Evaluation of the association of a variant in PNPLA3 and TM6SF2 with fibrosis progression in patients with chronic hepatitis C infection after eradication: A retrospective study.

The relationship of single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 with outcomes in patients with hepatitis C infection (HCV) is unclear. This study aimed to evaluate the association of PNPLA3, TM6SF2, and MBOAT7 with the baseline fibrosis stage and progression of liver fibrosis after HCV eradication with direct antiviral agents (DAAs). A total of 171 patients who received the DAAs at the Peking University First Hospital between June 2015 and June 2020 were included in the retrospective cohort. Transient elastography was used to determine liver stiffness measurements (LSMs) at the baseline, the end of treatment (EOT), 24 weeks after treatment (W24), and the last follow-up (LFU) visit. We used the QIAamp Blood Mini Kit (Qiagen) for whole blood genomic DNA extraction and polymerase chain reaction for PNPLA3, TM6SF2, and MBOAT7 amplification of the target gene. The PNPLA3 rs738409 SNP was associated with the baseline fibrosis stage in multivariate logistic regression analysis adjusted for other factors, and the adjusted odds ratio (OR) for advanced fibrosis (≥F3) at baseline was 2.52 (95% confidence interval[CI] = 1.096-5.794, p = 0.03). The G and GG alleles were predictive of advanced fibrosis (OR = 1.98, 95% CI = 1.021-4.196, p = 0.015; OR = 3.12, 95% CI = 1.572-6.536, p = 0.005). Similarly, the OR of TM6SF2 rs58542926 at baseline was 2.608 (95% CI = 1.081-6.29, p = 0.033). T and TT alleles were predictive of advanced fibrosis (OR = 2.3, 95% CI = 1.005-5.98, p = 0.007; OR = 3.05, 95% CI = 1.32-6.87, p = 0.001). After adjustment, the MBOAT7 rs641738 T plus TT alleles were not independently associated with the baseline fibrosis stage (95% CI = 0.707-2.959, p = 0.312). At the EOT, there were 35 patients and 136 patients in the fibrosis improvement and fibrosis non-improvement group, respectively. Logistic regression analysis showed that the G allele in PNPLA3 rs738409 was associated with fibrosis progression (OR = 2.47, 95% CI = 1.125-5.89, p = 0.003). The GG alleles were predictive of fibrosis progression (OR = 2.95, 95% CI = 1.35-6.35, p = 0.005). Similarly, the ORs of the T and TT alleles in TM6SF2 rs58542926 for fibrosis progression were 1.82 and 2.21, respectively (95% CI = 1.006-5.373, p = 0.045; 95% CI = 1.18-5.75, p = 0.01). At the W24 visit, we found that there was an association between the G allele in PNPLA3 rs738409 and fibrosis progression (OR = 2.218, 95% CI = 1.095-5.631, p = 0.015). Moreover, GG alleles were also predictive for fibrosis progression (OR = 2.558, 95% CI = 1.252-5.15, p = 0.008). Similarly, the OR of T allele and TT alleles in TM6SF2 rs58542926 for fibrosis progression was 2.056 and 2.652 (95% CI = 1.013-5.592, p = 0.038; 95% CI = 1.25-5.956, p = 0.015). For additional affirmation, we surveyed fibrosis progression utilizing the Cox proportional hazards model. G and GG alleles in PNPLA3 rs738409 were associated with an increased risk of progression to advanced fibrosis in multivariate model (hazard ratio [HR]1.566, 95% CI = 1.02-2.575, p = 0.017; and HR2.109, 95% CI = 1.36-3.271, p = 0.001, respectively). Besides, T and TT alleles in TM6SF2 rs58542926 were associated with an increased risk of progression to advanced fibrosis in multivariate model (HR = 1.322, 95% CI = 1.003-1.857, p = 0.045; and HR = 1.855, 95% CI = 1.35-2.765, p = 0.006, respectively). In contrast, rs641738 in MBOAT7 did not show a significant trend in the univariate and multivariate models. The PNPLA3 CG/GG SNP at rs738409 and TM6SF2 CT/TT SNP at rs58542926 were associated with the baseline fibrosis stage and fibrosis progression after HCV eradication with DAAs.

The Clinical Characteristics of Fever-Ward Pediatric Patients with a Definite Epidemiological History During the Early COVID-19 Epidemic Period.

OBJECTIVE: The number of children presenting with coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is increasing, and we aimed to assess the clinical characteristics of pediatric patients with a definite epidemiological history during the early COVID-19 epidemic. METHODS: Retrospective analysis was performed on the clinical data of children admitted to the fever ward of Xiangyang Central Hospital in Hubei province between January 1, 2020 and March 17, 2020. According to definite epidemiological history, patients with SARS-CoV-2 nucleic acid test (NAT) positive detection were grouped as confirmed cases, and patients with two consecutive negative NATs were grouped as suspected cases. We compared the clinical characteristics of the two groups. RESULTS: A total of 47 (47/127, 37%) cases had a definite epidemiological history, of which 32 (68.1%) were suspected, with a median age of 5.5 years (interquartile range [IQR]: 0.7-10.3), and 15 (31.9%) were confirmed, with a median age of 9 years (IQR: 4-14). Statistically significant differences in age, family cluster of infection, and numbers of patients with clinical symptoms and fever (P<0.05) were found between the two groups, but no statistically significant differences in leucocyte and lymphocyte counts were observed (P>0.05). Significant differences were found in the computed tomography (CT) manifestation of ground glass opacity (GGO) between the two groups (P<0.05). CONCLUSION: Children of older age and from family clusters of infection were more easily diagnosed as having COVID-19. GGO changes on chest CT was more likely in confirmed cases. Although obvious clinical manifestations increase our awareness of COVID-19, children without manifestations of fever or cough should not be ignored as they may be asymptomatic carriers.

Clinical characteristics of COVID-19 in family clusters: a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world and reports of children during early epidemic period showed features of family clusters. The aim of this study is to assess clinical profiles of COVID-19 in family clusters with children. METHODS: We performed a systematic literature review of English database (PubMed, Web of Science) and Chinese database (" www.cnki.net ", " www.cqvip.com " and " www.Wanfangdata.com.cn ") to identify papers on family clusters of COVID-19 with children and their family members. RESULTS: Eighteen studies involving 34 children and 98 adults from 28 families were included. Fever, cough and ground-grass opacity change of chest computed tomography (CT) were the dominant features, whereas proportion of asymptomatic infections for children was higher than adults with statistical significance (32.4% and 13.3%, respectively, P < 0.05). Median time of longer incubation period (10 days) and shorter duration of pharyngeal swab nucleic acid test positive period (11 days) were seen in children than adults (7 and 17 days, respectively) with statistical significance (P < 0.05). There were statistically significant differences in lymphopenia, increased C-reactive protein and abnormal chest CT between children and adult patients (P < 0.05). Twenty-seven families reported adults as first case of COVID-19 in family clusters. CONCLUSIONS: The same virus strain can cause milder disease in children compared with their caregivers. Children of COVID-19 were infected by adults in family during the early epidemic period. Asymptomatic patients can transmit the virus.

Clinical features of pediatric patients with coronavirus disease (COVID-19).

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. OBJECTIVES: To assess clinical profiles of pediatric COVID-19. STUDY DESIGN: A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. RESULTS: All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10-26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1-23 days). CONCLUSIONS: COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.