Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Hepatitis C virus infection is a global public health issue， and the emergence of direct-acting antiviral agents has brought revolutionary breakthroughs in the treatment of hepatitis C patients. Although direct-acting antiviral agents have a marked therapeutic effect in adult patients， there are still many challenges in the treatment of special populations such as pregnant women， infants， young children， and adolescents. This article reviews the current status of antiviral therapy for these special populations with hepatitis C and the problems that need to be solved， in order to provide reference and guidance for clinical workers.

Objective:To explore the efficacy and safety profile of tenofovir alafenamide fumarate (TAF) in the treatment of patients with decompensated hepatitis B cirrhosis.Methods:A two-way cohort study method was used to enroll patients with decompensated hepatitis B cirrhosis who visited four medical centers, including Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, from April 2021 to April 2024 and were treated with TAF and followed up for 48 weeks. The primary efficacy indicator was hepatitis B virus (HBV) DNA seronegative conversion rate at 48-weeks, and the secondary efficacy indicator was alanine aminotransferase (ALT) return to normal rate at 48-weeks. Relevant safety indicators, adverse drug reactions (ADRs), and clinical adverse outcomes were collected.Results:A total of 74 cases were included. Of these, 52 were males with an average age of (53.14 ± 9.15) years. Twenty-five and thirty-three cases completed 24 and 48 weeks of follow-up, respectively. The HBV DNA negative conversion rate was 96.97% (32/33), which was higher than the baseline of 58.1% (43/74) following 48 weeks of TAF treatment. The ALT return to normal rate was 72.73% (24/33), which was higher than the baseline of 47.30% (35/74); however, the renal function and blood lipid levels did not change significantly compared with the baseline level after completing 48 weeks of treatment (P>0.05). During the follow-up period, one case developed hepatocellular carcinoma, and no other adverse clinical outcomes, such as liver transplantation or death, were reported.Conclusion:TAF has a good efficacy and safety profile in the treatment of patients with decompensated hepatitis B cirrhosis.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). Conclusions People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Objective:To explore the efficacy and safety profile of tenofovir alafenamide fumarate (TAF) in the treatment of patients with decompensated hepatitis B cirrhosis.Methods:A two-way cohort study method was used to enroll patients with decompensated hepatitis B cirrhosis who visited four medical centers, including Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, from April 2021 to April 2024 and were treated with TAF and followed up for 48 weeks. The primary efficacy indicator was hepatitis B virus (HBV) DNA seronegative conversion rate at 48-weeks, and the secondary efficacy indicator was alanine aminotransferase (ALT) return to normal rate at 48-weeks. Relevant safety indicators, adverse drug reactions (ADRs), and clinical adverse outcomes were collected.Results:A total of 74 cases were included. Of these, 52 were males with an average age of (53.14 ± 9.15) years. Twenty-five and thirty-three cases completed 24 and 48 weeks of follow-up, respectively. The HBV DNA negative conversion rate was 96.97% (32/33), which was higher than the baseline of 58.1% (43/74) following 48 weeks of TAF treatment. The ALT return to normal rate was 72.73% (24/33), which was higher than the baseline of 47.30% (35/74); however, the renal function and blood lipid levels did not change significantly compared with the baseline level after completing 48 weeks of treatment (P>0.05). During the follow-up period, one case developed hepatocellular carcinoma, and no other adverse clinical outcomes, such as liver transplantation or death, were reported.Conclusion:TAF has a good efficacy and safety profile in the treatment of patients with decompensated hepatitis B cirrhosis.

In 2022, Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association, organized domestic experts to update the guideline for the prevention and treatment of hepatitis C from the aspects of epidemiology, population screening and prevention, laboratory testing, simplification of diagnostic processes and treatment regimens, and antiviral therapy for special populations. This article aims to interpret the treatment of special populations not specifically mentioned in the new guideline, including pregnant women and patients with hepatocellular carcinoma, as well as other issues that need to be solved, in order to provide a reference for clinicians in practical work.

Objective:To analyze the clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections in children, and to provide reference basis for the SARS-CoV-2 vaccination in children.Methods:A total of 97 children aged 3 to 14 years and diagnosed with coronavirus disease 2019 (COVID-19) admitted to Xi′an People′s Hospital (Xi′an Fourth Hospital) from December 27, 2021 to February 7, 2022 were included. According to the COVID-19 vaccination status, the enrolled children were divided into unvaccinated group, partially vaccinated group and fully vaccinated group, and the clinical data of the children in the three groups were collected and compared. Chi-square test, two independent sample t-test and Kruskal-Wallis H test were used for statistical analysis. Results:Totally 97 children including 49 males and 48 females were enrolled, with 87(89.7%) children of mild type, 10(10.3%) children of common type, and no severe or critical case. The proportions of unvaccinated, partially vaccinated and fully vaccinated preschool-aged children (3 to 6 years old) were 56.5%(13/23), 30.8%(12/39) and 17.1%(6/35), respectively, while those of school-aged children (7 to 14 years old) were 43.5%(10/23), 69.2%(27/39) and 82.9%(29/35), respectively. The vaccination proportion in preschool-aged children was significantly lower than that in school-age children ( χ2=9.94, P=0.007). The proportion of the children with fever in fully vaccinated group was 17.1%(6/35), which was lower than that in unvaccinated group (43.5%, 10/23), and the difference was statistically significant ( χ2=4.82, P=0.028). The cycle threshold (Ct) values of the open reading frame ( ORF)1 ab gene in the unvaccinated, partially vaccinated and fully vaccinated groups were 33.77(26.87, 36.58), 35.23 (33.45, 38.57) and 37.12 (34.91, 39.39), respectively, and there was a statistically significant difference among the groups ( H=7.76, P=0.021). The Ct values of the nucleocapsid protein ( N) gene in the three groups were 32.26(25.85, 36.18), 35.12(33.18, 37.96) and 37.26(34.27, 39.24), respectively, and the difference among the groups was statistically significant ( H=7.84, P=0.020). The Ct values of ORF1 ab gene and N gene in fully vaccinated group were higher than those in unvaccinated group, and the differences were statistically significant ( Z=-2.69, P=0.007 and Z=-2.39, P=0.017, respectively). The duration of viral shedding in fully vaccinated children was (9.9±4.1) d, which was shorter than that in unvaccinated children ((12.8±3.7) d), and the difference was statistically significant ( t=2.72, P=0.009). Conclusions:The majority of children with breakthrough infections with SARS-CoV-2 are mild. Vaccination may effectively shorten the duration of viral shedding. And fully vaccination is associated with mild clinical symptoms and lower serum viral load compared to unvaccinated children.

Objective:To investigate the dynamic changes of routine laboratory parameters during the course of hemorrhagic fever with renal syndrome (HFRS) and estimate the predictive value for the severity of the disease.Methods:A retrospective cohort study was conducted, which enrolled 394 HFRS patients admitted to the Second Affiliated Hospital of Air Force Medical University (374 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (20 cases) from January 2019 to January 2022. The patients were divided into mild (mild and moderate) and severe (severe and critical) groups.The basic information, personal history, past history, treatment, complications and other clinical data of patients were collected and the results of the laboratory examinations in the morning at day 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 of hospitalization and before discharge were recorded. The dynamic changes of the patients′ routine laboratory indicators and the dynamic predictive values of each indicator for severe condition were analyzed. Mann-Whitney U test and chi-square test were used for comparison, and receiver operator characteristic (ROC) curve was used for predictive value evaluation. Results:The age of 212 patients in the mild group was 38(27, 61) years, and that of 182 patients in the severe group was 49(32, 64) years, the difference was statistically significant ( Z=-2.24, P=0.025). The incidences of acute pancreatitis, acute respiratory distress syndrome, multiple organ dysfunction syndrome, the utilization rates of blood purification and mechanical ventilation in the severe group were 6.0%(11/182), 12.6%(23/182), 19.8%(36/182), 89.6%(163/182) and 22.5%(41/182), respectively, and those in the mild group were 0(0/212), 0(0/212), 0(0/212), 15.6%(33/212) and 0.5%(1/212) respectively, and the differences were all statistically significant ( χ2=13.18, 28.45, 46.15, 214.48 and 50.02, respectively, all P<0.05). The levels of white blood cell count, lymphocyte count, monocyte count and neutrophil count were all increased rapidly after onset and peaked at days 4 to 6 of illness, with the counts of 14.2(9.7, 20.7)×10 9/L, 4.2(2.3, 6.2)×10 9/L, 1.5 (0.8, 3.3)×10 9/L and 8.3(4.3, 11.4)×10 9/L, respectively. Aspartate aminotransferase peaked (102(66, 178) U/L) within three days after onset and then decreased rapidly, returned to normal level by day 12. Blood urea nitrogen and creatinine both increased steadily after onset, peaked at day 9 to 10, with the levels of 13.2(7.7, 19.1) mmol/L and 255.4(122.9, 400.9) μmol/L, respectively. Prothrombin time, activated partial thromboplastin time, fibrinogen degradation products and D-dimer levels at day 3 after onset were 12.7(12.0, 13.2) s, 38.7(33.5, 51.9) s, 12.6(6.9, 32.0) mg/L and 4.9(2.2, 13.7) mg/L, respectively.Platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset had decent predictive values for estimating severity, of which the area under curve (AUC) values were 0.801(95% confidence interval (95% CI) 0.727 to 0.875), 0.824(95% CI 0.770 to 0.878), 0.862(95% CI 0.805 to 0.919) and 0.810(95% CI 0.722 to 0.897), respectively. Conclusions:Routine blood count, liver function and coagulation are important reference indicators for early warning of severe disease of HFRS, while with the progress of the disease, renal function indicators are effective in differentiating the severity of the disease. The platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset have predictive values for severe HFRS.