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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination had been demonstrated as an effective way to reduce the risk of coronavirus disease 2019 (COVID-19), and only a few vaccines suffered from SARS-CoV-2 infection. However, limited data concerning the clinical features of these vaccines infected with SARS-CoV-2 can be identified. Methods: We retrospectively collected and analyzed epidemiological and clinical characteristics data of the imported COVID-19 cases who received Chinese inactivated vaccines abroad. Data were extracted from electronic medical records from a designated hospital in the Shaanxi Province of China between March 22 and May 17, 2021. Results: Totally, 46 confirmed SARS-CoV-2 infection patients were enrolled. The mean age was 40.5 years (range 20– 61), 41 (89.1%) are male. Eighteen (39.1%) patients were from Pakistan. Fourteen (30.4%) patients had at least one comorbidity. Forty (87.0%) and 6 cases were fully vaccinated and partly vaccinated. The time interval between vaccination and infection was 88 days (IQR, 33– 123), 31 (67.4%) and 15 (32.6%) were asymptomatic and symptomatic cases, respectively. Fever (3/46, 6.5%) was the most common symptom; however, none had a body temperature higher than 38.0°C, and no severe case was observed. Notably, the rate of SARS-CoV-2 shedding discontinuation at 7 days after hospitalization in asymptomatic cases was higher than symptomatic one (93.5% vs 40%, P < 0.0001). Conclusion: Individuals who received Chinese inactivated vaccines abroad remain to have the probability of being infected with SARS-CoV-2, but all the vaccines infected with SARS-CoV-2 were asymptomatic or had mild symptoms with favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

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 200 000 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%. [ABSTRACT FROM AUTHOR]

Even though the COVID-19 epidemic in China has been successfully put under control within a few months, it is still very important to infer the origin time and genetic diversity from the perspective of the whole genome sequence of its agent, SARS-CoV-2. Yet, the sequence of the entire virus genome from China in the current public database is very unevenly distributed with reference to time and place of collection. In particular, only one sequence was obtained in Henan province, adjacent to China's worst-case province, Hubei Province. Herein, we used high-throughput sequencing techniques to get 19 whole-genome sequences of SARS-CoV-2 from 18 severe patients admitted to the First Affiliated Hospital of Zhengzhou University, a provincial designated hospital for the treatment of severe COVID-19 cases in Henan province. The demographic, baseline, and clinical characteristics of these patients were described. To investigate the molecular epidemiology of SARS-CoV-2 of the current COVID-19 outbreak in China, 729 genome sequences (including 19 sequences from this study) sampled from Mainland China were analyzed with state-of-the-art comprehensive methods, including likelihood-mapping, split network, ML phylogenetic, and Bayesian time-scaled phylogenetic analyses. We estimated that the evolutionary rate and the time to the most recent common ancestor (TMRCA) of SARS-CoV-2 from Mainland China were 9.25 × 10−4 substitutions per site per year (95% BCI: 6.75 × 10−4 to 1.28 × 10−3) and October 1, 2019 (95% BCI: August 22, 2019 to November 6, 2019), respectively. Our results contribute to studying the molecular epidemiology and genetic diversity of SARS-CoV-2 over time in Mainland China. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel extraction method for silkworm pupa protein has been demonstrated. • The CH-IL extraction increased protein content by 12.14%. • The solubility, emulsification, and foaming capacity of the CH-IL extracted protein were enhanced. Silkworm (Bombyx mori) pupa protein (SPP) is a high-quality source of animal protein with substantial nutritional benefits and health value. To develop an efficient extraction method for SPP that is environmentally friendly, we selected choline hydroxide ionic liquid (CH-IL) as the extraction solvent and performed orthogonal experiments to optimize the extraction conditions. We demonstrated that 3% CH-IL, a solid-to-liquid ratio (g/mL) of 1:30, an extraction temperature of 40 °C, and an extraction time of 1 h facilitated the most efficient extraction. Compared to the conventional alkali solubilization–acid precipitation method, the CH-IL extraction increased protein content by 12.14%. Protein structure analysis showed that the β-sheet content increased by 10.98% and that of disulfide bonds reduced by 16.4%. The processing properties of the CH-IL extracted protein showed that the solubility, emulsification, and foaming capacity were enhanced by 82.87%, 15.44%, and 18.97%, respectively. The physical properties of SPP remarkably improved relative to the increased stretching of the polypeptide chains. The findings of this study provide technical knowledge that will enhance the processing performance of pupal proteins. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: CCL22 played critical roles in Tregs recruitment. The upstream regulators modulating CCL22 in hepatocellular carcinoma (HCC) were not clearly understood. Methods: MiR‐23a, p‐p65, p65, CCL22, and Foxp3 levels were monitored by RT‐qPCR and western blotting. Immunofluorescence assay was used to perform the costaining of Foxp3 and CD4 on liver tissues. Transwell assay was applied to evaluate the migration ability of Tregs. Dual‐luciferase assay was performed to determine relationship of miR‐23a/CCL22 and p65/miR‐23a. Chromatin immunoprecipitation (ChIP) was applied to detect the direct binding of p65 to miR‐23a promoter. Xenograft tumor models were developed to investigate the functions of p65 and miR‐23a in vivo. Results: HBV infection was associated with reduced survival and increased Tregs recruitment in HCC patients. MiR‐23a was decreased, whereas p65, CCL22, and Foxp3 were increased in HBV+ tumors. MiR‐23a was inversely correlated with CCL22 and Foxp3 expression in HCC. MiR‐23a directly targeted CCL22 3'UTR, leading to CCL22 reduction and attenuated Tregs recruitment. Meanwhile, p65 functioned as a transcription repressor of miR‐23a by directly binding to its promoter. Inhibition of p65 induced miR‐23 expression, leading to less CCL22 expression and Tregs recruitment in vitro. CCL22 was the indispensable effector underlying p65/miR‐23a axis and Tregs recruitment. MiR‐23a inhibitor promoted xenografted tumor growth accompanying with upregulation of CCL22, whereas p65 inhibition exerted opposite effects. Conclusion: Blockage of p65 disinhibited miR‐23a expression, leading to CCL22 reduction and repress Tregs recruitment. Targeting p65/miR‐23a/CCL22 axis was a novel approach for HBV+ HCC treatment. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐17A is pro‐inflammatory cytokine which has been identified as a noninvasive marker of the pathogenesis of non‐alcoholic steatohepatitis (NASH). However, the underlying role of IL‐17A in NASH progression remains unclear. This study was designed to investigate the biological function and molecular mechanism of IL‐17A in the induction of NASH. The results showed that IL‐17A was highly expressed in high‐fat diet (HFD)‐induced NASH mouse model. Intravenous injection of IL‐17A exacerbated steatohepatitis process via promoting hepatocyte apoptosis. Furthermore, IL‐17A‐induced apoptosis was mediated by ERK1/2/p65 signaling pathway. In conclusion, we demonstrated that IL‐17A‐mediated ERK1/2/p65 signaling pathway was a promising target for the treatment of NASH. © 2018 IUBMB Life, 71(3):302–309, 2019 [ABSTRACT FROM AUTHOR]

Background & Aims Few patients from developing countries can afford brand name direct-acting antiviral agents for treating hepatitis C virus (HCV) infection, and controversy regarding the bioequivalence of generics exists. This study aimed to observe the safety and efficacy of 8 or 12 weeks of generic ledipasvir-sofosbuvir with or without ribavirin for Chinese genotype 1b HCV-infected patients. Methods In this open-labelled observational study, 63 cirrhotic (group 1) and 65 non-cirrhotic (group 2) patients were administered generic ledipasvir-sofosbuvir plus 1000–1200 mg of ribavirin daily for 12 and 8 weeks, respectively; and 64 non-cirrhotic patients (group 3) received ledipasvir-sofosbuvir for 8 weeks. The primary efficacy endpoint was undetectable HCV RNA at week 12 (SVR12) after cessation of therapy. Safety and pharmacokinetic data were collected. Results One hundred and eighty-seven patients completed treatment, and the latest undetectable HCV RNA was observed in three patients with cirrhosis at week 5 during treatment. Intention-to-treat analysis revealed 96.8% (61/63), 96.9% (63/65), and 96.9% (62/64) of SVR12 rates in groups 1, 2, and 3, respectively. One patient in group 3 relapsed at post-treatment week 4. The regimens were generally well-tolerated. The most common adverse events were fatigue (17.8%), diarrhea (10.9%), and headache (9.9%). Four patients discontinued therapy due to diarrhea and vomiting. One patient from group 2 discontinued treatment on day 29 because of drug-unaffordability; fortunately, she achieved SVR12. Conclusion This study demonstrated that 8 or 12 weeks of generic ledipasvir-sofosbuvir with or without ribavirin are safe and effective for patients with genotype 1b HCV infection. Lay summary The price of Harvoni® has led to restrictions and access limitations in many developing and even developed countries with limited healthcare budgets. Gilead approved generic ledipasvir-sofosbuvir costs far less than Harvoni® and presents a similar cure rate for patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Dysfunctional hepatitis C virus ( HCV) specific CD4+ T cells are known to contribute to inadequate adaptive immunity in chronic hepatitis C ( CHC), although the underlying mechanisms remain largely undefined. In this study, OX40 ligand ( OX40 L) expression was investigated in 41 treatment-naïve CHC patients, 20 sustained virological responders and 36 healthy subjects. We observed that OX40 L expression was significantly upregulated in peripheral monocytes in CHC patients compared with sustained virological responders and healthy subjects. OX40 L upregulation correlated significantly with plasma viral load rather than serum alanine aminotransaminase levels. Furthermore, longitudinal analyses indicated that upregulated OX40 L expression on monocytes is closely associated with rapid or early virological responses in patients receiving pegylated IFN-α/ribavirin treatment. In vitro, HCV core antigen strongly stimulated monocyte expression of OX40 L and blockade of TLR2 signaling significantly downregulated OX40 L expression. More importantly, elevated OX40 L expression was also shown to be closely associated with elevation of the HCV-specific CD4+ T-cell response and in vitro blockade of OX40 L expressed on monocytes led to impaired CD4+ T-cell function. These findings, therefore, implicate OX40 L expression can be used as a marker to evaluate antiviral treatment efficacy and extend the notion that enhancement of OX40 L expression could be a good way for immunotherapy in CHC patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to articles "Unexpected early tumor recurrence in patients with hepatitis C virus -related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution," by M. Reig, Z. Marino, and C. Perello in the 2016 issue and "Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with SVR following IFN-free DAA treatment," by K. Kozbial, S. Moser, and R. Schwarzer in the 2016 issue.

The article presents a study on co-infection of Hepatitis C Virus and Hepatitis B Virus in patients infected with human immunodeficiency virus in early to middle 1990s in China.

Introduction: Data on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking., Methods: The current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa ® ) and 5 days of nirmatrelvir/ritonavir (Paxlovid ® ) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment., Results: In late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient's symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband's HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife's HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment., Conclusion: The older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment., Discussion: This study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zeng, Lv, Chen and Pan.)