Cirrhotic patients and older people

The global population is aging,and so the number of older cirrhotic patients is increasing.Older patients are characterised by a risk of frailty and comorbidities,and age is a risk factor for mortality in cirrhotic patients.The incidence of nonalcoholic fatty liver disease as an aetiology of cirrhosis is increasing,while that of chronic viral hepatitis is decreasing.Also,cirrhosis is frequently idiopathic.The management of portal hypertension in older cirrhotic patients is similar to that in younger patients,despite the greater risk of treatment-related adverse events of the former.The prevalence of hepatocellular carcinoma increases with age,but its treatment is unaffected.Liver transplantation is generally recommended for patients<70 years of age.Despite the increasing prevalence of cirrhosis in older people,little data are available and few recommendations have been proposed.This review suggests that comorbidities have a considerable impact on older cirrhotic patients.

HIV Genetic Diversity, Virological Failure, and Drug Resistance in Libreville, Capital of Gabon, before a Total Dolutegravir-Based Regimen Transition

Context: The Human Immunodeficiency Virus (HIV) continues to be the main public health challenge in Gabon. The latest studies highlight a high rate of virological failure and HIV drug resistance in semi-rural Gabon. In Libreville, virological failure data is sparse, data on HIV drug resistance for the former first line and new first-line regimen is lacking. Methods: Between January 28th, 2019, and January 31st, 2020, we received patient living with HIV (PLWHA) for CD4 counts, HIV-1 viral load, and/or genotyping of HIV-1 mutation drug resistance. We used the BD FACSPresto for CD4 count, the Biocentric Generic HIV viral load test for HIV-1 quantification, and the HIV-1 drug resistance mutation genotyping (ARNS protocol). Results: A total of 1129 HIV-1 patients have been enrolled for this study. The median age was 46 years old and the median of CD4 was 386 cells per cubic millimeter. The virological suppression success was observed at 62.7% of patients on the former first line regimen and 70.6% of the patient on DBR. We successfully amplified and analyzed 76 sequences and noticed the presence of the nineteen different subtypes with the predominance of the subtypes CRF02-AG (37.95%), followed by subtype A (22.3%). For HIV drug resistance analyses, 108 (65.1%) had resistance mutation to nucleoside reverse transcriptase inhibitors (NRTIs);of these, 91 (84%) present M184V/I. When looking for NNRTI mutations, 119 (71.7%) sequences had at least one mutation. Of these, 82 had K103N (68.9%), representing the main NNRTI mutations. The pattern showing the high level of resistance (HLR) in all molecules of NRTIs and NNRTIs, except for the TDF (intermediate resistance) was M41L-E44DL74I-M184-L210W-T215Y-K101P-K103N-V106I. Conclusion: This report paints a picture of a relatively female-dominated HIV-infected Gabonese population with a low level of immunity. The level of drug resistance with the former first-line regimen suggests the need to monitor the drug Dolutegravir resistance.

A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells

SATB1(Special A-T rich Binding protein 1)is a cell type-specific factor that regulates the genetic network in developing T cells and neurons.In T cells,SATB1 is required for lineage commitment,VDJ recombination,development and maturation.Considering that its expression varies during B-cell differentiation,the involvement of SATB1 needs to be clarified in this lineage.Using a KO mouse model in which SATB1 was deleted from the pro-B-cell stage,we examined the consequences of SATB1 deletion in naive and activated B-cell subsets.Our model indicates first,unlike its essential function in T cells,that SATB1 is dispensable for B-cell development and the establishment of a broad IgH repertoire.Second,we show that SATB1 exhibits an ambivalent function in mature B cells,acting sequentially as a positive and negative regulator of Ig gene transcription in naive and activated cells,respectively.Third,our study indicates that the negative regulatory function of SATB1 in B cells extends to the germinal center response,in which this factor limits somatic hypermutation of Ig genes.