Introduction Malnutrition is a common complication of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) typically associated with poor prognosis. Despite nutritional treatment, the outcomes for these patients are limited by the symptoms and complications associated with ACLF. So far, the benefits of nutritional interventions in these populations have not been proven. This study aims to explore a new nutritional intervention method for patients with HBV-ACLF and evaluate its safety and efficacy. Methods and analysis This study is an investigator-initiated, nonblind, randomised controlled clinical trial. We will recruit 60 patients with HBV-ACLF according to the Chinese Group on the Study of Severe Hepatitis B criteria hospitalised in the Infectious Diseases Department of the Third Affiliated Hospital of Sun Yat-Sen University. Eligible patients will be randomly allocated to the nutrition support group (intervention group) and the control group in a 1:1 ratio. Patients in the nutrition support group will receive 10 days of tailor-made nutrition therapy consisting of oral nutritional supplements and supplementary parenteral nutrition. Patients in the control group will receive standard nutrition with dietary advice. All assessments will be conducted at baseline, 30 days and 90 days. The primary outcome measure is the liver transplant-free mortality rate. The secondary indicators include the incidence of clinical adverse outcomes and changes in indicators such as muscle mass, muscle strength, physical function and quality of life (EQ-5D scale). Ethics and dissemination This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University (approval number: II2023-242-03). The results and conclusions of the clinical trial will be published in academic conferences or journals. Trial registration number NCT06128421.

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

As the primary receptor for HIV-1 entry, human CD4 is widely recognized as the hallmark of HIV-1 target cells. However, viral negative factor (Nef) and viral protein U (Vpu) down-regulate surface CD4 on infected cells, raising an intriguing question: If an infected CD4 ⁺ T cell survives and establishes latency, can CD4 expression recover? By tracking the fate of HIV-1–infected CD4 ⁺ T cells, we unexpectedly found that a subset of these cells directly convert to CD8 ⁺ T cells. T cell receptor (TCR) sequencing and single-cell RNA sequencing data revealed that these induced CD8 ⁺ T cells primarily originated from regulatory CD4 ⁺ T cells, which retained a regulatory-like phenotype postconversion. Mechanistically, HIV-1 viral protein R (Vpr) specifically induced this conversion by up-regulating transforming growth factor–β1 (TGF-β1), which, in turn, activates a TGF-β–dependent signaling pathway essential for CD8 lineage reprogramming. Critically, ex vivo analyses confirmed that CD8 ⁺ T cells from both untreated and antiretroviral therapy (ART)–suppressed people living with HIV-1 (PLWH) harbor transcriptionally active viral RNA or intact proviral DNA. Furthermore, we identified that human leukocyte antigen (HLA) class II–restricted CD8 ⁺ T cells, which were present in PLWH but absent in healthy controls, share TCR clonotypes with their antigen-specific CD4 ⁺ T cell counterparts, providing direct evidence for HIV-1–driven CD4-to-CD8 conversion in vivo. Collectively, these findings uncover a viral mechanism of host-cell reprogramming, demonstrate that CD8 ⁺ T cells constitute a previously overlooked component of the HIV-1 reservoir, and broaden our understanding of latent reservoir heterogeneity, an essential consideration for future cure strategies.

Background: Short-term mortality is high in patients with acute-on-chronic liver failure (ACLF), defined by the rapid deterioration of underlying chronic liver diseases. Current prediction models cannot estimate dynamic prognosis adequately. This study used both longitudinal and survival data to develop and validate a dynamic prediction model for ACLF. Methods: Adult patients with ACLF from a retrospective cohort, including 943 patients from 2014 to 2019 at the Third Affiliated Hospital of Sun Yat-sen University, were included. The progression of temporal indices was described using a mixed-effects model, and subject-specific prediction risk models with time-to-event data were constructed using a joint model (JM). The model was validated by testing the data using the area under the curve (AUC) and Brier score. Results: The AUCs for JM ranged from 0.808 to 0.840 when predicting 28-day mortality and from0.747 to 0.811 when predicting 90-day mortality in patients with ACLF. The linearity of the calibration curves was good, with the Brier scores ranging from 0.083 to 0.205. The performance of the ACLF-JM for 90-day predictions was superior (P < 0.001) to that of the Model for End-Stage Liver Disease score. Conclusions: It is possible to construct individualized dynamic event prediction models for patients with ACLF by jointly modeling longitudinal data with time-to-event outcomes. This JM provides a potentially valuable evidence-based tool for liver transplantation in clinical practice.