 0.85 (95% CI: 0.65-0.96). There were increased overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up to 1.67 (95% CI, 1.55-1.80) for viral hepatitis. Statin use was associated with decreased risks of liver-specific mortality and morbidity, and reduced total mortality foremost among patients with alcoholic liver disease. Angiotensin -converting enzyme inhibitors was associated with reduced liver-related mortality among patients with alcoholic liver disease.

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Section: Discussionmentioning

confidence: 92%

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Stokkeland

Lageborn

Ekbom

et al. 2017

Basic Clin Pharma Tox

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“…In ALD patients, a combination of the ARB candesartan and ursodeoxycholic acid (UDCA) improved the patient's fibrosis scores compared to UDCA treatment alone (110). However since other clinical trials did not show any effect, more studies are needed to prove the efficacy of RAS antagonists in hepatic fibrosis (111,112).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Reversal of liver fibrosis: From fiction to reality

Zoubek

Trautwein

Strnad

2017

Best Practice & Research Clinical Gastroenterology

122

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“…Finally, Ang II also contributes to the oxidative stress in the fibrotic liver. Therefore, Ang II and its interaction with AT1-R are considered to play an important role in liver fibrogenesis and its blocking by ACE inhibitors (ACEi) or AT1-R blockers (ARBs) may be an effective therapeutic option for treatment of liver fibrosis and they are already in clinical trials, for example, Losartan [71], Irbesartan [72], and Candesartan and Moexipril [73] (Table 1). Losartan, Irbesartan, and Candesartan share similarities in the chemical structure and they all are AT1-R blockers, in contrast to Moexipril, which is an ACE inhibitor.…”

Section: Developments In Targeted Therapy Related To Liver Fibrosismentioning

confidence: 99%

“…However, long-term treatment with Irbesartan (ARB and antihypertensive drug) in severe fibrosis with chronic hepatitis C showed no substantial improvement in fibrosis scores, arterial pressure, and organ stiffness in the treated group, despite the fact that treatment was safe and well tolerated [72]. In addition, ACE inhibitor Moexipril treatment did not show beneficial effects in primary biliary cirrhosis patients [73]. Furthermore, in HALT-C cohort study, ACEi/ARB therapy did not retard the progression of fibrosis [76].…”

Section: Developments In Targeted Therapy Related To Liver Fibrosismentioning

confidence: 99%

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

Bansal

Nagórniewicz

Prakash

2016

Mediators of Inflammation

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Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.

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Moexipril for Treatment of Primary Biliary Cirrhosis in Patients with an Incomplete Response to Ursodeoxycholic Acid

Cited by 12 publications

References 45 publications

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Reversal of liver fibrosis: From fiction to reality

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

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