Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

Background: The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Methods: Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Results: Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. Conclusions: The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS: This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS: For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION: The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS: gov). The trial number is ChiCTR2000040343.

Accurate prediction of HCC risk after SVR in patients with hepatitis C cirrhosis based on longitudinal data.

BACKGROUND: Most existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model. METHODS: A total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison. RESULTS: During a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838-0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively). CONCLUSIONS: Our longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.

Using multi-tissue transcriptome-wide association study to identify candidate susceptibility genes for respiratory infectious diseases.

Objective: We explore the candidate susceptibility genes for influenza A virus (IAV), measles, rubella, and mumps and their underlying biological mechanisms. Methods: We downloaded the genome-wide association study summary data of four virus-specific immunoglobulin G (IgG) level data sets (anti-IAV IgG, anti-measles IgG, anti-rubella IgG, and anti-mumps virus IgG levels) and integrated them with reference models of three potential tissues from the Genotype-Tissue Expression (GTEx) project, namely, whole blood, lung, and transformed fibroblast cells, to identify genes whose expression is predicted to be associated with IAV, measles, mumps, and rubella. Results: We identified 19 significant genes (ULK4, AC010132.11, SURF1, NIPAL2, TRAP1, TAF1C, AC000078.5, RP4-639F20.1, RMDN2, ATP1B3, SRSF12, RP11-477D19.2, TFB1M, XXyac-YX65C7_A.2, TAF1C, PCGF2, and BNIP1) associated with IAV at a Bonferroni-corrected threshold of p < 0.05; 14 significant genes (SOAT1, COLGALT2, AC021860.1, HCG11, METTL21B, MRPL10, GSTM4, PAQR6, RP11-617D20.1, SNX8, METTL21B, ANKRD27, CBWD2, and TSFM) associated with measles at a Bonferroni-corrected threshold of p < 0.05; 15 significant genes (MTOR, LAMC1, TRIM38, U91328.21, POLR2J, SCRN2, Smpd4, UBN1, CNTROB, SCRN2, HOXB-AS1, SLC14A1, AC007566.10, AC093668.2, and CPD) associated with mumps at a Bonferroni-corrected threshold of p < 0.05; and 13 significant genes (JAGN1, RRP12, RP11-452K12.7, CASP7, AP3S2, IL17RC, FAM86HP, AMACR, RRP12, PPP2R1B, C11orf1, DLAT, and TMEM117) associated with rubella at a Bonferroni-corrected threshold of p < 0.05. Conclusions: We have identified several candidate genes for IAV, measles, mumps, and rubella in multiple tissues. Our research may further our understanding of the pathogenesis of infectious respiratory diseases.

Trajectories of De Ritis ratio with risk of hepatocellular carcinoma and liver-related mortality following direct-acting antivirals for HCV: a retrospective longitudinal study up to 10 years.

The De Ritis ratio has good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has remained controversial. This study was to identify different trajectories of De Ritis ratio in those hepatitis C patients cured and analyze the relationship between trajectory groups and risk of hepatocellular carcinoma (HCC) with liver-related mortality by the retrospective cohort study. This retrospective longitudinal cohort included 1241 patients with hepatitis C who underwent antiviral therapy since follow-up in 2012. De Ritis ratio trajectories were identified by the latent class growth mixed model. Patients were grouped into subgroups by De Ritis ratio according to longitudinal trajectories. The endpoints were HCC and liver-related mortality. Three distinct trajectory groups were characterized for serum De Ritis ratio: low-stable, middle-stable and high-rising. Fifty-one HCC and 11 liver-related mortality were recorded and tracked. Compared to the low-stable group, the adjusted hazard ratios (HRs) and 95% confidence interval (CI) associated with HCC and liver-related mortality were 2.02 (1.12 to 3.63), 9.36 (3.61 to 24.29), for the middle-stable, and high-rising group, respectively. Notably, the high-rising trajectory group still had prognostic significance after adjusting for preoperative levels. Likewise, for the high-rising trajectory group of sustained virological response, the HRs (95% CI) were 2.85 (1.03 to 10.75) for HCC and liver-related mortality, and in patients with cirrhosis, the HRs (95% CI) were 3.44 (1.64 to 7.19) and 4.35 (1.27 to 14.84) in the middle-stable trajectory group and the high-rising trajectory group, respectively. The dynamic measurements of De Ritis ratio are recommended to monitor the prognosis of Hepatitis C patients.

Repeated Measurement of FIB-4 to Predict Long-Term Risk of HCC Development Up to 10 Years After SVR.

Purpose: It is unclear whether and how the long-term risk of hepatocellular carcinoma (HCC) will change in hepatitis C virus (HCV) infected patients who have reached sustained virologic response (SVR) with direct-acting antivirals (DAA). In this study, we assessed the long-term risk of HCC up to 10 years after SVR using fibrosis 4 score (FIB-4) and its dynamic changes. Patients and Methods: A total of 701 DAA-treated patients who achieved SVR between January 2012 to October 2020 were enrolled in the study. The FIB-4 score of each patient was measured at the date of SVR and each follow-up visit annually. Patients were followed until December 31, 2021, with the longest follow-up time being 9.82 years. Results: Following SVR, 27 cases of HCC were observed. The annual incidence rate of HCC remained stable with no obvious downward trend. Patients with a FIB-4 >3.25 at baseline or anytime during follow-up were at a higher risk of developing HCC than those whose FIB-4 remained below 3.25. Patients with cirrhosis and patients with no cirrhosis but a FIB-4 >3.25 were at higher risk of developing HCC than patients with no cirrhosis and a FIB-4 ≦3.25. Conclusion: FIB-4 >3.25 measured at SVR or any time post-SVR was associated with HCC risks. The repeated measurement of FIB-4 revealed a better predictive ability of HCC risks than the simple measurement of FIB-4 at baseline. The additional stratification of patients by combining FIB-4 and cirrhosis leads to more accurately identifying high-risk patients. Surveillance of HCC is recommended for virologically cured patients with a FIB-4 >3.25 at SVR or anytime afterward and patients diagnosed with cirrhosis.