Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A_2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl₄)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl₄ twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl₄ injection. In order to confirm that the action of PDRN occurs through the adenosine A_2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A_2A receptor antagonist, was treated with PDRN. Administration of CCl₄ impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl₄. Administration of CCl₄ activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

Purpose: This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate. Experimental Design: We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG–non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo. Results: High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models. Conclusions: Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC.

Introduction: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. Methods: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled. Results: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0–74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894). Conclusions: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Introduction: In spite of the high frequency of recurrence of hepatocellular carcinoma (HCC) after resection, little evidence exists to directly help to plan a reasonable schedule for the frequency and intensity of postoperative surveillance for recurrence. Methods: 1,918 consecutive patients with Child-Turcott-Pugh class A who had T1- or T2-staged HCCs detected by active surveillance and underwent curative resection for their tumors at 3 teaching hospitals in Korea, followed by recurrence screening at 6-monthly or shorter intervals. To set an evidence-based timetable for postoperative surveillance, we investigated the annual hazard rate of recurrence through postoperative year 10 in patients undergoing hepatectomy for HCC, and the clinical and morphological phenotypes associated with early versus late recurrence. Results: The estimated hazard rate for recurrence peaked during year 0–1 (21.7%), with a subsequent gradual decrease through 5 years, followed by stabilization at <7.0% until year 10, except in the case of cirrhotics, who had a rate of 10.5% during year 4–5. Multivariate time-to-recurrence analysis by recurrence period revealed that serum alpha-fetoprotein ≥200 ng/mL, larger size of tumor, tumor multiplicity, microvascular invasion, capsular invasion, and higher METAVIR fibrosis stage were significantly related to disease recurrence within 5 years after resection, while cirrhosis (METAVIR F4) alone was related to disease recurrence beyond 5 years (Ps < 0.05). Post-relapse overall survival was better in the latter group (p = 0.033). Conclusions: Our chronological and morphological insights into recurrence after resection of primary HCCs may help implement an optimal intensity of surveillance for recurrence.