Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China.

BACKGROUND: Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. PATIENTS AND METHODS: 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. RESULTS: DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups. CONCLUSION: In this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

A case report on mixed pulmonary infection of Nocardia nova, Mycobacterium tuberculosis, and Aspergillus fumigatus based on metagenomic next-generation sequencing.

Background: Pulmonary infection is one of the common complications of long-term use of glucocorticoids. Severe infections not only increase the length of hospital stay and treatment costs but also cause progression or recurrence of the primary disease. Case description: Herein, we reported a case of mixed pulmonary infection secondary to glucocorticoid use. Rare pathogens such as Nocardia nova, Mycobacterium tuberculosis, Aspergillus fumigatus, and cytomegalovirus were detected by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid and lung puncture tissue. Combining the results of conventional pathogen detection and clinical symptoms, the patient was diagnosed with mixed pulmonary infection by multiple pathogens. After timely targeted medication, the patient was finally discharged with a good prognosis. Conclusion: To our knowledge, this is the first case report on mixed pulmonary infection with pathogens including Nocardia nova, Mycobacterium tuberculosis, Aspergillus fumigatus, and human cytomegalovirus. As a new clinical diagnostic method, mNGS has great advantages in diagnosis of diseases such as mixed infections.

Efficacy and safety of direct-acting antiviral therapies and baseline predictors for treatment outcomes in hepatitis C patients: A multicenter, real-world study in Guangdong, China.

The data on direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients in southern China with multiple genotypes circulating are limited. This study aims to evaluate the efficacy and safety of DAA regimens among CHC patients in Guangdong, China. A total of 220 patients receiving a variety of DAA were enrolled. The primary outcome was sustained virologic response (SVR) at 12 weeks. Resistance associated substitutions (RASs) were evaluated by deep sequencing. The overall SVR rate was 96.4%, and was 97.7% for genotype 1, 100% for genotype 2, 91.9% for genotype 3, 95.7% for genotype 6, and 100% for untyped. The overall incidence of adverse events (AEs) was 8.2% (18/220) and all the AEs were mild. Nonstructural proteins 5A RAS, 30K/31M, and Y93H were most prevalent at baseline and the end of treatment in non-SVR patients, respectively. Logistics regression showed that elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at baseline were specifically associated with non-SVR in patients with genotype 3 and 6 infections (p = 0.029 and p = 0.017) but not genotype 1 infection (p = 0.746 and p = 0.971), and baseline AST was the best predictor for SVR in genotypes 3 and 6 patients (area under curve = 0.890). Our studies demonstrated all DAA regimens achieved ideal SVR and were well tolerated. NS5A RAS were prevalent in non-SVR patients. Elevated ALT and AST as baseline predictors for non-SVR in genotypes 3 and 6 infections warrant further research in a larger cohort.

SARS-CoV-2: minireview and review of first case in Foshan, China.

The first case of #COVID19 in Foshan provides a reference for the treatment of severe #SARSCoV2 pneumonia https://bit.ly/3eD81qj.

[Observation on effect of peg interferon lphaa-2a treating lamivudine resistant chronic hepatitis B].

OBJECTIVE: To observe the efficacy and safety of PEG-interferon alpha-2a (PEG-IFNalpha-2a) treatment on lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients. METHODS: Eighty-one patients with lamivudine-resistant HBeAg (+) chronic hepatitis B patients were enrolled and divided into PEG-IFNalpha-2a treatment group (40 cases) and adefovir dipivoxil (ADV) control group (41 cases). Two groups were combined with LAM in the first 12 weeks(w). The ALT normalization rate, the HBV DNA and HBeAg negative rate, and the HBeAg seroconversion rate were observed in 12 W, 24 W, 48 W. RESULTS: The ALT normalization rate in 12 W, 24 W of PEG-IFNalpha-2a group was 62.5% and 80.0%. And it was higher than that of ADV group. The HBeAg negative rate and HBeAg seroconversion rate in 48 W of PEG-IFNalpha-2a group were 60% and 57.5% , which were higher than that of ADV group. The difference was statistically significant (P < 0.05). CONCLUSION: PEG-IFNalpha-2a treatment of lamivudine-resistant HBeAg (+) chronic hepatitis B is superior to ADV, and its security is well.

[Therapeutic application of molecular adsorbent recirculation system in the treatment of multiple organ dysfunction syndrome patients].

OBJECTIVE: To assess the effectiveness of molecular adsorbent recirculation system (MARS) to remove nitric oxide(NO) and cytokines in multiple organ dysfunction syndrome(MODS) in patients with severe liver failure. METHODS: Single MARS treatment were performed for 198 times with duration ranging from 6 to 24 hours on 61 MODS patients (42M/19F). The efficacy was evaluated by sequential organ failure assessment, biochemical parameters and the levels of pro-inflammatory cytokines. RESULTS: The MARS therapy resulted in a significant removal of NO and certain cytokines such as tumor necrosis factor-alpha(TNF-alpha), interleukin-2(IL-2), IL-6, IL-8, and lipopolysaccharide-binding protein(LBP), together with marked reduction of other non-water soluble albumin bound toxins and water soluble toxins. These were associated with an improvement of the patients' clinical conditions, including deranged hemodynamics, respiratory function, cardiovascular and renal functions, hepatic encephalopathy, thus resulting in a marked decrease of sequential organ failure assessment(SOFA) score and improved outcome. Twenty-five patients were able to be discharged from the hospital, and successful liver transplantation could be performed in 6 patients. The overall survival rate of 61 patients was 41.0%. CONCLUSION: MARS could be used for the treatment of MODS patients associated with elevated levels of NO and cytokines with satisfactory results.