BACKGROUND Nucleoside/nucleotide analogs are currently the core drugs for antiviral treatment of chronic hepatitis B (CHB). Among them, entecavir (ETV) and tenofovir alafenamide fumarate (TAF) exhibit potent antiviral effects with low resistance rates and are recommended as first-line treatment regimens in domestic and international guidelines. AIM To evaluate bone and renal safety in patients with CHB receiving initial treatment with TAF or ETV. METHODS This study included 95 treatment-naive patients with CHB and were treated at the Infectious Diseases Department of Henan Provincial People's Hospital from August 2019 to June 2020. They were assigned to either the TAF group (n = 45, 25 mg/day) or the ETV group (n = 50, 0.5 mg/day) according to the antiviral treatment plan. Patients' basic clinical data were collected. Their bone mineral density, bone-related markers, and various renal function indicators were also measured and compared. RESULTS The study cohort had a mean age of 41.01 +/- 11.67 years and a cirrhosis prevalence of 18.9%. At baseline, serum Ca (2.33 +/- 0.13 vs 2.30 +/- 0.15, t = 0.935, P = 0.352), serum P (1.12 +/- 0.21 vs 1.12 +/- 0.19, t = 0.026, P = 0.980), and 25-hydroxyvitamin D3 [25(OH)D] (22.67 +/- 7.98 vs 24.96 +/- 11.30, t = 1.122, P = 0.265) were comparable across groups. When the follow-up was extended to 96W, the abnormality rates of urinary A1M (4.4% vs 20.0%, chi(2) = 5.193, P = 0.023), N-acetyl-beta-D-glucosaminidase (6.7% vs 24.0%, chi(2) = 5.352, P = 0.021), and urine cystatin (4.4% vs 18.0%, chi(2) = 4.251, P = 0.039) exhibited marked between-group differences. CONCLUSION For patients with CHB on long-term nucleoside drug use, comprehensive monitoring of bone and renal safety should be conducted as treatment duration increases. In this study, TAF outperforms ETV in renal tubular safety after long-term application.

Background and Aims:The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation.Methods: Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals.Therapeutic response related data were recorded and compared at multiple time points.Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR).Results: We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations.They were also comparable in baseline HBV DNA levels and HBeAg positivity.Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months.First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months).On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004];G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR.Conclusions: In CHB patients receiving initial antivi-ral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

OBJECTIVES:Pegylated interferon α-2b (PegIFNα-2b) therapy can help inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) achieve clinical cure. To explore and compare the efficacy, safety, and relevant influential factors of PegIFNα-2b monotherapy and PegIFNα-2b-based immunotherapy for IHCs.METHODS:This exploratory, prospective, single-center, randomized controlled trial enrolled 40 IHCs who were randomized into group A (PegIFNα-2b treatment for 68 weeks) and group B (two cycles of PegIFNα-2b treatment with a lead-in period of GM-CSF and vaccine treatment before each cycle). The primary endpoint was 68-week HBsAg loss rate.RESULTS:At week 68, the HBsAg loss rates were 45.45% [full analysis set (FAS)] and 46.67% [per-protocol set (PPS)]. There was no statistically significant difference in HBsAg loss rate between groups A and B ( P  > 0.05). Univariate analysis revealed that age ≤40 years old, baseline HBsAg <200 IU/ml, and 24-week HBsAg decline ≥2 log 10 IU/ml were significantly associated with HBsAg loss in FAS population ( P  < 0.05). Multivariate analysis showed that only 24-week HBsAg decline ≥2 log 10 IU/ml was the independent influencing factor in both FAS and PPS populations ( P  < 0.05). The adverse events were common and mild, and the therapies were well-tolerated.CONCLUSION:Treatment of IHCs with PegIFNα-2b-based therapy could result in a high HBsAg loss rate. The HBsAg loss rate of combined immunotherapy was similar to that of PegIFNα-2b monotherapy, and the safety was good.CLINICALTRIALSGOV ID:NCT05451420.

我国是慢性乙型病毒性肝炎(以下简称"慢乙肝")的高发国家,中国疾病预防控制中心流行病学数据显示,我国一般人群中乙型肝炎病毒表面抗原(HBsAg)流行率为6.1％,据此推算慢性HBV感染者约8600万.慢乙肝控制不佳所导致的肝硬化、肝衰竭、肝癌等疾病负担十分沉重,除建议应早期规范抗病毒治疗,以降低HBV相关不良事件发生率之外,同时应当鼓励有一定治疗基础、且自身条件满足的"优势患者"积极追求临床治愈,为实现WHO提出的"2030年消除病毒性肝炎的公共卫生危害"做出努力.

ObjectiveTo investigate the effect of pegylated interferon α-2b (PEG-IFNα-2b) on HBsAg clearance in the treatment of chronic hepatitis B (CHB) in a real-world setting. MethodsA retrospective analysis was performed for 411 CHB patients who attended Department of Infectious Diseases, Henan Provincial People’s Hospital, from June 2017 to January 2021, and all these patients were treated with PEG-IFNα-2b. Related clinical data were collected, including sex, age, antiviral treatment regimen, baseline HBsAg level, and post-treatment HBsAg level, and HBsAg clearance rate was observed at 24, 48, and 96 weeks. HBsAg clearance rate at different time points of follow-up was compared between the patients with different baseline HBsAg levels (＜500 IU/mL, 500-1 500 IU/mL, and 1 501-5 000 IU/mL) or with the use of PEG-IFNα-2b after different previous treatment conditions and regimens. The independent-samples t test was used for comparison of continuous data between two groups, and the chi-square test and the trend chi-square test were used for comparison of categorical data between groups. ResultsThe HBsAg clearance rate was 9.9% (26/263) in the patients who completed 24 weeks of treatment, 19.7% (25/127) in the patients who completed 48 weeks of treatment, and 41.7% (30/72) in the patients who completed 96 weeks of treatment. There was a significant difference in HBsAg clearance rate between the patients with different baseline HBsAg levels at 24, 48, and 96 weeks of treatment (χ2=52.265, 32.764, and 30.918, all P＜001), and HBsAg clearance rate gradually increased over the time of treatment (χ2trend=44.517, 29.147, and 22.260, all P＜0.01). Compared with the HBsAg ＜500 IU/mL group, the 500-1 500 IU/mL group and the 1 501-5 000 IU/mL group had a significant reduction in HBsAg clearance rate at 24, 48, and 96 weeks of follow-up (all P＜0.001). As for the comparison of the patients with different treatment conditions (previously untreated or treatment-experienced) and treatment regimens (monotherapy or combined therapy) at 24, 48, and 96 weeks of treatment, there was a significant difference in fame/female ration between the previously untreated group and the treatment-experienced group (χ2=5.029, P=0.025), and there was no significant difference in HBsAg clearance rate between the previously untreated group and the treatment-experienced group and between the monotherapy group and the combined therapy group (all P＞0.05). ConclusionPEG-IFNα-2b has a marked effect on HBsAg clearance in the treatment of CHB, and patients with a lower baseline HBsAg level tend to have a higher HBsAg clearance rate. HBsAg clearance rate tends to increase over the time of treatment. A baseline HBsAg level of 500 IU/mL can be used as the cut-off point to identify the dominant population.

Objective:To investigate the efficacy of metagenomic next generation sequencing (mNGS) in the etiological diagnosis of patients with spinal infection, so as to provide reference for timely diagnosis and treatment.Methods:A total of 40 patients with suspected spinal infection admitted to the Department of Infectious Diseases in Henan Provincial People′s Hospital from January 2020 to July 2022 were included. The results of tissue culture, histopathological examination and tissue mNGS detection were analyzed retrospectively. According to the clinical diagnose, the patients were divided into the spinal infection group (28 cases) and the non-spinal infection group (12 cases). The positive rate, sensitivity and specificity of mNGS and tissue culture in the pathogen detection of patients with spinal infection were compared. McNemar test was used for statistical analysis.Results:There were 23 males and 17 females in 40 patients. The positive rate of mNGS was higher than that of tissue culture (75.0%(30/40) vs 12.5%(5/40)), and the difference was statistically significant ( χ2=0.08, P<0.001). Based on clinical diagnostic criteria, the sensitivity of mNGS in the diagnosis of spinal infection was higher than that of tissue culture (82.1% vs 17.9%), with a statistically significant difference ( χ2=0.02, P<0.001), while the specificity compared to the tissue culture (33.3% vs 100.0%), the difference was not statistically significant ( P>0.05). Conclusions:mNGS has a high pathogen detection rate and sensitivity in the etiological diagnosis of patients with spinal infection, which could provide clinical guidance for the diagnosis and treatment of patients with spinal infection.

目的:评估人工肝血液净化系统(Blood Purification-Artificial Liver Support System,BP-ALSS)用于新型冠状病毒感染重症肺炎疗效.方法:收集2020年1月23日至2020年2月16日收治于河南省人民医院的确诊为新型冠状病毒感染并合并重度肺部感染患者的临床资料,比较患者应用人工肝血液净化系统治疗前后血细胞计数、血气分析、细胞因子等指标的变化.结果:经过BP-ALSS治疗,6例患者治疗前后血液pH值、PCO2、PO2、SaO2(动脉血氧饱和度)、乳酸水平好转,临床症状得到改善,3例患者治疗后各项细胞因子较治疗前指标下降.结论:早期人工肝血液净化可快速降低新型冠状病毒感染重症肺炎的炎症介质水平,提高肺泡-动脉间氧的交换,对病情恢复具有促进作用,外周血淋巴细胞比例对早期感染评估具有一定诊断价值.

Objective:To analyze the liver pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and negative hepatitis B e antigen (HBeAg), and to evaluate the diagnostic value of different serological models for liver fibrosis.Methods:Retrospective analysis was conducted on the patients with HBeAg-negative CHB who had normal ALT and underwent liver biopsy from August 2016 to December 2019 in the Department of Infectious Diseases, Henan Provincial People′s Hospital. The clinical data, serum indicators of hepatitis B virus (HBV) and HBV DNA were collected. The liver fibrosis stages (S) was assessed by pathological examination. The diagnostic efficacies of gamma-glutamyl transpeptidase to platelet ratio (GPR), fibrosis 4 score (FIB-4), S index, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase to albumin ratio (γ-GT/ALB) for liver pathological fibrosis were analyzed by the receiver operating characteristic curves. Two variable correlation test was used to explore the relationship between the different models and pathological fibrosis of liver tissue. Chi-square test was used for statistical comparison.Results:The age of 448 patients was (37.98±9.82) years, and the male to female ratio was 1.286 ∶1. The proportions of S≥2 in patients with age>30 years, hepatitis B surface antigen (HBsAg)<2 000 IU/mL and HBV DNA≥2 000 IU/mL were higher than those in patients with age ≤30 years, HBsAg ≥2 000 IU/mL and HBV DNA<2 000 IU/mL, respectively, and the differences were all statistically significant ( χ2=7.68, P=0.006; χ2=11.44, P=0.001; χ2=9.12, P=0.003, respectively). There were 250 cases with pathological fibrosis stage S<2, 162 cases with S=2 and 36 cases with S≥3. FIB-4 (correlation coefficient 0.250), APRI (correlation coefficient 0.218), GPR (correlation coefficient 0.186), S index (correlation coefficient 0.184) and γ-GT/ALB (correlation coefficient 0.127) were positively correlated with the severity of liver fibrosis (all P<0.050). S index had the highest sensitivity (64.1%) in the diagnosis of significant liver fibrosis (S≥2), while γ-GT/ALB had the highest specificity (80.8%). In the diagnosis of severe liver fibrosis (S≥3), γ-GT/ALB had the highest sensitivity (77.8%), while APRI had the highest specificity (78.6%). Conclusions:The incidence of liver fibrosis in CHB patients with normal ALT and negative HBeAg is relatively high. The current serological diagnostic models are not suitable for the evaluation of liver fibrosis in these patients, and timely liver puncture is still necessary.

Objective: To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT). Methods: 721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test. Results: The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, χ2=6.182, P=0.013; Fibrosis grade, χ2=36.534, P=0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant (P<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences (P<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit P=0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. Conclusion: More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.

ObjectiveTo investigate whether there are differences in lymphocyte subsets between chronic hepatitis B (CHB) patients receiving different antiviral treatment regimens, and to determine related predictive factors for HBsAg decline. MethodsA retrospective analysis was performed for 68 treatment-experienced CHB patients who attended the outpatient service in Department of Infectious Diseases, Henan Provincial People’s Hospital, from October to December 2019, and according to the antiviral treatment regimen, they were divided into PEG-IFNα treatment group with 10 patients, PEG-IFNα+nucleos(t)ide analogues (NAs) treatment group with 21 patients, and NAs treatment group with 37 patients. Related data were recorded, including demographic features, blood routine, albumin, HBsAg, and measurement of lymphocyte subsets. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the multivariate logistic regression analysis was used to investigate independent influencing factors for HBsAg decline. ResultsThere were significant differences between the three groups in HBsAg decline (H=8.348, P=0.015), absolute value of lymphocytes (F=4.643, P=0.013), and T lymphocyte count (F=7.721, P=0001). The multivariate logistic regression analysis showed that sex (odds ratio ［OR］=0.227, 95% confidence interval ［CI］: 0.059-0.878, P=0.032), age (OR=0.931, 95%CI: 0.868-0.999, P=0.047), antiviral treatment regimen (PEG-IFN-α treatment group vs NAs treatment group: OR=9.600, 95%CI: 1.982-46.498, P=0.005; PEG-IFN-α+NAs treatment group vs NAs treatment group: OR=4.800, 95%CI: 1.336-17.243,P=0.016), and T lymphocyte count (OR=0.804, 95%CI: 0.684-0.944, P=0.008) were independent influencing factors for HBsAg decline. ConclusionFor CHB patients receiving PEG-IFNα alone or in combination with NAs, monitoring of lymphocyte subsets during the treatment process may help to judge HBsAg decline, and the lower the absolute value of T lymphocytes, the greater the possibility of HBsAg decline.

Objective:To evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in patients with genotype 1 chronic hepatitis C in the real-world.Methods:This was an open-label, single-center, retrospective real-world study. A total of 103 genotype 1 chronic hepatitis C patients who were treated with EBR/GZR in Henan Provincial People′s Hospital from May 2018 to October 2019 were enrolled.And the clinical baseline characteristics of patients and the effectiveness and safety of antiviral therapy were respectively evaluated.Results:A total of 103 patients were enrolled in the study with an age of (47.6±13.9) years. Fifty-five (53.4%) patients were male and 48(46.6%) were female. One point nine percent (2/103) patients were genotype 1a hepatitis C and 98.1%(101/103) were genotype 1b hepatitis C. Seventeen genotype 1b hepatitis C patients were previously treated with interferon, and three patients co-infected with hepatitis B virus (HBV). Among the 103 cases, 35 had underlying diseases and 26 had combined medication. Ninty-eight cases completed 12-week treatment and 89 cases completed 12-week follow-up after treatment.Overall, 89 cases achieved sustained virological response. The overall incidence of adverse reactions was 20.4%(21/103), and the main adverse reactions were fatigue, insomnia and anxiety. No serious adverse event occurred. The three patients with HBV co-infection had no hepatitis B activation after treatment.Conclusion:EBR/GZR is effective and safe in the patients with genotype 1 chronic hepatitis C in China.

Objective: To investigate the changes of bone mineral density and its related influencing factors in chronic hepatitis B patients treated with long-term entecavir monotherapy. Methods: 211 cases with chronic hepatitis B treated with entecavir monotherapy in the Department of Infectious Diseases of Henan Provincial People's Hospital from June 2018 to September 2019 were retrospectively collected. Age, gender, body mass index, number of years of medication use, presence or absence of liver cirrhosis and current bone mineral density level (using dual-energy X-ray detection, taking lumbar L1 ~ 4 and left femur as observation region) and other related data were collected. 211 cases general situation was descriptively analyzed by case-control study design. Two independent sample t-tests were used to compare the differences in serum calcium, phosphorus, and renal function levels in patients with different medication durations. Univariate logistic regression was used to screen the influencing factors of bone mineral density level. Significant variables of univariate analysis were included in multivariate logistic regression to obtain the independent influencing factors leading to the decrease of bone mineral density level. The test level was set as α = 0.05. Results: The average age of 211 cases with chronic hepatitis B was (42.36 ± 11.10) years. The average medication time use was (2.52 ± 1.94) years. The body mass index (23.95 ± 3.11), and male-to-female ratio was 2.25/1. The incidence of liver cirrhosis was 35.5%. The incidence of low bone mass in the two observation sites (lumbar spine L1~4 and left femur) was 24.6% and 29.4%, respectively. There were statistically significant differences in serum calcium, phosphorus and renal function levels among patients with different entecavir treatment duration (≥3 years and < 3 years) (P < 0.05). Univariate analysis result showed that the influencing factors of BMD were age, the number of years of medication use, gender, liver cirrhosis (L1~4 of the lumbar spine region) and age, the number of years of medication, and gender (left femoral region). The variables that entered the two models after the multivariate analysis were age (L1~4 region of lumbar spine: OR = 2.225, left femur OR = 1.660), gender (L1~4 region of lumbar spine: OR = 3.048, left femur OR = 2.496), number of years of medication use (L1~4 region of lumbar spine: OR = 1.387, left femur OR = 1.276). Conclusion: Age, gender, and the number of years of medication use are independent factors that influence the bone mineral density of patients with chronic hepatitis B treated with long-term entecavir. Low bone mass risk at the two observation sites is 2.225 and 1.66 times the normal level for every 10 years of age increase. Compared with men, the risk of low bone mass at the two observation sites is 3.048 and 2.496 times for women, and for every additional year of medication use, the risk of low bone mass at the two observation sites is 1.387 and 1.276 times the normal level. Female patients with older age and prolonged medication use are at high risk of developing bone mineral density reduction.

ObjectiveTo investigate the status of abnormal renal function markers and related influencing factors in chronic hepatitis B (CHB) patients receiving oral antiviral drugs for a long time. MethodsA retrospective analysis was performed for the clinical data of 681 CHB patients who attended Henan Provincial People’s Hospital from January to December 2019 and received long-term oral administration of entecavir (ETV)/tenofovir disoproxil fumarate (TDF). All patients received the measurement of blood renal function markers (urea, creatinine, retinol-binding protein ［RBP］, cystatin C ［Cys-C］, and β2-microglobulin ［β2-MG］), urinary renal function markers (α1-microglobulin ［α1-MG］, Cys-C, and N-acetyl-β-D-glucosaminidase ［NAG］), and urine routine parameters. The incidence rate of abnormal renal function markers were analyzed. The McNemar’s test was used for comparison of categorical data between groups, and the multivariate logistic regression analysis was used to investigate independent influencing factors for abnormal renal markers in urine. ResultsThe 681 patients had a mean age of 39.8±11.0 years and received medication for 1.88 (0.80-3.16) years. There were 417 male patients and 264 female patients, and the incidence rate of liver cirrhosis was 27.02% (184/681). Of all 681 patients, 442 received ETV and 239 received TDF. The measurement of blood renal function markers showed that urea, creatinine, retinol-binding protein, Cys-C, and β2-MG had an abnormal rate of 6.9% (47/681), 0.15% (1/681), 0(0/681), 2.21% (15/681), and 5.03% (30/681), respectively, and the abnormal rate of urinary protein was 7.29% (49/672). The measurement of urinary renal function markers showed that α1-MG, NAG, and Cys-C had an abnormal rate of 38.62% (263/681), 37.74% (257/681), and 19.38% (132/681), respectively. The abnormal rate of urine test was higher than that of blood test (P＜0.001). The multivariate logistic regression analysis with urinary α1-MG as the dependent variable showed that sex (odds ratio ［OR］=0.293, 95% confidence interval ［CI］: 0.204-0.419, P＜0.05), age (OR=1298, 95%CI: 1.108-1.521, P＜0.05), and type of nucleoside drug (OR=2.100, 95%CI: 1.431-3.083, P＜0.05) were influencing factors. The multivariate logistic regression analysis with urinary NAG as the dependent variable showed that age (OR=1.177, 95%CI: 1.008-1.375, P=0.040) was an influencing factor. ConclusionCompared with blood renal function markers, urinary renal function markers can identify renal injury earlier in CHB patients, and the elderly patients and the patients receiving TDF are more likely to develop abnormal renal function. However, it is not observed whether the duration of medication and liver cirrhosis can increase the risk of renal injury in CHB patients.

[目的]探讨新型冠状病毒肺炎(COVID-19)患者的血常规特点,分析血常规指标变化与临床分型的相关性.[方法]回顾性分析129例COVID-19成年患者首诊及治疗后(转归前)血常规及C反应蛋白的检测结果,计算中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、淋巴细胞与单核细胞比值(LMR),比较非重症组(93例)和重症组(36例)治疗后和首诊时上述指标的差异,观察治疗后血常规指标变化与患者预后的相关性.[结果]129例患者的平均年龄为(46.9±17.4)岁,男女性比例为1.2:1.白细胞下降者(<4×109/L)35例(27.1％),淋巴细胞下降者(<1.1×109/L)59例(45.7％).两组患者的年龄、治疗天数、血常规指标差异有统计学意义;治疗前后差异有统计学意义的指标为白细胞数、中性粒细胞百分比、淋巴细胞数、淋巴细胞百分比、单核细胞数、单核细胞百分比、红细胞数、血红蛋白量、C反应蛋白、NLR;两组患者治疗前后血红蛋白量差值、血小板计数差值及NLR差值比较,差异有统计学意义(P<0.05).[结论]COVID-19患者年龄越大、淋巴细胞数越低、NLR和PLR越高、LMR越低以及C反应蛋白越高则患者重症的发生风险就越大.在治疗后均可出现粒细胞数的增加,尤其是淋巴细胞数的明显增加,以及C反应蛋白和NLR的下降.淋巴细胞计数、NLR、C反应蛋白水平变化能够预测COVID-19患者的重症风险及评估治疗的疗效.

Objective:To evaluate the efficacy of artificial liver blood purification system in the treatment of severe and critical patients with corona virus disease 2019(COVID-19), and to observe the dynamic changes of lymphocyte subsets and cytokines after treatment.Methods:A total of six patients with COVID-19 admitted to the ward of public health center of Henan Provincial People′s Hospital from January 31 to February 18, 2020 were enrolled, including three severe cases and three critical cases. The protocals of artificial liver treatment were developed according to the patients′ conditions, and the patients′ epidemiological history, clinical characteristics, and laboratory examination data were retrospectively analyzed. At the same time, dynamic changes of lymphocyte subsets and cytokines were detected before and after artificial liver treatment.Results:By February 24, 2020, two severe patients were discharged after cured, and one case was discharged after improved, with an average stay of 19 days. Two critical patients were still hospitalized and one died. Three severe patients were all treated with hemofiltration, while two critical patients were treated with hemofiltration plus plasma exchange, and one was treated with continuous bedside hemofiltration.Among six patients, the ratio of neutrophils to lymphocytes before treatment were 6.42, 2.63, 15.00, 15.09, 12.04 and 30.41, respectively. After treatment, the ratio of neutrophils to lymphocytes became 4.77, 6.05, 4.86, 5.43, 32.77 and 23.46, respectively.The absolute numbers of lymphocytes in six patients before treatment were low, with a median of 382/μL. After treatment of artificial liver, the absolute numbers of lymphocytes increased, with a median of 476/μL. Cytokines were detected in three critical patients, and the interleukin 6 (IL-6) levels in two cases were 26 042.00 ng/L and 282.03 ng/L, respectively before treatment. After treatment, the levels decreased to 226.85 ng/L and 26.15 ng/L, respectively. IL-6 continued increasing from 30.14 ng/L to 709.25 ng/L in one another critical patient, who eventually died.Conclusions:In severe and critical patients with COVID-19, artificial liver treatment can reduce inflammation and increase the absolute numbers of lymphocytes and the subsets. The IL-6 level may be correlated with disease progression and may be a useful prognostic factor for early identification of severe and critical COVID-19.

目的:了解新型冠状病毒肺炎(COVID-19)患者的早期临床特点。方法:回顾性分析2019年12月20日至2020年2月7日就诊于河南省人民医院、信阳市中心医院、巩义市人民医院的44例COVID-19确诊患者的临床资料。比较轻型/普通型组(40例)和重型/危重型组(4例)患者的临床表现，以及淋巴细胞计数、C反应蛋白、乳酸脱氢酶和总胆红素等实验室检查指标。组间比较采用 t检验、秩和检验。 结果:44例患者中，36例患者有武汉市旅居史，6例为本地确诊病例，2例流行病学史不详。患者初次就诊时发热30例(68.2%)，咽部不适4例(9.1%)，乏力9例(20.5%)。在疾病早期进展中43例出现发热(97.7%)，其中低热21例，中度热16例，高热5例，超高热1例。与轻型/普通型组患者相比，重型/危重型组患者的发热时间更长[(7.55±3.56) d比(13.75±2.22) d， t＝3.397， P＝0.001]，淋巴细胞计数更低[1.12(0.83，1.23)×10 9/L比0.38(0.04，0.49)×10 9/L， Z＝2.780, P<0.01]，C反应蛋白更高[10.60(3.64, 19.75) mg/L比41.50(33.00, 64.00) mg/L， Z＝2.234， P＝0.021]，总胆红素更高[6.9(5.4, 9.4) μmol/L比11.3(9.9, 28.5) μmol/L， Z＝2.275， P＝0.016]，乳酸脱氢酶更高[210(174，252) U/L比480(471，489) U/L， Z＝2.102， P＝0.024]，差异均有统计学意义。 结论:发热是COVID-19患者的主要临床症状。重型/危重型患者与轻型/普通型患者相比，发热持续时间更长，体温更高，淋巴细胞计数更低，C反应蛋白、乳酸脱氢酶、总胆红素水平更高。

Objective:To study whether gene mutation pattern of Gilbert’s syndrome (GS) is combined with viral hepatitis and its relationship with relevant clinical data.Methods:Clinical data of GS patients combined with viral hepatitis who was admitted to the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2013 to December 2018 was retrospectively analyzed. The relationship between gene mutation pattern, general data (age, gender, etc.) and liver biochemical indexes was analyzed. The differences of the above data in patients with or without combined viral hepatitis were analyzed. The measurement data were compared by t-test. The categorical data was compared by the χ2 test. The median and interquartile range of non-normally distributed data was used to indicate the central and discrete tendency. Results:A total of 107 GS eligible cases data were collected. The male to female ratio was 4.94:1 (89:18). The average age of onset was (36.36 ± 12.51) years. Alanine aminotransferase and total bilirubin levels were normal or slightly elevated, while aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase were all within the normal range. There were 49 cases in the combined viral hepatitis group (36 cases with HBV and 13 cases with HCV), and 58 cases in the GS alone group. Total bilirubin level in GS alone group was higher than the combined viral hepatitis group ( z = 0.035, P < 0.05), and there were no statistically significant differences in gender, age, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyltransferase ( P > 0.05). Uridine diphosphate glucuronide transferase 1A1 (UGT1A1), specifically encoded by GS was detected in all 107 cases. Mutations was mainly occurred in the upstream promoter PBREM-3263 (-3279) (86 cases) and TATA box TA insertion mutation (71 cases), and GGA-AGA Gly71Arg (57 cases) mutation in EXON1 of the coding region. All mutation forms had manifestations of homozygous and heterozygous abnormalities. The combined incidence of main mutation forms in the genetic testing data were sequenced as: A2 + B2 + C2 (17 cases, 25.23%), A1 + B1 (17 cases, 15.89%), A2 (11 cases, 10.28%), C2 (10 Cases, 9.34%), A2 + B2 (7 cases, 6.54%), A1 + B2 (7 cases, 6.54%), C1 (7 cases, 6.54%), and there was no statistically significant difference between different mutation combinations in patients with or without hepatitis ( P > 0.05). The results of total data analysis showed that the total bilirubin level in the single-site mutation group was higher than the multi-site mutation group (Z=2.019, P = 0.043), and other biochemical indicators had no effect ( P > 0.05) and the differences were not statistically significant. Further analysis showed that the total bilirubin level of the single-site mutation subgroup in the GS alone group was higher than the multi-site mutation subgroup ( Z = 1.999, P = 0.046), and the statistical difference was similar to the combined viral hepatitis group ( P > 0.05). Different mutation combinations had no effect on biochemical indexes, and had no relationship with combined viral hepatitis ( P > 0.05). Conclusion:GS is common in patients with combined viral hepatitis, and there is no significant difference between the incidence of gene mutation, mutation forms, biochemical indexes, and non-hepatitis group. The increase in the number of GS mutation sites does not aggravate the deterioration of bilirubin levels due to the decrease in the content and activity of uridine diphosphate glucuronosyltransferase, and the combination of different mutation sites does not affect the changes of various biochemical indexes, and at the same time it is not related to hepatitis.

1 病例资料 患儿男性,5岁,主诉“体检发现丙型肝炎抗体阳性2年”于2017年8月23日入本院.患儿2年前体检发现抗-HCV阳性,当时无纳差、乏力、腹胀、恶心等不适,未治疗,定期每6个月于本院门诊复查.2017年8月10日于本院门诊随诊检查肝功能:ALT 37 U/L,AST 47 U/L,HCV RNA:2 954 969 IU/ml(采用实时荧光定量PCR,Abbott m2000全自动核酸检测仪,雅培原装试剂,检测下限为12 IU/ml),门诊以“慢性丙型肝炎”为诊断收入本院感染科.患儿既往体健,无高血压,无冠心病,无血脂异常,无脑血管疾病,无HIV、HBV感染病史,否认“结核、疟疾”病史.预防接种随社会进行,无手术史,无外伤史,无输血史,无献血史,无食物、药物过敏史.父亲体健,母亲患有“慢性丙型肝炎”.

Objective To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C.Methods Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province,Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted.All patients received OBV/PTV/RTV+DSV antiviral therapy.HCV RNA levels were measured at baseline,weeks 1,2,3,4,8,12,and 24,then 12 weeks,and 24 weeks after completion of treatment;patients' comorbidity,concomitant medications,and clinical adverse events were recorded.Results 108 patients were enrolled in the study,with an average age of 49.1 years,44 patients were male (40.8％),96.3％ (104/108) were newly diagnosed,and four patients had previous treatment history,of whom three were treated with IFN and one with IFN + DAA.Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks,after discontinuation of the drug.Overall,89 cases (100％) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment,which was significantly higher than the baseline HCV RNA level (301776IU/ML),and was judged as failure of treatment;and follow-up was discontinued.Of all enrolled patients,19 (17.6％) had underlying diseases and 15 (13.9％) had combined medications.During treatment,adverse events (AE) occurred in 11 patients (10.1％).The main adverse events were pruritus and elevated bilirubin.Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Objective To explore the efficacy and safety of daclatasvir (DCV ) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C .Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included .Hepatitis C virus (HCV ) RNA levels were tested before treatment ,1 week ,2 weeks ,3 weeks ,4 weeks ,8 weeks ,12 weeks and 24 weeks after treatment , and 12 weeks after the end of the treatment .The comorbidities ,combined use of drugs and adverse clinical events were registered .T test was used to compare the measurement data with normal distribution and M (P25,P75) was used for measurement data with non-normal distribution .Results A total of 29 patients with GT1b were included ,with 4 cirrhosis cases and 25 non cirrhotic cases .Seven patients had history of previous interferon and ribavirin combination treatment .There were 9 patients with comorbidity and 7 patients with combined medication . Finally , 25 patients completed a 24-week course of antiviral treatment ;3 patients were lost to follow-up ,and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound .Of the 26 followed up patients ,25 achieved sustained virological response at 12-week (SVR12 ) , and one patient failed .And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure .No severe adverse clinical events occurred in 26 patients .Conclusions DCV combined with ASV is effective and safe in the treatment of GT 1b chronic hepatitis C .However , the effect of RAV on therapeutic efficacy should be concerned during the treatment .