Intracellular Cholestasis in HCV and HBV Infection

Postnikova, Olga A.; Nepomnyashchikh, G. I.; Yudanov, A. V.; Nepomnyashchikh, D. L.; Kapustina, V. I.; Isayenko, V. I.

doi:10.1007/s10517-012-1854-x

Cited by 8 publications

(8 citation statements)

References 6 publications

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“…Apart from the suspected mediators and their origin, the onset of pruritus is closely associated with the development of intrahepatic cholestasis[ 31 ]. Although hepatic disorders such as chronic infection with viral hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis are considered the main cause of intrahepatic cholestasis[ 32 , 33 ], the elevation of bile salts and μ-opioids levels in patients with intrahepatic cholestasis is largely associated with pruritus[ 34 ]. To date, the causative link between bile salts levels and severity of pruritus has not yet been investigated.…”

Section: Mechanisms Of Hcv Infection and Treatment- Associated Pruritmentioning

confidence: 99%

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

Alhmada¹,

Selimović²,

Murad³

et al. 2017

WJG

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In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients’ sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.

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Section: Mechanisms Of Hcv Infection and Treatment- Associated Pruritmentioning

confidence: 99%

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

Alhmada¹,

Selimović²,

Murad³

et al. 2017

WJG

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“…On the basis of immune interactions between virus and host, HBV infection can have diverse clinical manifestations, including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma 7 . However, cholestatic hepatitis due to HBV infection were reported very rarely in literature 5 . Our patient represents a typical case of acute HBV infection acquired at the age of 56 years and expected to resolve spontaneously.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical evidence of hepatitis; jaundice and occasionally acute liver failure develops in rest one third of patients with acute HBV infection 7 . Cholestatic hepatitis is one of very rare manifestations of acute HBV infection, but when develop it leads to prolonged hospital stay and increased medical expenses 5 . Rapid improvement of the clinical symptoms and signs have been reported in patients with cholestatic hepatitis A (HAV) after use of corticosteroid 6 .…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment of Severely Cholestatic Acute Hepatitis B With Oral Corticosteroid

Mallick

Nath

Praharaj

et al. 2020

ABCD, arq. bras. cir. dig.

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“…Cholestasis is a common risk factor that is complicated in enterohepatic diseases, especially in liver diseases including fibrosis, cirrhosis, and hepatitis. [1][2][3] Clinical studies revealed that cholestasis is negatively associated with hepatitis outcomes in chronic hepatitis B virus infection, and intrahepatic cholestasis of pregnancy (ICP) patients were more susceptible to Hepatitis B Virus (HBV) infection. 4 Notably, bile acids are overall accumulated in patients with hepatitis virus infection, 5 and mice infected with HBV showed an apparent enhancement of cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme promoting the bile acids de novo synthesis.…”

Section: Introductionmentioning

confidence: 99%

Bile acid restrained T cell activation explains cholestasis aggravated hepatitis B virus infection

Ding

Che

et al. 2022

The FASEB Journal

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Cholestasis is a common complication of hepatitis B virus (HBV) infection, characterized by increased intrahepatic and plasma bile acid levels. Cholestasis was found negatively associated with hepatitis outcome, however, the exact mechanism by which cholestasis impacts anti-viral immunity and impedes HBV clearance remains elusive. Here, we found that cholestatic mice are featured with dysfunctional T cells response, as indicated by decreased sub-population of CD25 + /CD69 + CD4 + and CD8 + cells, while CTLA-4 + CD4 + and CD8 + subsets were increased. Mechanistically, bile acids disrupt intracellular calcium homeostasis via inhibiting mitochondria calcium uptake and elevating cytoplasmic Ca 2+ concentration, leading to STIM1 and ORAI1 decoupling and impaired store-operated Ca 2+ entry which is essential for NFAT signaling and T cells activation. Moreover, in a transgenic mouse model of HBV infection, we confirmed that cholestasis compromised both CD4 + and CD8 + T cells activation resulting in poor viral clearance. Collectively, our results suggest that bile acids play pivotal roles in anti-HBV infection via controlling T cells activation and metabolism and that targeting the regulation of bile acids may be a therapeutic strategy for hostvirus defense.

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Intracellular Cholestasis in HCV and HBV Infection

Cited by 8 publications

References 6 publications

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies

Successful Treatment of Severely Cholestatic Acute Hepatitis B With Oral Corticosteroid

Bile acid restrained T cell activation explains cholestasis aggravated hepatitis B virus infection

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