Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy

Abstract

Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Diffusion tensor imaging of the abdominal organs: Influence of oriented intravoxel flow compartments

“…34 If not promptly treated, hepatic C virus infections progressively evolve from chronic inflammation to fibrosis or to even more severe disease progression (eg, cirrhosis and hepatocellular carcinoma). 35 In particular, the early detection of diffusive liver disorders (acute hepatitis and early In conclusion, this study proved that accounting for pseudo-diffusion intravoxel dephasing affects the estimation of the diffusion tensor metrics in both liver and kidneys. In the liver, mesoscopic fluid movements (due to blood or bile flow) may be at the origin of the pseudo-diffusion dynamics.…”

Improvement of liver disease and inflammation in patients with advanced HCV-related cirrhosis after antiviral therapy

“…In a recent article on HIV/HCV-coinfected patients, we showed that plasma biomarkers of bacterial translocation, in ammation, endothelial dysfunction, and coagulopathy increased with the increase of liver brosis severity, particularly in patients with LSM ≥ 40 KPa [36]. However, the eradication of HCV with antiviral therapy can stop this pathological process of the liver, at least almost entirely [35]. Additionally, the decrease in in ammation biomarker levels could also indicate a lower risk of developing comorbidities in cirrhotic patients who achieved SVR with DAA therapy [2,25].…”

“…Several reports have also shown a signi cant decrease in plasma biomarkers related to in ammation and immune activation after SVR with all-oral DAAs in HIV/HCV-coinfected patients [18,[30][31][32][33][34]. However, DAA therapy alone does not completely block uncontrolled in ammation and liver injury, particularly with advanced liver disease [35]. Thus, some cirrhotic patients who achieve SVR with DAAs remain at risk of cirrhosis progression and developing hepatocellular carcinoma [2].…”

Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus‐1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub‐study A5334s

“…Raltegravir is metabolized by hepatic glucuronidation primarily by UGT1A1. Inflammation associated with chronic HCV infection accelerates hepatocyte damage, and could affect liver uptake and reduce drug metabolizing enzyme activity, resulting in decreased clearance of drugs that undergo hepatic metabolism . HCV infection rapidly clears from the plasma and liver with DAA therapy .…”