Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced a worldwide pandemic. The main clinical manifestations of COVID-19 patients have been fever, cough, dyspnea, and other respiratory symptoms. However, some patients’ initial symptoms have been nausea, vomiting, diarrhea and other gastrointestinal symptoms, and SARS-CoV-2 RNA could be found in their stool samples. Studies have shown that the gastrointestinal tract highly-expressed angiotensin-converting enzyme 2 is used by SARS-CoV-2 to enter cells. Therefore, exploring the damage caused by SARS-CoV-2 to the gastrointestinal tract and whether it could replicate in the gastrointestinal tract and transmit through fecal-oral route has significance for the diagnosis, treatment and prevention of COVID-19. We combined the current clinical data about COVID-19 patients with gastrointestinal symptoms as well as its pathogenic mechanism and prevention methods herein to review the relationship between the disease and gastrointestinal symptoms.

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addition to the clinical characteristics and genetic history, electromyography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possibility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.

Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes.

Trial registration: ClinicalTrials.gov NCT00388674.

Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later developed alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilaprevir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.

Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalopathy and impaired synthetic function (international normalized ratio of ≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulopathy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagulable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.

Our previous studies evidenced that quercetin (Q) could be ingested and metabolized by macrophages, and exerted both prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effects on lipopolysaccharide-treated macrophages ex vivo. To ascertain potential mechanism of anti-inflammatory action by Q, the present study evaluated changes of pro-/anti-inflammatory cytokines and components of inflammation-related intracellular signaling pathways in activated macrophages.

In this ex vivo study, BALB/c mice were first administered intraperitoneally injected with lipopolysaccharide for 12 h; then, mouse peritoneal macrophages were isolated and treated with Q for 3 h in vitro. Quercetin 3-glucuronide (a major metabolite of Q) and dexamethasone (a glucocorticoid) were selected to perform comparative analysis. Relative gene expression amounts of pro-/anti-inflammatory cytokines (TNF-α/IL-10) and components involved in inflammation-related intracellular signaling pathways in macrophages (TLR2, TLR4, NF-κB, JAK2, and STAT3) were measured using two-step reverse transcription and real-time quantitative polymerase chain reaction. STAT3 protein phosphorylation was determined using an in-cell enzyme-linked immunosorbent assay method.

Q decreased TNF-α gene expression amounts and ratios of pro-/anti-inflammatory (TNF-α/IL-10) cytokine gene expressions but increased IL-10 gene expression amounts in activated inflammatory macrophages, supporting a substantial anti-inflammatory potential of Q treatments. Importantly, Q inhibited TLR2 gene expression and phosphorylation of STAT3 protein in the activated inflammatory macrophages.

Our results are the first to suggest that Q inhibits lipopolysaccharide-induced inflammation ex vivo through suppression of TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. Q has potential further application for treating inflammation-associated diseases.

Chronic hepatitis B or C viral infection is a common cause of liver cirrhosis and hepatocellular carcinoma. Fibrosis regression can be achieved after long-term antiviral therapy (AVT). Monitoring of dynamic changes in liver fibrosis after treatment is essential for establishing prognosis and formulation of a follow-up surveillance program. Routine surveillance of fibrosis after AVT by liver biopsy, the gold standard for fibrosis assessment, is hindered by its invasive nature, sampling error and observer variability. Elastography is a noninvasive quantitative alternative that has been widely used and validated for the staging of liver fibrosis prior to treatment. Recently, increasing research interest has been focused on the role of elastography in longitudinal assessment of liver fibrosis after AVT. In this review, the basic principles, acquisition techniques, diagnostic performances, and strengths and limitations of ultrasound elastography and magnetic resonance elastography are presented. Emerging evidence regarding the use of elastography techniques for the monitoring of liver fibrosis after AVT is summarized. Current challenges and future directions are also discussed, designed to optimize the application of these techniques in clinical practice.

Tumor immune escape plays an important role in carcinogenesis. Nature killer (NK) cells are human innate immune cells that do not need antigen sensitization prior to their activation. NK cells directly or indirectly kill tumor cells through cytotoxicity and immune regulation, but they are also involved in tumor immune escape. In this study, we reviewed the mechanism of NK cell-related tumor immune escape. The current knowledge on tumor cell alteration and the impact of inhibitory factors and the joint influence of other cells that lead to NK cell dysfunction and ultimately result in tumor immune escape have been researched and discussed. Understanding the potential mechanisms for restoration of the anti-tumor function of immune cells is of critical significance for discovering novel approaches for the treatment of tumors.

To explore the law of Prof. Yao Naili's traditional Chinese medicine treatment of chronic gastritis.

The chronic gastritis cases treated by Prof. Yao Naili at the specialist outpatient clinic of Beijing Tongrentang Traditional Chinese Medicine Hospital from October 2017 to March 2019 were reviewed. The data on the four traditional Chinese medicine diagnostic methods were extracted and standardized to form the database of Prof. Yao Naili's traditional Chinese medicine prescriptions for the treatment of chronic gastritis. SPSS 20.0 was used for the descriptive statistical analysis of the categorical data, and factor analysis was performed for continuous data.

The records of 113 cases were included. The traditional Chinese medicinal substances frequently used by Yao Naili for treating chronic gastritis included Glycyrrhiza uralensis, Poria cocos, Rhizoma Atractylodis Macrocephalae, Rhizoma Pinelliae Preparata, and Coptis chinensis. Factor analysis: three key traditional Chinese medicine combinations (common factors) were extracted, namely Coptis chinensis and Scutellaria baicalensis (Common Factor 1), Poria cocos and Ligusticum wallichii (Common Factor 2), and Pseudostellaria heterophylla (Common Factor 3).

Prof. Yao Naili's treatment of chronic gastritis is mainly based on strengthening the spleen and tonifying the stomach. The treatments are mainly based on drugs with functions such as promoting blood and qi circulation, strengthening the spleen, tonifying qi, and nourishing yin. Focusing on the pathogenesis, multiple methods are combined, such as removing stasis and dredging collaterals, clearing heat and detoxification, as well as promoting qi circulation and relieving pain.

Nonalcoholic fatty pancreatic disease (NAFPD) is characterized by increased fat accumulation in the pancreas. It is a component of metabolic syndromes and often coexists with nonalcoholic fatty liver disease. A definitive NAFPD diagnosis is closely associated with acute and chronic pancreatitis, type 2 diabetes, pancreatic fibrosis, and pancreatic cancer. Recent research indicates that NAFPD is also closely associated with cardiovascular disease, liver fibrosis, and liver cancer. The prevalence of NAFPD ranges from 11% to 69% and increases with age. Notably, the prevalence of NAFPD among obese children is two-fold greater than among nonobese children, and the high prevalence and complexity of the disease have garnered much attention. Meanwhile, joint efforts and collaborations from multiple disciplines, including hepatopathy, gastroenterology, endocrinology and metabolism, cardiovascular disease, imaging, and pathology, are required to enhance our understanding of NAFPD and fully comprehend its clinical significance. These efforts will also allow further explorations on its pathogenesis, diagnosis, and treatment. Herein, we conducted a literature review on the pathogenesis of NAFPD, and the author's perspectives on key future prospects in NAFPD research are also proposed.

Hepatic veno-occlusive disease (HVOD), also known as hepatic sinusoidal obstruction syndrome (HSOS), is a specific type of hepatic vascular disease. The most common cause of HSOS in Western countries is the pretreatment of bone marrow hematopoietic stem cell transplantation (HSCT). In China, the most common cause is the ingestion of plants containing pyrrolidine alkaloids (PAs). In the case of HSCT-HSOS in Europe and the United States, relevant examinations, warning symptoms, and disease staging standards before and after transplantation have been clarified; however, there is a lack of corresponding imaging standards. In China, because there are no obvious early clinical symptoms and effective diagnostic methods for PA-HSOS, the disease can go undiagnosed or be misdiagnosed, and the lack of clinical staging is not conducive to the guidance of clinical diagnosis and treatment. In this article, we review the etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of HSOS in order to provide a reference for clinicians and researchers and contribute to future efforts aimed at establishing highly specific indicators for the diagnosis and prognosis of this disease.

To investigate the correlations of pathological grade and HBV-DNA level with the occurrence of gallbladder diseases in patients with chronic hepatitis B, and to improve clinicians' understanding of this disease.

A total of 282 inpatients with chronic hepatitis B undergoing liver biopsy in Beijing Youan Hospital, Capital Medical University from January 2014 to April 2017 were enrolled. Data on liver pathological grade, HBsAg, HBeAg, HBV-DNA, and gallbladder disease conditions were retrospectively analyzed, and SPSS 19.0 software was used for statistical analysis.

The incidence of gallbladder diseases in chronic hepatitis B patients were not significantly different among different HBsAg levels, between positive and negative HBeAg, or among different HBV-DNA groups (P>0.05). The higher the G grade and S stage of the liver pathology, the higher the incidence of gallbladder wall thickening, with a statistically significant difference (P<0.05).

Gallbladder wall thickening indicates that the degree of liver fibrosis in chronic hepatitis B patients is relatively high and can be used as one of the indexes to evaluate the progression of chronic hepatitis B.

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety.

Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment.

Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy.

Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

Background and Aims: Glecaprevir/pibrentasvir is a pangenotypic regimen recently approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the present review was to summarize the findings from clinical trials to understand how patient-related factors influence glecaprevir/pibrentasvir efficacy (sustained virologic response rates at 12 weeks’ after treatment [referred to as SVR12]) and safety.

Methods: Data from 21 phase III clinical trials were analyzed.

Results: The integrated efficacy analysis included 4,817 patients. Findings showed 97.5% of all included patients with chronic HCV achieved SVR12 in the intention-to-treat population. SVR12 rate was >95% across subgroups of interest. The integrated safety analysis included 4,015 patients. Findings showed that 64.1% of patients reported an adverse event, and <0.1% of patients reported a serious adverse event related to glecaprevir/pibrentasvir.

Conclusions: These results indicate that the 8- or 12-week glecaprevir/pibrentasvir treatment is effective for patients infected with HCV genotypes 1-6 without or with compensated cirrhosis, with good safety profiles, irrespective of treatment-experience. Glecaprevir/pibrentasvir is a good option for patients with human immunodeficiency virus/HCV coinfection and comorbid HCV and severe renal impairment.