Liver Research最新文献

{"title":"Unveiling the effect of estrogen receptors in alcoholic liver disease: A novel outlook","authors":"Sukriti Baweja ,&nbsp;Ashmit Mittal ,&nbsp;Swati Thangariyal ,&nbsp;P. Debishree Subudhi ,&nbsp;Shivani Gautam ,&nbsp;Rashmi Kaul","doi":"10.1016/j.livres.2023.10.002","DOIUrl":"10.1016/j.livres.2023.10.002","url":null,"abstract":"<div><div>Alcoholic liver disease (ALD) has a multifaceted development, progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis, irreversible liver damage that can even result in hepatocellular carcinoma. The prevalence of ALD is increasing globally, particularly among middle-aged adults. Gender-based studies have revealed that ALD affects more men; however, disease progression differs between men and women. Despite this, the molecular understanding of alcohol-induced liver injury among genders and its association with changes in sex hormone metabolism, particularly with estrogen and estrogen receptors (ERs) in ALD, remains poor. This review focuses on experimental and human studies describing alcohol and its association with estrogen metabolism and signaling via ERs. Chronic alcohol consumption affects the immune response, and whether estrogen has any contributory effect remains inadequately studied. This review also discusses various therapeutic approaches currently in use and future approaches that can affect the response or progression via estrogen signaling. The role of gender on alcohol consumption and its association with steroid hormones must be elucidated for a better understanding of the pathogenesis of ALD, the development of effective therapeutic approaches, and better disease management in both men and women, as ALD remains a major public health concern.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 333-341"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy modulates physiologic and adaptive response in the liver","authors":"Trinh Van Le ,&nbsp;Nhung Hai Truong ,&nbsp;Ai Xuan L. Holterman","doi":"10.1016/j.livres.2023.12.001","DOIUrl":"10.1016/j.livres.2023.12.001","url":null,"abstract":"<div><div>Autophagy is a physiological process that is ubiquitous and essential to the disposal or recycling of damaged cellular organelles and misfolded proteins to maintain organ homeostasis and survival. Its importance in the regulation of liver function in normal and pathological conditions is increasingly recognized. This review summarizes how autophagy regulates epithelial cell- and non-epithelial cell-specific function in the liver and how it differentially participates in hepatic homeostasis, hepatic injury response to stress-induced liver damage such as cholestasis, sepsis, non-alcoholic and alcohol-associated liver disease, viral hepatitis, hepatic fibrosis, hepatocellular and cholangiocellular carcinoma, and aging. Autophagy-based interventional studies for liver diseases that are currently registered in <span><span>clinicatrials.gov</span><svg><path></path></svg></span> are summarized. Given the broad and multidirectional autophagy response in the liver, a more refined understanding of the liver cell-specific autophagy activities in a context-dependent manner is necessary.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 304-320"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138620867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic impacts of rifampicin and doxorubicin against thioacetamide-induced hepatocellular carcinoma in rats","authors":"Zahraa R. Elshahawy ,&nbsp;Entsar A. Saad ,&nbsp;Rana R. El-Sadda","doi":"10.1016/j.livres.2023.11.005","DOIUrl":"10.1016/j.livres.2023.11.005","url":null,"abstract":"<div><h3>Background and aims</h3><div>Combination therapy is a promising new strategy that has been proposed to increase the efficacy of cancer treatment. We aimed to investigate the anti-cancer activity of rifampicin monotherapy and its combination with doxorubicin against hepatocellular carcinoma (HCC).</div></div><div><h3>Materials and methods</h3><div>The <em>in vitro</em> half maximal inhibitory concentration (IC₅₀) and selectivity index (SI) of the drugs under investigation against HepG2 and human lung fibroblast (WI38) cell lines were determined. For the <em>in vivo</em> experiment, male Sprague-Dawley albino rats were injected with thioacetamide at 200 mg/kg twice a week for 90 days; HCC development was confirmed histopathologically. Following HCC induction, the rats were treated with intraperitoneal doxorubicin, rifampicin, or their combination for 45 or 90 days. After sacrifice, the livers were examined histopathologically. The levels of aminotransferases, albumin, bilirubin, malondialdehyde, superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and nitric oxide were measured by spectrophotometry. Alpha-fetoprotein, cancer antigen 19-9, tumor necrosis factor-alpha, interleukin-6, Bcl-2-associated X protein, caspase 3, caspase 8, and p53 were estimated using ELISA.</div></div><div><h3>Results</h3><div><em>In vitro,</em> the combination of doxorubicin and rifampicin showed the highest SI of 3.43. <em>In vivo,</em> among the measured markers, the levels of TAC, CAT, SOD, and p53 decreased (<em>P</em> &lt; 0.001) and the rest of the measured marker levels increased (<em>P</em> &lt; 0.001) in the HCC-bearing rats; after treatment in all groups, all these changes improved toward normal in a time-dependent manner. The combination of doxorubicin and rifampicin optimized the effects of the two individual drugs and exerted the best antioxidant effects.</div></div><div><h3>Conclusions</h3><div>In general, compared with rifampicin or doxorubicin alone, combination therapy has favorable outcomes. Based on our results, the combination of rifampicin and doxorubicin might be applicable for HCC chemotherapy.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 352-360"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models","authors":"Tingting Sha ,&nbsp;Yujia You ,&nbsp;Xiaoyan Miao ,&nbsp;Huan Deng ,&nbsp;Wei Zhang ,&nbsp;Huolin Ye ,&nbsp;Ping Wang ,&nbsp;Rongqin Zheng ,&nbsp;Jie Ren ,&nbsp;Tinghui Yin","doi":"10.1016/j.livres.2023.11.002","DOIUrl":"10.1016/j.livres.2023.11.002","url":null,"abstract":"<div><h3>Background and objective</h3><div>Noninvasive non-alcoholic steatohepatitis (NASH) assessment is a clinical challenge to the management of non-alcoholic fatty liver disease. We aim to develop diagnostic models based on sequential ultrasound molecular imaging (USMI) for the noninvasive identification of NASH in mouse models.</div></div><div><h3>Methods</h3><div>Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University. Forty-nine C57BL/6 mice were divided into normal control, non-alcoholic fatty liver, NASH, and hepatitis groups. Sequential USMI was implemented using CD36-targeted microbubbles (MBs-CD36) and intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles (MBs-ICAM-1) to visualize hepatic steatosis and inflammation. The targeting signal of USMI was quantified as the normalized intensity difference (NID) with the destruction-replenishment method. Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBs-ICAM-1 and pathological inflammation score. Finally, diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.</div></div><div><h3>Results</h3><div>MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice. NID-MBs-CD36 values increased with the progression of steatosis, while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation. A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade (r_s = 0.9078, <em>P</em> &lt; 0.0001) and between NID-MBs-ICAM-1 and pathological inflammation grade (r_s = 0.9071, <em>P</em> &lt; 0.0001). Among various sequential USMI-based diagnostic models, the serial testing model showed high diagnostic performance in detecting NASH, with 95% sensitivity, 97% specificity, 95% positive predictive values, 97% negative predictive values, and 96% accuracy.</div></div><div><h3>Conclusions</h3><div>Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation. Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 342-351"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139301470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-depth analysis of de novo lipogenesis in non-alcoholic fatty liver disease: Mechanism and pharmacological interventions","authors":"Zhixian Zhu ,&nbsp;Xiaoxun Zhang ,&nbsp;Qiong Pan ,&nbsp;Liangjun Zhang ,&nbsp;Jin Chai","doi":"10.1016/j.livres.2023.11.003","DOIUrl":"10.1016/j.livres.2023.11.003","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) is characterized by the abnormal buildup of lipids in the liver tissue. Non-alcoholic fatty liver (NAFL) may progress to non-alcoholic steatohepatitis. Triglycerides in the liver can originate from various sources, including <em>de novo</em> lipogenesis (DNL). Research indicates that DNL significantly escalates in NAFLD, worsening steatosis. However, the precise regulatory mechanism of DNL in the development of this disease is not fully understood. Therefore, the targeted reduction of DNL could be a crucial therapeutic strategy. Currently, numerous pharmaceutical agents targeting DNL have been developed, attracting significant attention. This review examines the mechanism of DNL upregulation in NAFLD, assessing its potential as a therapeutic target for hepatic steatosis. Furthermore, we thoroughly examine hepatocellular lipotoxicity and provide an extensive review of the application and limitations of relevant therapeutic drugs, with a focus on key enzymes involved in DNL. The implementation of these pharmacological strategies is expected to significantly improve the management and overall outcomes for patients with NAFLD.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 285-295"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139303326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation of autophagy-related gene ATG7 increases the risk of severe disease in patients with non-alcoholic fatty liver disease","authors":"Mary Miu Yee Waye","doi":"10.1016/j.livres.2023.10.001","DOIUrl":"10.1016/j.livres.2023.10.001","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 4","pages":"Pages 365-366"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135922500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver retransplants using living donors: An approach for management","authors":"Hasan Al Harakeh,&nbsp;Christopher Hughes,&nbsp;Amit Tevar,&nbsp;Vikram Gunabushanam,&nbsp;Eishan Ashwat,&nbsp;Hao Liu,&nbsp;Abhinav Humar","doi":"10.1016/j.livres.2023.09.003","DOIUrl":"https://doi.org/10.1016/j.livres.2023.09.003","url":null,"abstract":"<div><h3>Background and aims</h3><p>Many centers do not offer living donor transplants for patients in need of a liver retransplant. We aimed to study our liver retransplant outcomes using living donors and compared them with those of retransplants performed using deceased donors.</p></div><div><h3>Methods</h3><p>This study retrospectively analyzed all retransplants performed at our center between 2009 and 2023, and outcomes of living donor retransplants were compared with deceased donor retransplants using standard statistical tests.</p></div><div><h3>Results</h3><p>Between January 2009 and March 2023, a total of 77 retransplants, 60 with deceased donors and 17 with living donors, were performed. Important demographic differences between the two groups included a higher model for end-stage liver disease score in the deceased donor group (32.1 ± 6.1 <em>vs</em>. 19.4 ± 5.7, <em>P</em> &lt; 0.001) and a higher number of early retransplants (within 3 months of the initial transplant), which accounted for 35% of deceased donor transplants but 0 of living donor transplants (<em>P</em> &lt; 0.01). Overall, the patient and graft survival rates were comparable between the two groups. The patient survival rates at 1 and 3 years after transplant were 73% and 67% in the deceased donor group and 84% and 73% in the living donor group, respectively (<em>P</em> = 0.57). The hospital length of stay and blood product use were both better in the living donor group. Biliary complications did not show significant different between the two groups (<em>P</em> = 0.33).</p></div><div><h3>Conclusions</h3><p>Living donors can provide acceptable outcomes for those in need of a retransplant, with results comparable to those seen with deceased donors. A systematic approach to the patient in the pre-, peri-, and post-transplantation period is important in these complicated cases.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 252-255"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and risk factors of hepatitis B virus-related cirrhosis/hepatocellular carcinoma: A single-center retrospective study","authors":"Feng Chen ,&nbsp;Qianhui Li ,&nbsp;Xiaomin Xu ,&nbsp;Fei Wang","doi":"10.1016/j.livres.2023.07.004","DOIUrl":"10.1016/j.livres.2023.07.004","url":null,"abstract":"<div><h3>Background and aims</h3><p>Hepatitis B virus (HBV) infection is a major global health problem which progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Early prediction of disease changes and intervention are essential to slow disease progression and protect liver function. This study aimed to analyze the clinical characteristics of patients with HBV-related LC and HCC at different serum alanine aminotransferase (ALT) levels and explore the risk factors of HBV infection progressing to LC/HCC.</p></div><div><h3>Methods</h3><p>A total of 379 patients with HBV infection treated in The Third People's Hospital of Shenzhen between January 2014 and December 2016 without any antiviral drug therapy were enrolled. Patients were divided into the LC/HCC and non-LC/HCC groups based on clinical diagnosis, which was determined through imaging and expressions of pathological and laboratory test markers, and patients with LC/HCC were further divided into three groups according to the serum ALT levels. Differences in general information, clinical symptoms, and expression levels of serological indices of the above groups were compared and analyzed, logistic regression was used to analyze the risk factors for LC/HCC development, and the clinical diagnostic efficacy of indicators was judged by the receiver operator characteristic (ROC).</p></div><div><h3>Results</h3><p>LC/HCC mainly occurred in the ALT normal and mildly elevated groups, with 70.83% of patients with HCC having an LC background. In the comparison of different ALT level groups, the moderately–severely elevated group had the highest proportion of patients with skin jaundice, abdominal varices, rebound tenderness, higher white blood cell and neutrophil (NEUT) counts; and higher levels of aspartate aminotransferase, glutamyl transpeptidase, total bilirubin, and direct bilirubin. The LC/HCC group was older and had significantly higher proportions of male patients, alcohol consumption, and combined hypertension than the non-LC/HCC group (all <em>P</em> &lt; 0.05). Logistic regression analysis showed that age, combined hypertension, abdominal varicose veins, subcostal palpation, and NEUT count were risk factors for LC/HCC development; and the area under the curve for this model on the ROC analysis was 0.935 (95% confidence interval 0.899–0.972) with specificity and sensitivity of 97.4% and 70.7%, respectively.</p></div><div><h3>Conclusions</h3><p>Advanced age, combined hypertension, abdominal varicose veins, subcostal palpation, and high NEUT count are risk factors for LC/HCC development in patients with untreated HBV infection.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 237-243"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47219675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level","authors":"Brian I. Carr ,&nbsp;Vito Guerra ,&nbsp;Volkan Ince ,&nbsp;Burak Isik ,&nbsp;Sezai Yilmaz","doi":"10.1016/j.livres.2023.07.003","DOIUrl":"10.1016/j.livres.2023.07.003","url":null,"abstract":"<div><h3>Background and aims</h3><p>Hepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database.</p></div><div><h3>Methods</h3><p>An 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels.</p></div><div><h3>Results</h3><p>The percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters.</p></div><div><h3>Conclusions</h3><p>A statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 256-262"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48148863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged existence of SARS-CoV-2 RNAs in the extracellular vesicles of respiratory specimens from patients with negative reverse transcription-polymerase chain reaction","authors":"P. Debishree Subudhi ,&nbsp;Sheetalnath Rooge ,&nbsp;Chhagan Bihari ,&nbsp;Swati Thangariyal ,&nbsp;Sivang Goswami ,&nbsp;Reshu Agarwal ,&nbsp;Savneet Kaur ,&nbsp;Ekta Gupta ,&nbsp;Sukriti Baweja","doi":"10.1016/j.livres.2023.09.004","DOIUrl":"https://doi.org/10.1016/j.livres.2023.09.004","url":null,"abstract":"<div><h3>Background and aim</h3><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily in the respiratory tract, particularly in patients with underlying comorbidities. This study aimed to investigate the presence of the virus inside the extracellular vesicles (EVs) in patients with and without chronic liver disease (CLD).</p></div><div><h3>Methods</h3><p>Eighty patients with positive SARS-CoV-2, including twenty-four patients with CLD and fifty-six patients without CLD, and five healthy controls with negative SARS-CoV-2 were enrolled. Nasal swab specimens were tested for the detection of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). Patients with coronavirus disease 2019 (COVID-19) were followed up on days 7 and 14. Nasal swab, collected in viral transport media (VTM), and plasma samples were investigated at each time point. EVs were isolated from the nasal swabs (collected in VTM) and plasma using differential ultracentrifugation and estimated at each time point. The transmission or replication by the EVs was assessed in Vero E6 cells.</p></div><div><h3>Results</h3><p>In patients with baseline RT-PCR positive, SARS-CoV-2 RNAs inside the EVs were found in 68/80 (85%) patients with higher viral load in the nasal swabs than in the EVs (cycle threshold (Ct) value, 23.4 ± 5.7 <em>vs</em>. 30.3 ± 5.0, <em>P</em> &lt; 0.001). On follow-up at day 7, of the 32 patients negative for COVID-19, 15 (46.9%) had virus persistence in the EVs (Ct value, 30.7 ± 2.7), and on day 14, of the 56 patients with negative SARS-CoV-2, 16 patients (28.6%) had positive SARS-CoV-2 RNAs in the EVs (Ct value, 31.4 ± 3.0). The mean viral load decreased on days 7 and 14 compared to baseline in the nasal swabs (<em>P</em> &lt; 0.001) but not in the EVs. Additionally, SARS-CoV-2 RNAs were undetectable in the plasma, but 12.5% of patients were positive in the plasma EVs. Significantly prolonged and high viral load was found in the EVs on day 14 in COVID-19 patients combined with CLD compared with COVID-19 patients (<em>P</em> = 0.0004). We found significant higher levels of EV-associated with endothelial cells and hepatocytes in the COVID-19 + CLD group than COVID-19 group (<em>P</em> = 0.032 and <em>P</em> = 0.002, respectively), suggesting more endothelial cells and hepatocytes cellular injury in liver disease patients with COVID-19. Interestingly, we also found EVs could transmit SARS-CoV-2 RNAs into Vero E6 cells at 24 h post-infection.</p></div><div><h3>Conclusions</h3><p>The identification of SARS-CoV-2 RNAs in the EVs in patients with negative RT-PCR indicates the persistence of infection and likely recurrence of the infection. It is suggestive of another route of transmission as EVs harbor SARS-CoV-2 RNAs. EV-associated RNAs may determine the ongoing inflammation and clinical course of subjects with undetectable SARS-CoV-2 virus and this may have relevance to better management of patients with CLD.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 228-236"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}