Objective:To compare the effects of intraoperative administration or non-administration of tranexamic acid (TXA) on early postoperative inflammatory response and clinical outcomes in elderly male patients with intertrochanteric femur fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 elderly male patients with intertrochanteric femur fractures admitted to Zhongda Hospital Affiliated to Southeast University from January 2020 to December 2022, aged 62-96 years [(79.9±8.4)years]. According to the modified Evans classification, the fractures were classified as types I-III in 33 patients and types IV-V in 59. All the patients were treated with proximal femoral intramedullary nail fixation. Among them, 46 patients received intraoperative TXA (TXA group), while 46 patients did not (non-TXA group). The operative duration, intraoperative blood loss, length of postoperative hospital stay were compared between the two groups. The serum interleukin-6 (IL-6) levels and visual analogue scale (VAS) scores at 1, 3, 5, and 7 days postoperatively were detected. The complication rate and mortality within 1 year postoperatively were also compared between the two groups.Results:All the patients were followed up for 1-12 months [(10.9±2.8)months]. No significant difference was found in the operative duration between the groups ( P>0.05). The intraoperative blood loss and length of postoperative hospital stay were 150.0(100.0, 200.0)ml and (6.8±1.9)days in the TXA group, less or shorter than those in the non-TXA group [200.0(150.0, 262.5)ml and (7.7±2.0)days] ( P<0.05). At 1, 3, and 5 days postoperatively, the IL-6 levels in the TXA group were 84.5(66.3, 100.1)pg/ml, 48.9(36.8, 61.2)pg/ml, and 27.9(19.4, 37.5)pg/ml, which were all lower than those in the non-TXA group [110.3(83.1, 162.9)pg/ml, 63.7(44.2, 84.2)pg/ml, and 32.7(22.4, 42.9)pg/ml] ( P<0.05). No statistically significant difference in the IL-6 level was observed between the two groups at 7 days postoperatively ( P>0.05). At 1 and 3 days after operation, the VAS scores in the TXA group were (4.3±0.9)points and (2.5±0.9)points, lower than those in the non-TXA group [(6.8±1.2)points and (3.0±1.2)points] ( P<0.05). There were no statistically significant differences in VAS scores between the two groups at 5 and 7 days postoperatively ( P>0.05). The complication rate within one year after operation was 28% (13/46) in the TXA group, significantly lower than 50% (23/46) in the non-TXA group ( P<0.05). No significant difference was observed in the mortality within 1 year postoperatively between the two groups ( P>0.05). Conclusion:Compared with non-administration of TXA, intraoperative administration of TXA can effectively reduce the intraoperative blood loss, shorten the length of postoperative hospital stay, significantly lower early postoperative inflammation levels, reduce early postoperative pain intensity, and decrease the incidence of complications in elderly male patients with intertrochanteric femur fractures, with no significant difference in mortality within 1 year after operation between the two groups.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

Objective:To compare the effects of intraoperative administration or non-administration of tranexamic acid (TXA) on early postoperative inflammatory response and clinical outcomes in elderly male patients with intertrochanteric femur fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 elderly male patients with intertrochanteric femur fractures admitted to Zhongda Hospital Affiliated to Southeast University from January 2020 to December 2022, aged 62-96 years [(79.9±8.4)years]. According to the modified Evans classification, the fractures were classified as types I-III in 33 patients and types IV-V in 59. All the patients were treated with proximal femoral intramedullary nail fixation. Among them, 46 patients received intraoperative TXA (TXA group), while 46 patients did not (non-TXA group). The operative duration, intraoperative blood loss, length of postoperative hospital stay were compared between the two groups. The serum interleukin-6 (IL-6) levels and visual analogue scale (VAS) scores at 1, 3, 5, and 7 days postoperatively were detected. The complication rate and mortality within 1 year postoperatively were also compared between the two groups.Results:All the patients were followed up for 1-12 months [(10.9±2.8)months]. No significant difference was found in the operative duration between the groups ( P>0.05). The intraoperative blood loss and length of postoperative hospital stay were 150.0(100.0, 200.0)ml and (6.8±1.9)days in the TXA group, less or shorter than those in the non-TXA group [200.0(150.0, 262.5)ml and (7.7±2.0)days] ( P<0.05). At 1, 3, and 5 days postoperatively, the IL-6 levels in the TXA group were 84.5(66.3, 100.1)pg/ml, 48.9(36.8, 61.2)pg/ml, and 27.9(19.4, 37.5)pg/ml, which were all lower than those in the non-TXA group [110.3(83.1, 162.9)pg/ml, 63.7(44.2, 84.2)pg/ml, and 32.7(22.4, 42.9)pg/ml] ( P<0.05). No statistically significant difference in the IL-6 level was observed between the two groups at 7 days postoperatively ( P>0.05). At 1 and 3 days after operation, the VAS scores in the TXA group were (4.3±0.9)points and (2.5±0.9)points, lower than those in the non-TXA group [(6.8±1.2)points and (3.0±1.2)points] ( P<0.05). There were no statistically significant differences in VAS scores between the two groups at 5 and 7 days postoperatively ( P>0.05). The complication rate within one year after operation was 28% (13/46) in the TXA group, significantly lower than 50% (23/46) in the non-TXA group ( P<0.05). No significant difference was observed in the mortality within 1 year postoperatively between the two groups ( P>0.05). Conclusion:Compared with non-administration of TXA, intraoperative administration of TXA can effectively reduce the intraoperative blood loss, shorten the length of postoperative hospital stay, significantly lower early postoperative inflammation levels, reduce early postoperative pain intensity, and decrease the incidence of complications in elderly male patients with intertrochanteric femur fractures, with no significant difference in mortality within 1 year after operation between the two groups.

Objective:To compare the effectiveness of awake prone positioning (APP) care combined with standardized nursing and standardized nursing care in the prevention of early postoperative pulmonary complications (PPCs) in elderly patients with hip fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 84 elderly patients with hip fracture Admitted to Zhongda Hospital Affiliated to Southeast University from February 2021 to August 2021. There were 31 males and 53 females, aged 67-96 years [(82.3±6.3)years]. Fracture types were femoral neck fracture ( n=45) and intertrochanteric fracture ( n=39). Surgical procedures included closed reduction internal fixation ( n=39), hip hemiarthroplasty ( n=35), and total hip arthroplasty ( n=10). Among them, 42 patients received standardized nursing care and APP intervention (APP combined with standardized nursing care group), while the remaining 42 patients received standardized nursing care only (standardized nursing care group). The incidence rate of PPCs (including pneumonia, respiratory failure, pleural effusion, atelectasis and pulmonary edema) within 30 postoperative days, arterial oxygen pressure (PaO 2), arterial carbon dioxide pressure (PaCO 2), arterial oxygen saturation (SaO 2) on the 4th postoperative day, difference in PaO 2 between the 4th postoperative day and emergency visit, clinical pulmonary infection score (CPIS) on the 4th postoperative day, and number of adverse events related to APP were compared between the two groups. Results:All the patients were followed up for 30-90 days [(86.1±16.5)days]. The incidence rates of PPCs and type 1 postoperative respiratory failure in the APP combined with standardized nursing care group were 16.7% (7/42) and 4.8% (2/42), and were 35.7% (15/42) and 21.4% (9/42) in the standardized nursing care group (all P<0.05). The PaO 2 and SaO 2 on the 4th postoperative day, and difference in PaO 2 between the 4th postoperative day and emergency visit were (82.0±8.8)mmHg, 0.96±0.01, and 3.2 (-1.9, 8.0)mmHg in the APP combined with standardized nursing care group, and were (74.3±12.1)mmHg, 0.94±0.03, and -7.6 (-17.2, 1.1)mmHg in the standardized nursing care group (all P<0.01). The CPIS on the 4th postoperative day was 2.0 (1.0, 3.0)points in the APP combined with standardized nursing care group and 4.0 (1.0, 7.0)points in the standardized nursing care group ( P<0.05). No statistically significant differences were observed in the incidence of pneumonia, type I respiratory failure, pleural effusion, atelectasis and pulmonary edema within 30 postoperative days, as well as PaCO 2 on the 4th postoperative day between the two groups (all P>0.05). None of the patients experienced adverse events related to APP. Conclusion:For elderly patients with hip fracture, compared with standardized nursing care, application of APP combined with standardized nursing care can significantly decrease the incidence rate of early PPCs, especially type I respiratory failure, and improve postoperative oxygenation.

Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.

Objective:To investigate the risk factors for preoperative hypoxemia in geriatric patients with hip fracture.Methods:A case-control study was used to analyze the clinical data of 99 geriatric patients with hip fracture admitted to Zhongda Hospital affiliated to Southeast University between November 2020 and August 2021. There were 29 males and 70 females, aged 67-96 years [(82.6±6.2)years]. The patients were divided into hypoxemia group ( n=51) and non-hypoxemia group ( n=48) using partial arterial partial pressure of oxygen (PaO 2)<80 mmHg while breathing room air at emergency as the reference standard. The two groups were compared in terms of sex, age, fracture types, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, pulmonary diseases diagnosed by preoperative chest CT [atelectasis, pleural effusion, chronic obstructive pulmonary disease (COPD)], time from injury to visit, New York Heart Association (NYHA) classification, Barthel index, KATZ index, modified Medicine Research Council (mMRC) dyspnea scale, numeric rating scale (NRS), smoking, drinking, comorbidities (hypertension, diabetes mellitus, Parkinson′s disease, Alzheimer′s disease, cerebral infarction, coronary atherosclerotic heart disease), body temperature, blood routine test at first examination (erythrocyte count, leukocyte count, C-reactive protein, hemoglobin), biochemistry (serum albumin, blood glucose, blood creatinine, blood urea nitrogen), electrolyte (serum potassium, serum sodium), and other related examinations [D-dimer, brain natriuretic peptide (BNP), lactic acid]. Univariate analysis was performed to the correlation of those indicators with preoperative hypoxemia. Multivariate Logistic regression analysis was used to identify the independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture. Results:Differences in sex, age, fracture types, BMI, pulmonary diseases diagnosed by preoperative chest CT, time from injury to visit, Barthel index, KATZ index, NRS, smoking, drinking, comorbidities, body temperature, first laboratory results of erythrocyte count, biochemistry, electrolyte and other related examinations were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination, C-reaction protein and hemoglobin (all P<0.05). Univariate analysis indicated that ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination and C-reaction protein were correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture (all P<0.05). Multivariate Logistic regressions analysis indicated that higher mMRC dyspnea scale ( OR=2.30, 95% CI 1.10-4.81, P<0.05), higher leukocyte count at first examination ( OR=1.24, 95% CI 1.05-1.45, P<0.05), higher level of C-reaction protein ( OR=1.02, 95% CI 1.01-1.03, P<0.05) and higher level of hemoglobin ( OR=1.04, 95% CI 1.01-1.07, P<0.05) were significantly correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture. Conclusion:Higher mMRC dyspnea scale, higher leukocyte count, higher level of C-reaction protein and higher level of hemoglobin are independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture.

Objective:To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type.Methods:A retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results:The BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene ( CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. Conclusion:CACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.

Objective:To identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy (EOSRD).Methods:A retrospective clinical study. One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study. After the detailed history of the patients was collected, all participants underwent best corrected visual acuity (BCVA), slit-lamp, fundus biomicroscopy with the slit lamp, untra-widefield fundus color photography, spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ff-ERG). The subject’s peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted. A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing, and Sanger sequencing was performed for the clear pathogenic mutation sites; the analysis software was used for bioinformatics analysis of the mutation sites.Results:A 6-year-old female proband developed poor night vision in both eyes after 1 year old. The BCVA of both eyes were 0.1. The color of the optic disc was slightly lighter; the diameter of the retinal vessels was slightly reduced, and extensive pigment changes can be seen in the retina outside the vascular arch. SD-OCT examination showed that the outer membrane, ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent. The visual area outside the fovea was neuroepithelial outer plexiform layer, outer nuclear layer, outer membrane, ellipsoid zone. The chimera zone gradually disappeared, and the thickness of the pigment epithelial layer was not uniform. In ff-ERG examination, the functions of the binocular cone and rod system were severely decreased. The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein (TULP1) gene of the proband, and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1 (CNGB1) gene. Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species; bioinformatics analysis results showed that TULP1 gene c.921C>A (p.Cys307*) had translation termination in the protein conserved region, CNGB1 gene c.3121C>T (p.Arg1041Trp) and c.3488G>A (p.Gly1163Glu) had amino acid polarity changes in the protein conserved region, which led to major changes in the protein spatial structure.Conclusion:TULP1 gene c.921C>A homozygous mutation, CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.

Objective:To investigate the effect of programmed death receptor (PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer.Methods:Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected. At the same time, all of the above-mentioned hepatitis B virus (HBV) patients were treated with nucleos(t)ide analogues. Patients clinical diagnostic data, laboratory test results, tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety, therapeutic anti-tumor effect, HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy, high viral load treatment condition, and HBV reactivation safety issues. Statistical analysis was performed by non-parametric rank sum test.Results:Therapeutic anti-tumor effect and safety profile were good in patients. The complete remission rate was reached 27.6%. Adverse reactions were mostly mild, and the incidence of serious adverse reactions was low. After 12 weeks of follow-up, HBV DNA and hepatitis B surface antigen (HBsAg) was quantitatively decreased ( P < 0.05). HBV DNA and HBsAg were decreased more significantly in patients with progressive disease (PD), stable disease (SD) and partial response (PR) ( P < 0.05). Five patients with HBV DNA ≥ 10 4 IU/ml had responded well to the tumor treatment without serious adverse reactions. One patient had a slight increase in HBV DNA and alanine aminotransferase, while there was no HBV reactivation and correlated liver damage. Conclusion:Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile. PD-1 treatment has a certain effect on HBV. Compared with non-responders, patients with tumor response have better antiviral treatment efficacy. The safety of treatment in patients with high viral load is manageable, and there are no safety issues related to HBV reactivation.