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1.
Front Cell Infect Microbiol ; 12: 726263, 2022.
Article in English | MEDLINE | ID: covidwho-2198679

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction. Discussion: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver. Conclusion: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Gastrointestinal Diseases , Liver Neoplasms , Aged , COVID-19/complications , Humans , Liver/pathology , Liver Neoplasms/pathology , Pandemics , SARS-CoV-2
2.
BMC Prim Care ; 23(1): 297, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2139156

ABSTRACT

BACKGROUND: Sustained, routine care is vital to the health of people with HIV (PWH) and decreasing transmission of HIV. We evaluated whether the identification of PWH at-risk of falling out of care and prompts for outreach were effective in retaining PWH in care in the United States. METHODS: In this cluster randomized controlled trial, 20 AIDS Healthcare Foundation Healthcare Centers (HCCs) were randomized to the intervention (n = 10) or control (n = 10) arm; all maintained existing retention efforts. The intervention included daily automated flags in CHORUS™, a mobile app and web-based reporting solution utilizing electronic health record data, that identified PWH at-risk of falling out of care to clinic staff. Among flagged PWH, the association between the intervention and visits after a flag was assessed using logistic regression models fit with generalized estimating equations (independent correlation structure) to account for clustering. To adjust for differences between HCCs, models included geographic region, number of PWH at HCC, and proportions of PWH who self-identified as Hispanic or had the Ryan White Program as a payer. RESULTS: Of 15,875 PWH in care, 56% were flagged; 76% (intervention) and 75% (control) resulted in a visit, of which 76% were within 2 months of the flag. In adjusted analyses, flags had higher odds of being followed by a visit (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.97, 1.21) or a visit within 2 months (OR: 1.07, 95% CI: 0.97, 1.17) at intervention than control HCCs. Among at-risk PWH with viral loads at baseline and study end, the proportion with < 50 copies/mL increased in both study arms, but more so at intervention (65% to 74%) than control (62% to 67%) HCCs. CONCLUSION: Despite challenges of the COVID-19 pandemic, adding an intervention to existing retention efforts, and the reality that behavior change takes time, PWH flagged as at-risk of falling out of care were marginally more likely to return for care at intervention than control HCCs and a greater proportion achieved undetectability. Sustained use of the retention module in CHORUS™ has the potential to streamline retention efforts, retain more PWH in care, and ultimately decrease transmission of HIV. TRIAL REGISTRATION: The study was first registered at Clinical Trials.gov (NCT04147832, https://clinicaltrials.gov/show/NCT04147832 ) on 01/11/2019.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , HIV Infections , Liver Neoplasms , Retention in Care , Humans , United States/epidemiology , HIV Infections/epidemiology , Pandemics , COVID-19/epidemiology , Ambulatory Care Facilities
3.
World J Gastroenterol ; 28(40): 5818-5826, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2110319

ABSTRACT

There is increasing incidence and prevalence of acute and chronic liver diseases (CLDs) all over the world which influence the quality of life and can give rise to life threatening complications. The burden of advanced liver disease due to hepatitis B has been controlled by antivirals but its eradication is difficult soon. Highly effective directly acting antiviral therapy has reduced the burden of hepatitis C but is partially offset by increasing IV drug abuse. Non-alcoholic fatty liver disease pandemic is on and there is recent alarming increase in alcohol related liver disease, both of which have no drug cure apart from control of the risk factors. Genetic factors have been identified in progression of all forms of CLD. Due to better management of complications of CLD, the life span of patients have increased spiking the number of hepatocellular carcinoma (HCC) and patients needing liver transplantation (LT). The present severe acute respiratory syndrome coronavirus pandemic has affected the outcome CLD including LT in addition to causing acute hepatitis. Better diagnostics and therapeutics are available for liver fibrosis, portal hypertension, HCC and post LT management and many drugs are under trial. The present review summarises the current scenario of the epidemiology and the advances in diagnosis and treatment of liver diseases including their complications like portal hypertension, HCC and LT.


Subject(s)
Carcinoma, Hepatocellular , Hypertension, Portal , Liver Neoplasms , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Liver Neoplasms/diagnosis , Quality of Life , Liver Transplantation/adverse effects , Liver Cirrhosis/pathology , Antiviral Agents/therapeutic use , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/therapy , Hypertension, Portal/etiology
4.
Intern Med ; 61(20): 3017-3028, 2022 Oct 15.
Article in English | MEDLINE | ID: covidwho-2079919

ABSTRACT

Objective This retrospective, single-center study assessed the effects of interferon (IFN)-free treatment of hepatitis C virus (HCV) infection, which has been approved for seven years; calculated the incidence of hepatocellular carcinoma (HCC) after achieving a sustained virologic response (SVR); and elucidated problems with follow-up for surveillance of post-SVR HCC, particularly the impact of the coronavirus disease 2019 (COVID-19) pandemic. Methods We summarized the SVR achievement rate of 286 HCV-infected patients who received 301 IFN-free treatments and analyzed the cumulative incidence of initial HCC and the cumulative continuation rate of follow-up after SVR in the 253 patients who achieved SVR and did not have a history of HCC. Results Among 286 patients who received IFN-free treatments, 14 dropped out, and the 272 remaining patients achieved an SVR after receiving up to third-line treatment. Post-SVR HCC occurred in 18 (7.1%) of the 253 patients without a history of HCC, with a cumulative incidence at 3 and 5 years after SVR of 6.6% and 10.0%, respectively; the incidence of cirrhosis at those time points was 18.2% and 24.6%, respectively.Of the 253 patients analyzed, 58 (22.9%) discontinued follow-up after SVR. Patients who had no experience with IFN-based therapy tended to drop out after SVR. Notably, the number of dropouts per month has increased since the start of the pandemic. Conclusion Currently, IFN-free treatment is showing great efficacy. However, the incidence of HCC after SVR should continue to be monitored. In this study, the COVID-19 pandemic did not affect treatment outcomes, but it may affect surveillance for post-SVR HCC.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Hepacivirus , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Interferons/therapeutic use , Liver Neoplasms/epidemiology , Liver Neoplasms/virology , Patient Dropouts , Retrospective Studies , Sustained Virologic Response
5.
J Microbiol ; 60(11): 1106-1112, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2075669

ABSTRACT

Due to the evolutionary arms race between hosts and viruses, viruses must adapt to host translation systems to rapidly synthesize viral proteins. Highly expressed genes in hosts have a codon bias related to tRNA abundance, the primary RNA translation rate determinant. We calculated the relative synonymous codon usage (RSCU) of three hepatitis viruses (HAV, HBV, and HCV), SARS-CoV-2, 30 human tissues, and hepatocellular carcinoma (HCC). After comparing RSCU between viruses and human tissues, we calculated the codon adaptation index (CAI) of viral and human genes. HBV and HCV showed the highest correlations with HCC and the normal liver, while SARS-CoV-2 had the strongest association with lungs. In addition, based on HCC RSCU, the CAI of HBV and HCV genes was the highest. HBV and HCV preferentially adapt to the tRNA pool in HCC, facilitating viral RNA translation. After an initial trigger, rapid HBV/HCV translation and replication may change normal liver cells into HCC cells. Our findings reveal a novel perspective on virus-mediated oncogenesis.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Hepatitis B , Hepatitis C , Liver Neoplasms , Humans , Liver Neoplasms/complications , Liver Neoplasms/genetics , Hepatitis B virus/genetics , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/genetics , Hepatitis B/complications , Hepatitis B/genetics , Transcriptome , SARS-CoV-2 , Codon , Carcinogenesis , RNA, Transfer , Hepatitis C/genetics
6.
Front Immunol ; 13: 978760, 2022.
Article in English | MEDLINE | ID: covidwho-2043449

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Comorbidity , Humans , Immune Checkpoint Inhibitors , Immunologic Memory , Morbidity , SARS-CoV-2 , Transcriptome , Tumor Microenvironment/genetics
7.
Front Immunol ; 13: 985781, 2022.
Article in English | MEDLINE | ID: covidwho-2022758

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , COVID-19/complications , COVID-19/drug therapy , Vitamin D/therapeutic use , Molecular Docking Simulation , Toll-Like Receptor 4/metabolism , Vitamins/therapeutic use , MicroRNAs/genetics , Antiviral Agents/therapeutic use , Cytokines/metabolism , Retinol-Binding Proteins, Plasma
10.
Ann Surg ; 276(3): 545-553, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2008693

ABSTRACT

OBJECTIVE: This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population. BACKGROUND: Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients. METHODS: In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance. RESULTS: From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32-282). Median overall survival for treated patients was 32 months. CONCLUSIONS: Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program's success. Next steps include expanding the program to additional at-risk populations.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Hepatitis C/complications , Humans , Liver Cirrhosis/complications , Middle Aged , Retrospective Studies , Safety-net Providers
11.
Medicine (Baltimore) ; 101(35): e30315, 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2008669

ABSTRACT

RATIONALE: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available. PATIENT CONCERNS: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening. DIAGNOSIS: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. LESSONS: We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Adult , Carcinoma, Hepatocellular/etiology , Child , Cholesterol Esters , Female , Humans , Liver Cirrhosis , Liver Neoplasms/etiology , Male , Middle Aged , Triglycerides , Wolman Disease , Young Adult
13.
J Med Virol ; 94(11): 5553-5559, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1925951

ABSTRACT

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.


Subject(s)
COVID-19 Vaccines , COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunogenicity, Vaccine , Prospective Studies , SARS-CoV-2 , Vaccination/adverse effects
14.
PLoS One ; 17(5): e0269249, 2022.
Article in English | MEDLINE | ID: covidwho-1923706

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19), which poses a major threat to humans worldwide. With the continuous progress of the pandemic, a growing number of people are infected with SARS-CoV-2, including hepatocellular carcinoma (HCC) patients. However, the relationship between COVID-19 and HCC has not been fully elucidated. In order to provide better treatment for HCC patients infected with SARS-CoV-2, it's urgently needed to identify common targets and find effective drugs for both. In our study, transcriptomic analysis was performed on both selected lung epithelial cell datasets of COVID-19 patients and the datasets of HCC patients to identify the synergistic effect of COVID-19 in HCC patients. What's more, common differentially expressed genes were identified, and a protein-protein interactions network was designed. Then, hub genes and basic modules were detected based on the protein-protein interactions network. Next, functional analysis was performed using gene ontology terminology and the Kyoto Encyclopedia of Genes and Genomes pathway. Finally, protein-protein interactions revealed COVID-19 interaction with key proteins associated with HCC and further identified transcription factor (TF) genes and microRNAs (miRNA) with differentially expressed gene interactions and transcription factor activity. This study reveals that COVID-19 and HCC are closely linked at the molecular level and proposes drugs that may play an important role in HCC patients with COVID-19. More importantly, according to the results of our research, two critical drugs, Ilomastat and Palmatine, may be effective for HCC patients with COVID-19, which provides clinicians with a novel therapeutic idea when facing possible complications in HCC patients with COVID-19.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , COVID-19/complications , COVID-19/drug therapy , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/complications , Liver Neoplasms/genetics , SARS-CoV-2 , Transcription Factors
15.
Liver Int ; 42(8): 1891-1901, 2022 08.
Article in English | MEDLINE | ID: covidwho-1909488

ABSTRACT

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , COVID-19/complications , COVID-19 Testing , Cohort Studies , Cross-Sectional Studies , Humans , Retrospective Studies , SARS-CoV-2
16.
Biosci Trends ; 16(3): 178-188, 2022 Jul 20.
Article in English | MEDLINE | ID: covidwho-1903774

ABSTRACT

Liver resection is the standard curative treatment for liver cancer. Advances in surgical techniques over the last 30 years, including the preoperative assessment of the future liver remnant, have improved the safety of liver resection. In addition, advances in nonsurgical multidisciplinary treatment have increased the opportunities for tumor downstaging. Consequently, the indications for resection of more advanced liver cancer have expanded. Laparoscopic and robot-assisted liver resections have also gradually become more widespread. These techniques should be performed in stages, depending on the difficulty of the procedure. Advances in preoperative simulation and intraoperative navigation technology may have also lowered the threshold for their performance and may have promoted their widespread use. New insights and experiences gained from laparoscopic surgery may be applicable in open surgery. Liver transplantation, which is usually indicated for patients with poor liver function, has also become safer with advances in perioperative management. The indications for liver transplantation in liver cancer are also expanding. Although the coronavirus disease 2019 pandemic has forced the postponement of liver resection and transplantation procedures, liver surgeons should appropriately tailor the surgical plan to the individual patient as part of multidisciplinary treatment. This review may provide an entry point for future clinical research by identifying currently unresolved issues regarding liver cancer, and particularly hepatocellular carcinoma.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Humans , Liver Neoplasms/surgery
17.
Am J Physiol Cell Physiol ; 323(2): C289-C294, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1891935

ABSTRACT

Syndecan-1 (SDC-1) is a heparan sulfate (HS)/chondroitin sulfate proteoglycan (PG) of the cell surface and the extracellular matrix (ECM), which regulates a broad spectrum of physiological and pathological processes such as cell proliferation, migration, inflammation, matrix remodeling, wound healing, and tumorigenesis. Syndecan-1 represents the major PG of the liver, expressed by hepatocytes and cholangiocytes, and its elevated expression is a characteristic feature of liver diseases. The highest syndecan-1 expression is found in liver cirrhosis and in hepatocellular carcinoma (HCC) developed in cirrhotic livers. In addition, as being a hepatitis C receptor, hepatitis C virus (HCV)-infected livers produce extremely large amounts of syndecan-1. The serum levels of the cleaved (shedded) extracellular domain have clinical significance, as their increased concentration reflects on poor prognosis in cirrhosis as well as in cancer. In vivo experiments confirmed that syndecan-1 protects against early stages of fibrogenesis mainly by enhanced clearance of transforming growth factor ß1 (TGFß1) and thrombospondin-1 (THBS1) via circulation, and against hepatocarcinogenesis by interfering with several signaling pathways and enhancing cell cycle blockade. In addition, syndecan-1 is capable to hinder lipid metabolism and ribosomal biogenesis in induced cancer models. These observations together with its participation in the uptake of viruses (e.g., HCV and SARS-CoV-2) indicate that syndecan-1 is a central player in liver pathologies.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Liver , Syndecan-1 , Humans , Liver/physiopathology , Proteoglycans/metabolism , Syndecan-1/genetics , Syndecan-1/metabolism
18.
Brief Bioinform ; 23(5)2022 09 20.
Article in English | MEDLINE | ID: covidwho-1860818

ABSTRACT

Many statistical methods for pathway analysis have been used to identify pathways associated with the disease along with biological factors such as genes and proteins. However, most pathway analysis methods neglect the complex nonlinear relationship between biological factors and pathways. In this study, we propose a Deep-learning pathway analysis using Hierarchical structured CoMponent models (DeepHisCoM) that utilize deep learning to consider a nonlinear complex contribution of biological factors to pathways by constructing a multilayered model which accounts for hierarchical biological structure. Through simulation studies, DeepHisCoM was shown to have a higher power in the nonlinear pathway effect and comparable power for the linear pathway effect when compared to the conventional pathway methods. Application to hepatocellular carcinoma (HCC) omics datasets, including metabolomic, transcriptomic and metagenomic datasets, demonstrated that DeepHisCoM successfully identified three well-known pathways that are highly associated with HCC, such as lysine degradation, valine, leucine and isoleucine biosynthesis and phenylalanine, tyrosine and tryptophan. Application to the coronavirus disease-2019 (COVID-19) single-nucleotide polymorphism (SNP) dataset also showed that DeepHisCoM identified four pathways that are highly associated with the severity of COVID-19, such as mitogen-activated protein kinase (MAPK) signaling pathway, gonadotropin-releasing hormone (GnRH) signaling pathway, hypertrophic cardiomyopathy and dilated cardiomyopathy. Codes are available at https://github.com/chanwoo-park-official/DeepHisCoM.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Deep Learning , Liver Neoplasms , Humans , Biological Factors , Carcinoma, Hepatocellular/genetics , Gonadotropin-Releasing Hormone , Isoleucine , Leucine , Lysine , Mitogen-Activated Protein Kinases , Phenylalanine , Tryptophan , Tyrosine , Valine
19.
Can J Gastroenterol Hepatol ; 2022: 5900468, 2022.
Article in English | MEDLINE | ID: covidwho-1854483

ABSTRACT

Introduction: Several studies have demonstrated that thromboembolic events increased in patients with coronavirus infection, usually occurring in elderly patients with severe illness, associated with comorbid diseases such as diabetes and hypertension. Portal vein thrombosis (PVT) is a rare venous thromboembolic disease occurring typically in patients with an underlying disease such as decompensated cirrhosis with or without hepatocellular carcinoma (HCC). Aim: To evaluate incidence of occurrence of acute PVT in cirrhotic patients infected with 2019 coronavirus disease (COVID-19). Methods: This cross-sectional, observational study involved 70 patients of the liver cirrhosis: (group A) 28 patients with liver cirrhosis infected with COVID-19, and 42 patients with liver cirrhosis as the control group matched for age and sex (group B). All patients were subjected to thorough medical history, routine investigations (complete blood count, liver, and renal function tests), imaging in the form of abdominal and Doppler ultrasonography to assess the presence of acute PVT, serum ferritin, D-dimer, C-reactive protein, and PCR of COVID-19 for group A only. Results: There was a significant difference between the two groups regarding Doppler ultrasound findings as 3 of the patients in group A had PVT (10.7%), 2 of them had HCC diagnosed by triphasic CT abdomen, and only 1 patient in group B had PVT (2.3%) (p < 0.05). Conclusion: In cirrhotic patients infected with COVID-19, portal vein thrombosis may be a potential complication even in the absence of hepatocellular carcinoma; further prospective studies with longer follow-up may be needed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Venous Thrombosis , Aged , COVID-19/complications , Carcinoma, Hepatocellular/complications , Cross-Sectional Studies , Humans , Liver Cirrhosis/complications , Portal Vein , Prospective Studies , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
20.
BMJ Open Gastroenterol ; 9(1)2022 04.
Article in English | MEDLINE | ID: covidwho-1807372

ABSTRACT

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , COVID-19/epidemiology , Carcinoma, Hepatocellular/epidemiology , Humans , Liver Neoplasms/epidemiology , Pandemics , Retrospective Studies
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