Pattern Recognition Receptors and Liver Failure

Wu, Jun; Meng, Han; Li, Jia; Yang, Xiaoli; Zhen, Xin; Schlaak, J.F.; Yang, Dong-liang; Lu, Mengji

doi:10.1615/critrevimmunol.2019031012

Cited by 3 publications

(5 citation statements)

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“…25 As an important part of innate immune cells, neutrophils play an indispensable role in fighting viral infections. 26 We found that the number of neutrophils increased during ETV treatment. Naumenko et al 27 revealed that when the liver tissue was infected by HBV, neutrophils were rapidly recruited from the peripheral circulation to the infected site, driven by inflammatory factors and chemokines, and participated in removal of the pathogen.…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

Zhang¹,

Huang²,

Sun³

et al. 2021

J Clin Transl Hepatol

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Background and Aims:The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity. Methods: Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t) ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively. Results: Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA. Conclusions: HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 63%

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

Zhang¹,

Huang²,

Sun³

et al. 2021

J Clin Transl Hepatol

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“…Renal I/R injury is an important clinical problem and primary cause of AKI, which leads to increased risk of developing chronic kidney disease ( 33 ). Inflammation is an important pathological feature of ischemic injury and occurs as a consequence of immune cell activation via recognition of pathogen- and damage-associated molecular patterns ( 34 ). Moreover, it was previously reported that the NLRP3 inflammasome serves a role in a range of kidney diseases by regulating inflammation, pyroptosis, apoptosis and fibrosis ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide attenuates renal I/R‑induced activation of the inflammatory response and apoptosis via regulating Nrf2‑mediated NLRP3 signaling pathway inhibition

Wang

Liu

et al. 2021

Mol Med Rep

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Renal ischemia/reperfusion (I/R) injury can lead to acute renal failure, delayed graft function and graft rejection. Nucleotide-binding oligomerization domain NOD-like receptor containing pyrin domain 3 (NLRP3)-mediated inflammation participates in the development of renal injury. Nrf2 accelerates NLRP3 signaling pathway activation and further regulates the inflammatory response. In addition, hydrogen sulfide serves a protective role in renal injury; however, the detailed underlying mechanism remains poorly understood. The present study investigated whether Nrf2 and NLRP3 pathway participate in hydrogen sulfide-regulated renal I/R-induced activation of the inflammatory response and apoptosis. Wild-type and Nrf2-knockout (KO) mice underwent surgery to induce renal I/R via clamping of the bilateral renal pedicles. A total of 20 mg/kg MCC950 (an NLRP3 inhibitor) was injected intraperitoneally daily for 14 days prior to surgery. Renal tissue and blood were collected from the I/R model mice to analyze NLRP3 and Nrf2 mRNA expression levels, NLRP3, PYD and CARD domain containing, caspase-1, IL-1β, Nrf2 and heme oxygenase 1 protein expression levels, cell apoptosis, the secretion of tumor necrosis factor-α, IL-1β and IL-6 cytokines and renal histopathology and function. Renal I/R activated the NLRP3 and Nrf2 signaling pathways. Conversely, MCC950 treatment inhibited activation of the NLRP3 signaling pathway, and prevented I/R-induced renal injury, release of cytokines and apoptosis in renal I/R model mice. Sodium hydrosulfide (NaHS) not only alleviated upregulation of NLRP3 protein expression levels, but also relieved renal injury, release of cytokines and cell apoptosis induced by renal I/R in wild-type mice, but not in Nrf2-KO mice. NaHS alleviated NLRP3 inflammasome activation, renal injury, the inflammatory response and cell apoptosis via the Nrf2 signaling pathway in renal I/R model mice.

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“…While viral replication can be controlled and the progression of liver disease can be prevented in most patients that are treated with the currently licensed antiviral drugs against HBV, the long-term control of an infection (“functional cure”) is rarely seen, as HBsAg levels remain mostly elevated despite effective antiviral therapy. It has been demonstrated that HBsAg itself may suppress innate immune responses against HBV in particular, and thus promote the chronicity of an infection [ 41 , 42 , 43 , 44 ]. Therefore, several approaches are being developed that are aiming at HBsAg elimination.…”

Section: Current Therapy Of Chronic Hepatitis Bmentioning

confidence: 99%

“…b. Immune-activating strategies (IASs). Our own in vitro and in vivo data have suggested that the activation of the innate immune system may efficiently suppress HBV replication, while high levels of HBsAg may attenuate this immune activation [ 41 , 42 , 43 , 44 ]. Human data also suggest that HCV, which activates the innate immune system, can suppress HBV replication in HCV/HBV-coinfected patients.…”

Section: Current Therapy Of Chronic Hepatitis Bmentioning

confidence: 99%

Current Therapy of Chronic Viral Hepatitis B, C and D

Schlaak¹

2023

JPM

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The majority of chronic viral hepatitis cases are induced via infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). These patients are at increased risk for progressive liver disease leading to cirrhosis as well as hepatocellular carcinoma (HCC). HBV infection is well controlled by the currently available nucleosides as well as nucleotides, and the development of cirrhosis can be prevented. Additionally, it has been shown that HBV-induced liver fibrosis can regress during successful antiviral treatment; however, a “functional cure”, i.e., loss of HBsAg, is a rare event when these drugs are used. Therefore, novel therapeutic strategies are aiming at the selective suppression of HBsAg levels in combination with immunostimulation. The development of directly acting antivirals (DAAs) has revolutionized HCV therapy, as almost all patients can be cured via this treatment. Additionally, DAA therapy has few, if any, side effects, and is generally well tolerated by patients. HDV remains the most challenging type of chronic viral hepatitis. Although novel therapeutic options have recently been approved, response rates are still less favorable compared to HBV and HCV. This review discusses current and future options for the treatment of chronic HBV, HCV, and HDV infection.

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Pattern Recognition Receptors and Liver Failure

Cited by 3 publications

References 0 publications

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

Hydrogen sulfide attenuates renal I/R‑induced activation of the inflammatory response and apoptosis via regulating Nrf2‑mediated NLRP3 signaling pathway inhibition

Current Therapy of Chronic Viral Hepatitis B, C and D

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