CHESS-ALARM score to stratify decompensation risk in compensated advanced chronic liver disease patients: An international multicenter study.

BACKGROUND AND AIM: A combination of platelet and elastography (PE criteria) was proposed to identify compensated advanced chronic liver disease (cACLD) patients at risk of liver decompensation. We aim to validate and refine PE criteria by developing a new predictive score to predict decompensation in Asian cACLD patients. METHODS: An international cohort of 633 cACLD patients with liver stiffness measurement (LSM) and esophagogastroduodenoscopy performed were included. We validated PE criteria to predict first liver decompensation using competing risk analysis, with death and hepatocellular carcinoma as competing events. We developed a predictive model using proportional subdistribution hazard regression. Prognostic accuracy was compared with the model of end-stage liver disease (MELD), albumin-bilirubin (ALBI), and ALBI-FIB-4 score using time-dependent area under operative characteristic curve (tAUC). RESULTS: Sixty patients developed decompensation over the median follow-up of 39 months. Favorable Baveno VI status ruled out cACLD patients at risk of liver decompensation. LSM > 25 kPa was suboptimal to predict cACLD patients who will develop liver decompensation. We developed CHESS-ALARM score by incorporating age, platelet, and gender into LSM. CHESS-ALARM score (tAUC = 0.86, 95% confidence interval [CI]: 0.79-0.94) has significantly higher accuracy than MELD (tAUC: 0.61), ALBI (tAUC: 0.62), ALBI-FIB-4 (tAUC: 0.70), and LSM > 25 kPa (tAUC: 0.54) to predict liver decompensation at 5 years (P < 0.05 for all). Patients with CHESS-ALARM score ≥ -0.37 had an 11-fold higher risk of decompensation (subdistribution hazard ratio = 11.2, 95% CI: 5.1-24.5). CONCLUSION: CHESS-ALARM score can be readily incorporated into clinical practice of cACLD patients to estimate individual risk of liver decompensation; however, more data are required in morbidly obese cACLD patients of nonviral etiology.

Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV.

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS: The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Efficacy and Safety of Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C Virus Infection: A Real-World Single-Center Experience in Tianjin, China.

OBJECTIVE: Toward the limited real-world data concerning the treatment response to brand direct-acting antiviral agents (DAAs) therapy, we proposed to evaluate the efficacy and safety of DAAs for the treatment of chronic hepatitis C virus (HCV) in mainland China. METHODS: In this retrospective, single-center, cohort study, all HCV-infected adult patients treated with brand DAA drugs covered by Tianjin local health insurance (Apr 2018-Sept 2019) and responding to other specific inclusion criteria were recruited. The five available DAA regimens included sofosbuvir + ribavirin (SOF + RBV), elbasvir/grazoprevir (EBR/GZR), ombitasvir/paritaprevir/ritonavir/dasabuvir (OBV/PTV/r/DSV) ± RBV, daclatasvir + asunaprevir (DCV + ASV), and SOF + DCV ± RBV. Demographic, virologic, clinical, and adverse effects data obtained during and after DAAs treatment were collected. We evaluated the rate of sustained virological response at 12 weeks post-treatment (SVR12), the incidence of adverse effects, and assessed the factors associated with SVR12. RESULTS: Four hundred ninety-four patients finished the treatment and completed the 12-week post-treatment follow-up. The overall SVR12 rate was estimated at 96.96%. SVR rates greater than 95% were achieved in most of the HCV genotypes with the exception of GT1a (0%), GT3a (93.33%), and GT3b (88.24%). SVR12 for patients treated with DCV + ASV, EBR/GZR, OBV/PTV/r/DSV ± RBV, SOF + DCV ± RBV, and SOF + RBV for 12 or 24 weeks was 86.67%, 100%, 98.11%, 97.56%, and 95.06%, respectively. Subjects with compensated cirrhosis (92.73%) and prior treatment experience (77.78%) had significantly lower SVR rates when compared to chronic hepatitis C (98.15%) and treatment-naive (97.69%) groups. In Tianjin, the available DAA regimens were generally well-tolerated, and not a single serious adverse event was reported. CONCLUSION: In this large real-life single-center HCV cohort from China, oral DAAs were highly effective and well-tolerated. Further and larger-scale studies are needed to evaluate their clinical safety and efficacy.

Decreased ratio of influenza-specific IgG versus IgM in response to influenza vaccination in antiretroviral-treated HIV-infected African Americans compared to Caucasians, and its direct correlation with the percentages of peripheral Tfh cells.

BACKGROUND: Racial differences have been observed in the rate of bacterial infection and disease progression in HIV. Here, we evaluate racial differences in seasonal influenza vaccine responses. METHODS: 16 healthy controls (9 Caucasians (CC) and 7 African Americans (AA)) and 26 antiretroviral therapy (ART)-treated aviremic HIV+ subjects (11 CC and 15 AA) were enrolled in the current study. Blood was collected at pre-vaccination (D0) and day 14 (D14) following seasonal influenza vaccination. Serologic responses were characterized in plasma by ELISA. B and T cells were assessed by flow cytometry ex vivo. RESULTS: The absolute counts of CD4+ CD3+ T cells and CD19+ B cells were similar in healthy controls and HIV-infected individuals, and similar in CC and AA in the two study groups. However, the percentage of peripheral T follicular helper (pTfh) cells was decreased in HIV+ AA compared to HIV+ CC. There were no racial differences in IgG antibody responses against vaccination in the two study groups. However, the ratio of anti-influenza-specific IgG versus IgM induction following vaccination was decreased in HIV+ AA compared to HIV+ CC, which was directly correlated with the percentages of pTfh cells. This racial difference and correlation were not demonstrable in healthy controls. CONCLUSION: Here we report that HIV + AA has decreased fold induction of IgG versus IgM after influenza vaccination, which may suggest impaired class-switching from IgM to IgG in AA HIV-infected individuals.

Progressive Multifocal Leukoencephalopathy Diagnosed by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid in an HIV Patient.

Metagenomic next-generation sequencing (mNGS) is a novel approach to identify pathogens undetected by conventional methods. Herein, we report a case in which mNGS was used to identify JC virus from the cerebrospinal fluid sample of an HIV positive patient with progressive multifocal leukoencephalopathy (PML).

Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection.

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking.

Cigarette smoking has been shown to cause pathological alterations in the liver. However, how hepatic metabolism is altered during cigarette smoking­induced inflammation remains to be fully elucidated. In the present study, a rat model of smoking was established to examine the effects of cigarette smoking on inflammation, autophagy activity, and the expression of nuclear receptor and CYP in the liver. Elevated expression of interleukin 1ß and activation of autophagy in the liver were observed upon smoking exposure in rats. Cigarette smoking induced a significant reduction in the mRNA expression levels of cytochromes, including cytochrome P450 (Cyp)1A2, Cyp2D4 and Cyp3A2. Accordingly, a decrease was also observed in glucocorticoid receptor (GR), a regulator of the expression of Cyp. Activation of the GR signal in human hepatic LO2 cells did not affect autophagic genes, however, it led to the upregulation of hCYP1A2, hCYP2C19 and hCYP3A4, and the downregulation of hCYP2C9. The GR antagonist, RU486, eliminated this effect, suggesting the importance of GR in liver metabolism upon cigarette smoking.