The occult progression of chronic hepatitis C (CHC) is one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). Recently, antiviral treatment of CHC has achieved great progress with the advent of direct-acting antiviral drugs (DAA), especially for special populations including advanced liver disease and HCC. However, DAA and HCC-related issues have also become one of the important concerns of current CHC treatment. This article summarizes the recent research progresses made in the diagnosis and treatment of HCV-related HCC.

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.

OBJECTIVETo investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus (HCV) infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.

METHODSSixty-six consecutive,interferon (IFN)-na(i)ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study. All patients were given a 48-to 72-week course of IFN plus ribavirin (RBV) combined therapy,with a low accelerating dosage regimen using either:pegylated (PEG)-IFNa-2b at 1.0-1.5 mug/kg/week,PEG-IFNa-2a at 90-180 mug,or standard IFN-a-2b at 3MU,every other day.RBV was given at 800 to 1000 mg/day. All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.

RESULTSAt the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response (NVR). Among the patients with HCV genotype 1, 65.9% achieved end-of-treatment virological response (ETVR) and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR. The positive and negative predictive values of early virological response (EVR) for ETVR were 95.7% and 75.0% respectively, and for SVR were 65.2% and 100% respectively. Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score (t =4.564,11.486,2.303,2.699,3.694 respectively, all P less than 0.05).Compared with the NVR patients, the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma, and had improved survival (x2=18.756,6.992,7.580, respectively, all P less than 0.05).Twelve (18.2%) patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.

CONCLUSIONAntiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.

Alanine Transaminase ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; Drug Therapy, Combination ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; diagnosis ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Kaplan-Meier Estimate ; Liver Cirrhosis ; drug therapy ; virology ; Liver Neoplasms ; Polyethylene Glycols ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Treatment Outcome

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.

Objective:To analyze the clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome (HFRS) in underage patients, and to construct the severe disease risk model.Methods:A total of 170 HFRS patients (<18 years old) from the Second Affiliated Hospital of Air Force Medical University (153 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (17 cases) from January 2009 to December 2021 were included. According to the severity of the disease, the patients were divided into mild and severe groups. Baseline demographic data, symptoms, signs, laboratory examination on admission and prognosis were analyzed between the two groups. Statistical comparisons were performed using the Mann-Whitney U test and chi-square test.Binary logistic regression was used to analyze the independent risk factors of patients with severe disease, and the severe disease risk model was built.The receiver operator characteristic curve was used to analyze the value of the risk model in predicting severity of disease. Results:Among the 170 underage patients, 132 (77.6%) were males, aged (14.9±3.1) years, including 124 cases in mild group and 46 cases in severe group. One hundred and sixty-nine cases (99.4%) had fever, 119 cases (70.0%) had headache, 106 cases (62.4%) had lumbago, 158 cases (92.9%) had skin and mucous congestion, and 101 cases (59.4%) had nausea and vomiting. Renal percussive pain was found in 139(81.8%) patients. The incidence of nausea and vomiting and bleeding of skin and mucosa in the severe group were 71.7%(33/46) and 67.4%(31/46), respectively, which were both higher than those in the mild group (54.8%(68/124) and 44.4%(55/124), respectively), and the differences were statistically significant ( χ2=3.97 and 7.12, respectively, both P<0.05). There were significant differences in platelet count, activated partial thromboplastin time (APTT), serum creatinine (SCr), aspartate aminotransferase, alanine aminotransferase, leukocyte count, total bilirubin and albumin levels between the two groups ( Z=-4.14, -4.04, -4.87, -3.90, -4.07, -2.60, -2.78 and t=2.50, respectively, all P<0.05). Binary logistic regression analysis showed that chemosis (odds ratio ( OR)=8.035, 95% confidence interval (95% CI) 2.946 to 21.916), SCr ( OR=1.010, 95% CI 1.006 to 1.015) and APTT ( OR=1.049, 95% CI 1.003 to 1.098) were the independent risk factors for severe HFRS in the underage patients. The risk model was constructed as: Logit(P)=-10.323+ 2.084×chemosis (no=0, grade Ⅰ=1, grade Ⅱ=2, grade Ⅲ=3)+ 0.010×SCr (μmol/L)+ 0.048×APTT (s). The area under the curve to predict severity of disease in underage HFRS patients was 0.868, with an optimal cut-off value of -4.39, with a sensitivity of 73.90% and a specificity of 91.10%. According to the internal verification of the data of the study based on the severe disease risk model, 34 out of 46 patients with severe disease were severe (sensitivity, 73.91%), 113 out of 124 patients with mild disease were mild (specificity, 91.13%). Conclusions:The clinical manifestations of the underage HFRS patients are not typical.The main manifestations are fever, headache and lumbago, nausea and vomiting, and the incidences of skin and mucous congestion and renal percussive pain are high.Chemosis, SCr and APTT are independent risk factors for severe disease in underage patients with HFRS. The severe disease risk model could effectively predict the severity of disease.

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 analyze the clinical characteristics and prognosis of pregnant women with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 11 pregnant women with HFRS admitted to The Second Affiliated Hospital of Xi′an Jiaotong University (four cases), The Second Affiliated Hospital of Air Force Medical University (four cases), The First Affiliated Hospital of Xi′an Jiaotong University (one case) and Central Hospital of Xianyang City (two cases) between November 2009 and February 2019 were included as the study group, and 24 age-matched non-pregnant women with HFRS were selected as the control group. The age, complications, clinical classification and laboratory indexes of the two groups were analyzed retrospectively, and the clinical outcomes of pregnant women and their fetuses in the study group were followed up. The data between two groups were compared using Mann-Whitney U test or chi-square test. Results:Patients in the study and control groups were 29 (22, 33) and 32 (24, 37) years old, respectively. Seven of 11 patients in study group were severe and critical cases, which was significantly higher than that in the control group (16.7%(4/24), χ2=7.722, P=0.015). In the study group, 10 patients had hypervolemic syndrome, 10 patients had pulmonary edema and six patients had overlapping hypotension shock phase and oliguria phase, which were all higher than those in the control group ((2/24, 8.3%), (2/24, 8.3%) and (2/24, 8.3%), respectively; χ2=22.828, 22.828 and 9.135, respectively, all P<0.01). Compared with the control group, the pregnant patients in study group had a higher urea nitrogen maximum and serum creatinine maximum, and the differences were both statistically significant ( Z=-2.453 and -2.336, respectively, both P<0.05), while they had a lower serum albumin minimum, hemoglobin maximum and hemoglobin minimum, and the differences were all statistically significant ( Z=-3.742, -3.350 and -4.034, respectively, all P<0.01). All pregnant women with HFRS recovered. Nine pregnant women gave birth to nine healthy infants. All of them received breastfeeding and the feeding duration were more than six months. No abnormal growth and development were found during an average follow-up of three years. Conclusions:Pregnancy can aggravate the severity of HFRS, and pregnant women have higher risk of the multiple stages overlap and the complications such as hypervolemic syndrome and acute pulmonary edema. After recovery from HFRS, mother may carry to full-term pregnancy.

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.

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.

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.