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BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.
Subject(s)
Antiviral Agents , Drug Therapy, Combination , Hepatitis B, Chronic , Interferon-alpha , Polyethylene Glycols , Recombinant Proteins , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Male , Female , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/administration & dosage , Child , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Polyethylene Glycols/therapeutic use , Polyethylene Glycols/adverse effects , Polyethylene Glycols/administration & dosage , Interferon-alpha/therapeutic use , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Child, Preschool , Treatment Outcome , Interferon alpha-2/therapeutic use , Interferon alpha-2/administration & dosage , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/drug effects , DNA, Viral/blood , Alanine/therapeutic use , Alanine/analogs & derivativesABSTRACT
Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.
Subject(s)
Atrial Fibrillation , Gastrointestinal Microbiome , Microbiota , Humans , Gastrointestinal Microbiome/physiology , Atrial Fibrillation/therapyABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.
Subject(s)
Ablation Techniques , Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Humans , Animals , Mice , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Ablation Techniques/adverse effects , Ablation Techniques/methods , Catheter Ablation/adverse effects , Catheter Ablation/methods , Treatment OutcomeSubject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Microbiota , Humans , Bacteria , Bile Ducts, IntrahepaticABSTRACT
Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between "good" and "potentially pathogenic" microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.
Subject(s)
Gastrointestinal Microbiome , Hepatitis B, Chronic , Liver Neoplasms , Animals , Antiviral Agents , Hepatitis B virus , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/therapy , Humans , Inventions , Liver Cirrhosis/complications , Liver Neoplasms/complications , RifaximinABSTRACT
Introduction: To date, little is known about the real-world protective role of Chinese inactivated and recombinant coronavirus disease 2019 (COVID-19) vaccines under the background of the long-term "Dynamic Zero COVID-19 Case" (i.e., no infection source) in China, especially when facing the widespread Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection. Methods: In this prospective, single-center cohort study, the clinical characteristics of post-vaccination Omicron SARS-CoV-2 variant infection were investigated in the initial largest outbreak of Omicron SARS-CoV-2 variant infection that occurred between the 8 January, 2022 and 29 January, 2022 in Anyang City, Henan Province, China. The primary endpoints were the rates of severe and critical diseases or death. The secondary endpoints were the SARS-CoV-2 shedding duration and length of hospitalization. Results: A total of 380 post-vaccination patients infected with the Omicron SARS-CoV-2 variant were enrolled. The median age was 18 (interquartile range [IQR] 17-35) years, 219 (57.6%) cases were female, and 247 (65.0%) cases were students. Before confirmation of Omicron SARS-CoV-2 variant infection, patients had 3 (IQR 2-4) days of dry cough (40.3%), nasal congestion (26.3%), and sore throat (26.3%). On admission, 294 (77.4%) cases had normal chest computerized tomography (CT) imaging. Additionally, only 5 (1.3%), 30 (7.9%), 4 (4/342, 1.2%), and 7 (7/379, 0.2%) patients had lymphocyte counts <800 per mm3, C-reactive protein levels >10 mg/L, lactate dehydrogenase levels ≥250 U/L, and D-dimer levels ≥0.5 mg/L on admission, respectively. During hospitalization, 308 (81.1%) and 72 (18.9%) were identified as mild and moderate cases, respectively, and no one progressed to severe and critical types, with a SARS-CoV-2 shedding period and length of hospital stay of 17 (IQR 12-22) and 19 (IQR 15-24) days, respectively. Conclusion: The current study found that approximately 80% of individuals infected with the Omicron SARS-CoV-2 variant were mild, approximately 20% of patients were moderate, and no severe, critical, or fatal cases were identified in a prospective cohort including 380 participants vaccinated with non-mRNA-based vaccines. Discussion: This study supports the consideration of policy adjustments and changes to prevent and control the Omicron-predominant COVID-19 in China and other regions with high SARS-CoV-2 vaccination rates.
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BACKGROUND: Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. METHODS: We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. RESULTS: The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. CONCLUSIONS: This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.
Subject(s)
COVID-19 , Gastrointestinal Microbiome , Follow-Up Studies , Humans , Metabolomics , RNA, Ribosomal, 16S/geneticsABSTRACT
Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.
Subject(s)
Hepatitis C, Chronic , Sofosbuvir , Antiviral Agents/therapeutic use , Drug Therapy, Combination , Female , Fluorenes/therapeutic use , Genotype , Hepacivirus/genetics , Humans , Infant, Newborn , Pregnancy , Pregnant Women , Sofosbuvir/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. METHODS: Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. RESULTS: One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. CONCLUSIONS: TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.
Subject(s)
Cleft Lip , Cleft Palate , Hepatitis B, Chronic , Hepatitis B , Female , Humans , Pregnancy , Infant, Newborn , Adult , Hepatitis B Surface Antigens , Hepatitis B, Chronic/drug therapy , Pregnant Women , Prospective Studies , Cleft Lip/chemically induced , Cleft Lip/drug therapy , Cleft Palate/chemically induced , Cleft Palate/drug therapy , Tenofovir/adverse effects , Adenine/adverse effects , China , Antiviral Agents/adverse effects , Hepatitis B/diagnosisABSTRACT
BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.
Subject(s)
COVID-19/complications , Liver/virology , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19/blood , COVID-19/epidemiology , Female , Humans , Liver/pathology , Liver Function Tests/methods , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Severity of Illness IndexABSTRACT
BACKGROUND: Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS: In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS: A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS: Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
Subject(s)
Hepatitis B, Chronic , Non-alcoholic Fatty Liver Disease , Antiviral Agents/adverse effects , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/drug therapy , Prognosis , Treatment Outcome , Weight GainABSTRACT
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China. AIM: To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients. METHODS: This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A (n = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96th week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates. RESULTS: For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 vs 5.73 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% vs 77.97%, 31.00% vs 27.27%, and 20.22% vs 15.79%, respectively, in Group A vs Group B; P > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 vs 4.70 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% vs 94.12% in Group A vs Group B, respectively; P > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% vs 84.57% in Group A vs Group B, respectively; P > 0.05), and similar incidences of adverse events were observed (106 vs 104 in Group A vs Group B, respectively; P > 0.05). CONCLUSION: Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and the main reason is the unclear pathogenesis of HCC, which leads to a high fatality rate of HCC. Therefore, it is of great clinical significance to explore the molecular mechanism of HCC and find a targeted therapeutic approach from the molecular level. MATERIALS AND METHODS: MicroRNA-15a-5p (miR-15a-5p) expression level was measured by bioinformatics and qRT-PCR. Luciferase assay and RIP assays were used to verify the relationship between programmed cell death protein 1 (PD1) PD 1 with miR-15a-5p. Exosomes were identified using TEM, Zetasizer Nano ZS, and western blot. Edu, Transwell, and scratch assay were performed to explore the role of miR-15a-5p or exo-miR-15a-5p on HepG2 cells progression. RESULTS: MicroRNA-15a-5p (miR-15a-5p) was decreased in HCC tissues and cell lines, which indicated a poor prognosis. Overexpression of miR-15a-5p inhibited viability, proliferation, migration and invasion of HepG2 cells. Then, we isolated exosomes from cancer cells, and found that miR-15a-5p was packaged into exosomes from cancer cells. Furthermore, exo-miR-15a-5p was secreted into CD8+ T cells, then directly inhibited PD1 expression via targeted binding. Then, we co-cultured CD8+ T cells transfected with PD1 with HepG2 transfected with miR-15a-5p, PD1 remitted the inhibitory role of miR-15a-5p on HCC progression. CONCLUSION: Together, present study revealed exo-miR-15a-5p from cancer cells inhibited PD1 expression in CD8+ T cells, which suppressed the development of HCC.
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BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200â 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Pregnancy Complications, Infectious , Alanine , Antiviral Agents/adverse effects , Female , Hepatitis B/drug therapy , Hepatitis B/prevention & control , Hepatitis B, Chronic/drug therapy , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/prevention & control , Prospective Studies , Tenofovir/analogs & derivatives , Viral LoadSubject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Plasma , SARS-CoV-2 , Virus Shedding , COVID-19 SerotherapyABSTRACT
BACKGROUND: None of the current guidelines recommend antiviral therapy for inactive hepatitis B virus (HBV) carriers (IHCs). METHODS: In this real-world, multicenter, nonrandomized study, 32 participants meeting the inclusion criteria were enrolled 1:1 for treatment with peginterferon α-2b or monitoring without treatment based on participant preference. The expected treatment duration was 48 weeks. The primary end point was hepatitis B surface antigen (HBsAg) loss. The HBV vaccine could be injected after HBsAg loss. RESULTS: All patients had HBsAg levels of <20 IU/mL. The mean baseline HBsAg levels were 6.6 IU/mL and 5.8 IU/mL in the treated and untreated groups, respectively. Fifteen (93.8%) participants achieved HBsAg loss, 5 obtained HBsAg seroconversion after undergoing a mean of 19.7 weeks of therapy in the treated group, and no one in the follow-up group achieved HBsAg loss during a mean follow-up time of 12.6 months (P < .0001). Generally, the therapy was well tolerated. Nine of 11 individuals who exhibited HBsAg loss benefited from receiving the HBV vaccine. CONCLUSIONS: This study provides justification for further studies of short-course peginterferon α-2b for the functional cure of IHCs with low HBsAg levels. Additionally, HBV vaccine injection is beneficial after interferon-induced HBsAg loss.
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The number of liver cancer patients is likely to continue to increase in the coming decades due to the aging of the population and changing risk factors. Traditional treatments cannot meet the needs of all patients. New treatment methods evolved from pulsed electric field ablation are expected to lead to breakthroughs in the treatment of liver cancer. This paper reviews the safety and efficacy of irreversible electroporation in clinical studies, the methods to detect and evaluate its ablation effect, the improvements in equipment and its antitumor effect, and animal and clinical trials on electrochemotherapy. We also summarize studies on the most novel nanosecond pulsed electric field ablation techniques in vitro and in vivo. These research results are certain to promote the progress of pulsed electric field in the treatment of liver cancer.
Subject(s)
Electrochemotherapy , Liver Neoplasms , Animals , Electrochemotherapy/adverse effects , Electroporation , Humans , Liver Neoplasms/therapyABSTRACT
Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.