Role of Early On-Treatment Serum HBV RNA Declines in Predicting Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk prediction models established in patients with chronic hepatitis B receiving a nucleos(t)ide analogue (NA) rarely include viral factors because of mediocre predictability of traditional viral markers. Here, we investigate the role of serum hepatitis B virus (HBV) RNA, a novel biomarker, in predicting HCC risk in NA-treated patients. METHODS: A total of 1374 NA-treated patients were enrolled from 2 prospective chronic hepatitis B cohorts. Serum HBV RNA was detected at baseline, year 1, 2 and 3 of treatment. Cox proportional-hazard model was used to investigate the association of HBV RNA kinetics with HCC risk. RESULTS: After a median follow-up of 5.4 years, 76 patients developed HCC. HBV RNA declines at year 1 (adjusted hazard ratio, 0.70, P = .009) and 2 (adjusted hazard ratio, 0.71; P = .016) were independently associated with HCC risk. Patients with less HBV RNA decline at year 1 (≤0.4 log10 copies/mL) or 2 (≤0.6 log10 copies/mL) had 2.22- and 2.09-folds higher HCC risk, respectively, than those with more declines. When incorporating these early on-treatment HBV RNA declines into existing HCC risk scores, including PAGE-B (age, sex, and platelets), modified PAGE-B (mPAGE-B) (age, sex, platelets, and albumin), and aMAP (age, sex, platelets, and albumin-bilirubin score) score, they could enhance their predictive performance (ie, C-index 0.814 vs 0.78 [model (PAGE-B + year-1 HBV RNA decline) vs PAGE-B score based on baseline parameters]). CONCLUSIONS: Serum HBV RNA declines at year 1 and 2 were significantly associated with on-treatment HCC risk. Incorporating early on-treatment HBV RNA declines into HCC risk prediction models can be useful tools to guide appropriate surveillance strategies in NA-treated patients.

A dynamic model to predict early occurrence of acute kidney injury in ICU hospitalized cirrhotic patients: a MIMIC database analysis.

BACKGROUND: This study aimed to develop a tool for predicting the early occurrence of acute kidney injury (AKI) in ICU hospitalized cirrhotic patients. METHODS: Eligible patients with cirrhosis were identified from the Medical Information Mart for Intensive Care database. Demographic data, laboratory examinations, and interventions were obtained. After splitting the population into training and validation cohorts, the least absolute shrinkage and selection operator regression model was used to select factors and construct the dynamic online nomogram. Calibration and discrimination were used to assess nomogram performance, and clinical utility was evaluated by decision curve analysis (DCA). RESULTS: A total of 1254 patients were included in the analysis, and 745 developed AKI. The mean arterial pressure, white blood cell count, total bilirubin level, Glasgow Coma Score, creatinine, heart rate, platelet count and albumin level were identified as predictors of AKI. The developed model had a good ability to differentiate AKI from non-AKI, with AUCs of 0.797 and 0.750 in the training and validation cohorts, respectively. Moreover, the nomogram model showed good calibration. DCA showed that the nomogram had a superior overall net benefit within wide and practical ranges of threshold probabilities. CONCLUSIONS: The dynamic online nomogram can be an easy-to-use tool for predicting the early occurrence of AKI in critically ill patients with cirrhosis.

The burden and predictors of 30-day unplanned readmission in patients with acute liver failure: a national representative database study.

BACKGROUND: Liver diseases were significant source of early readmission burden. This study aimed to evaluate the 30-day unplanned readmission rates, causes of readmissions, readmission costs, and predictors of readmission in patients with acute liver failure (ALF). METHODS: Patients admitted for ALF from 2019 National Readmission Database were enrolled. Weighted multivariable logistic regression models were applied and based on Directed Acyclic Graphs. Incidence, causes, cost, and predictors of 30-day unplanned readmissions were identified. RESULTS: A total of 3,281 patients with ALF were enrolled, of whom 600 (18.3%) were readmitted within 30 days. The mean time from discharge to early readmission was 12.6 days. The average hospital cost and charge of readmission were $19,629 and $86,228, respectively. The readmissions were mainly due to liver-related events (26.6%), followed by infection (20.9%). The predictive factors independently associated with readmissions were age, male sex (OR 1.227, 95% CI 1.023-1.472; P = 0.028), renal failure (OR 1.401, 95% CI 1.139-1.723; P = 0.001), diabetes with chronic complications (OR 1.327, 95% CI 1.053-1.672; P = 0.017), complicated hypertension (OR 1.436, 95% CI 1.111-1.857; P = 0.006), peritoneal drainage (OR 1.600, 95% CI 1.092-2.345; P = 0.016), etc. CONCLUSIONS: Patients with ALF are at relatively high risk of early readmission, which imposes a heavy medical and economic burden on society. We need to increase the emphasis placed on early readmission of patients with ALF and establish clinical strategies for their management.

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis. PATIENTS AND METHODS: A retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed. RESULTS: After a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40-4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87-17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM. CONCLUSIONS: Elder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Drug delivery strategy in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC. Video Abstract.

Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). METHODS: Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed. RESULTS: Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. CONCLUSIONS: Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

High body mass index is a significant risk factor for the progression and prognosis of imported COVID-19: a multicenter, retrospective cohort study.

BACKGROUND: Coronavirus disease 2019(COVID-19) has spread worldwide. The present study aimed to characterize the clinical features and outcomes of imported COVID-19 patients with high body mass index (BMI) and the independent association of BMI with disease severity. METHODS: In this retrospective cohort study, 455 imported COVID-19 patients were admitted and discharged in Zhejiang province by February 28, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment, and outcome data were collected, analyzed and compared between patients with BMI ≥ 24and < 24. RESULTS: A total of 268 patients had BMI < 24, and 187 patients had BMI ≥ 24. Those with high BMI were mostly men, had a smoking history, fever, cough, and sputum than those with BMI < 24. A large number of patients with BMI ≥ 24 were diagnosed as severe/critical types. Some biochemical indicators were significantly elevated in patients with BMI ≥ 24. Also, acute liver injury was the most common complication in these patients. The median days from illness onset to severe acute respiratory syndrome coronavirus 2 detection, duration of hospitalization, and days from illness onset to discharge were significantly longer in patients with BMI ≥ 24 than those with BMI < 24. High BMI, exposure to Wuhan, any coexisting medical condition, high temperature, C-reactive protein (CRP), and increased lactate dehydrogenase (LDH) were independent risk factors for severe/critical COVID-19. After adjusting for age, sex and above factors, BMI was still independently associated with progression to severe/critical illness (P = 0.0040). Hemoglobin, alanine aminotransferase (ALT), CRP, and serum creatinine (Scr) were independent risk factors associated with high BMI. CONCLUSIONS: Contrasted with the imported COVID-19 patients with BMI < 24, high proportion of COVID-19 patients with BMI ≥ 24 in our study, especially those with elevated CRP and LDH, developed to severe type, with longer hospitalization duration and anti-virus course. Thus, high BMI is a risk factor for the progression and prognosis of imported COVID-19.

A fatal case of Exophiala dermatitidis meningoencephalitis in an immunocompetent host: A case report and literature review.

BACKGROUND: Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. CASE PRESENTATION: A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600-800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. CONCLUSIONS: CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.

Predictors of COVID-19 Infection: A Prevalence Study of Hospitalized Patients.

AIM: To find the predictors of coronavirus disease 2019 (COVID-19) in hospitalized patients. METHODS: A prevalence study compared the characteristics of COVID-19 patients with non-COVID-19 patients from January 19, 2020, to February 18, 2020, during the COVID-19 outbreak. Laboratory test results and pulmonary chest imaging of confirmed COVID-19 and non-COVID-19 patients were collected by retrieving medical records in our center. RESULTS: 96 COVID-19 patients and 122 non-COVID-19 patients were enrolled in this study. COVID-19 patients were older (53 vs. 39; P < 0.001) and had higher body mass index (BMI) than non-COVID-19 group (24.21 ± 3.51 vs. 23.00 ± 3.27, P = 0.011); however, differences in gender were not observed between the two groups. Logistic regression analysis showed that exposure history (OR: 23.34, P < 0.001), rhinorrhea (odds radio (OR): 0.12, P = 0.006), alanine aminotransferase (ALT) (OR: 1.03, P = 0.049), lactate dehydrogenase (LDH) (OR: 1.01, P = 0.020), lymphocyte (OR: 0.27, P = 0.007), and bilateral involvement on chest CT imaging (OR: 23.01, P < 0.001) were independent risk factors for COVID-19. Moreover, bilateral involvement on chest CT imaging (AUC = 0.904, P < 0.001) had significantly higher AUC than others in predicting COVID-19. CONCLUSIONS: Exposure history, elevated ALT and LDH, absence of rhinorrhea, lymphopenia, and bilateral involvement on chest CT imaging provide robust evidence for the diagnosis of COVID-19, especially in resource-limited conditions where nucleic acid detection is not readily available.

Clinical Characteristics and Factors Associated With Long-Term Viral Excretion in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Single-Center 28-Day Study.

BACKGROUND: Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited. METHODS: In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding. RESULTS: Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12-19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35-.98]), immunoglobulin use (HR, 0.42 [95% CI, .24-.76]), APACHE II score (HR, 0.89 [95% CI, .84-.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. CONCLUSIONS: SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.

Combining Hepatitis B Virus RNA and Hepatitis B Core-Related Antigen: Guidance for Safely Stopping Nucleos(t)ide Analogues in Hepatitis B e Antigen-Positive Patients With Chronic Hepatitis B.

BACKGROUND: Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. METHODS: The evaluation cohort included 127 hepatitis B e antigen (HBeAg)-positive patients from a multicenter prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA < 50 IU/mL for > 48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analyzed. RESULTS: At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg < 4 log10 U/mL at EOT (low-risk group), whereas 46.8% patients with positive HBV RNA and HBcrAg ≥ 4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year posttreatment follow-up (P < .001); the corresponding incidences in the validation cohort were 0% and 69.4% (P < .001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs 1.3%, P = .002). CONCLUSIONS: Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive patients with CHB.The combination of hepatitis B virus RNA and hepatitis B core-related antigen performed satisfactorily in predicting clinical relapse and hepatitis B surface antigen loss after stopping nucleos(t)ide analogue treatment among noncirrhotic hepatitis B e antigen-positive patients with chronic hepatitis B and could be used to guide safe discontinuation.

Decreased B Cells on Admission Associated With Prolonged Viral RNA Shedding From the Respiratory Tract in Coronavirus Disease 2019: A Case-Control Study.

The viral RNA shedding time (VST) for severe acute respiratory syndrome coronavirus 2 has not been well characterized. Clinical data were collected and compared between patients with short and long VSTs (in the lower and upper quartiles, respectively). The probability of recurrent positive reverse-transcription polymerase chain reaction results decreased sharply to 4.8% after 3 consecutive negative results. A series of ≥3 consecutive negative results was suitable as a criterion for the end of viral RNA shedding. The VST for shedding from the respiratory tract was significantly shorter in patients with normal B-cell counts on admission than in those with decreased B-cell counts (median [interquartile range], 11 [9-13] vs 16 [12-20] days, respectively; P = .001).

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Factors Associated With Fatality Due to Avian Influenza A(H7N9) Infection in China.

BACKGROUND: The high case fatality rate of influenza A(H7N9)-infected patients has been a major clinical concern. METHODS: To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013-2017, of which 109 (31.1%) had died, and systematically analyzed the patients' clinical characteristics and risk factors for death. RESULTS: The median age at time of infection was 57 years, whereas the median age at time of death was 61 years, significantly older than those who survived. In contrast to previous studies, we found nosocomial infections comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), extracorporeal membrane oxygenation (14%), continuous renal replacement therapy (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation, and secondary bacterial infection were independent risk factors for death. Age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death. CONCLUSIONS: Death among H7N9 virus-infected patients occurred rapidly after hospital admission, especially among older patients, followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality.Characterization of 350 hospitalized avian influenza A(H7N9)-infected patients in China shows that age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death.

Analysis of Epidemiological and Clinical Features in Older Patients With Coronavirus Disease 2019 (COVID-19) Outside Wuhan.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has become a large threat to public health in China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 outside Wuhan. METHODS: A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from 17 January to 12 February 2020. Epidemiological, clinical, and treatment data were analyzed between older (≥ 60 years) and younger (< 60 years) patients. RESULTS: A total of 788 patients with confirmed COVID-19 were selected; 136 were older patients with corresponding mean age of 68.28 ±â€…7.31 years. There was a significantly higher frequency of women in older patient group compared with younger patients (57.35% vs 46.47%, P = .021). The presence of coexisting medical conditions was significantly higher in older patients compared with younger patients (55.15% vs 21.93%, P < .001), including the rate of hypertension, diabetes, heart disease, and chronic obstructive pulmonary disease. Significantly higher rates of severe clinical type (older vs younger groups: 16.18% vs 5.98%, P < .001), critical clinical type (8.82% vs 0.77%, P < .001), shortness of breath (12.50% vs 3.07%, P < .001), and temperature of > 39.0°C (13.97% vs 7.21%, P = .010) were observed in older patients compared with younger patients. Finally, higher rates of intensive care unit admission (9.56% vs 1.38%, P < .001) and methylprednisolone application (28.68% vs 9.36%, P < .001) were also identified in older patients compared with younger ones. CONCLUSIONS: The specific epidemiological and clinical features of older COVID-19 patients included significantly higher female sex, body temperature, comorbidities, and rate of severe and critical type disease.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China.

A woman with coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.

Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy.

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.