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.

Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

Pegylated Interferon Alpha for Chronic Hepatitis B Virus Infection

Chronic hepatitis B (CHB) is a potentially life-threatening and prevalent disease worldwide. Far from attaining the ultimate treatment goal, hepatitis B virus (HBV) infection eradication, the two current therapeutic options aim to prevent progression to end-stage liver disease, maintaining long-term suppression of HBV replication. Pegylated interferon-α (PEG-INFα) is often poorly tolerated and disregarded considering the orally administered nucleos(t)ide analogues. However, PEG-INFα may achieve similar treatment endpoints with a finite course of treatment. We report a case of PEG-INFα-treated CHB that attained sustained off-treatment virological response with only 16 weeks of treatment, with loss of both HBeAg and HBsAg (this latter the optimal treatment endpoint).

Vagaries of the Host Response to Chronic Hepatitis B Virus Infection: What is the Ultimate Outcome of So-called “Asymptomatic HBV Carriers” Observed Over Several Decades?

Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease. Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver. Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.

Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection

Background & aims There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. Design We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. Results Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. Conclusions HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words)

A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.