Wei Chao

Electronics Research Institute · Shandong University

The phenotype of cryoglobulinemia in hepatitis B virus (HBV) carriers remains elusive. A 7-year prospective cohort of 648 hepatitis B e antigen (HBeAg)-negative Taiwanese HBV carriers [males: 344 (53%)] was conducted. Among 648, 189 (29.2%) had cryoglobulinemia, and 26 (4.0%) had cryoglobulinemic syndrome (CS). More females; higher levels of rheuma...

Background and Aim Hepatitis B virus (HBV) reactivation could develop after withdrawal following a finite course of nucleoside analog (NA) therapy, leading to virological and clinical relapses. The genetic heterogeneity in the HBV surface and polymerase genes during finite NA therapy has not been carefully studied. Methods Seven chronic HBV‐infect...

Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV’s involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan’s National H...

Background. EcoHIV is a chimeric HIV that replicates in mice in CD4+ T cells, macrophages, and microglia (but not in neurons), causing lasting neurocognitive impairment resembling neurocognitive disease in people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures to investigate the indirect ef...

IL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood. Because the IL-33 receptor, ST2, acts via cascad...

This study aimed to compare the efficacy of shorter vs. longer tenofovir disoproxil fumarate (TDF) prophylaxis in preventing hepatitis B virus (HBV) relapse in cancer patients with chronic hepatitis B (CHB) undergoing chemotherapy. This phase IV, prospective randomized trial enrolled cancer patients with CHB from 2014 to 2019 in Taiwan. Included pa...

Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients...

The impacts of patatin‐like phospholipase domain‐containing protein 3 ( PNPLA3 ) I148M‐rs738409, methylenetetrahydrofolate reductase ( MTHFR ) Ala222Val‐rs1801133, and aldehyde dehydrogenase 2 ( ALDH2 ) Glu504Lys‐rs671 on the outcomes of Taiwanese patients with steatotic liver disease (SLD) have remained elusive. An 8‐year prospective cohort study...

Antiretroviral therapy controls immunodeficiency in people with HIV but many develop mild neurocognitive disorder. Here we investigated HIV brain disease by infecting mice with the chimeric HIV, EcoHIV, and probing changes in brain gene expression during infection and reversal with polyinosinic-polycytidylic acid (poly I:C). EcoHIV-infected C57BL/6...

A complete investigation of the clinical outcomes after treatment cessation in HBeAg‐positive patients with HBeAg loss is limited. We retrospectively recruited 242 HBeAg‐positive patients with HBeAg loss after a median duration of 37.2 months with tenofovir (TDF, n=77) or entecavir (ETV, n=165) treatment. There were 77 (31.8%) patients with sustain...

RNA editing of the hepatitis delta virus (HDV) is essential for generating the large delta antigen, which is crucial for virion assembly. In HDV genotype 1 (HDV-1), editing occurs within the context of the unbranched rod-like structure characteristic of HDV RNA, while RNA editing in HDV-3 requires a branched double-hairpin structure. The regulation...

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte rati...

Purpose: Hepatocellular carcinoma (HCC) is one of the most severe complications in chronic hepatitis B virus (HBV) infection. HCC can still develop in patients with chronic HBV (CHB) infection undergoing antiviral therapy. Several effective scoring systems for the prediction of HCC risk in CHB patients have been established. However, very few of t...

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to...

Severe traumatic injury leads to marked systemic inflammation and multiorgan injury. Endogenous drivers such as extracellular nucleic acid may play a role in mediating innate immune response and the downstream pathogenesis. Here, we explored the role of plasma extracellular RNA (exRNA) and its sensing mechanism in inflammation and organ injury in a...

HIV enters the brain within days of infection causing neurocognitive impairment (NCI) in up to half of infected people despite suppressive antiretroviral therapy. The virus is believed to enter the brain in infected monocytes through chemotaxis to the major monocyte chemokine, CCL2, but the roles of CCL2 in established NCI are not fully defined. We...

Background and aim: World Health Organization sets up an ambitious and attainable goal to eliminate hepatitis C (HCV) by 2030. The previous diagnosed HCV patients lost to follow-up were considered as an important target group for HCV elimination. We conducted a call back program to retrieve the lost to follow-up HCV patients and link them to care...

Cortical neural dynamics mediate information processing for the cerebral cortex, implicated in fundamental biological processes, such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes cortical network into an aberrant state, and...

Gut bacterial/viral dysbiosis, changes in circulating metabolites, and plasma cytokines/chemokines have been previously associated with various liver diseases. Here, we analyzed the associations between fecal microbial composition, circulating metabolites, and plasma cytokines/chemokines in patients with liver cirrhosis (LC) and hepatocellular carc...

HIV enters the brain within days of infection causing neurocognitive impairment (NCI) in up to half of infected people despite suppressive antiretroviral therapy. The virus is believed to enter the brain in infected monocytes through chemotaxis to the major monocyte chemokine, CCL2, but direct demonstration of the role of CCL2 in NCI pathogenesis i...

Sepsis and trauma remain the leading causes of morbidity and mortality. Our understanding of the molecular pathogenesis in development of multiple organ dysfunction in sepsis and trauma has evolved as more focus is on secondary injury from innate immunity, inflammation, and the potential role of endogenous danger molecules. Studies of the past seve...

Extracellular vesicles (EVs) have emerged as promising therapeutic entities in part due to their potential to regulate multiple signaling pathways in target cells. This potential is derived from the broad array of constituent and/or cargo molecules associated with EVs. Among these, microRNAs (miRNAs) are commonly implicated as important and have be...

Thirty-eight million people worldwide are living with HIV, PWH, a major public health problem. Antiretroviral therapy (ART) revolutionized HIV treatment and significantly increased the lifespan of PWH. However, approximately 15-50% of PWH develop HIV associated neurocognitive disorders (HIV-NCI), a spectrum of cognitive deficits, that negatively im...

Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underl...

Extracellular vesicles (EVs) have emerged as promising therapeutic entities in part due to their potential to regulate multiple signaling pathways in target cells. This potential is derived from the broad array of constituent and/or cargo molecules associated with EVs. Among these, microRNAs (miRNAs) are commonly implicated as important and have be...

Toll-like receptor 7 (TLR7), the sensor for single-stranded RNA, contributes to systemic inflammation and mortality in murine polymicrobial sepsis. Recent studies show that extracellular miR-146a-5p serves as a TLR7 ligand and plays an important role in regulating host innate immunity. However, the role of miR-146a-5p and TLR7 signaling in pulmonar...

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited. We aimed to explore the efficacy after 1-year TAF treatment. A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF tre...

Background Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has wreaked havoc worldwide since December 2019. Currently, no effective medical treatments have been approved. As the epidemic continues to spread, SARS-CoV-2 mutants emerge, some of which become more infectious with increasing vaccine resi...

Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-ris...

Background: The results of long-term renal evolution in HCV-infected patients using sofosbuvir and velpatasvir (SOF/VEL), with or without ribavirin (RBV), are lacking. Aims: We evaluated the renal safety for HCV-infected patients receiving SOF/VEL. Methods: Between 1 June 2019 and 6 July 2020, we included 594 HCV-infected patients receiving SOF/VEL...

The World Health Organization estimates ~180,000 deaths occur annually from burn-related injuries. Many victims that survive the initial burn trauma succumb to bacterial infections that lead to sepsis during treatment. Although advancements in burn care continue to improve in high-income countries due to their burn centers and advanced research, lo...

Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its...

Sepsis-associated encephalopathy (SAE) occurs in sepsis survivors and is associated with breakdown of the blood-brain barrier (BBB), brain inflammation, and neurological dysfunction. We have previously identified a group of extracellular microRNAs (ex-miRNAs), such as miR-146a-5p, that were upregulated in the plasma of septic mice and human, and ca...

Background: Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection. Methods: We prospectively recruited patients with DILI from multiple centers in Taiwa...

Of the 486,000 burn injuries that required medical treatment in the USA in 2016, 40,000 people were hospitalized, with > 3,000 fatalities. After burn injury, humans are at increased risk of sepsis and mortality from infections caused by Pseudomonas aeruginosa (PA), an opportunistic pathogen. We hypothesize that systemic events were initiated from t...

Background: Sepsis-induced cardiomyopathy (SIC) is a major contributing factor for morbidity and mortality in sepsis. Accumulative evidence has suggested that cardiac mitochondrial oxidative phosphorylation is attenuated in sepsis, but the underlying molecular mechanisms remain incompletely understood. Methods: Adult male mice of 9-12 weeks old...

A correction to this paper has been published: https://doi.org/10.1007/s11481-021-09992-5

Background and aims: Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan. Methods: This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019. Pati...

Background and Aim Ropeginterferon alfa-2b (P1101) is a novel long-acting mono-PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N-terminus, allowing every-two-week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia...

Background & Aims Severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liv...

Nivolumab monotherapy has a modest objective response rate (ORR) in hepatocellular carcinoma (HCC). To overcome the lack of biomarkers that predict delayed alpha-fetoprotein (AFP) response beyond 4 weeks, we applied a novel 50-10 rule of AFP response for unresectable HCC patients under nivolumab monotherapy and proposed an algorithm based on on-tre...

Sepsis is a deadly condition lacking a specific treatment despite decades of research. This has prompted the exploration of new approaches, with extracellular vesicles (EVs) emerging as a focal area. EVs are nanosized, cell‐derived particles that transport bioactive components (i.e., proteins, DNA, and RNA) between cells, enabling both normal physi...

Significance: Sepsis is a critical clinical syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. Despite decades of intensive research, sepsis remains a leading cause of in-hospital mortality with few specific treatments. Recent Advances: Toll-like receptors (TLRs) are a part of the innate immune s...

Background and Aims Patients with chronic hepatitis B (CHB) are at an increased risk of disease progression. The influence of hepatic steatosis (HS) to liver fibrosis was controversial. We aim to investigate the association between HS and liver fibrosis and explore the predicting factors for advanced fibrosis. Methods CHB patients undergoing liver...

New antiviral therapies against hepatitis B virus (HBV) focus on the elimination of covalently closed circular DNA (cccDNA). However, traditional cccDNA-specific quantitative PCR (qPCR) has a narrow effective range, hindering a reliable comparison between the levels of biopsy-derived cccDNAs. Collaterally, the prognostic role of cccDNA in HBV-relat...

Sepsis-induced cardiomyopathy (SIC) is a major contributing factor for morbidity and mortality in sepsis, but the underlying mechanisms are poorly understood. Previous work has suggested that mitochondrial oxidative phosphorylation is altered in mice with SIC, but the molecular mechanisms remain unidentified. Here, we performed a proteomic analysis...

Background: Aeromedical evacuation can expose traumatically injured patients to low pressure (hypobaria) and hypoxia. Here we sought to assess the impact of hypobaria on inflammation, organ injury, and mortality in a mouse model of polytrauma. Methods: Eight to 12 week-old male C57BL/6J mice were subjected to sham or polytrauma consisting of bow...

Introduction: Sepsis-induced acute lung injury (ALI) has substantial morbidity and mortality. Diffused alveolar damage as a result of increased endothelial cell (EC) permeability is a hallmark of ALI. We have previously demonstrated that certain uridine-rich extracellular (ex) miRNAs such as miR-146a activate innate immune response and possess a po...

Introduction: Transient myocardial ischemic/reperfusion injury (I/R) leads to cellular RNA release into extracellular (ex) space. Ex-RNAs and certain uridine-rich miRNAs activate innate immune response via TLR7-MyD88 pathway. Systemic administration of RNase reduces myocardial inflammation and infarct size after I/R, suggesting a pivotal role of ex...

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of poly...

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applicat...

Previous studies have demonstrated that transient myocardial ischemia leads to release of cellular nucleic acids such as RNA. Extracellular RNA reportedly plays a pivotal role in myocardial inflammation and ischemic injury in animals. RNA profiling has identified that numerous microRNA (miRNAs), such as ss-miR-146a-5p, are upregulated in plasma fol...

The current study demonstrates that miR-146a mediates acute lung inflammation in a TLR7-dependent manner. The downstream mediators of miR-146aTLR7 signaling in regulating lung inflammation and barrier function warrant further investigation.

Background: The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS. Methods: We retrospectivel...

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC...

HIV associated neurocognitive impairment afflicts roughly half of infected individuals on antiretroviral therapy. This disease currently has no treatment. We have previously shown that type I interferon is induced by and partially controls infection and neuropathogenesis in mice infected by chimeric HIV, EcoHIV. Here we investigate the intentional...

Based on their identification as physiological nucleic acid carriers in humans and other organisms, extracellular vesicles (EVs) have been explored as therapeutic delivery vehicles for DNA, RNA, and other cargo. However, efficient loading and functional delivery of nucleic acids remain a challenge, largely because of potential sources of degradatio...

HIV-associated neurocognitive disorders (HAND) have been linked to dysregulation of glutamate metabolism in the central nervous system (CNS) culminating in elevated extracellular glutamate and disrupted glutamatergic neurotransmission. Increased glutamate synthesis via upregulation of glutaminase (GLS) activity in brain immune cells has been identi...

We examined the seroprevalence change of anti‐hepatitis D virus (HDV) antibodies in Taiwan during 2006 – 2019. Totally 1147 patients who had chronic HBV infection were assessed. Of them, 51 (4.4%) were positive for anti‐HDV antibodies. Comparison between anti‐HDV‐positive and negative groups was performed to examine clinical and virological factors...

HIV neuropathogenesis has been attributed in large measure to neurotoxicity of viral proteins and inflammatory factors produced by infected monocytic cells in the brain. We show here that HIV expression in mouse brain causes lasting memory impairment by a mechanism involving injury to hippocampal synaptodendritic arbors and neuronal function but no...

Background: Sepsis is a life-threatening condition often manifested as marked inflammation and severe coagulopathy. Toll-like receptors (TLRs) play a pivotal role in inflammation, organ dysfunction, and mortality in animal sepsis. Objectives: Here we investigated the role of TLR signaling in mediating sepsis-induced coagulopathy (SIC) in a mouse...

What we already know about this topic: Toll-like receptor 7 responds to elevated single-stranded RNA by increasing cytokine production. Sepsis is characterized by elevated plasma levels of tissue damage (and pathogen)-associated molecular patterns, including RNA. What this article tells us that is new: Using murine models of bacterial sepsis, kn...

Background: Acute lung injury (ALI) remains a significant source of morbidity and mortality in the septic patient population. Inflammation and endothelial barrier dysfunction are the key pathologies responsible for sepsis-induced ALI. We have recently demonstrated a specific group of miRNAs including miR-146a that were released into the circulation...

In chronic hepatitis B (CHB) patients, withdrawal of nucleos(t)ide analogues (NAs) can put patients at risk of hepatitis relapses. Here, we examined a dose‐reducing strategy. From 2008‐March to 2016‐September, 48 CHB patients who had received full‐dose NA (35 entecavir; 13 tenofovir) and achieved complete virological response (lasting for > 1 year)...

We have previously reported that a group of host cellular microRNAs (miRNAs; miR-34a-5p, miR-122-5p, miR-145-5p, miR-146a-5p, miR-210-3p) are released into the blood during sepsis, some of which are capable of inducing complement activation, cytokine production, and leukocyte migration. Extracellular vesicles (EVs) have been proposed as vehicles fo...

Background: Seroclearance of hepatitis B surface antigen (HBsAg) has been rarely achieved in the treatment of chronic hepatitis B (CHB) patients. We administered HBsAg-based recombinant vaccine in patients with low HBsAg concentrations. Methods: Twenty hepatitis B e antigen-negative patients, with HBsAg < 1000 IU/ml, were enrolled. Vaccines were...