Biliary tract cancers (BTCs) comprise a group of heterogeneous poor prognosis cancers with increasing incidence recent years. The combination chemotherapy with cisplatin and gemcitabine is the first-line therapy for advanced BTC. There remains no accepted standard treatment in the second-line setting. Nowadays, more and more novel treatment strategies have entered development, with some encouraging results being seen. Here, we review the current treatment status and clinical characteristics of BTC, the role of immunotherapy in BTC as well as the design of clinical trials for oncology drugs for BTC which aim to focus on the future profiles of clinical care and resolution of BTC.

Hepatitis C virus (HCV) genotype (GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes. Hence, early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients. Nevertheless, compared with other genotypes, GT3 is difficult-to-treat with direct-acting antivirals, especially in the presence of cirrhosis. Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world (North America, Europe, and Oceania). In China, GT3 infection comprises 8.7–11.7% of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries. Unlike the Western countries, where GT3a is the predominant subtype, GT3a and 3b each affect roughly half of Chinese GT3-infected patients, with 94–96% of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions. Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure, making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled. This review includes discussions on the epidemiology of HCV GT3 in China, recommendations from guidelines, and clinical data from both Western countries and China. The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.

Renal transplant patients often require periodic imaging to evaluate the transplant vessel anastomosis for potential vascular complications. The use of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques is encouraged in these patients because they are at increased risk of nephrogenic systemic fibrosis (NSF) due to their renal insufficiency. This study aimed to evaluate the performance of two NCE-MRA techniques (three-dimensional [3D] balanced steady-state free precession [bSSFP] with inversion recovery and quiescent-interval slice-selective [QISS]) for the evaluation of renal allograft vasculature in patients with clinical suspicion, or Doppler ultrasound, or both of arterial anastomotic stenosis.

A total of 43 patients were included in this retrospective study. Two radiologists independently scored the images from 3D bSSFP and QISS MRA sequences for image quality and confidence in anastomosis interpretation, and the degree of stenosis at the arterial anastomosis. Correlations with digital subtraction angiography (DSA) were carried out when available. In addition, inter-rater agreement was calculated.

In total, 43 patients underwent QISS and 3D bSSFP MRA. For QISS, all cases were adequate for evaluation. For 3D SSFP, 86% of cases were adequate for evaluation. There was a good-to-excellent inter-rater agreement for all scores and an excellent correlation between NCE-MRA and DSA results when available (12 patients).

QISS and 3D SSFP showed good inter-rater agreement for image quality and stenosis grade, with more cases being of adequate image quality that used QISS. Further study is required; however, NCE-MRA shows potential as a risk-free alternative to CTA and contrast-enhanced MRA (CE-MRA) for the evaluation of arterial anastomoses in renal transplant patients.

It is critical but challenging to predict the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This study systematically summarized and evaluated the quality and performance of available clinical prediction models (CPMs).

A keyword search of articles on HBV-ACLF CPMs published in PubMed from January 1995 to April 2020 was performed. Both the quality and performance of the CPMs were assessed.

Fifty-two CPMs were identified, of which 31 were HBV-ACLF specific. The modeling data were mostly derived from retrospective (83.87%) and single-center (96.77%) cohorts, with sample sizes ranging from 46 to 1,202. Three-month mortality was the most common endpoint. The Asian Pacific Association for the Study of the Liver consensus (51.92%) and Chinese Medical Association liver failure guidelines (40.38%) were commonly used for HBV-ACLF diagnosis. Serum bilirubin (67.74%), the international normalized ratio (54.84%), and hepatic encephalopathy (51.61%) were the most frequent variables used in models. Model discrimination was commonly evaluated (88.46%), but model calibration was seldom performed. The model for end-stage liver disease score was the most widely used (84.62%); however, varying performance was reported among the studies.

Substantial limitations lie in the quality of HBV-ACLF-specific CPMs. Disease severity of study populations may impact model performance. The clinical utility of CPMs in predicting short-term prognosis of HBV-ACLF remains to be undefined.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that microRNAs are widely involved in tumor migration and metastasis by regulation of target genes. miR-7-5p has been confirmed to inhibit tumor metastasis and to be related to prognosis for several malignant tumors. Our study investigated the underlying functions of miR-7-5p in ICC.

The expression of miR-7-5p in ICC tissues but also in ICC cell lines was analyzed by real-time PCR. By analyzing the relationship between the clinicopathological parameters of 60 ICC patients and the expression level of miR-7-5p, the effect of miR-7-5p on the prognosis was clarified. After transfected with miR-7-5p mimics or miR-7-5p inhibitor, cell counting kit-8 assay was applied to evaluate the cells proliferation, flow cytometry was applied to analyze the cells apoptosis, wound healing assay and transwell chamber assay were applied to analyze the cell invasion and migration. A luciferase reporter assay was identified the relationship of miR-7-5p and myeloid differentiation factor 88 (MyD88). Western blotting was used to analyze the proteins expression. And immunochemistry was performed to determine the expression of MYD88 in ICC tissues.

Our data showed the expression of miR-7-5p was down-regulated not only in ICC tissues but also in ICC cell lines compared with normal controls. Low expression of miR-7-5p was notably associated with poor prognosis in ICC patients. miR-7-5p negatively regulated cell proliferation, migration, invasion and apoptosis in ICC cells. We further verified that MyD88 was a novel target of miR-7-5p and was significantly overexpressed in ICC tissues. Overexpression of MyD88 counteracted the effects of miR-7-5p in ICC cells.

The present findings suggest that miR-7-5p plays a pivotal role in ICC invasion by regulating MyD88. Ampliative insight into the key factors of ICC invasion may result in the development of new treatment options for ICC.

Metabolic-associated fatty liver disease (MAFLD) is driven by high caloric intake and sedentary lifestyle. Migration towards high income countries may induce these driving factors; yet, the influence of such on the prevalence of MAFLD is clearly understudied. Here, we investigated the Fatty Liver Index (FLI), a proxy of steatosis in MAFLD, after migration of Ghanaian subjects.

Cross-sectional data of 5282 rural, urban and migrant participants from the Research on Obesity and Diabetes among African Migrants (also known as RODAM) study were analyzed with logistic regression for geographical differences in FLI and associations with type 2 diabetes mellitus (T2DM), waist-to-hip ratio, and 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD).

Both FLI and the proportion with an FLI indicative of MAFLD steatosis (FLI ≥60) were higher in migrants compared with non-migrants. Prevalence of elevated FLI (FLI ≥60) in non-migrant males was 4.2% compared to 28.9% in migrants. For females, a similar gradient was observed, from 13.6% to 36.6% respectively. Compared to rural residents, the odds for a FLI ≥60 were higher in migrants living in urban Europe (odds ratio [OR] 9.02, 95% confidence interval [CI]: 5.02–16.20 for men, and 4.00, 95% CI: 3.00–5.34 for women). Compared to controls, the ORs for FLI ≥60 were 2.43 (95% CI: 1.73–3.41) for male T2DM cases and 2.02 (95% CI: 1.52–2.69) for female T2DM cases. One-unit higher FLI was associated with an elevated (≥7.5%) 10-year ASCVD risk (OR: 1.051, 95% CI: 1.041–1.062 for men, and 1.020, 95% CI: 1.015–1.026 for women).

FLI as a proxy for MAFLD increased stepwise in Ghanaians from rural areas, through urban areas, to Europe. Our results clearly warrant awareness for MAFLD in migrant population as well as confirmation with imaging modalities.

Currently, insufficient clinical data are available to address whether low-level viremia (LLV) observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs. This study compared the clinical outcomes of patients with a maintained virological response (MVR) and patients who experienced LLV and their treatment strategies.

A retrospective cohort of 674 patients with chronic hepatitis B virus (HBV) infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period. End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma (HCC).

During a median 42-month follow-up, end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR (7.73% and 15.85% vs. 0.77% and 5.52% at 5 and 10 years, respectively; p=0.000). The trend was consistent after propensity score matching. In the high-risk group of four HCC risk models, LLV patients had a higher risk of HCC development (p<0.05). By Cox proportional hazard model analysis, LLV was an independent risk factor for end-stage liver disease and HCC (hazard ratio [HR]=6.280, confidence interval [CI]=2.081–18.951, p=0.001; HR=5.108, CI=1.392–18.737, respectively; p=0.014). Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred (p<0.05).

LLV is an independent risk factor for end-stage liver disease and HCC, and treatment adjustments can be considered.

Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic causing death worldwide, particularly in individuals with comorbidities or in the elderly population. The increased pro-inflammatory cytokines in patients with severe COVID-19 can be considered macrophage activation syndrome or a cytokine storm. It has been reported that an autocrine loop of interleukin (IL) 1 beta (IL-1β) over-secretion leads to a cytokine storm of IL-6, IL-18, ferritin, interferon-gamma, etc. from macrophages. Several features of COVID-19, such as the cytokine profile including pro-inflammatory cytokine levels, subsets of immune cells, serological markers, and clinical symptoms resemble a cytokine storm commonly triggered by viral infections. Although the pathophysiology and management of severe COVID-19 remains uncertain, the use of an easily obtained autologous anti-inflammatory cocktail, termed autologous conditioned serum (ACS), can be hypothesized. ACS consists of a variety of anti-inflammatory cytokines, including mainly IL-1 receptor antagonist (IL-1Ra; as much as 140-fold greater than plasma), and several growth factors. Post-mortem findings of COVID-19 patients reveal that the main pathological events are localized to the alveoli. Therefore, administering ACS via the same pathway as the viral trigger may have a positive impact on treatment. ACS should be discussed for the management of COVID-19 to target and lessen the overactive immune response while still allowing time for the host immune system to clear the virus. To balance the cytokine storm, it could be suggested to administer ACS by the same pathway as the viral trigger, using a nebulizer to directly reach the most intensely affected location: the alveoli.

Timely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients.

The nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively.

Multivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602–0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set.

The novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients.

Mucinous cystic tumor of the gallbladder is an extremely rare benign tumor, with potential for malignant degeneration. Mucinous cystic tumors of the cystic duct are divided into mucinous cystadenoma and mucinous cystadenocarcinoma. Currently, cystadenoma is generally considered to be a precancerous lesion of cystadenocarcinoma. At present, there are few cases reported worldwide, and there are no relevant guidelines for diagnosis and treatment of this disease. This article presents the collected clinical data of a patient with mucinous cystic tumor of the gallbladder who was admitted to the First Affiliated Hospital of Hunan Normal University, with the characteristics of the disease summarized in combination with a focused literature review.

Primary biliary cholangitis (PBC) is a chronic liver disease that negatively affects the health-related quality of life (HRQoL) of patients. Furthermore, the HRQoL of Chinese patients has been neglected for a long time. The present study aimed to assess the HRQoL of Chinese patients with PBC and explore the clinical variables correlating to the improvement of itch and fatigue.

This was an observational, cross-sectional study. The PBC-40 and itch numerical rating scales were used to evaluate the symptoms and HRQoL of patients.

A total of 383 patients were recruited, and 86.4% were female, with a median age of 55 years (range: 49–63 years). We found that females had significantly higher scores than males in symptoms (p=0.033) and cognitive domains (p=0.021), and the fatigue domain was higher in elderly patients (p=0.007). Meanwhile, patients whose body mass index was <18.5 had the highest scores in the symptoms (p=0.009), fatigue (p=0.010), and cognitive (p=0.019) domains. Age at participation (odds ratio [OR]=1.068, p=0.015) and albumin level at 12 months after ursodeoxycholic acid treatment (OR=208.807, p=0.025) were independent factors that affected the improvement of the itch and fatigue domains, respectively.

The HRQoL of Chinese patients with PBC was significantly impaired depending on sex, age, and body mass index. Age and albumin level were significantly associated with the improvement of itch and fatigue, respectively. Therefore, treatment and support aimed at these two factors can be provided to improve the HRQoL of patients.

Chronic hepatitis B is the main cause of liver cancer. However, the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase (ALT). People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment. However, the truth is not as optimistic as we thought. We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients.

Medline, Embase, and Cochrane Library were searched up to January 10th 2020, to identify studies of these patients with liver biopsy. The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis. Potential heterogeneity was explored by subgroup analysis and meta-regression. Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis. The secondary outcome was to find the risk factors of significant histological changes.

Nineteen eligible studies, with 2,771 participants, were included. The pooled proportion of significant inflammation or fibrosis was 35% [95% confidence interval (CI): 27 to 43] and 30% (95% CI: 25 to 36), respectively. The pooled proportion of cirrhosis was 3% [95% CI: 1 to 5, (12 studies; 1,755 participants)]. In subgroup analysis, old age [vs. young (<40 years-old), 44% vs. 26%, p=0.012] was significantly associated with higher fibrosis stage as well as cirrhosis [vs. young (<40 years-old), 4.8% vs. 1.8%, p<0.001].

About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes, and some even have cirrhosis.

Coronavirus disease 2019 (COVID-19) is a global threat, affecting more than 100 million people and causing over 2 million deaths. Liver laboratory test abnormalities are an extrapulmonary manifestation of COVID-19, yet characterization of hepatic injury is incomplete. Our objective was to further characterize and identify causes of liver injury in patients with COVID-19.

We conducted a retrospective cohort study of 551 patients hospitalized with COVID-19 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center between March 1, 2020 and May 31, 2020. We analyzed patient demographics, liver laboratory test results, vital signs, other relevant test results, and clinical outcomes (mortality and intensive care unit admission).

Abnormal liver laboratory tests were common on hospital admission for COVID-19 and the incidence increased during hospitalization. Of those with elevated serum alanine aminotransferase and/or alkaline phosphatase activities on admission, 58.2% had a cholestatic injury pattern, 35.2% mixed, and 6.6% hepatocellular. Comorbid liver disease was not associated with outcome; however, abnormal direct bilirubin or albumin on admission were associated with intensive care unit stay and mortality. On average, patients who died had greater magnitudes of abnormalities in all liver laboratory tests than those who survived. Ischemic hepatitis was a mechanism of severe hepatocellular injury in some patients.

Liver laboratory test abnormalities are common in hospitalized patients with COVID-19, and some are associated with increased odds of intensive care unit stay or death. Severe hepatocellular injury is likely attributable to secondary effects such as systemic inflammatory response syndrome, sepsis, and ischemic hepatitis.

Screening for hepatopulmonary syndrome in cirrhotic patients is limited due to the need to perform contrast enhanced echocardiography (CEE) and arterial blood gas (ABG) analysis. We aimed to develop a simple and quick method to screen for the presence of intrapulmonary vascular dilation (IPVD) using noninvasive and easily available variables with machine learning (ML) algorithms.

Cirrhotic patients were enrolled from our hospital. All eligible patients underwent CEE, ABG analysis and physical examination. We developed a two-step model based on three ML algorithms, namely, adaptive boosting (termed AdaBoost), gradient boosting decision tree (termed GBDT) and eXtreme gradient boosting (termed Xgboost). Noninvasive variables were input in the first step (the NI model), and for the second step (the NIBG model), a combination of noninvasive variables and ABG results were used. Model performance was determined by the area under the curve of receiver operating characteristics (AUCROCs), precision, recall, F1-score and accuracy.

A total of 193 cirrhotic patients were ultimately analyzed. The AUCROCs of the NI and NIBG models were 0.850 (0.738–0.962) and 0.867 (0.760–0.973), respectively, and both had an accuracy of 87.2%. For both negative and positive cases, the recall values of the NI and NIBG models were both 0.867 (0.760–0.973) and 0.875 (0.771–0.979), respectively, and the precisions were 0.813 (0.690–0.935) and 0.913 (0.825–1.000), respectively.

We developed a two-step model based on ML using noninvasive variables and ABG results to screen for the presence of IPVD in cirrhotic patients. This model may partly solve the problem of limited access to CEE and ABG by a large numbers of cirrhotic patients.

In recent years, gene editing technologies have made significant progress in understanding gene function and regulation. The Clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) system has emerged as a versatile tool for gene editing and genome engineering. In the last few years, CRISPR-Cas9 technology has been widely applied to cancer research, mainly to understand the mechanisms of oncogenesis, drug-target identification, and the development of various cell-based therapies. When combined with genome sequence information, this technology has also shown promise to cure heritable genetic disorders. This review summarizes some of the recent developments and preclinical applications of CRISPR-Cas9 technology in cancer research and therapy. We will discuss how CRISPR based approaches have been used as a tool to identify cancer-specific vulnerabilities and potential applications in cancer therapy.

Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).

Chinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.

Of the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log10 IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (−0.4 vs. −3.2 mL/min; p=0.014) and less percentage change in bone mineral density vs. TDF at hip (−0.95% vs. −1.93%) and spine (+0.35% vs. −1.40%).

In chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.

The novel coronavirus-related coronavirus disease 2019 (COVID-19) pandemic has been relentless in disrupting and overwhelming healthcare the world over. Clinical outcomes of COVID-19 in patients with chronic comorbidities, especially in those with metabolic syndrome, are well documented. Chronic liver disease and cirrhosis patients are a special sub-group, among whom the management of COVID-19 is challenging. Understanding the pathophysiology of COVID-19 in patients with cirrhosis and portal hypertension improves our identification of at-risk patients for disease progression that will further help compartmentalize generalized and specialized treatment options in this special patient group. In this exhaustive review, we critically review the impact of COVID-19 on the liver and in chronic liver disease and cirrhosis patients. We further discuss common features associated with the pathophysiology of COVID-19 and cirrhosis, based on the renin-angiotensin system and deliberate current literature on guidelines for the treatment of COVID-19 and extrapolate the same to the cirrhosis population to provide a concise and stepwise, evidence-based management for cirrhosis patients with severe and critical COVID-19. There are no specific management guidelines for cirrhosis patients with COVID-19 and current recommendations for treatment are as per guidelines for general population. Nevertheless, specific issues like avoiding corticosteroids in decompensated patients with variceal bleeding, suspected sepsis, high grade hepatic encephalopathy and acute kidney injury, use of early mechanical ventilation strategies in those with severe ascites and hepatopulmonary syndrome, avoidance of remdesivir in advanced liver disease, and application of liver-specific severity scores for prognostication and identification of futility need to be highlighted.

There are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus transhepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). Therefore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC.

A total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups.

Thirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3%, 77.8% and 66.7% in the HR group and 80.6%, 72.2% and 52.8% in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6%, 57.3% and 42.3% in the HR group and 66.1%, 45.8% and 39.3% in the CK-SBRT+TACE group, respectively (OS: p=0.143; PFS: p=0.445). Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS.

CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.

Despite the availability of several therapeutic strategies and many drugs, the ability to cure most cancers remains a challenge. Natural products have been used for the treatment of numerous diseases, including cancer. The present review delineates various preclinical studies performed in vitro and in vivo that explore the anticancer potential of berberine, an isoquinoline alkaloid found in numerous plants as a secondary metabolite. Berberine can kill various types of human cancer cells in an optimal concentration- and duration-dependent manner and inhibit the growth of various types of cancers in animal models by elevating oxidative stress. In addition, berberine suppresses cell migration, invasion and epithelial-to-mesenchymal transition in different types of cancer cells. Mechanistically, berberine can induce cancer cell DNA fragmentation/apoptosis through extrinsic and intrinsic pathways, autophagy and necrosis. The cytotoxic effects of berberine in different types of cancer cells are mediated by its ability to induce oxidative stress and cell cycle arrest, and inhibit cell migration, invasion and epithelial-to-mesenchymal transition as well as matrix metalloproteinases through the modulation of Wnt and β-catenin signaling. A single clinical study has shown some promise in gastric cancer patients. Though berberine is a relatively safe compound, it should not be prescribed to pregnant or lactating women to avoid adverse effects on developing fetuses and neonates.

With the rapid development of research on coronavirus disease 2019 (COVID-19), more and more attention has been drawn to its damage to extrapulmonary organs. There are increasing lines of evidence showing that liver injury is closely related to the severity of COVID-19, which may have an adverse impact on the progression and prognosis of the patients. What is more, severe acute respiratory syndrome coronavirus-2 infection, cytokine storm, ischemia/hypoxia reperfusion injury, aggravation of the primary liver disease and drug-induced liver injury may all contribute to the hepatic damage in COVID-19 patients; although, the drug-induced liver injury, especially idiosyncratic drug-induced liver injury, requires further causality confirmation by the updated Roussel Uclaf Causality Assessment Method published in 2016. Up to now, there is no specific regimen for COVID-19, and COVID-19-related liver injury is mainly controlled by symptomatic and supportive treatment. Here, we review the clinical features of abnormal liver enzymes in COVID-19 and pathogenesis of COVID-19-related liver injury based on the current evidence, which may provide help for clinicians and researchers in exploring the pathogenesis and developing treatment strategies.