Evaluation of hepatic fibrosis in patients with chronic hepatitis B virus by non-invasive methods: Aspartate-to-platelet ratio index, Fibrosis-4, fibrotest and fibroscan

Background: The process of hepatic fibrosis is common to the various etiologies of chronic liver disease such as viral hepatitis B. Objective: To evaluate hepatic fibrosis by non-invasive markers such as Aspartate-to-Platelet Ratio Index (APRI), fibrosis-4 (FIB-4), fibrotest and fibroscan. Patients and Method: This was a descriptive study during a period of 32 months. Included in our study were the records of outpatients, chronic carriers of hepatitis B virus without viral co-infection C, D or HIV, followed in the Gastroenterology unit of the Campus Teaching Hospital of Lome-Togo. Results: We retained 222 patients. Among the patients, 148 patients (66.67%) were classified in Phase 3 (inactive carrying). Only 10 patients (4.50%) had a APRI score indicating a fibrosis stage ≥ F4 (presence of cirrhosis). A FIB-4 score indicating the presence of cirrhosis was found in 12 patients (5.40%). The most represented stage at fibrotest was the F0 stage (45.45%). Cirrhosis was noted in 6.06% of cases at fibroscan. Patients with APRI score ≤ 2 (96.23%) had a FIB-4 score ≤ 3.25, (p = 0.0088). Conclusion: The evaluation of hepatic fibrosis during chronic hepatopathies is essential for patients care because it influences therapeutic decisions.

New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

Forsythiaside A Regulates Activation of Hepatic Stellate Cells by Inhibiting NOX4-Dependent ROS

Hepatic stellate cells (HSCs) activation is an important step in the process of hepatic fibrosis. NOX4 and reactive oxygen species expressed in HSCs play an important role in liver fibrosis. Forsythiaside A (FA), a phenylethanoid glycoside extracted and isolated from Forsythiae Fructus, has significant antioxidant activities. However, it is not clear whether FA can play a role in inhibiting the HSCs activation through regulating NOX4/ROS pathway. Therefore, our purpose is to explore the effect and mechanism of FA on HSCs activation to alleviate liver fibrosis. LX2 cells were activated by TGF-β1 in vitro. MTT assay and Wound Healing assay were used to investigate the effect of FA on TGF-β1-induced LX2 cell proliferation and migration. Elisa kit was used to measure the expression of MMP-1 and TIMP-1. Western blot and RT-qPCR were used to investigate the expression of fibrosis-related COLI, α-SMA, MMP-1 and TIMP-1, and inflammation-related TNF-α, IL-6 and IL-1β. The hydroxyproline content was characterized using a biochemical kit. The mechanism of FA to inhibit HSCs activation and apoptosis was detected by DCF-DA probe, RT-qPCR, western blot and flow cytometry. NOX4 siRNA was used to futher verify the effect of FA on NOX4/ROS pathway. The results showed that FA inhibited the proliferation and migration of LX2 cells and adjusted the expression of MMP-1, TIMP-1, COLI, α-SMA, TNF-α, IL-6 and IL-1β as well as promoted collagen metabolism to show potential in anti-hepatic fibrosis. Mechanically, FA down-regulated NOX4/ROS signaling pathway to improve oxidation imbalances, and subsequently inhibited PI3K/Akt pathway to suppress proliferation. FA also promoted the apoptosis of LX2 cells by Bax/Bcl2 pathway. Furthermore, the effects of FA on TGF-β1-induced increased ROS levels and α-SMA and COLI expression were weaken by silencing NOX4. In conclusion, FA had potential in anti-hepatic fibrosis at least in part by remolding of extracellular matrix and improving oxidation imbalances to inhibit the activation of HSCs and promote HSCs apoptosis.

Chitooligosaccharides alleviate hepatic fibrosis by regulating the polarization of M1 and M2 macrophages

Chitooligosaccharide (COS) ameliorated hepatic fibrosis, possibly by regulating the M1 and M2 polarization of the liver macrophages, which was reflected in the modulation of the JAK1/STAT6 and JAK2/STAT1 pathways.