Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.

SARS-CoV-2 vs. Hepatitis Virus Infection Risk in the Hemodialysis Population: What Should We Expect?

Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been implemented to minimize the risk of transmission and acquisition in this population worldwide, the reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence varies across studies but is higher than in the general population. On the contrary, the screening for hepatitis viruses (HBV and HCV) has seen significant improvements in recent years, with vaccination in the case of HBV and effective viral infection treatment for HCV. In this sense, a universal SARS-CoV-2 screening and contact precaution appear to be effective in preventing further transmission. Finally, regarding the progress, an international consensus with updated protocols that prioritize between old and new indicators would seem a reasonable tool to address these unexpended changes for the nephrology community.

The role of SOCS proteins in the development of virus- induced hepatocellular carcinoma

Background Liver cancer has become one of the most common cancers and has a high mortality rate. Hepatocellular carcinoma is one of the most common liver cancers, and its occurrence and development process are associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Main body The serious consequences of chronic hepatitis virus infections are related to the viral invasion strategy. Furthermore, the viral escape mechanism has evolved during long-term struggles with the host. Studies have increasingly shown that suppressor of cytokine signaling (SOCS) proteins participate in the viral escape process. SOCS proteins play an important role in regulating cytokine signaling, particularly the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Cytokines stimulate the expression of SOCS proteins, in turn, SOCS proteins inhibit cytokine signaling by blocking the JAK-STAT signaling pathway, thereby achieving homeostasis. By utilizing SOCS proteins, chronic hepatitis virus infection may destroy the host’s antiviral responses to achieve persistent infection. Conclusions This review provides recent knowledge regarding the role of SOCS proteins during chronic hepatitis virus infection and provides some new ideas for the future treatment of chronic hepatitis.

A Bioinformatic Analysis of Correlations between Polymeric Immunoglobulin Receptor (PIGR) and Liver Fibrosis Progression

Objective. This study is aimed at investigating the enriched functions of polymeric immunoglobulin receptor (PIGR) and its correlations with liver fibrosis stage. Methods. PIGR mRNA expression in normal liver, liver fibrosis, hepatic stellate cells (HSCs), and hepatitis virus infection samples was calculated in Gene Expression Omnibus (GEO) and Oncomine databases. Enrichment analysis of PIGR-related genes was conducted in Metascape and Gene Set Enrichment Analysis (GSEA). Logistic model and ROC curve were performed to evaluate the correlations between pIgR and liver fibrosis. Results. PIGR mRNA was upregulated in advanced liver fibrosis, cirrhosis compared to normal liver (all p < 0.05 ). PIGR mRNA was also overexpressed in activated HSCs compared to senescent HSCs, liver stem/progenitor cells, and reverted HSCs (all p < 0.05 ). Enrichment analysis revealed that PIGR-related genes involved in the defense response to virus and interferon (IFN) signaling. In GEO series, PIGR mRNA was also upregulated by hepatitis virus B, C, D, and E infection (all p < 0.05 ). After adjusting age and gender, multivariate logistic regression models revealed that high PIGR in the liver was a risk factor for liver fibrosis ( OR = 82.2 , p < 0.001 ). The area under curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of PIGR for liver fibrosis stage >2 were 0.84, 0.86, 0.7, 0.61, and 0.90. Conclusion. PIGR was correlated with liver fibrosis and might involve in hepatitis virus infection and HSC transdifferentiation.