The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.

With an increasing understanding of hepatitis B, the antiviral indications have been broadening gradually. To evaluate the effectiveness of tenofovir alafenamide (TAF) in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and detectable hepatitis B virus (HBV) DNA, those who are ineligible for broader antiviral criteria from the Chinese CHB prevention guide (2019).

A total of 117 patients were recruited and their data were collected from paper or electronic medical records. HBV DNA and liver function were measured at baseline and throughout the 24-week follow-up. The effectiveness endpoint was complete virological response. The safety endpoint was the first occurrence of any clinical adverse event during the treatment.

Among the 117 patients, 45 had normal ALT as well as detectable HBV DNA and they were not recommended for antiviral therapy according to Chinese Guidelines (2019). After TAF antiviral therapy, the rates of patients who achieved HBV DNA <20 IU/mL at 4, 12 and 24 weeks were 77.1%, 96.7% and 96.8% respectively. Among them, the undetectable rates of HBV DNA in patients with low baseline viral load at 4, 12 and 24 weeks were 92.3%, 100% and 100%, while the rates of those with high baseline viral load were 68.2%, 94.1% and 94.4%. Compared with 71.4%, 94.4% and 94.7% in the high baseline group, the undetectable rates of HBV DNA at 4, 12 and 24 weeks in the low baseline liver stiffness group were 85.7%, 100% and 100%. There was no statistical significance among the above groups.

CHB patients who had normal ALT and detectable HBV DNA and did not meet “CHB prevention guide (2019)”, could achieve complete virological response in 24 weeks after antiviral treatment by TAF.

In recent years, the prevalence of non-alcoholic fatty liver disease combined with metabolic dysfunction in children has increased rapidly. Current international guidelines for the management of metabolic-associated fatty liver disease do not recommend any specific drug therapy or its exact effect and safety margin. Appropriate drug therapies for children are even more scarce. Traditional Chinese medicine has good advantages in the prevention and treatment of metabolic-associated fatty liver disease. The author reviewed and analyzed a case with complete clinical data treated in our hospital using traditional Chinese medicine alone and discussed the diagnosis and treatment process. This report aimed to provide a reference for clinical practice.

Globally Severe acute malnutrition(SAM) affects more than 29 million children under the age of five. Demographic and Health Survey and Multiple Indicators in Chad (EDS-MICS) of 2014-2015 survey found an acute malnutrition level of 13% out of which 9% was moderate and 4% was severe. The Causes of SAMS are multifactorial, relating to multiple domains such as society, culture, environment, education, livelihoods, agriculture, water, hygiene, etc. Despite this established evidence, the evidence of parental knowledge is unknown.

The objective of our study was to determine the explanatory factors of SAM and its level of knowledge, understanding by the parents.

A prospective descriptive study was conducted in 238 children aged 6-59 months admitted to therapeutic nutritional unit Alerte Santé of Ndjamena from November 15 to December 30, 2017.

During the study, the male sex (58.8%), the age group of 12-17 months (26.9%) and 6-8 months (24.4%) were the most represented and are the majorities in the urban area (72.3%). We were able to identify the various explanatory factors among which the level of education of mothers (62.2%), exclusive breastfeeding (2.3%), the food taboo (81%) are not insignificant. Malnutrition would be decompensated by the breakdown of food access (59%) and digestive diseases (74.8%) and respiratory diseases (73.5%). We found that parents have poor knowledge of malnutrition (87%).

A good understanding of these main factors of malnutrition by parents might help to effectively combat severe acute malnutrition.

Nonalcoholic fatty pancreatic disease (NAFPD) has an incidence of 11.05% −69.7%. Owing to the lack of standardized screening tools, the prevalence of NAFPD widely varies among studies depending on the ethnic groups analyzed and the different diagnostic methods adopted. Obesity is a chronic disease attributable to multiple psychosocial factors, and its prevalence has reached epidemic proportions worldwide, showing doubling in the last 3 decades. Obesity is closely associated with conditions such as hyperlipidemia, type 2 diabetes mellitus (T2DM), cardiovascular disease, metabolic syndrome, and cancer. Diet and exercise are the central components of NAFPD prevention and treatment, whereas the progress in pharmacologic treatment has been lagging. Studies have demonstrated that glucagon-like peptide-1 (GLP-1) can lower blood glucose, and also has effects of reducing body weight and the risk of cardiovascular disease. Thus, the role of GLP-1 in T2DM and NAFPD warrants further investigations.

Functional dyspepsia is a common health problem found in society. Few of multifactorial aspects which become the underlying cause of functional dyspepsia are anxiety and psychosocial problem. Esophagogastroduodenoscopy (EGD) examination can display exact information to patient with functional dyspepsia and expected to increase patient's quality of life. It is still necessary to evaluate the advantages of EGD examination in improving patient's quality of life.A Randomized double blind controlled trial was conducted to compare between group of patients who have been given an empiric treatment(Proton pump inhibitor and prokinetic agents) and other who have been given a placebo for 2 weeks after underwent EGD examination in patients with functional dyspepsia. The primary outcome of this study is the decrease of NDI-SF score on both of groups at the end of study.A total of 42 patients (22 in EGD+placebo group [Group I] and 20 in EGD + treatment group[Group II]) were enrolled. NDI-SF score decreased significantly in both groups, Group I (26.23±8.43 vs 19.59±7.62, P=0.001) and Group II (27.32±7.57 vs 19.21±5.68, P=0.002), 15 days after underwent EGD examination. NDI-SF score improvement between two groups 15 days after EGD was not significantly different (P=0.814). This study showed improvement in quality of life of patients whom diagnosed with functional dyspepsia after EGD examination in both groups. This improvement was not significantly different between two groups and showed the placebo effect of EGD on functional dyspepsia patient.

To investigate the mechanism of the active ingredients of Smilax china L. in the treatment of hepatic fibrosis (HF).

The targets of the active ingredients of Smilax china L. were predicted using the TCMSP database, PubChem database, Babel software, Swiss Target Prediction platform, SEA platform, and UniProt database. The targets for HF were obtained using the DisGeNET database. Venn diagram platforms were used to intersect the active ingredients of Smilax china L. and HF targets. The key targets were selected using the STRING database to construct a protein-protein interaction network model. The key compounds were selected using the Cytoscape software to construct an active Smilax china L. ingredient-action target network. The intersection target was used for GO enrichment analysis and KEGG metabolic pathway analysis by ClueGO. The DockThor program was used to connect the important active ingredients and compounds of Smilax china L. with the corresponding intersection targets by calculating the binding energy and using the PyMOL software to create visual images.

A total of 9 active ingredients, 209 targets, 56 targets, and 15 key targets related to HF were identified from Smilax china L. The biological processes associated with Smilax china L. for preventing HF mainly included collagen metabolism, positive regulation of vascular endothelial cell migration, muscle cell proliferation, and smooth muscle cell proliferation. The pathways mainly included the IL-17 signaling pathway, estrogen signaling pathway, prolactin signaling pathway, and pancreatic cancer pathway.

The mechanism of Smilax china L. in the treatment of HF was preliminarily explored. Smilax china L. has multi-component and multi-target characteristics, through which it can be used to treat HF.

Change of gut microbiota composition is associated with the outcome of hepatitis B virus (HBV) infection, yet the related mechanisms are not fully characterized. The objective of this study was to investigate the immune mechanism associated with HBV persistence induced by gut microbiota dysbiosis.

C57BL/6 mice were sterilized for gut-microbiota by using an antibiotic (ABX) mixture protocol, and were monitored for their serum endotoxin (lipopolysaccharide [LPS]) levels. An HBV-replicating mouse model was established by performing HBV-expressing plasmid pAAV/HBV1.2 hydrodynamic injection (HDI) with or without LPS, and was monitored for serum hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and cytokine levels. Kupffer cells (KCs) were purified from antibiotic-treated mice and HBV-replicating mice and analyzed for IL-10 production and T cell suppression ability.

ABX treatment resulted in increased serum LPS levels in mice. The KCs separated from both ABX-treated and LPS-treated HBV-replicating mice showed significantly increased IL-10 production and enhanced ability to suppress IFN-γ production of TCR-activated T cells than the KCs separated from their counterpart controls. HDI of pAAV/HBV1.2 in combination with LPS in mice led to a delayed HBV clearance and early elevation of serum IL-10 levels compared to pAAV/HBV1.2 HDI alone. Moreover, IL-10 function blockade or KC depletion led to accelerated HBV clearance in LPS-treated HBV-replicating mice.

Our results suggest that dysbiosis of the gut microbiota in mice leads to endotoxemia, which induces KC IL-10 production and strengthens KC-mediated T cell suppression, and thus facilitates HBV persistence.

Yes-associated protein-1 (YAP1) is a potent transcriptional co-activator and functions as an important downstream effector of the Hippo signaling pathway, which is key to regulating cell proliferation, apoptosis, and organ growth. YAP1 has been implicated as an oncogene for various human cancers including gastrointestinal cancers and hepatocellular carcinoma (HCC). YAP1 promotes tumorigenesis and cancer progression by multiple mechanisms, such as by promoting malignant phenotypes, expanding cancer stem cells, and inducing epithelial-mesenchymal transition. YAP1 overexpression or its activated forms are associated with advanced pathological grades and poor prognosis of cancer, and therefore targeting YAP1 may open a fertile avenue for cancer therapy. In this review, we summarize the recent evidence regarding the role of YAP1 in the carcinogenesis of gastrointestinal cancers and HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.

Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma. Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.

Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19 (0-50 ng/mL) for 6 weeks, followed by 6 weeks with medium alone. Cell proliferation, invasion, stem cell surface markers, oncofetoprotein expression, state of differentiation, epithelial-mesenchymal transition (EMT) and interleukin (IL)-6 expression were documented at various time intervals throughout the 12-week period.

FGF19 exposure was associated with significant increases in cell proliferation, de-differentiation, EMT and IL-6 expression. However, each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period. The remaining cell properties remained unaltered.

Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.

Liver penetration by a confined perforation of peptic ulcer is a rare but severe event. Its clinical and pathological features are unclear.

In total, 41 qualified English publications were identified using the PubMed database and one in-house case.

Among the 42 patients, 20 patients had liver involvement by a perforated duodenal ulcer and 22 by a gastric ulcer. Among the 23 cases of known ulcer histology, 2 ulcers were malignant and were adenocarcinomas in the gastric remnant and the remaining 21 ulcers were confirmed as histologically benign (for frequency of malignancy in duodenal versus gastric ulcers, p = 0.48). The presence of hepatocytes was the clue of diagnosis for 19 cases. The median ages of the patients were 64.5 years (95% Confidence Intervals [CI] 53.40–71.90) for duodenal ulcer and 65.5 years (95% CI: 59.23–70.95) for gastric ulcer, respectively. The male to female ratio was 1.5:1 for duodenal ulcers and 2:1 for gastric ulcers. Patients with liver involvement of a perforated gastric ulcer were more likely to have a larger ulcer (median largest dimension, 4.75 cm versus 2.5 cm, p = 0.014). Female patients with liver involvement of a gastric ulcer were older than male patients (median age 72 versus 60 years, p = 0.045). There were no differences in gender, region (Asia, Europe, America versus others), use of non-steroidal anti-inflammatory drugs (n = 15), H. Pylori positivity (n = 10), possible history of peptic ulcer disease (n = 19) or mortality (n = 32) between duodenal and gastric ulcers.

Careful histologic examination, clinicopathological correlation, and immunohistochemistry are critical to establish the diagnosis and avoid misdiagnosing liver involvement as malignancy.

The coronavirus disease 2019 (COVID-19) is associated with high morbidity and mortality, prompting overwhelmed hospital systems to reallocate resources to those stricken with the disease. In response, many liver transplantation programs unexpectedly came to an abrupt halt, significantly affecting the lives of living donors and recipients around the world. As the risk-benefit scale of liver transplantation has changed in the era of COVID-19, it is prudent to understand the impact of COVID-19 on those with underlying liver disease and those in need of a liver transplant. In this review, we discuss recommendations put forth by hepatology and transplant societies, summarize results from emerging studies, and propose strategies to appropriately risk stratify patients prior to transplantation.

We present a unique case of biopsy-proven syphilitic hepatitis which presented as severe acute liver injury with significant elevation in aminotransferases and bilirubin, and improved with antibiotic therapy. However, the patient returned weeks after initial presentation with new-onset acute liver injury and had developed hypergammaglobulinemia, positive autoantibody titers, and repeat liver biopsy demonstrating interface hepatitis, supporting a diagnosis of autoimmune hepatitis. He had an otherwise unrevealing etiologic workup, and responded to glucocorticoid therapy. We believe that syphilitic hepatitis and its treatment subsequently triggered an immunogenic response, leading to autoimmune hepatitis. Autoimmune hepatitis is a chronic liver disease thought to manifest as a result of predisposing genetic factors in combination with environmental insults, especially hepatotropic pathogens. Syphilis is a sexually transmitted disease caused by Treponema pallidum that has been associated with autoimmunity and the development of autoantibodies. We propose that in the setting of syphilitic hepatitis, a molecular mimicry event resulting from structural similarities between T. pallidum and liver antigens, as well as impaired regulatory T-cell function, led to the breakdown of immune tolerance and the onset of autoimmune hepatitis. To support this hypothesis, further molecular analyses and case series are necessary to determine if syphilitic hepatitis and its treatment are risk factors for the onset of autoimmune hepatitis. Autoimmune hepatitis should be considered early as the cause of acute liver injury in susceptible patients with risk factors for the disease, as prompt recognition and appropriate treatment may prevent progression of liver injury and result in improved outcomes.

Despite the advances in therapy, hepatitis B virus (HBV) and hepatitis C virus (HCV) still represent a significant global health burden, both as major causes of cirrhosis, hepatocellular carcinoma, and death worldwide. HBV is capable of incorporating its covalently closed circular DNA into the host cell’s hepatocyte genome, making it rather difficult to eradicate its chronic stage. Successful viral clearance depends on the complex interactions between the virus and host’s innate and adaptive immune response. One encouraging fact on hepatitis B is the development and effective distribution of the HBV vaccine. This has significantly reduced the spread of this virus. HCV is a RNA virus with high mutagenic capacity, thus enabling it to evade the immune system and have a high rate of chronic progression. High levels of HCV heterogeneity and its mutagenic capacity have made it difficult to create an effective vaccine. The recent advent of direct acting antivirals has ushered in a new era in hepatitis C therapy. Sustained virologic response is achieved with DAAs in 85–99% of cases. However, this still leads to a large population of treatment failures, so further advances in therapy are still needed. This article reviews the immunopathogenesis of HBV and HCV, their properties contributing to host immune system avoidance, chronic disease progression, vaccine efficacy and limitations, as well as treatment options and common pitfalls of said therapy.

Houttuynia cordata Thunb, which is a traditional Chinese herbal medicine, is commonly used as an anti-inflammatory, antiviral, and antibacterial agent in China. Emerging evidence shows that extracts of H. cordata Thunb have anticancer activity in human colorectal, leukemic, lung, and liver cancer cells; however, the specific active ingredients or compounds that responsible for these anticancer activities and their mechanism of action remain unknown. Sodium new houttuyfonate (SNH) is an additional product of the active ingredient houttuynin from H. cordata Thunb, which possesses anticancer activity; however, the molecular mechanisms that underlie its action have not been clarified. This study aims to explore the antitumor effect and related molecular mechanism of SNH on human non-small cell lung cancer (NSCLC).

The cytotoxicity of SNH against human lung cancer cells H1299 was investigated using WST-1 and apoptotic assays, and its antitumor molecular mechanism was explored using quantitative proteomics combined with various cellular and biochemical assays.

The results showed that SNH reduced the viability and enhanced the apoptosis of H1299 cells in a dose-dependent manner. Quantitative proteomics and ingenuity pathway analysis revealed that SNH downregulated the expression of cell cycle-related proteins, which included cyclin-dependent kinase 1 (CDK1), protein tyrosine phosphatase type IVA 2 (PTP4A2), and cyclin-dependent kinase 6 (CDK6), and upregulated the expression of Nrf2 (nuclear factor erythroid 2-related factor 2)-mediated oxidative stress response-related proteins in H1299 cells.

SNH-induced G0/G1 arrest and apoptosis in H1299 cells by the inhibition of cell cycle-related proteins that included CDK1, PTP4A2, CDK6, and activated the expression of Nrf2-mediated oxidative stress response-related proteins. These findings might provide new molecular mechanisms that underlie the antitumor activity of SNH against NSCLC and could implicate SNH as a novel therapeutic drug for NSCLC in the future.

Correct identification of small hepatocellular carcinomas (HCCs) and benign nodules in cirrhosis remains challenging, quantitative apparent diffusion coefficients (ADCs) have shown potential value in characterization of benign and malignant liver lesions. We aimed to explore the added value of ADCs in the identification of small (≤3 cm) HCCs and benign nodules categorized as Liver Imaging Reporting and Data System (LI-RADS) 3 (LR-3) and 4 (LR-4) in cirrhosis.

Ninety-seven cirrhosis patients with 109 small nodules (70 HCCs, 39 benign nodules) of LR-3 and 4 LR-4 based on major and ancillary magnetic resonance imaging features were included. Multiparametric quantitative ADCs of the lesions, including the mean ADC (ADCmean), minimum ADC (ADCmin), maximal ADC (ADCmax), ADC standard deviation (ADCstd), and mean ADC value ratio of lesion-to-liver parenchyma (ADCratio) were calculated. Regarding the joint diagnosis, a nomogram model was plotted using multivariate logistic regression analysis. The performance was assessed using the area under the receiver operating characteristic curve (AUC).

The ADCmean, ADCmin, ADCratio, and ADCstd were significantly associated with the identification of small HCC and benign nodules (p<0.001). For the joint diagnosis, the LI-RADS category (odds ratio [OR]=12.50), ADCmin (OR=0.14), and ADCratio (OR=0.12) were identified as independent factors for distinguishing HCCs from benign nodules. The joint nomogram model showed good calibration and discrimination, with a C-index of 0.947. Compared with the LI-RADS category alone, this nomogram model demonstrated a significant improvement in diagnostic performance, with AUC increasing from 0.820 to 0.967 (p=0.001).

The addition of quantitative ADCs could improve the identification of small HCC and benign nodules categorized as LR-3 and 4 LR-4 in patients with cirrhosis.

For high morbidity and mortality, hepatocellular carcinoma (HCC) becomes a major health issue worldwide. Nowadays, numerous non-coding RNAs (ncRNAs) are known to regulate the occurrence and pathogenesis of tumors. Some ncRNAs have also been developed as tumor biomarkers and therapeutic targets. However, the potential function of the small Cajal body-specific RNA (scaRNA) SCARNA16, a newly identified ncRNA, remains to be explored in HCC.

In both HCC cell lines and specimens from 120 enrolled patients, the expression values of SCARNA16 were detected. We divided patients into SCARNA16 high and low expression subgroups, and then analyzed the difference of various clinical characteristics and prognosis data between subgroups.

Compared to paired controls, SCARNA16 was significantly down-regulated in HCC cell lines and clinical specimens (p<0.01). Besides, HCC patients with lower SCARNA16 expression commonly presented with larger and more tumor lesions, more vessel carcinoma emboli, more capsular invasion and higher TNM stages (p<0.05). Moreover, SCARNA16 expression was negatively correlated with postoperative prognosis of HCC patients in 5-year follow-up, including tumor-free survival (TFS) (median time of low vs. high subgroups: 14 vs. 48 months, p=0.006) and overall survival (OS) (median time of low vs. high subgroups: 39 vs. 52 months, p=0.001). Besides, SCARNA16 acted as an independent prognostic biomarker in TFS (hazard ratio [HR]: 0.578, 95% CI: 0.345–0.969, p=0.038) and OS (HR: 0.366, 95% CI: 0.178–0.752, p=0.006).

Low expression patterns of SCARNA16 remarkably associated with severe clinical status and poor survival of patients, suggesting that SCARNA16 possesses potency as a novel biomarker for HCC.