Real-World Effectiveness of Direct-Acting Antiviral Regimens against Hepatitis C Virus (HCV) Genotype 3 Infection: A Systematic Review and Meta-Analysis.

Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.

Prevalence of NS5B resistance-associated variants in treatment-naïve Asian patients with chronic hepatitis C.

There is little information on the association between baseline non-structural protein (NS) 5b resistance-associated variants (RAVs) and treatment failure in hepatitis C patients. This study examined the frequencies of natural hepatitis C virus (HCV) NS5B resistance-associated variants (RAVs) in an Asian cohort. Samples from Asian HCV patients enrolled between October 2009 and September 2014 were analyzed for NS5B RAVs within the region from amino acid 230 to 371. Serum samples were tested by PCR genotyping, with sequence alignment performed using the neighbor-joining method. NS5B was detected by Sanger sequencing followed by Geno2pheno analysis. NS5B RAVs were detected in 80.52% (1199/1489) of patients; 68.4% (1019/1489) and 79.7% (1186/1489) were associated with resistance to sofosbuvir (SOF) and dasabuvir (DSV), respectively. These RAVs were present in 95% (1004/1058) of genotype 1b patients. When genotypes 1b and 2a were compared, SOF-associated RAVs were detected at a higher frequency in genotype 1b (94.8% [1004/1058] vs. 2.9% [9/309]; χ2 = 1054.433, P < 0.001), C316H/N was more common in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ2 = 1096.014, P < 0.001), M289F/L/I/W/V had a higher frequency in genotype 2a (0.7% [7/309] vs. 2.3% [7/1058]; χ2 = 4.589, P = 0.032), DSV-associated RAVs were most often found in genotype 1b (95.0% [1005/1058] vs. 40.1% 124/309]; χ2 = 500.577, P < 0.001), and frequency of C316Y/H/N/W was higher in genotype 1b (94.7% [1002/1058] vs. 0% [0/309]; χ2 = 1096.014, P < 0.001). In conclusion, baseline SOF and DSV RAVs are common in Asian HCV patients and predominantly occur in genotype 1b.

Epidemiological survey and risk factor analysis of fatty liver disease of adult residents, Beijing, China.

BACKGROUND AND AIM: With the changes in diet structure and lifestyle, the incidence of fatty liver disease is increasing in China, especially in cities. The goal of the present study was to accurately determine the prevalence and risk factors of fatty liver disease in Beijing residents, China. METHODS: By using random multistage stratification and cluster sampling, residents aged > 20 years in Dongcheng District and Tongzhou District were recruited, and questionnaire survey, physical examination, detection of fasting glucose, blood lipids and liver biochemistry, and ultrasonography of the liver, gallbladder, and spleen were carried out. Database EpiData 3.0 was employed for data input, followed by statistical analysis with SPSS version 11.0. RESULTS: A total of 3762 residents were included in the present study including 2328 males and 1434 females with a mean age of 46.37 ± 14.28 years (range 20-92 years). Ultrasonography revealed fatty liver in 1486 residents with a prevalence of 39.5%. Moreover, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease were found in 1177 (31.3%) and 309 (8.2%) residents, respectively. After adjustment of prevalence based on the age and gender constituents of Beijing residents, the standardized prevalence of overall fatty liver disease, NAFLD, and alcoholic fatty liver disease was 35.1%, 31.0%, and 4.1%, respectively. Binary logistic regression analysis revealed waist-to-hip ratio, diastolic pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and low density lipoprotein cholesterol were closely related to NAFLD. CONCLUSIONS: The Beijing residents have a high prevalence of fatty liver disease as much as 35.1%, which is characterized by NAFLD. Obesity, and glucose and lipid metabolism disorders are the main risk factors of fatty liver disease.

A Novel Diagnostic Nomogram for Noninvasive Evaluating Liver Fibrosis in Patients with Chronic Hepatitis B Virus Infection.

OBJECTIVE: To establish a novel nomogram for diagnosing liver fibrosis in patients with chronic hepatitis B virus (HBV) infection and verify the diagnostic performance of the established nomogram. METHODS: Patients with chronic HBV infection who met the inclusion and exclusion criteria were enrolled in this retrospective study; 70% and 30% of patients were randomly assigned to training dataset and validation dataset, respectively. The risk factors for liver fibrosis were screened using the univariate and multivariate logistic regression analyses. Based on the results, a nomogram was established and verified. RESULTS: 508 patients with chronic HBV infection were included in this study (n = 355 for training dataset and n = 153 for validation dataset). The logistic regression analysis showed that liver stiffness measurement (LSM), platelet (PLT) count, and prothrombin time (PT) were independent risk factors for liver fibrosis (P < 0.01), which were used to establish the nomogram. The consistency index (C-index) of the nomogram established for diagnosing liver fibrosis was 0.875. The calibration line and the ideal line were consistent, which indicated that diagnosis of liver fibrosis by the established model was accurate. The values of area under the receiver operator characteristic (ROC) curve (AUROC) for diagnosing liver fibrosis by the nomogram were 0.857 and 0.862 in the training dataset and validation dataset, respectively, which were noticeably higher than those in the well-known serological models, including the aspartate aminotransferase- (AST-) to-platelet ratio index (APRI) scoring model, fibrosis-4 (FIB-4) scoring model, APAG model (including age, PT, albumin, and γ-glutamyl transferase), and S-index model (all P < 0.05). CONCLUSION: LSM, PT, and PLT were found as independent risk factors for liver fibrosis. The established nomogram exhibited an excellent diagnostic performance, and it can more visually and individually evaluate the probability of liver fibrosis in patients with chronic HBV infection.

Management of Diabetes Mellitus in Patients with Chronic Liver Diseases.

Diabetes mellitus (DM) is a common chronic disease affecting humans globally. During the last few years, the incidence of diabetes has increased and has received more attention. In addition to growing DM populations, DM complications are involving injuries to more organs, such as the heart and cerebral vessel damage. DM complications can reduce quality of life and shorten life spans and eventually also impede social and economic development. Therefore, effective measures to curb the occurrence and development of diabetes assist in improving patients' quality of life, delay the progression of DM in the population, and ease a social burden. The liver is regarded as an important link in the management and control of DM, including the alleviation of glucose metabolism and lipid metabolism and others via glucose storage and endogenous glucose generation from glycogen stored in the liver. Liver cirrhosis is a very common chronic disease, which often lowers the quality of life and decreases life expectancy. According to a growing body of research, diabetes shows a close correlation with hepatitis, liver cirrhosis, and liver cancer. Moreover, coexistence of liver complications would accelerate the deterioration of patients with diabetes. Liver cirrhosis and diabetes influence each other. Thus, in addition to pharmacological treatments and lifestyle interventions, effective control of cirrhosis might assist in a better management of diabetes. When it comes to different etiologies of liver cirrhosis, different therapeutic methods, such as antiviral treatment, may be more effective. Effective control of cirrhosis might be a strategy for better management of diabetes.

[Retreatment with interferon of relapsed chronic hepatitis C patients].

OBJECTIVE: To evaluate the efficacy and investigate the influencing factors of the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed after a previous IFN treatment. METHODS: A retrospective study was designed to analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All patients were from a randomized, opened and multi-center clinical trial about the efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the treatment of chronic hepatitis C in China. There were 35 patients treated with PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the efficacy was sustained viral response (SVR) rate. The influence of viral concentration in serum, genotype and drug categories on the responses to IFN were analyzed. RESULTS: For all the patients, the end of treatment virus response (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG-IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00% respectively, P < 0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher than that of CIFNalpha-2a (45.71% and 20.00% respectively, P < 0.05). However, there was no significant difference between the high and low viral load groups. Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%, 11.11%), (P < 0.01, P < 0.05 respectively), but in patients with genotype non-1, there were no such differences between the two groups. CONCLUSION: Some relapsed patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha-2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be used in the relapsed cases with genotype 1. The viral load was not associated with the efficacy of IFN retreatment.

[Studies on IgG antibodies of SARS patients].

OBJECTIVE: To investigate the significance of detecting specific serum IgG antibodies in clinical diagnosis of SARS as well as affecting factors. METHODS: Enzyme-linked immunoassay kit for SARS coronavirus antibodies developed by HuaDa Biological Company was applied to detect specific serum IgG from SARS patients and the production of SARS specific antibodies among patients of different age groups, sex and with or without steroid treatment were statistically compared. RESULTS: Out of 121 patients studied, 71.1% were SARS specific IgG positive. Patients younger than 15 years, between 15 to 59 years, older than 59 years had positive rates of 60.0%, 70.2%, and 85.7%, respectively with no statistically significance (P=0.766); patients with or without steroid treatment showed positive rates of 70.6% and 72.4%, respectively (P=0.84); patients exhibiting either severe or light syndromes showed positive rates of 78.1% and 67.4%, respectively (P=0.493); both male and female patients showed the same positive rate of 71.1%. CONCLUSION: The sensitivity of the SARS specific IgG kit utilized needs to be further improved. The production of SARS IgG is not notably correlated with sex, age, seriousness of symptoms, and steroid treatment.

[The difference in distribution of HCV genotypes between patients infected with HCV by transfusion and non-transfusion routes].

OBJECTIVE: To investigate the HCV genotypes distribution in northern and southern cities in China and the difference between patients infected with HCV by transfusion and non-transfusion routes. METHODS: The HCV genotypes of the patients with chronic hepatitis C from 9 cities belonging to different regions were genotyped by the PCR products of 5 prime untranslated region NTR digested with restriction endonucleases, and the HCV genotypes distribution among different cities or between the patients infected with HCV through transfusion and other routes was analyzed. RESULTS: The HCV genotypes of 214 in 219 cases were determined; 197 patients were infected with monogenotype HCV. The major epidemic genotypes of HCV isolates in China were 1b (76.64%) and 2a (18.22%), but 5.14% of patients were infected with HCV belonging to genotype 3b and this was the first report that there is genotype 4a in China. The HCV genotype distribution was not different in northern and southern areas, but was significantly different between patients infected with HCV through transfusion and non-transfusion routes (P=0.036). In patients infected trough transfusion, the rates of monogenotype HCV infection and genotype 1b were 93.88% and 76.87%, respectively, which were higher than those (86.57% and 58.21%) in the patients infected with HCV through non-transfusion routes. The rate of patient infected with mixed genotype HCV strains in non-transfusion group was 13.43%, which was higher than that (6.12%) of patients in transfusion group. CONCLUSION: The HCV genotype distribution in northern and southern regions were similar, but was significantly different between the patients infected through transfusion and other routes.