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Journal of Infection in Developing... Apr 2024Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the...
INTRODUCTION
Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum β-klotho (KLB) as a promising biomarker in HBV-related liver diseases.
METHODOLOGY
This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters.
RESULTS
The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC.
CONCLUSIONS
Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.
Topics: Humans; Male; Female; Biomarkers; Middle Aged; Adult; Hepatitis B, Chronic; Klotho Proteins; Carcinoma, Hepatocellular; Glucuronidase; Liver Neoplasms; Liver Cirrhosis; Disease Progression; Enzyme-Linked Immunosorbent Assay; Aged
PubMed: 38728647
DOI: 10.3855/jidc.17870 -
Medicine May 2024Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic...
Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report.
INTRODUCTION
Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive.
PATIENT CONCERNS
A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years.
DIAGNOSIS
Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C.
INTERVENTIONS AND OUTCOMES
He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal.
LESSONS
The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.
Topics: Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Middle Aged; Disease Progression; Quinolines; Chemoembolization, Therapeutic; Phenylurea Compounds; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38728500
DOI: 10.1097/MD.0000000000038138 -
American Journal of Cancer Research 2024The impact of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD) on liver-related events (LREs) in patients with chronic hepatitis C...
The impact of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD) on liver-related events (LREs) in patients with chronic hepatitis C (CHC) who had achieved a sustained virologic response (SVR) to direct-acting antiviral agents (DAAs) is unknown. A total of 924 patients with cured CHC and documented body mass index (BMI) were included in the analysis, and the data period was from September 2012 to April 2022. Hepatic steatosis was identified either through ultrasonography or blood biomarkers. Metabolic dysfunction was defined as the presence of overweight or obesity (BMI ≥ 23 kg/m), type 2 diabetes mellitus (DM), and metabolic dysregulation. Patients may have more than one metabolic dysfunction. Variables at 12 or 24 weeks after DAA therapy (PW12) were used to identify predictors of LREs. The median age of the 924 patients was 58 (49-65) years. Of the participants, 418 (45.2%) were male. The median BMI was 24.01 (21.78-26.73) kg/m, and 174 (18.8%) patients had DM. A multivariable Cox regression analysis revealed that age, male, albumin, total bilirubin, alpha-fetoprotein (AFP), metabolic dysfunction (hazard ratio: 1.709, 95% confidence interval: 1.128-2.591, P = .011), and FIB-4 > 3.25 were independent predictors of LREs. Type 2 DM and metabolic dysregulation exhibited a larger time-dependent area under the receiver operating characteristic curve for LREs than did overweight or obesity. Moreover, metabolic dysfunction was identified to be an independent predictor of hepatocellular carcinoma. Metabolic dysfunction increased the risk of LREs and HCC in patients with CHC who had achieved an SVR to DAA therapy.
PubMed: 38726283
DOI: 10.62347/EQIR8735 -
Journal of Gastrointestinal Surgery :... Jul 2024This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with...
Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis.
BACKGROUND
This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI).
METHODS
A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses.
RESULTS
Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022).
CONCLUSION
Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Phenylurea Compounds; Quinolines; Middle Aged; Propensity Score; Neoplasm Recurrence, Local; Hepatectomy; Neoplasm Invasiveness; Aged; Neoplasm Staging; Retrospective Studies; Microvessels; Chemotherapy, Adjuvant; Antineoplastic Agents; Immune Checkpoint Inhibitors
PubMed: 38723996
DOI: 10.1016/j.gassur.2024.05.001 -
BMC Surgery May 2024Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to... (Comparative Study)
Comparative Study
Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of LAMWA and laparoscopic hepatectomy in the treatment of small HCC.This study included 140 patients who met the inclusion criteria. Among them, 68 patients received LAMWA and 72 patients underwent laparoscopic hepatectomy. The perioperative condition, liver function recovery, the alpha fetoprotein (AFP) level, morbidities, hospitalization time, overall survival (OS), disease-free survival (DFS) and recurrence rate between the two groups were compared. The rate of complete elimination of tumor tissue was 100% and the AFP level was returned to normal within 3 months after surgery in both groups (P > 0.05). The mean alanine transaminase (ALT) and aspartate transaminase (AST) peak in the LAMWA group was lower than that in the laparoscopic hepatectomy group (259.51 ± 188.75 VS 388.9 ± 173.65, P = 0.000) and (267.34 ± 190.65 VS 393.1 ± 185.67, P = 0.000), respectively. The mean operation time in the LAMWA group was shorter than that in the laparoscopic hepatectomy group (89 ± 31 min VS 259 ± 48 min, P = 0.000). The blood loss in the LAMWA group was less than that in the laparoscopic hepatectomy group (58.4 ± 64.0 ml VS 213.0 ± 108.2 ml, P = 0.000). Compared with the laparoscopic hepatectomy group, patients in the LAMWA group had lower mean hospital stay (4.8 ± 1.2d VS 11.5 ± 2.9d, P = 0.000). The morbidities of the LAMWA group and the hepatectomy group were 14.7%(10/68) and 34.7%(25/72), respectively (P = 0.006). The one-, three-, and five-year OS rates were 88.2%, 69.9%, 45.6% for the LAMWA group and 86.1%, 72.9%, 51.4% for the laparoscopic hepatectomy group (P = 0.693). The corresponding DFS rates for the two groups were 76.3%, 48.1%, 27.9% and 73.2%, 56.7%, 32.0% (P = 0.958). Laparoscopic-assisted microwave ablation is a safe and effective therapeutic option for selected small HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Laparoscopy; Hepatectomy; Male; Female; Middle Aged; Microwaves; Treatment Outcome; Aged; Retrospective Studies; Adult
PubMed: 38715071
DOI: 10.1186/s12893-024-02432-0 -
Journal of Cancer Research and Clinical... May 2024Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender,...
BACKGROUND
Currently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC.
METHODS
This study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan-Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA).
RESULTS
The ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility.
CONCLUSION
This research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Female; Male; Neoplasm Recurrence, Local; Middle Aged; Prognosis; alpha-Fetoproteins; Nomograms; Prothrombin; Retrospective Studies; Aged; Protein Precursors; Biomarkers, Tumor; Adult; ROC Curve; Plant Lectins; Biomarkers
PubMed: 38713414
DOI: 10.1007/s00432-024-05760-z -
A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide.BioRxiv : the Preprint Server For... Apr 2024Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a...
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis and well-differentiated HCC, characterized by increased fibrosis, altered liver architecture, and enhanced hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and HCC rat model successfully replicates the clinical progression of human HCC, including liver function impairment and early-stage liver cancer characteristics. It presents a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.
PubMed: 38712079
DOI: 10.1101/2024.04.18.590120 -
Frontiers in Immunology 2024For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after...
BACKGROUND
For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors.
METHODS
This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL.
RESULTS
The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy.
CONCLUSION
In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Immune Checkpoint Inhibitors; Male; Middle Aged; Female; Retrospective Studies; Disease Progression; China; Aged; Adult; Neoplasm Staging; alpha-Fetoproteins; Treatment Outcome; East Asian People
PubMed: 38711515
DOI: 10.3389/fimmu.2024.1310239 -
Cancer Diagnosis & Prognosis 2024Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its...
BACKGROUND/AIM
Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its noninvasiveness and convenience. Furthermore, it is known that the excretion and metabolism of some tumor markers are affected by impaired renal function. In the present study, we investigated the effect of improved renal function on pre-and post-transplantation changes in tumor marker levels [carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and prostate-specific antigen (PSA)] in renal transplant recipients.
PATIENTS AND METHODS
A total of 116 renal transplant recipients, who had not been diagnosed with malignancies between January 2012 and December 2019, were included, and tumor markers were investigated.
RESULTS
CEA showed a significant decrease after kidney transplantation, regardless of the dialysis type (3.6→2.6 ng/ml, p<0.001), while other tumor markers showed a significant increase (AFP: 3.6→3.7 ng/ml; CA19-9: 16.2→19.5 U/ml; PSA: 0.95→1.05 ng/ml; all p<0.05). Pre- and postoperative eGFR ratios and postoperative liver function were identified as factors influencing the postoperative CEA and CA19-9 values, while PSA was influenced by the duration of dialysis. No statistically significant factors were found for AFP levels.
CONCLUSION
Caution should be exercised when investigating tumor markers in patients with renal dysfunction, as tumor marker levels may vary depending on the pathophysiology of each patient.
PubMed: 38707724
DOI: 10.21873/cdp.10319 -
Heliyon May 2024In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is...
OBJECTIVE
In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis.
METHODS
We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction.
RESULTS
tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC.
CONCLUSION
tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.
PubMed: 38707447
DOI: 10.1016/j.heliyon.2024.e30084