A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Yalçın, Mustafa; Akarsu, Mesut; Çelik, Aslı; Sağol, Özgül; Tunali, Sunay; Ertener, Ozge; Bengi, Göksel; Akpınar, Hale

doi:10.5152/tjg.2014.5121

Cited by 14 publications

(13 citation statements)

References 25 publications

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“…Infliximab also reduced hepatic inflammation, necrosis and fibrosis in NASH rodents induced by methionine‐ and choline‐deficient diet . Similar effects were also shown with the use of adalimumab . In humans, pentoxifylline, a non‐selective phosphodiesterase inhibitor that reduced TNF production, has also been reported to induce biochemical liver enzymes improvement in NASH patients.…”

Section: Other Hepatic Manifestations Than Psc Affecting Ibd Patientssupporting

confidence: 54%

“…59 Similar effects were also shown with the use of adalimumab. 68 In humans, pentoxifylline, a non-selective phosphodiesterase inhibitor that reduced TNF production, has also been reported to induce biochemical liver enzymes improvement in NASH patients. Conversely, some case series reported the development of biopsy-proven NAFLD in patients receiving anti-TNFα, without changes in metabolic profiles and nutrition.…”

Section: Impact Of Ms In Ibd Patients Is Debated As This Population Canmentioning

confidence: 99%

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Hepatic manifestations of inflammatory bowel diseases

Restellini

Chazouillères

Frossard

2016

Liver International

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Inflammatory bowel diseases are associated with various hepatobiliary disorders, reported both in Crohn's disease and ulcerative colitis. They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions used in different studies. Fatty liver is considered as the most common hepatobiliary complication in inflammatory bowel diseases while primary sclerosing cholangitis is the most specific one. Less frequently, inflammatory bowel diseases-associated hepatobiliary disorders include: autoimmune hepatitis/ primary sclerosing cholangitis overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis and liver abscess. The spectrum of these manifestations varies according to the type of inflammatory bowel diseases. Treatments of inflammatory bowel diseases may cause liver toxicity, although incidence of serious complications remains low. However, early diagnosis of drug-induced liver injury is of major importance as it affects future clinical management. When facing abnormal liver tests, clinicians should undertake a full diagnostic work-up in order to determine whether the hepatic abnormalities are related to the inflammatory bowel diseases or not.Management of hepatic manifestations in inflammatory bowel diseases usually involves both hepatologists and gastroenterologists because of the complexity of some situations. K E Y W O R D Sdrug-induced liver injury, hepatotoxicity, inflammatory bowel disease, liver disease, primary sclerosing cholangitis

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Section: Other Hepatic Manifestations Than Psc Affecting Ibd Patientssupporting

confidence: 54%

Section: Impact Of Ms In Ibd Patients Is Debated As This Population Canmentioning

confidence: 99%

Hepatic manifestations of inflammatory bowel diseases

Restellini

Chazouillères

Frossard

2016

Liver International

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“…Plant flavonoids that are reportedly competitive inhibitors of PDE3 and PDE4 have also been reported to suppress lipogenic pathways and are being considered as potential therapeutic agents for obesity and hepatic steatosis [170]. The well-characterized PDE inhibitor, pentoxifylline, was also found to be protective against NASH induced by the methionine-choline deficient diet through suppressed TNFα production and alleviation of ER stress [171, 172]. Likewise, a meta-analysis of randomized, double-blinded, placebo-controlled trials for the clinical use of pentoxifylline in NAFLD reported that pentoxifylline improved NAFLD parameters such as elevated liver enzyme levels in patients [173].…”

Section: Therapeutic Interventions Via Camp Signalingmentioning

confidence: 99%

Role of cAMP and phosphodiesterase signaling in liver health and disease

Wahlang

McClain

Barve

et al. 2018

Cellular Signalling

108

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Liver disease is a significant health problem worldwide with mortality reaching around 2 million deaths a year. Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the major causes of chronic liver disease. Pathologically, NAFLD and ALD share similar patterns of hepatic disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. It is becoming increasingly important to identify new pharmacological targets, given that there is no FDA-approved therapy yet for either NAFLD or ALD. Since the evolution of liver diseases is a multifactorial process, several mechanisms involving parenchymal and non-parenchymal hepatic cells contribute to the initiation and progression of liver pathologies. Moreover, certain protective molecular pathways become repressed during liver injury including signaling pathways such as the cyclic adenosine monophosphate (cAMP) pathway. cAMP, a key second messenger molecule, regulates various cellular functions including lipid metabolism, inflammation, cell differentiation and injury by affecting gene/protein expression and function. This review addresses the current understanding of the role of cAMP metabolism and consequent cAMP signaling pathway(s) in the context of liver health and disease. The cAMP pathway is extremely sophisticated and complex with specific cellular functions dictated by numerous factors such abundance, localization and degradation by phosphodiesterases (PDEs). Furthermore, because of the distinct yet divergent roles of both of its effector molecules, the cAMP pathway is extensively targeted in liver injury to modify its role from physiological to therapeutic, depending on the hepatic condition. This review also examines the behavior of the cAMP-dependent pathway in NAFLD, ALD and in other liver diseases and focuses on PDE inhibition as an excellent therapeutic target in these conditions.

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“…Furthermore infliximab also reduced hepatic inflammation, necrosis and fibrosis in NASH rodents induced by methionine and choline deficient diet[41]. Similar effects were also shown with the use of adalimumab[42]. Finally pentoxifylline, a nonselective phosphodiesterase inhibitor that reduced TNF production, has also been reported to induce biochemical liver enzymes improvement in NASH patients[43].…”

Section: Pathogenesismentioning

confidence: 88%

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article

Chen

Battat

Khoury

et al. 2016

WJG

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Emerging data have highlighted the co-existence of non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease, largely due to differences in disease definition and diagnostic tools utilised in the studies. Age, obesity, insulin resistance and other metabolic conditions are common risks factors in observational studies. However, other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity, duration, steroid use and prior surgical intervention, in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability, gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity, however no definitive evidence exist linking them to the development of hepatic steatosis, nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification, intervention and improve patient outcomes.

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A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis

Cited by 14 publications

References 25 publications

Hepatic manifestations of inflammatory bowel diseases

Hepatic manifestations of inflammatory bowel diseases

Role of cAMP and phosphodiesterase signaling in liver health and disease

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article

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