Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Objective To compare the value of Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, CLIF Consortium Acute Decompensation (CLIF-C AD) score, and Freiburg index of post-transjugular intrahepatic portosystemic shunt (TIPS) survival (FIPS) score in predicting the survival of patients undergoing TIPS. Methods A retrospective analysis was performed for the clinical data of 447 patients with liver cirrhosis who underwent TIPS in several hospitals in southwest China, among whom there were 306 patients in the survival group and 62 in the death group. The scores of the above five models were calculated, and a survival analysis was performed based on these models. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Pearson chi-square test was used for comparison of categorical data between groups; a multivariate Cox regression analysis was used for correction analysis of known influencing factors with statistical significance which were not included in the scoring models; the Kaplan-Meier method was used to evaluate the discriminatory ability of each model in identifying risks in the surgical population, and the log-rank test was used for analysis. The area under the receiver operating characteristic curve (AUC), C-index at different time points, and calibration curve were used to evaluate the predictive ability of each scoring model. Results Compared with the death group, the survival group had significantly lower age ( Z =2.884, P < 0.05), higher albumin ( t =3.577, P < 0.05), and Na + ( Z =-3.756, P < 0.05) and significantly lower proportion of patients with alcoholic cirrhosis ( χ 2 =22.674, P < 0.05), aspartate aminotransferase ( Z =2.141, P < 0.05), prothrombin time ( Z =2.486, P < 0.05), international normalized ratio ( Z =2.429, P < 0.05), total bilirubin ( Z =3.754, P < 0.05), severity of ascites ( χ 2 =14.186, P < 0.05), and scores of the five models (all P < 0.05). Survival analysis showed that all scoring models effectively stratified the prognostic risk of the patients undergoing TIPS. Comparison of the C-index of each scoring model at different time points showed that Child-Pugh score had the strongest ability in predicting postoperative survival, followed by MELD-Na score, MELD score, and CLIF-C AD score, and FIPS score had a relatively poor predictive ability; in addition, the prediction efficiency of each score gradually decreased over time. Child-Pugh score had the largest AUC of 0.832 in predicting 1-year survival rate after surgery, and MELD-Na score had the largest AUC of 0.726 in predicting 3-year survival rate after surgery, but FIPS score had a poor ability in predicting 1- and 3-year survival rates. Conclusion All five scoring models can predict the survival of patients with liver cirrhosis after TIPS and can provide effective stratification of prognostic risk for such patients. Child-Pugh score has a better ability in predicting short-term survival, while MELD-Na score has a better ability in predicting long-term survival, but FIPS score has a relatively poor predictive ability in predicting both short-term and long-term survival.

Non-alcoholic fatty liver disease (NAFLD) is not a benign condition, especially in patients with non-alcoholic steatohepatitis (NASH) combined with liver fibrosis grades F2-4, who have a higher risk of liver-related events and mortality. Thus, this population is considered "at-risk" for developing NASH. China has a large NAFLD patient population, so how to screen for those with liver fibrosis is an important socio-economic concern. At the moment, serological models, liver stiffness detection based on vibration-controlled transient elastography, and magnetic resonance elastography (MRE) are the only non-invasive tests (NITs) for liver fibrosis. The prevention and treatment guidelines for NAFLD at home and abroad are reviewed here, based on the research progress of NITs in recent years, so as to suggest screening, evaluation pathways, and management for liver fibrosis in patients with NAFLD.

Objective To study the curative effects of traditional Chinese medicine paste combined with Baduanjin in treatment of osteoporotic vertebral compression fracture (OVCF) after percutaneous vertebroplasty (PVP). Methods 120 OVCF patients treated with PVP in our hospital from January 2016 to September 2017 were divided into the observation group (60 cases) and the control group (60 cases) according to the random number table method. The control group was given calcium carbonate D₃ chewable tablets orally with routine guidance. In addition to the same treatment as the control group, the observation group received the traditional Chinese medicine paste orally with Baduanjin exercise. Both groups were treated for 6 months and followed-up for 3 years. The curative effects in the two groups after 6 months treatment and the low back pain after 1, 3 and 6 months of treatment were recorded. The changes of bone mineral density (BMD), kyphosis angle (Cobb angle), anterior wall height of vertebral body (AVBH) and level of bone metabolism indexes in the two groups were compared before and after treatment for 6 months. The follow-up times and the incidences of push-back fracture after PVP during follow-up were recorded. Results After 6 months of treatment, the clinical cure rate of the observation group was 73.33%, which was higher than 53.33% of the control group(P<0.05). Compared with pretreatment, the scores of visual analogue scale (VAS) in the two groups gradually decreased after 3 and 6 months of treatment, and the observation group had a lower scores than the control group (P<0.05). After 6 months treatment, BMD and AVBH of lumbar vertebrae and femoral neck in both groups increased, and the observation group was higher than that in the control group. The Cobb angle and serum levels of Type I procollagen degradation products (β-Cross I), the n-terminal middle osteocalcin (N-MID Ost) and parathyroid hormone (PTH) decreased in both groups, and the observation group was lower than those in the control group (P<0.05). There was no significant difference in fracture incidence after PVP in the year 1, year 1 to 3 follow up between the two groups (P>0.05). During the 3 years follow-up, the incidence of push-body fracture after PVP in the observation group was 3.33%, which was lower than that in the control group 20.00%( P<0.05). Conclusion Traditional Chinese medicine paste combined with Baduanjin reduced the serum levels of β-Cross I, N-MID Ost and PTH, regulated bone metabolism, improved BMD and AVBH of lumbar vertebrae and femoral neck, reduced Cobb angle, promoted the recovery of lumbar function, alleviated patients' back pain, lowered the incidence of push-body fracture after PVP. The curative effects were remarkable.

For the high-risk population, early screening and diagnosis are important measures to achieve good control of liver cancer and reduce the burden of liver cancer, and determining the high-risk population of liver cancer and formulating appropriate liver cancer screening strategies are the key to realizing the early screening and diagnosis of liver cancer. The risk assessment model for liver cancer is an important method for rapid and convenient identification of the high-risk population of liver cancer. Based on the risk stratification of liver cancer, the methods such as imaging technology, serological markers, liquid biopsy, metabolomics, and glycomics can be used for accurate early screening and diagnosis of liver cancer, so as to achieve the goal of early treatment.

Objective:To investigate the prognosis and outcome of patients with chronic hepatitis C (CHC) related cirrhosis after achieved sustained virologic response (SVR) treated with direct-acting antiviral agent (DAA).Methods:Ninety-five patients diagnosed with CHC related cirrhosis who had complete data in Tianjin Second People′s Hospital from January 2014 to June 2017 were retrospectively followed up. Among them, 72 patients were treated with DAA and all of them achieved SVR, and the other 23 patients did not receive any antiviral therapy. The differences of mortality and incidence of hepatocellular carcinoma (HCC) between DAA treatment group and non-antiviral treatment group were compared. Statistical analysis was performed by independent sample t test, Mann-Whitney U test and chi-square test. Results:At the end of follow-up for three to 71 months, patients in DAA treatment group had a significant improvements in alanine aminotransferase, aspartate aminotransferase, albumin and liver stiffness measurement compared with those before treatment (42(23, 61) U/L vs 18(13, 28) U/L, 54(37, 75) U/L vs 23(18, 28) U/L, 39(33, 42) g/L vs 45(41, 48) g/L, 26(18, 37) kPa vs 15(11, 26) kPa, respectively, Z=-6.005, -7.008, -6.057 and -3.162, respectively, all P<0.01). However, there were no significant differences in incidence of HCC (12%(9/72) vs 17%(4/23)) and mortality (3%(2/72) vs 13%(3/23)) between the DAA treatment group and non-antiviral treatment group (both P>0.05). There was no significant difference of cumulative incidence of HCC in DAA treatment group compared with non-antiviral treatment group ( P=0.609). The age of patients progressed to HCC was older than those without HCC ((60.3±3.6) years vs (54.4±9.9) years, t=-3.948, P<0.01). In subgroup analysis, among the six patients with HCC, four had diabetes, the prevalence of diabetes in the patients without HCC was 17%(7/42); the level of fasting blood glucose (FBG) ((7.3±1.9) mmol/L vs (5.9±1.1) mmol/L) were higher in patients progressed to HCC than those without HCC in DAA treatment group with compensated cirrhosis ( χ2=7.430 and t=-2.442, respectively, both P=0.019). Conclusions:DAA treatment could notably improve liver function and alleviate liver fibrosis, but could not reduce the mortality and incidence of HCC in patients with CHC related cirrhosis significantly. Diabetes and high level FBG may be the risk factors for occurrence of HCC in patients with CHC related compensated cirrhosis.

Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired t test and paired rank sum test were used for statistical analysis. Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant ( Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant ( Z=-1.998 and -2.110, both P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant ( t=4.402 and 3.848, Z=-3.081 and -3.609; all P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance of Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all Z=-2.589, all P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, P=0.049). Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.