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1.
J Am Coll Radiol ; 19(1 Pt B): 184-191, 2022 01.
Article in English | MEDLINE | ID: covidwho-1627037

ABSTRACT

PURPOSE: The aim of this study was to assess racial/ethnic and socioeconomic disparities in the difference between atherosclerotic vascular disease prevalence measured by a multitask convolutional neural network (CNN) deep learning model using frontal chest radiographs (CXRs) and the prevalence reflected by administrative hierarchical condition category codes in two cohorts of patients with coronavirus disease 2019 (COVID-19). METHODS: A CNN model, previously published, was trained to predict atherosclerotic disease from ambulatory frontal CXRs. The model was then validated on two cohorts of patients with COVID-19: 814 ambulatory patients from a suburban location (presenting from March 14, 2020, to October 24, 2020, the internal ambulatory cohort) and 485 hospitalized patients from an inner-city location (hospitalized from March 14, 2020, to August 12, 2020, the external hospitalized cohort). The CNN model predictions were validated against electronic health record administrative codes in both cohorts and assessed using the area under the receiver operating characteristic curve (AUC). The CXRs from the ambulatory cohort were also reviewed by two board-certified radiologists and compared with the CNN-predicted values for the same cohort to produce a receiver operating characteristic curve and the AUC. The atherosclerosis diagnosis discrepancy, Δvasc, referring to the difference between the predicted value and presence or absence of the vascular disease HCC categorical code, was calculated. Linear regression was performed to determine the association of Δvasc with the covariates of age, sex, race/ethnicity, language preference, and social deprivation index. Logistic regression was used to look for an association between the presence of any hierarchical condition category codes with Δvasc and other covariates. RESULTS: The CNN prediction for vascular disease from frontal CXRs in the ambulatory cohort had an AUC of 0.85 (95% confidence interval, 0.82-0.89) and in the hospitalized cohort had an AUC of 0.69 (95% confidence interval, 0.64-0.75) against the electronic health record data. In the ambulatory cohort, the consensus radiologists' reading had an AUC of 0.89 (95% confidence interval, 0.86-0.92) relative to the CNN. Multivariate linear regression of Δvasc in the ambulatory cohort demonstrated significant negative associations with non-English-language preference (ß = -0.083, P < .05) and Black or Hispanic race/ethnicity (ß = -0.048, P < .05) and positive associations with age (ß = 0.005, P < .001) and sex (ß = 0.044, P < .05). For the hospitalized cohort, age was also significant (ß = 0.003, P < .01), as was social deprivation index (ß = 0.002, P < .05). The Δvasc variable (odds ratio [OR], 0.34), Black or Hispanic race/ethnicity (OR, 1.58), non-English-language preference (OR, 1.74), and site (OR, 0.22) were independent predictors of having one or more hierarchical condition category codes (P < .01 for all) in the combined patient cohort. CONCLUSIONS: A CNN model was predictive of aortic atherosclerosis in two cohorts (one ambulatory and one hospitalized) with COVID-19. The discrepancy between the CNN model and the administrative code, Δvasc, was associated with language preference in the ambulatory cohort; in the hospitalized cohort, this discrepancy was associated with social deprivation index. The absence of administrative code(s) was associated with Δvasc in the combined cohorts, suggesting that Δvasc is an independent predictor of health disparities. This may suggest that biomarkers extracted from routine imaging studies and compared with electronic health record data could play a role in enhancing value-based health care for traditionally underserved or disadvantaged patients for whom barriers to care exist.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Deep Learning , Liver Neoplasms , Humans , Radiography , Retrospective Studies , SARS-CoV-2
2.
Front Public Health ; 9: 767617, 2021.
Article in English | MEDLINE | ID: covidwho-1595348

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has greatly disrupted the normal treatment of patients with liver cancer and increased their risk of death. The weight of therapeutic safety was significantly amplified for decision-making to minimize the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, the safety and effectiveness of carbon ion radiotherapy (CIRT) for unresectable liver cancer (ULC) were evaluated, and Chinese experiences were shared to solve the predicament of ULC treatment caused by SARS-CoV-2. Worldwide studies were collected to evaluate CIRT for ULC as the world has become a community due to the COVID-19 pandemic. We not only searched five international databases including the Cochrane Library, Web of Science, PubMed, Embase, and Scopus but also performed supplementary retrieval with other sources. Chinese experiences of fighting against COVID-19 were introduced based on the advancements of CIRT in China and a prospective clinical trial of CIRT for treating ULC. A total of 19 studies involving 813 patients with ULC were included in the systematic review. The qualitative synthetic evaluation showed that compared with transarterial chemoembolization (TACE), CIRT could achieve superior overall survival, local control, and relative hepatic protection. The systematic results indicated that non-invasive CIRT could significantly minimize harms to patients with ULC and concurrently obtain superior anti-cancer effectiveness. According to the Chinese experience, CIRT allows telemedicine within the hospital (TMIH) to keep a sufficient person-to-person physical distance in the whole process of treatment for ULC, which is significant for cutting off the transmission route of SARS-CoV-2. Additionally, CIRT could maximize the utilization rate of hospitalization and outpatient care (UHO). Collectively, CIRT for ULC patients not only allows TMIH and the maximized UHO but also has the compatible advantages of safety and effectiveness. Therefore, CIRT should be identified as the optimal strategy for treating appropriate ULC when we need to minimize the risk of SARS-CoV-2 infection and to improve the capacity of medical service in the context of the unprecedented COVID-19 crisis.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Heavy Ion Radiotherapy , Liver Neoplasms , Carcinoma, Hepatocellular/radiotherapy , Humans , Liver Neoplasms/radiotherapy , Pandemics , Prospective Studies , SARS-CoV-2
3.
PLoS One ; 16(12): e0258450, 2021.
Article in English | MEDLINE | ID: covidwho-1581814

ABSTRACT

BACKGROUND AND AIMS: Patients with liver cirrhosis (LC) are considered to be at increased risk for mortality when acquiring SARS-CoV-2 infection and subsequently developing Corona Virus Disease 2019 (COVID-19). During the COVID-19 pandemic, hospitals are regarded as sites with increased risk of infection. Therefore, patient contacts are often limited to urgent indications, which could negatively affect disease monitoring. However, data regarding actual infection rates in cirrhotic patients is limited. The aim of this prospective study was to assess the incidence of COVID-19 in patients with LC with/without hepatocellular carcinoma (HCC) with physical presentation at our University Medical Center. METHODS: Patients were enrolled between 1st April and 30th June 2020 at the University Medical Center Hamburg-Eppendorf, Germany. Symptoms of upper airway infection at baseline and presence of SARS-CoV-2 antibodies (IgG/IgM/IgA) were assessed at baseline and follow-up (FU) using an Electro-chemiluminescence immunoassay (Roche Elecsys). FU visits, including liver function test, clinical assessment and symptom questionnaire, were conducted after 6-8 weeks (FU-1) and 6 months (FU-2). Prior to inclusion of the first patient, obligatory face masks and personal distance were implemented as protective measures. RESULTS: A total of 150 patients were enrolled, 23% (n = 35) also had diagnosis of HCC (median age: 64 years, range: 19-86), 69% were male. Liver function according to Child-Pugh score (CPS) was: CPS A: 46% (n = 62); CPS B: 37% (n = 50); CPS C: 17% (n = 23). Clinical symptoms indicating upper airway infection were present in 53% (n = 77): shortness of breath (n = 40) and coughing (n = 28) were the most frequent. For the 150 patients enrolled, 284 outpatient visits were registered and 33 patients were admitted to the University Medical Center during the follow-up period. After a median of 52 days, n = 110 patients completed FU-1 and n = 72 completed FU-2 after a median of 6.1 months. Only in one patient, an 80-year-old man with stable liver function (CPS A) and advanced HCC, SARS-CoV-2 antibodies were detected at baseline and FU-1, while antibody testing was negative in the remaining patients at baseline, FU-1 and FU-2. CONCLUSION: The incidence of COVID-19 at our tertiary medical center during the pandemic was low in LC and HCC patients, when simple protective measures were implemented. Therefore, a routine care for patients with chronic liver diseases does not increase the risk of SARS-CoV-2 infection and should be maintained with protective measures.


Subject(s)
COVID-19/epidemiology , Carcinoma, Hepatocellular/virology , Liver Cirrhosis/virology , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/complications , Cohort Studies , Female , Germany/epidemiology , Humans , Incidence , Liver Cirrhosis/complications , Liver Neoplasms/complications , Liver Neoplasms/virology , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2/pathogenicity , Tertiary Care Centers/trends
4.
Clin Mol Hepatol ; 27(4): 564-574, 2021 10.
Article in English | MEDLINE | ID: covidwho-1551487

ABSTRACT

BACKGROUND/AIMS: In July 2017, the Emprint™ next-generation microwave ablation system using thermosphere technology (Covidien, Boulder, CO, USA) was approved for use in Japan. This system can produce a predictable spherical ablation zone at higher temperatures than radiofrequency ablation (RFA). The aim of the present study was to elucidate whether this new microwave thermosphere ablation (MTA) could safely improve outcome compared to RFA, which is the standard of care for small hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 513 patients with 630 HCCs (≤3 cm) who were performed by percutaneous RFA (174 patients, 214 HCCs) or MTA (339 patients, 416 HCCs) between January 2016 and March 2020. RESULTS: Median ablation time was significantly shorter for MTA (240 seconds) than for RFA (721 seconds; P<0.001). A significant difference in 3-year local tumor progression rate was evident between the RFA group (22%) and MTA group (8%; P<0.001). Multivariable analysis revealed ablation procedure and tumor diameter as independent factors contributing to local tumor progression (MTA; P<0.001; hazard ratio, 0.565; 95% confidence interval, 0.437-0.731). In patients with primary HCC, a significant difference in overall survival was evident (RFA vs. MTA, 3-year, 77% vs. 95%, P=0.029). Ablation procedure and Child-Pugh score were independent factors contributing to survival. The total complication rate was significantly lower for MTA (8%) than for RFA (14%, P<0.05), particularly for bile duct injury (3% vs. 9%, respectively; P<0.05). CONCLUSION: Next-generation MTA for small HCC could provide safer, more curative treatment in a shorter ablation time than RFA.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Microwaves , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome
5.
In Vivo ; 35(6): 3377-3383, 2021.
Article in English | MEDLINE | ID: covidwho-1485630

ABSTRACT

BACKGROUND/AIM: Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS: We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS: Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION: Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/drug therapy , Liver Neoplasms/complications , Liver Neoplasms/drug therapy , Liver Neoplasms/epidemiology , Retrospective Studies , SARS-CoV-2
6.
Clin Mol Hepatol ; 27(4): 564-574, 2021 10.
Article in English | MEDLINE | ID: covidwho-1456286

ABSTRACT

BACKGROUND/AIMS: In July 2017, the Emprint™ next-generation microwave ablation system using thermosphere technology (Covidien, Boulder, CO, USA) was approved for use in Japan. This system can produce a predictable spherical ablation zone at higher temperatures than radiofrequency ablation (RFA). The aim of the present study was to elucidate whether this new microwave thermosphere ablation (MTA) could safely improve outcome compared to RFA, which is the standard of care for small hepatocellular carcinoma (HCC). METHODS: This retrospective study analyzed 513 patients with 630 HCCs (≤3 cm) who were performed by percutaneous RFA (174 patients, 214 HCCs) or MTA (339 patients, 416 HCCs) between January 2016 and March 2020. RESULTS: Median ablation time was significantly shorter for MTA (240 seconds) than for RFA (721 seconds; P<0.001). A significant difference in 3-year local tumor progression rate was evident between the RFA group (22%) and MTA group (8%; P<0.001). Multivariable analysis revealed ablation procedure and tumor diameter as independent factors contributing to local tumor progression (MTA; P<0.001; hazard ratio, 0.565; 95% confidence interval, 0.437-0.731). In patients with primary HCC, a significant difference in overall survival was evident (RFA vs. MTA, 3-year, 77% vs. 95%, P=0.029). Ablation procedure and Child-Pugh score were independent factors contributing to survival. The total complication rate was significantly lower for MTA (8%) than for RFA (14%, P<0.05), particularly for bile duct injury (3% vs. 9%, respectively; P<0.05). CONCLUSION: Next-generation MTA for small HCC could provide safer, more curative treatment in a shorter ablation time than RFA.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Microwaves , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome
7.
Clin Imaging ; 76: 123-129, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1454081

ABSTRACT

PURPOSE: Thermal ablation (TA) and transarterial chemoembolization (TACE) may be used alone or in combination (TACE+TA) for the treatment of hepatocellular carcinoma (HCC). The aim of our study was to compare the time to tumor progression (TTP) and overall survival (OS) for patients who received TA alone or TACE+TA for HCC tumors under 3 cm. MATERIALS AND METHODS: This HIPAA-compliant IRB-approved retrospective analysis included 85 therapy-naïve patients from 2010 to 2018 (63 males, 22 females, mean age 62.4 ± 8.5 years) who underwent either TA alone (n = 64) or TA in combination with drug-eluting beads (DEB)-TACE (n = 18) or Lipiodol-TACE (n = 3) for locoregional therapy of early stage HCC with maximum tumor diameter under 3 cm. Kaplan-Meier analysis was performed using the log-rank test to assess TTP and OS. RESULTS: All TA and TACE+TA treatments included were technically successful. TTP was 23.0 months in the TA group and 22.0 months in the TACE+TA group. There was no statistically significant difference in TTP (p = 0.64). Median OS was 69.7 months in the TA group and 64.6 months in the TACE+TA group. There was no statistically significant difference in OS (p = 0.14). The treatment cohorts had differences in AFP levels (p = 0.03) and BCLC stage (p = 0.047). Complication rates between patient groups were similar (p = 0.61). CONCLUSION: For patients with HCC under 3 cm, TA alone and TACE+TA have similar outcomes in terms of TTP and OS, suggesting that TACE+TA may not be needed for these tumors unless warranted by tumor location or other technical consideration.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Combined Modality Therapy , Female , Humans , Liver Neoplasms/therapy , Male , Middle Aged , Retrospective Studies , Treatment Outcome
8.
World J Gastroenterol ; 27(36): 6039-6052, 2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1448960

ABSTRACT

The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Liver Neoplasms/epidemiology , Pandemics , SARS-CoV-2
11.
PLoS One ; 16(8): e0256544, 2021.
Article in English | MEDLINE | ID: covidwho-1374151

ABSTRACT

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Subject(s)
COVID-19/epidemiology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , COVID-19/virology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Delayed Diagnosis , Female , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pandemics , Patients/psychology , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Rate , Telemedicine , Tertiary Care Centers
12.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Article in English | MEDLINE | ID: covidwho-1348035

ABSTRACT

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Carcinoma, Hepatocellular/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Neoplasm Proteins/genetics , Receptors, Virus/genetics , alpha-Fetoproteins/genetics , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Area Under Curve , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Databases, Genetic , Datasets as Topic , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Protective Factors , Protein Interaction Mapping , ROC Curve , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Survival Analysis , alpha-Fetoproteins/metabolism
14.
Cell Rep ; 36(7): 109530, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1330686

ABSTRACT

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.


Subject(s)
COVID-19/virology , DNA, Viral/genetics , Genome, Human , SARS-CoV-2/genetics , Sequence Analysis, DNA , Virus Integration , Aged , Animals , COVID-19/diagnosis , Carcinoma, Hepatocellular/virology , Chlorocebus aethiops , HEK293 Cells , Hepatitis B virus/genetics , Host-Pathogen Interactions , Humans , Liver Neoplasms/virology , Long Interspersed Nucleotide Elements , Male , Nanopore Sequencing , Vero Cells
15.
Microbiol Spectr ; 9(1): e0043921, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1329042

ABSTRACT

Hepatitis C virus (HCV) can cause acute and chronic infection that is associated with considerable liver-related morbidity and mortality. In recent years, there has been a shift in the treatment paradigm with the discovery and approval of agents that target specific proteins vital for viral replication. We employed a cell culture-adapted strain of HCV and human hepatoma-derived cells lines to test the effects of our novel small-molecule compound (AO13) on HCV. Virus inhibition was tested by analyzing RNA replication, protein expression, and virus production in virus-infected cells treated with AO13. Treatment with AO13 inhibited virus spread in cell culture and showed a 100-fold reduction in the levels of infectious virus production. AO13 significantly reduced the level of viral RNA contained within cell culture fluids and reduced the cellular levels of HCV core protein, suggesting that the compound might act on a late step in the viral life cycle. Finally, we observed that AO13 did not affect the release of infectious virus from infected cells. Docking studies and molecular dynamics analyses suggested that AO13 might target the NS5B RNA polymerase, however, real-time RT-PCR analyses of cellular levels of HCV RNA showed only an ∼2-fold reduction in viral RNA levels in the presence of AO13. Taken together, this study revealed that AO13 showed consistent, but low-level antiviral effect against HCV, although the mechanism of action remains unclear. IMPORTANCE The discovery of curative antiviral drugs for a chronic disease such as HCV infection has encouraged drug discovery in the context of other viruses for which no curative drugs currently exist. Since we currently face a novel virus that has caused a pandemic, the need for new antiviral agents is more apparent than ever. We describe here a novel compound that shows a modest antiviral effect against HCV that could serve as a lead compound for future drug development against other important viruses such as SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Cell Culture Techniques , Hepacivirus/drug effects , Virus Replication/drug effects , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular , Cell Line , Hepacivirus/genetics , Hepacivirus/physiology , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Life Cycle Stages , Liver , Liver Neoplasms , Molecular Docking Simulation , RNA, Viral , SARS-CoV-2 , Viral Nonstructural Proteins , Virus Release/drug effects
16.
Clin Gastroenterol Hepatol ; 19(8): 1520-1530, 2021 08.
Article in English | MEDLINE | ID: covidwho-1317650

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/epidemiology , Pandemics , SARS-CoV-2 , alpha-Fetoproteins
17.
Mol Immunol ; 137: 221-227, 2021 09.
Article in English | MEDLINE | ID: covidwho-1313337

ABSTRACT

Natural Killer (NK) cells are considered the first line of defense against viral infections and tumors. Several factors affect NK cytotoxic activity rendering it dysfunctional and thereby impeding the ability to scavenge abnormal cells as a part of immune escaping mechanisms induced by different types of cancers. NK cells play a crucial role augmenting the activity of various types of anticancer mAb since dysfunctional NK cells are the main reason for the low response to these therapies. To this light, we examined the phenotypic characters of the circulating NK cells isolated from HCC patients compared to healthy controls. Then, dysfunctional NK cells, from HCC patients, were reactivated with cytokines cocktail and their cytotoxic activity with the anti-EGFR mAb "cetuximab" was investigated. This showed a downregulation of patients NK cells activating receptors (NKP30, NKP46, NKG2D and CD16) as well as CD56 and up-regulation of NKG2A inhibitory receptor. We also reported an increase in aberrant CD56- NK cells subset in peripheral blood of HCC patients compared to healthy controls. Thus, confirming the dysfunctionality of peripheral NK cells isolated from HCC patients. Cytokines re-activation of those NK cells lead to upregulation of NK activating receptors and downregulation of inhibitory receptor. Moreover, the percentage of aberrant CD56- NK cells subset was reduced. Here, we proved that advanced HCC patients have an increased percentage of more immature and noncytotoxic NK cell subsets in their peripheral blood, which might account for the low cytotoxicity noticed in those patients. A significant improvement in the cytotoxicity against HCC was noticed upon using reactivated NK cells combined with cetuximab. Therefore, this study highlights the potential recruitment of NK immune cells along with cetuximab to enhance cytotoxicity against HCC.


Subject(s)
Antibody-Dependent Cell Cytotoxicity/immunology , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Hepatocellular/therapy , Cetuximab/therapeutic use , Cytokines/pharmacology , Killer Cells, Natural/immunology , Liver Neoplasms/therapy , CD56 Antigen/metabolism , Cell Line, Tumor , Humans , Lymphocyte Activation/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism
18.
World J Gastroenterol ; 27(25): 3780-3789, 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1302602

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has impacted hospital organization, with the necessity to quickly react to face the pandemic. The management of the oncological patient has been modified by necessity due to different allocation of nurses and doctors, requiring new strategies to guarantee the correct assistance to the patients. Hepatocellular carcinoma, considered as one of the most aggressive types of liver cancer, has also required a different management during this period in order to optimize the management of patients at risk for and with this cancer. The aim of this document is to review recommendations on hepatocellular carcinoma surveillance and management, including surgery, liver transplantation, interventional radiology, oncology, and radiotherapy. Publications and guidelines from the main scientific societies worldwide regarding the management of hepatocellular carcinoma during the COVID-19 pandemic were reviewed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Pandemics , SARS-CoV-2
19.
Transpl Immunol ; 68: 101435, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294281

ABSTRACT

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.


Subject(s)
Antifungal Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Carcinoma, Hepatocellular/therapy , Cytomegalovirus Infections , Cytomegalovirus , Graft vs Host Disease/drug therapy , Liver Neoplasms/therapy , Liver Transplantation , SARS-CoV-2 , Acute Disease , Cytomegalovirus Infections/drug therapy , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/virology , Humans , Male , Middle Aged
20.
Aging (Albany NY) ; 13(12): 15785-15800, 2021 06 27.
Article in English | MEDLINE | ID: covidwho-1285613

ABSTRACT

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.


Subject(s)
COVID-19/drug therapy , Immunity/drug effects , SARS-CoV-2/drug effects , Vitamin A/pharmacology , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/virology , Carcinoma, Hepatocellular/genetics , Cholangiocarcinoma/genetics , Computational Biology , Female , Humans , Inflammation/drug therapy , Inflammation/etiology , Liver Neoplasms/genetics , Male , Molecular Docking Simulation , Proportional Hazards Models , Signal Transduction/drug effects
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