Single-cell RNA-sequencing of virus-specific cellular immune responses in chronic hepatitis B patients.

Chronic hepatitis B (CHB) is a major global health challenge. CHB can be controlled by antivirals but a therapeutic cure is lacking. CHB is characterized by limited HBV-specific T cell reactivity and functionality and expression of inhibitory receptors. The mechanisms driving these T cell phenotypes are only partially understood. Here, we created a single-cell RNA-sequencing dataset of HBV immune responses in patients to contribute to a better understanding of the dysregulated immunity. Blood samples of a well-defined cohort of 21 CHB and 10 healthy controls, including a subset of 5 matched liver biopsies, were collected. scRNA-seq data of total immune cells (55,825) plus sorted HBV-specific (1,963), non-naive (32,773) and PD1+ T cells (96,631) was generated using the 10X Genomics platform (186,123 cells) or the full-length Smart-seq2 protocol (1,069 cells). The shared transcript count matrices of single-cells serve as a valuable resource describing transcriptional changes underlying dysfunctional HBV-related T cell responses in blood and liver tissue and offers the opportunity to identify targets or biomarkers for HBV-related immune exhaustion.

A novel approach to reducing hepatotoxicity related to fungal prophylaxis in pediatric lung transplant recipients.

BACKGROUND: Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first-line agent, has been shown to cause hepatotoxicity. We describe a single-center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post-transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post-operative course. METHODS: This is a retrospective review of patients in the age 0-18 who received a lung transplant from June 2016-May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results. RESULTS: Forty-two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post-operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post-transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post-transplant, but this difference was not found to be statistically significant (p = .507). CONCLUSIONS: An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post-lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post-lung transplant are warranted.

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). AIM: To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. RESULTS: Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. CONCLUSION: This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.

Hepatitis B virus reactivation in patients treated with monoclonal antibodies.

Hepatitis B virus (HBV) reactivation poses a significant clinical challenge, especially in patients undergoing immunosuppressive therapies, including monoclonal antibody treatments. This manuscript briefly explores the complex relationship between monoclonal antibody therapy and HBV reactivation, drawing upon current literature and clinical case studies. It delves into the mechanisms underlying this phenomenon, highlighting the importance of risk assessment, monitoring, and prophylactic measures for patients at risk. The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy, ultimately facilitating informed clinical decision-making and improved patient care. This paper will also briefly review the definition of HBV activation, assess the risks of reactivation, especially in patients treated with monoclonal antibodies, and consider management for patients with regard to screening, prophylaxis, and treatment. A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

Perilipin 2 inhibits replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions.

Hepatitis B virus (HBV) infection poses a global health concern without a definitive cure; however, antiviral medications can effectively suppress viral replication. This study delves into the intricate interplay between lipid metabolism and HBV replication, implicating molecular mechanisms such as the stearoyl coenzyme A desaturase 1 autophagy pathway, SAC1-like phosphatidylinositol phosphatase, and galectin-9 mediated selective autophagy of viral core proteins in regulating HBV replication. Within lipid droplets, perilipin 2 (PLIN2) emerges as a pivotal guardian, with its overexpression protecting against autophagy and downregulation stimulating triglyceride catabolism through the autophagy pathway. This editorial discusses the correlation between hepatic steatosis and HBV replication, emphasizing the role of PLIN2 in this process. The study underscores the multifaceted roles of lipid metabolism, autophagy, and perilipins in HBV replication, shedding light on potential therapeutic avenues.

Global trends in hepatitis C-related hepatocellular carcinoma mortality: A public database analysis (1999-2019).

BACKGROUND: Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma (HCC). However, there are marked variations in the incidence and mortality rates of HCC across different geographical regions. With the advent of new widely available treatment modalities, such as direct-acting antivirals, it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C. Furthermore, gender disparities in HCC mortality related to Hepatitis C are a crucial, yet underexplored aspect that adds to the disease's global impact. While some studies shed light on gender-specific trends, there is a lack of comprehensive data on global and regional mortality rates, particularly those highlighting gender disparities. This gap in knowledge hinders the development of targeted interventions and resource allocation strategies. AIM: To understand the global and regional trends in Hepatitis C-related HCC mortality rates from 1990 to 2019, along with gender disparities. METHODS: We utilized the Global Burden of Disease database, a comprehensive repository for global health metrics to age-standardized mortality rates due to Hepatitis C-related HCC from 1999 to 2019. Rates were evaluated per 100000 population and assessed by World Bank-defined regions. Temporal trends were determined using Joinpoint software and the Average Annual Percent Change (AAPC) method, and results were reported with 95% confidence intervals (CI). RESULTS: From 1990 to 2019, overall, there was a significant decline in HCC-related mortality rates with an AAPC of -0.80% (95%CI: -0.83 to -0.77). Females demonstrated a marked decrease in mortality with an AAPC of -1.06% (95%CI: -1.09 to -1.03), whereas the male cohort had a lower AAPC of -0.52% (95%CI: -0.55 to -0.48). Regionally, East Asia and the Pacific demonstrated a significant decline with an AAPC of -2.05% (95%CI: -2.10 to -2.00), whereas Europe and Central Asia observed an uptrend with an AAPC of 0.72% (95%CI: 0.69 to 0.74). Latin America and the Caribbean also showed an uptrend with an AAPC of 0.06% (95%CI: 0.02 to 0.11). In the Middle East and North Africa, the AAPC was non-significant at 0.02% (95%CI: -0.09 to 0.12). North America, in contrast, displayed a significant upward trend with an AAPC of 2.63% (95%CI: 2.57 to 2.67). South Asia (AAPC -0.22%, 95%CI: -0.26 to -0.16) and Sub-Saharan Africa (AAPC -0.14%, 95%CI: -0.15 to -0.12) trends significantly declined over the study period. CONCLUSION: Our study reports disparities in Hepatitis C-related HCC mortality between 1999 to 2019, both regionally and between genders. While East Asia and the Pacific regions showed a promising decline in mortality, North America has experienced a concerning rise in mortality. These regional variations highlight the need for healthcare policymakers and practitioners to tailor public health strategies and interventions. The data serves as a call to action, particularly for regions where mortality rates are not improving, emphasizing the necessity for a nuanced, region-specific approach to combat the global challenge of HCC secondary to Hepatitis C.

Dengue induced acute liver failure: A meta summary of case reports.

BACKGROUND: Dengue fever is the most common cause of viral hemorrhagic fever, with more than 400 million cases being reported annually, worldwide. Even though hepatic involvement is common, acute liver failure (ALF) is a rare complication of dengue fever. AIM: To analyze the demographic profile, symptomology, hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports. METHODS: A systematic search was performed from multiple databases including PubMed, Reference Citation Analysis, Science Direct, and Google Scholar. The search terms used were "dengue" OR "severe dengue" OR "dengue shock syndrome" OR "dengue haemorrhagic syndrome" OR "dengue fever" AND "acute liver failure" OR "hepatic failure" OR "liver injury". The inclusion criteria were: (1) Case reports or case series with individual patient details; (2) Reported acute liver failure secondary to dengue infection; and (3) Published in English language and on adult humans. The data were extracted for patient demographics, clinical symptomatology, clinical interventions, hospital and intensive care unit course, need for organ support and clinical outcomes. RESULTS: Data from 19 case reports fulfilling the predefined inclusion criteria were included. The median age of patients was 38 years (inter quartile range: Q3-Q1 26.5 years) with a female preponderance (52.6%). The median days from diagnosis of dengue to development of ALF was 4.5 d. The increase in aspartate aminotransferase was higher than that in alanine aminotransferase (median 4625 U/L vs 3100 U/L). All the patients had one or more organ failure, with neurological failure present in 73.7% cases. 42.1% patients required vasopressor support and hepatic encephalopathy was the most reported complication in 13 (68.4%) cases. Most of the patients were managed conservatively and 2 patients were taken up for liver transplantation. Only 1 death was reported (5.3%). CONCLUSION: Dengue infection may rarely lead to ALF. These patients may frequently require intensive care and organ support. Even though most of these patients may improve with supportive care, liver transplantation may be a therapeutic option in refractory cases.

Development of a multiplex polymerase chain reaction assay for detection of hepatitis C virus, hepatitis B virus, and human immunodeficiency virus 1.

BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus 1 (HIV-1) are the most epidemic blood-borne viruses, posing threats to human health and causing economic losses to nations for combating the infection transmission. The diagnostic methodologies that depend on the detection of viral nucleic acids are much more expensive, but they are more accurate than serological testing. AIM: To develop a rapid, cost-effective, and accurate diagnostic multiplex polymerase chain reaction (PCR) assay for simultaneous detection of HCV, HBV, and HIV-1. METHODS: The design of the proposed PCR assay targets the amplification of a short conserved region featured with a distinguishable melting profile and electrophoretic molecular weight inside each viral genome. Therefore, this diagnostic method will be appropriate for application in both conventional (combined with electrophoresis) and real-time PCR facilities. Confirmatory in silico investigations were conducted to prove the capability of the approached PCR assay to detect variants of each virus. Then, Egyptian isolates of each virus were subjected to the wet lab examination using the given diagnostic assay. RESULTS: The in silico investigations confirmed that the PCR primers can match many viral variants in a multiplex PCR assay. The wet lab experiment proved the efficiency of the assay in distinguishing each viral type through high-resolution melting analysis. Compared to related published assays, the proposed assay in the current study is more sensitive and competitive with many expensive PCR assays. CONCLUSION: This study provides a simple, cost-effective, and sensitive diagnostic PCR assay facilitating the detection of the most epidemic blood-borne viruses; this makes the proposed assay promising to be substitutive for the mistakable and cheap serological-based assays.

Chronic hepatitis B and occult infection in chemotherapy patients - evaluation in oncology and hemato-oncology settings: The CHOICE study.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis. AIM: To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy. METHODS: In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc. RESULTS: The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3). CONCLUSION: The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.

Leukocytoclastic vasculitis in a patient with ankylosing spondylitis: A case report.

Key Clinical Message: Although the concurrent occurrence of vasculitis with AS is uncommon, when patients diagnosed with AS exhibit symptoms including skin petechiae, purpura, abdominal discomfort, malaise, elevated ESR, and reduced complement levels, vigilant monitoring for vasculitis is advisable following the exclusion of secondary vasculitis triggers such as malignancies, infections, and pharmaceutical agents. Abstract: The primary characteristic of ankylosing spondylitis (AS) involves inflammation occurring within the sacroiliac joint and the spine, leading to destruction and eventual ankylosis. A notably infrequent complication associated with AS is vasculitis, with limited reports linking AS to vasculitis. This case study documents a 48-year-old male, diagnosed with HLA-B27-positive AS for the past 15 years, who developed abdominal pain and skin lesions following the cessation of his medication on his own. Subsequent clinical evaluations identified leukocytoclastic vasculitis (LCV) related to AS after excluding all other potential causes of LCV, including drug-related sources, cancer, hepatitis B and C viruses, Henoch-Schönlein purpura (HSP), and IgA nephropathy.

The Forgotten Virus, Hepatitis D: A Review of Epidemiology, Diagnosis, and Current Treatment Strategies.

Hepatitis D virus (HDV) is an RNA subvirus that infects patients with co-existing hepatitis B virus (HBV) infections. HDV burden is estimated to be approximately 15-20 million people worldwide. Despite HDV severity, screening for HDV remains inadequate. HDV screening would benefit from a revamped approach that automatically reflexes testing when individuals are diagnosed with HBV if HBsAg-positive, to total anti-HDV, and then to quantitative HDV-RNA polymerase chain reaction (PCR) rather than only testing those at high risk sequentially. There are no current treatments in the United States that are Food and Drug Administration (FDA)-approved for the treatment of HDV; however, bulevirtide (BLV) is approved in the European Union conditionally and is under review with the United States FDA. Current treatment strategies in many countries are centered on the use of pegylated-interferon-alfa-2a (PEG-IFNa-2a). There are other therapies in development globally that have shown promise, including BLV, pegylated-interferon-lambda (PEG-IFN-lambda), and lonafarnib (LNF). LNF has shown substantial response in the LOWR trials. BLV is a well-tolerated drug, but it is not finite therapy and has shown significant on-treatment responses in the MYR clinical trials, and the FDA cited concerns with the manufacturing and patient preparation of the drug that have delayed approval. The PDUFA date for BLV in the United States is mid-2024. Current studies with both BLV and LNF are limited in providing sustained virological response (SVR); future trials will need to demonstrate more substantial SVR with possible triple combination trials as options.

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors.

BACKGROUND: Patients with liver cancer complicated by portal hypertension present complex challenges in treatment. AIM: To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition. METHODS: Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group (n = 50) and a control group (n = 50) according to the treatment regimen. The research group received radiofrequency ablation (RFA) in combination with sorafenib, and the control group only received RFA. The short-term efficacy of both the research and control groups was observed. Liver function and portal hypertension were compared before and after treatment. Alpha-fetoprotein (AFP), glypican-3 (GPC-3), and AFP-L3 levels were compared between the two groups prior to and after treatment. The occurrence of adverse reactions in both groups was observed. The 3-year survival rate was compared between the two groups. Basic data were compared between the survival and non-surviving groups. To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension, multivariate logistic regression analysis was employed. RESULTS: When comparing the two groups, the research group's total effective rate (82.00%) was significantly greater than that of the control group (56.00%; P < 0.05). Following treatment, alanine aminotransferase and aspartate aminotransferase levels increased, and portal vein pressure decreased in both groups. The degree of improvement for every index was substantially greater in the research group than in the control group (P < 0.05). Following treatment, the AFP, GPC-3, and AFP-L3 levels in both groups decreased, with the research group having significantly lower levels than the control group (P < 0.05). The incidence of diarrhea, rash, nausea and vomiting, and fatigue in the research group was significantly greater than that in the control group (P < 0.05). The 1-, 2-, and 3-year survival rates of the research group (94.00%, 84.00%, and 72.00%, respectively) were significantly greater than those of the control group (80.00%, 64.00%, and 40.00%, respectively; P < 0.05). Significant differences were observed between the survival group and the non-surviving group in terms of Child-Pugh grade, history of hepatitis, number of tumors, tumor size, use of sorafenib, stage of liver cancer, histological differentiation, history of splenectomy and other basic data (P < 0.05). Logistic regression analysis demonstrated that high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, no use of sorafenib, liver cancer stage IIIC, and previous splenectomy were independent risk factors for poor prognosis in patients with liver cancer complicated with portal hypertension (P < 0.05). CONCLUSION: Patients suffering from liver cancer complicated by portal hypertension benefit from the combination of RFA and sorafenib therapy because it effectively restores liver function and increases survival rates. The prognosis of patients suffering from liver cancer complicated by portal hypertension is strongly associated with factors such as high Child-Pugh grade, tumor size (6-10 cm), history of hepatitis, lack of sorafenib use, liver cancer at stage IIIC, and prior splenectomy.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Clinical characteristics and prognostic implications of immune-related hepatitis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a retrospective study.

Background: With the widespread use of immune checkpoint inhibitors (ICIs), patients inevitably experience immune-related adverse events (irAEs). Therefore, the study was conducted on the clinical characteristics and outcomes of patients with non-small cell lung cancer (NSCLC) with immune-related hepatitis (ir-hepatitis). Methods: We identified patients with advanced NSCLC who developed ir-hepatitis after immunotherapy between June 2016 and December 2022. Their irAEs were categorized according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE 4.03). Kaplan-Meier curves and log-rank tests were used to analyze survival. Results: A total of 35 patients were enrolled in the study. The numbers of mild (grade 1-2) and severe (grade 3-4) ir-hepatitis cases were 13 (grade 1, 3; grade 2, 10) and 22 (grade 3, 17; grade 4, 5), respectively. The median onset time of ir-hepatitis was 1.6 months. The median progression-free survival (mPFS) was 8.3 months. PFS differed between patients with early ir-hepatitis developing within two treatment cycles and those with ir-hepatitis developing more than two treatment cycles (5.5 vs. 12.7 months, P=0.004). Patients with severe rather than mild ir-hepatitis tended to poorer PFS survival (5.8 vs. 11.2 months, P=0.130). The appearance of ir-hepatitis within two treatment cycles (P=0.002) and higher severity grades of ir-hepatitis (P=0.005) were independent risk factors for PFS. Conclusions: Early and severe ir-hepatitis are associated with worse survival benefits, which still required more basic and perspective studies.

Development of novel prognostic models based on dynamic changes in risk factors for hepatitis B associated acute-on-chronic liver failure:a 10-year retrospective study.

Background/Aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality, and early prediction is critical to reduce the deaths of ACLF patients. To date, however, the prognostic accuracy of current models for ACLF is unsatisfactory, particularly, in patients with hepatitis B virus (HBV) infection. This study aims to develop novel prognostic models based on the dynamic changes in variables to predict the short-term mortality of HBV-associated ACLF (HBV-ACLF). Methods: A retrospective cohort study was conducted, with the population comprised in whom ACLF was confirmed.319 patients were enrolled and their clinical data were collected on Days 1 and 7 following hospital admission. Univariate and multivariate analyses were performed to identify risk factors for 28 and 90-day mortality. The dynamic alterations in the risk factors were further analyzed, and Days 1 and 7 prognostic models were constructed. Receiver operating characteristic (ROC) analysis were used to identify and compared the predictors of prognosis among our model. Results: Univariate and multivariate analyses revealed significant risk factors at Days 1 and 7, which when combined with the clinically important parameters, were used to establish the Days 1 and 7 prognostic models. For 28-day mortality, the predictive accuracy of the Day 1 prognostic model was significantly higher than that of the albumin-bilirubin (ALBI) model. For 90-day mortality, the predictive accuracy of the Days 1 and 7 prognostic models was significantly higher than that of the Model of End-Stage Liver Disease (MELD), MELD-sodium (MELD-Na), and ALBI prognostic models. Conclusions: The prognostic models established in this study were superior to the existing prognostic scoring systems to accurately predict short-term mortality, and therefore, could be potential novel prognostic tools for HBV-ACLF.

Prevalence of Sexually Transmitted Infections and Predictors for Loss to Follow Up among Marginalized Homeless and Migrant Communities: a Cross-Sectional Study.

Background: In Europe and Italy, marginalized communities have a higher risk for both contracting sexually transmitted infections (STI) and progressing towards adverse outcomes. Objectives: This study focuses on the screening of HIV, HBV, HCV, and syphilis among homeless individuals and agricultural migrant workers living in Apulia, Italy. It aims to assess STI prevalence and investigate factors that might hinder return to collect test results. In addition, it explores STI knowledge, attitudes, and practices among these vulnerable populations. Methods: A cross-sectional study was conducted from September 1, 2022, to September 30, 2023. Participants were recruited from community health centers and migrant camps. Blood tests for HBV, HCV, HIV, and syphilis were performed, and Knowledge, Attitude, and Practices (KAP) survey were conducted via face-to-face interviews. Descriptive and logistic regression analyses were used to assess factors influencing the return for test results. Results: A total of 149 persons were recruited, including 64 agricultural migrant workers and 85 homeless people. Overall, 24.8% (n = 37) tested positive for at least one infection, and only 50.3% (n = 75) of the screened participants returned to collect their test results. Significant disparities in STI knowledge and healthcare access were observed between the two populations, with only 14.1% (n = 9) of migrants having access to primary healthcare. At multivariable analysis, the strongest predictor for not returning for test results was being positive for HCV. Conclusions: Among homeless people and agricultural migrant workers, STI prevalence was high, and only half of the population returned to collect test results. The study underscores the urgent need for targeted interventions and policy reevaluation to address healthcare disparities in marginalized communities.

Molecular characterization of the nonstructural 5A (NS5A) region of hepatitis C virus in Thai blood donors.

Direct acting antivirals (DAAs) have been developed for hepatitis C virus (HCV) therapy, and they are usually effective, however resistance to DAA regimens has also been reported to have a significant impact. Resistance associated substitutions (RASs) in the NS5A region are known to be correlated with failure of DAA therapy. HCV genotypes 3a and 1 are the most prevalent genotypes in Thailand. This study analyzed the type and frequency of RASs associated with DAA failure, focusing on the NS5A region. Serum samples of HCV genotype 3a, 1a, and 1b infection from Thai blood donors were selected. The NS5A region was amplified using reverse transcription-polymerase chain reaction (RT-PCR). A phylogenetic tree was constructed to identify the genotypes of HCV. Nucleotide sequencing and amino acid sequencing were conducted to determine the prevalence of RASs. Construction of the phylogenetic tree indicated that 29 samples were genotype 3a, 11 samples were genotype 1a, and 9 were genotype 1b. Both HCV genotypes 1a and 3a can be categorized into two subclades. Results showed that the NS5A substitutions A30V/K, A62T/V/I/M/P/S/L, and S98G were present in HCV genotype 3a. In HCV genotype 1a, only NS5A RASs H54Y was detected. NS5A amino acid substitutions Q54H and P58L were found in HCV genotype 1b. In conclusion, NS5A RASs at amino acid positions 30, 62, 54, 58, and 98 are present within HCV genotypes 3a and 1. While keeping in mind that additional information was not available on the anonymous blood donors tested in this study, these findings can contribute to understand the NS5A mutation. Further study with known patients under drug treatment is recommended.