The recent outbreak of 2019 novel coronavirus infection has involved more than 110,000 people and 105 countries. Many efforts have been made to prevent, contain and treat the related disease (named as coronavirus disease 2019). However, many blind spots might not yet receive needed attention. I here discuss eight blind spots that may interest related parties. If these issues remain outstanding, they will likely lead to many severe harms to the public, healthcare providers and the economy. Additional research is therefore needed to better understand and address these blind spots in fighting the outbreak of coronavirus disease 2019.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena. PBC is characterized by high serum levels of anti-mitochondrial antibodies (AMA) and progressive non-suppurative inflammation of small and medium-sized intrahepatic bile ducts, which could lead to cholestasis, liver fibrosis, cirrhosis, and ultimately liver failure. Apoptosis is the main mechanism of programmed cell death and is an important mechanism to regulate and maintain tissue growth and homeostasis. The clearance of apoptotic cells is a highly regulated process, which is essential to avoid the cell contents from flowing out and to limit the immune response to the generated antigens. Here, we provide a brief overview of the role of apoptosis in the pathogenesis of PBC.

This report expounds on the theoretical origin, anatomical basis, and scientific connotations of "liver governs growth", the definition of precancerous changes in the liver and the core mechanism of malignant transformation, as well as the key pathogenesis in traditional Chinese medicine based on the theory that the "liver governs growth". It also summarizes part of the authors' research achievements in intervening in a malignant transformation during precancerous changes in the liver through traditional Chinese medicine. We hope that this paper can provide insights and methods for further exploration in this area.

Hepatocellular carcinoma (HCC) is the most common neoplasm among all primary liver cancers, and hepatitis B virus (HBV) infection is the leading etiology of HCC worldwide. To identify genes significantly associated with poor survival, along with new insight into the underlying mechanisms and therapeutic targets, we conducted a bioinformatics analysis on HBV-related HCC. First, the microarray datasets GSE121248 and GSE55092 were obtained from the Gene Expression Omnibus database, which were screened for genes differentially expressed in cancer and non-cancer tissues in both datasets according to an adjusted p value < 0.05 and |log fold change| > 1.5. A total of 286 differentially expressed genes (79 up-regulated and 207 down-regulated) were selected for function enrichment analyses, including Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The proteinprotein interaction network and modular analysis were constructed by Cytoscape software. Subsequently, KEGG analysis of 42 hub genes was performed, and Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis were used to validate the differential expression profile and survival associations. In addition, the Connectivity Map (CMAP) database was used to predict small-molecules with activity that might reverse the biological state of HBV-related HCC. Collectively, these analyses identified nine hub genes (BUB1, BUB1B, CCNB1, CCNB2, CDC20, CDK1, MAD2L1, PTTG1, TTK) in the cell cycle pathway as candidate targets. Moreover, compounds targeting cell cycle arrest and apoptosis such as apigenin, resveratrol, and chrysin were selected as candidates with potential therapeutic application for HBV-related HCC.

China has had a high prevalence of hepatitis B virus infection (HBV) infection since the 20th century. Vertical mother-to-child transmission always leads to family aggregation of HBV infection. This study investigated the HBV infection status of a four-generation family by telephone consultation and review of outpatient and hospitalization medical records. The first generation consisted of 1 female relative born in 1906 who died of ascites due to cirrhosis at 60 years of age. The second generation consisted of 4 people born between the 1920s and 1930s. All of them had an HBV infection. One male relative died from ascites due to cirrhosis at 43 years of age. One female relative, aged 90 years, was an HBV carrier. Her liver function had been normal for a long time. Another female relative, aged 86 years. She had hepatic failure at age 40 years.One female relative died from liver cancer at age 66 years. The third generation consisted of 13 people. Six people had HBV infection, of whom 5 were male and one was female. One male relative died from liver cancer at age 48 years. Another male relative was diagnosed as having cirrhosis at 45 years old. The fourth generation consisted of 21 people, none of whom had an HBV infection. They were born between the 1960s and 1980s. Conclusions: This four-generation family has an obvious family aggregation of HBV infection. The infection rate was higher and the infection severity was greater in males than in females. The spread of HBV infection in this family was reduced in every succeeding generation.

We explored inhibiting effects of Xiaoliusan (XLS) on hepatocellular carcinoma (HCC) cell growth by examining differential gene expression in HepG2 cells after XLS treatments.

HepG2 cells were treated for 24 h with either XLS ('treatment') or with PBS ('control') for 24 h to assess the effects of XLS on HepG2 proliferation. Differential gene expression was examined using a gene chip, and GO enrichment, KEGG pathway enrichment, and protein interaction network analyses were performed.

XLS inhibited HepG2 proliferation in a dose-dependent manner, with an IC50 of 1.45 mg/mL. The whole-genome ChIP test of XLS-treated cells showed differential expression of 802 genes, 283 of which were up-regulated and 519 were down-regulated, compared with control cells. Using inductive analysis, we found that differentially expressed genes were mainly genes associated with the extracellular matrix (COL1A1, COL1A2, and ECM-receptor interaction pathway, among others) and with cell differentiation and proliferation (RAC1, MYC, and PI3KAkt signaling pathway, among others).

XLS inhibited HCC cell growth by targeting extracellular matrix genes in the tumor microenvironment and tumor growth, however, further research would be needed to elucidate the underlying mechanisms.

Production of lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria promotes the survival of cancer cells. Systemic level of LPS is considered a biomarker for microbial translocation. The association between LPS and the risk of colorectal tumors is not well known. The goal of this study was to examine the association between LPS serum levels and risk of advanced colorectal adenoma (ACA).

In this colonoscopy clinic-based case-control study, cases were male patients with a diagnosis of ACA, and controls were polyp-free male participants. Cases and controls were individually matched by age, ethnicity, and blood collection time. Information on demographics, lifestyle, and medical history was obtained using structured questionnaires. Serum levels of LPS were quantitated using the kinetic limulus amebocyte lysate assay. Multivariable conditional logistic regression model was used to estimate the odds ratio and its 95% confidence interval of the ACA in association with serum LPS adjusting for cigarette smoking, body mass index, and medical history.

We examined 43 cases and 43 paired controls, with a mean age of 62 years. There was no significant difference in serum LPS levels between the cases and controls (0.28 vs. 0.25 endotoxin units (EU)/mL, P = 0.58 for the non-parametric test). The adjusted odds ratio and its 95% confidence interval of ACA was 1.83 (0.40–8.24) in multivariable logistic regression model.

Serum levels of LPS were not statistically significantly associated with an increased risk of ACA in this preliminary study.

Background and Aims: The World Health Organization (WHO) Western Pacific Region set a target of eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) by 2030. To assess the feasibility of this target in China, we carried out an epidemiological study to investigate the status quo of MTCT in the real-world setting.

Methods: One thousand and eight hepatitis B surface antigen-positive pregnant women were enrolled at 10 hospitals. Immunoprophylaxis was administered to infants. In addition, mothers with HBV DNA level >2,000,000 IU/mL were advised to initiate antiviral therapy during late pregnancy. A health application called SHIELD was used to manage the study.

Results: Nine hundred and five of the enrolled mothers, with 924 infants, completed the follow-up. Birth-dose hepatitis B vaccine and hepatitis B immunoglobulin were received by 99.7% and 99.7% of infants, respectively, within 24 h after birth. There were 446 mothers who received antiviral therapy, including 72.3% of the mothers with HBV DNA level >2,000,000 IU/mL and 21.0% of the mothers with HBV DNA level <2,000,000 IU/mL. Eight infants were infected with HBV. The overall rate of MTCT was 0.9%. Birth defects were rare (0.5% among infants with maternal antiviral exposure versus 0.7% among infants without exposure; p=1.00).

Conclusions:The MTCT rate was lower than the WHO Western Pacific Region elimination MTCT target in this real-world study, indicating that a comprehensive management composed of immunoprophylaxis to infants and antiviral prophylaxis to mothers may be a feasible strategy to achieve the 2030 WHO elimination goal.

We repurposed the antifibrotic drug pirfenidone—which is approved for treatment of idiopathic lung fibrosis—in a series of patients with nonalcoholic steatohepatitis-related cirrhosis. Our report demonstrates the observed improvements in necroinflammation and regression of cirrhosis with pirfenidone use for 12-weeks, associated with classical hepatic repair complex features on follow-up liver biopsies. This novel work could help stimulate further randomized trials of pirfenidone in patients with nonalcoholic steatohepatitis-related liver fibrosis or cirrhosis, for whom no recommended drug treatments exists currently.

HIV-1 vertically infected children stand a high risk of HIV-1 drug resistance (HIVDR), especially after failure to prevention of mother to child transmission (PMTCT) and pediatric antiretroviral therapy (ART). Thus, surveillance of HIVDR might contribute in delineating optimal pediatric regimens. The objective of this study was to evaluate HIVDR and subtype distribution among ART-naïve and ART-failing children.

A study was conducted throughout 2017 amongst 102 children/adolescents at the “Chantal BIYA International Reference Centre” (CIRCB) in Cameroon. HIVDR testing was performed in protease-reverse transcriptase (RT) region and interpreted using the Stanford HIVdbv8.5; subtyping was performed using MEGA v7.0.26; and data were analyzed using Epi-info v7.1.3.3, with p < 0.05 considered statistically significant.

Sequences were generated from 63 participants (19 ART-naïve, 44 ART-failure); the median-age was respectively 6 [IQR:3.5–11] and 144 [IQR:116.25–185] months for ART-naïve and ART-failing (median ART-duration: 23.55 [IQR:7.61–60.91] months, 63.6% receiving non-nucleoside RT inhibitors [NNRTI]-based regimens). Among ART-naïve children, overall-HIVDR was 52.6% (10/19), with 31.6% (6/19) to NNRTI, 26.3% (5/19) to nucleoside RT inhibitors (NRTI) and 15.8% (3/19) to ritonavir-boosted protease inhibitor (PI/r). Among ART-failing children, overall-HIVDR was 97.7% (43/44), with 95.4% (42/44) to NNRTI, 90.9% (40/44) to NRTI and 18.2% (8/44) to PI/r. Multi-drug resistance was found in 21.05% (4/19) ART-naïve versus 85.7% (24/28) on NNRTI-based and 50% (8/16) on PI-based regimens; OR = 4.36, p = 0.045. CRF02_AG was prevalent (68.2%), without any effect on HIVDR (p = 0.99).

The high rates of HIVDR, in both ART-naïve and ART-failing children, suggest using genotypic HIV-1 drug resistance testing for selecting optimal pediatric ART-regimens. Multi-drug resistance is concerning among children failing ART and prompts the need of new drugs (integrase inhibitors, darunavir/ritonavir) for optimal pediatric ART management.

Background and Aims: Liver biopsy remains the gold standard for staging of chronic liver disease following orthotopic liver transplantation. Noninvasive assessment of fibrosis with Fibro-test (FT) is well-studied in immunocompetent populations with chronic hepatitis C virus infection. The aim of this study is to investigate the diagnostic value of FT in the assessment of hepatic fibrosis in the allografts of liver transplant recipients with evidence of recurrent hepatitis C.

Methods: We retrospectively compared liver biopsies and FT performed within a median of 1 month of each other in orthotopic liver transplantation recipients with recurrent hepatitis C.

Results: The study population comprised 22 patients, most of them male (19/22), and with median age of 62 years. For all patients, there was at least a one-stage difference in fibrosis as assessed by liver biopsy compared to FT, while for the majority (16/22) there was at least a two-stage difference. The absence of correlation between the two modalities was statistically demonstrated (Mann-Whitney U test, p = 0.01). In detecting significant fibrosis (a METAVIR stage of F2 and above), an FT cut-off of 0.5 showed moderate sensitivity (77%) and negative predictive value (80%), but suboptimal specificity (61%) and positive predictive value (58%).

Conclusions: In post-transplant patients with recurrent hepatitis C, FT appears to be inaccurately assessing the degree of allograft fibrosis, therefore limiting its reliability as a staging tool.

Primary biliary cholangitis, formerly known as primary biliary cirrhosis, is a chronic, autoimmune, and cholestatic disease ameliorating the biliary epithelial system causing fibrosis and end-stage liver disease, over time. Patients range from an asymptomatic phase early in the disease course, to symptoms of decompensated cirrhosis later in its course. This review focuses on the current consensus on the epidemiology, diagnosis, and management of patients with primary biliary cholangitis. We also discuss established medical management as well as novel and investigational therapeutics in the pipeline for management of PBC.

Portal cavernoma cholangiopathy (PCC) is one of the most harrowing complications of extrahepatic portal venous obstruction, as it determines the long-term hepatobiliary outcome. Although symptomatic PCC is rare in children, asymptomatic PCC is as common as that in adults. However, there are major gaps in the literature with regard to the best imaging strategy and management modality in children. Moreover, natural history of PCC and effect of portosystemic shunt surgeries in children are unclear. Neglected PCC would lead to difficult or recalcitrant biliary strictures that will require endoscopic therapy or bilioenteric anastomosis, both of which are challenging in the presence of extensive collaterals. There are limited studies on the effect of portosystemic shunt surgeries on the outcome of PCC in children compared to adults. In this review, we aimed to collate all existing literature on PCC in childhood and also compare with adult studies. We highlight the difficulties of this disease to provide a comprehensive platform to foster further research on PCC exclusively in children.

Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related death. Gut microbiota are part of a complex microbe-based ecosystem of the human body, and changes in the microbiota can lead to a variety of diseases. All currently used CRC detection methods, including endoscopy, guaiac-based fecal occult blood test and fecal immunochemical test, have many limitations. Therefore, establishing novel screening methods which are accurate, inexpensive and non-invasive is indicated. Random forest models, as a superiority machine learning model, are increasingly used in research to select biomarkers. In this review, we summarized progressions of the diagnoses of CRC based on the random forest model of gut microbiota. We concluded that some cancer-associated bacteria in gut microbiota could be used as biomarkers for detecting early CRC. We also aimed to discuss how to select possible markers of colorectal diseases based on gut microbiota using the random forest model.

A healthy oral environment features a rapid turnover rate of epithelium cells capable of regeneration and repair, with the oral epithelium contributing as a physical barrier and immune defense. However, the oral cavity can be subjected to unique damage, such as ulcerations. Honey is reported as a therapeutic agent for wound healing, due to its antioxidant, antibacterial and anti-inflammatory properties.

A systematic review was performed following the PRISMA 2015 Guidelines, to assess the efficacy and safety of the therapeutic use of honey in the oral cavity. Four electronic databases were searched (PubMed, Cochrane Library, Scopus, and Web of Science) for randomized controlled trials examining the effect of honey on oral cavity conditions.

In total, 2,832 records were identified, and after applying exclusion criteria, 13 studies were included. Honey was applied topically throughout, for chemotherapy or radiotherapy-induced oral mucositis (n = 11), dental wounds (n = 1), and recurrent aphthous stomatitis (n = 1), all of which are ulcerations with different pathologies. In the majority of studies (12/13), honey reduced the severity and/or duration of the condition compared with control groups (all p<0.05). However, a group treated with Manuka honey (n = 1) experienced adverse effects and considerable participant attrition.

Honey is an effective treatment for a range of oral ulcerative conditions. Future research should focus on compositional analysis of honeys to determine those with optimal beneficial properties, and whether Manuka honey is safe to use in the oral cavity.

Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial pathogenesis and heterogenous clinical manifestations. NAFLD, once believed to be an innocuous condition, has now become the most common cause of chronic liver disease in many countries worldwide. NAFLD is already highly prevalent in the general population, and owing to a rising incidence of obesity and diabetes mellitus, the incidence of NAFLD and its impact on global healthcare are expected to increase in the future. A subset of patients with NAFLD develops progressive liver disease leading to cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent years. Moreover, HCC can occur in NAFLD even in absence of cirrhosis. Compared with the general population, NAFLD increases the risk of liver-related, cardiovascular and all-cause mortality. NAFLD is bidirectionally associated with metabolic syndrome. NAFLD increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis, cardiovascular diseases, diabetes mellitus, and chronic kidney disease. In addition, NAFLD is linked to colorectal polyps, polycystic ovarian syndrome, osteoporosis, obstructive sleep apnea, stroke, and various extrahepatic malignancies. Extended resection of steatotic liver is associated with increased risk of liver failure and mortality. There is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation, and the recurrence of NAFLD in such patients is almost universal. This review discusses the growing burden of NAFLD, its outcomes, and adverse associations with various diseases.

Background and Aims: Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B.

Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed.

Results: Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016.

Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.