Jin-Sheng Guo

Hepatic stellate cells (HSC) are the major source of myofibroblasts (MFB) in fibrosis and cancer- associated fibroblasts (CAF) in both primary and metastatic liver cancer. Over the past few decades, there has been significant progress in understanding the cellular and molecular mechanisms by which liver fibrosis and HCC occur, as well as the key roles of HSC in their pathogenesis. HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects. Recent advances in omics, particularly single-cell sequencing and spatial transcriptomics, hold promise for identifying new HSC targets for diagnosing and treating liver fibrosis/cirrhosis and liver cancer.

Hepatic stellate cells (HSC) are the major source of myofibroblasts (MFB) in fibrosis and cancer associated fibroblasts (CAF) in both primary and metastatic liver cancer. Over the past few decades, there has been significant progress in understanding the cellular and molecular mechanisms by which liver fibrosis and HCC occur and the key roles of HSC in the pathogenesis. HSC targeted approaches via specific surface markers and receptors may enable selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects. Recent advances in omics, particularly single-cell sequencing and spatial transcriptomics, hold promise for identifying new HSC targets for diagnosing and treating liver fibrosis/cirrhosis and liver cancer.

Hepatitis B virus (HBV) infection is a major risk factor of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Pathogenesis of HBV-induced cirrhosis and HCC involves viral factors and virus-triggered local inflammatory and immune responses, the latter leading to progressive fibrosis, cirrhosis and carcinogenesis. Antiviral therapeutics suppress HBV replication and reduce the risks of cirrhosis and HCC. We discuss the current knowledge on the pathogenesis of HBV-induced cirrhosis and HCC, focusing on mechanisms of current and emerging antiviral therapeutics.

Hepatitis C viral infections present a significant global health challenge, carrying substantial economic implications. These infections manifest in various clinical forms, including acute and chronic hepatitis, liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC emerge as the primary contributors to mortality in hepatitis virus-induced liver diseases. To alleviate the public health impact of this disease, it is imperative to enhance the diagnosis and treatment rates among hepatitis C virus-infected individuals. The advent of direct-acting antivirals (DAAs), especially pan-genotypic regimens such as a combination of sofosbuvir and velpatasvir, has shown remarkable progress in achieving hepatitis C cure. However, potential obstacles, such as drug adverse effects and resistance-associated substitutions (RASs), warrant attention. Managing chronic hepatitis C (CHC) requires tailored treatment plans, vigilant monitoring, and judicious re-treatment strategies.

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

糖原累积病（GSD）1a型是由于葡萄糖-6-磷酸酶催化亚单位缺陷所致的常染色体隐性遗传病，属于一种罕见的遗传代谢性疾病。现报道1例GSD-1a青年女性患者，具有典型症状和体征，即不耐受空腹状态，生长发育不良，肝肿大伴多发性肝腺瘤；生物化学特征表现为一系列代谢紊乱，包括非酮症性低血糖，空腹高乳酸、高尿酸、高脂血症。患者进而通过外周血全外显子组基因检测发现NM_000151.3：c.648G＞T纯合变异而明确为GSD-1a的诊断与分型。GSD-1a的治疗主要包括饮食管理，旨在维持正常的血糖水平；纠正继发性代谢紊乱；监测和处理肝腺瘤与腺瘤癌变等的并发症。

Aim: This is a Chinese population-based study aimed to determine the causes and clinical features of drug-induced liver injury (DILI) from traditional Chinese medicines (TCMs) and current Western m

Objective: Pre-S1 antigen (pre-S1) is a component of hepatitis B virus large surface antigen (L-HBsAg). This study aimed to investigate the association between clinical pre-S1 antigen (pre-S1) status and adverse prognostic events in chronic hepatitis B (CHB) patients. Methods: This study retrospectively enrolled 840 CHB patients with comprehensive clinical data, including 144 patients with multiple follow-up of pre-S1 status. All patients were tested for serum pre-S1 and divided into pre-S1 positive and negative groups. Single factor and logistic multiple regression analyses were performed to explore the association between pre-S1 and other HBV biomarkers with the risk of hepatocellular carcinoma (HCC) in CHB patients. The pre-S1 region sequences of HBV DNA were obtained from one pre-S1 positive and two pre-S1 negative treatment-naïve patients using polymerase chain reaction (PCR) amplification followed by Sanger sequencing. Results: The quantitative HBsAg level was significantly higher in the pre-S1 positive group than that in the pre-S1 negative group (Z=− 15.983, P< 0.001). The positive rate of pre-S1 increased significantly with the increase in HBsAg level (χ²=317.963, P< 0.001) and HBV DNA load (χ²=15.745, P< 0.001). The pre-S1 negative group had a higher HCC risk than the pre-S1 positive group (Z=− 2.00, P=0.045, OR=1.61). Moreover, patients in the sustained pre-S1 negative group had a higher HCC risk (Z=− 2.56, P=0.011, OR=7.12) than those in the sustained pre-S1 positive group. The sequencing results revealed mutations in the pre-S1 region from samples of pre-S1 negative patients, including frameshift and deletion mutations. Conclusion: Pre-S1 is a biomarker that indicates the presence and replication of HBV. Pre-S1 sustained negativity attributed to pre-S1 mutations in CHB patients may be associated with a higher risk of HCC, which has clinical significance and warrant further investigations.

In recent years, marine-derived bioactive compounds have gained increasing attention because of their higher biodiversity vs land-derived compounds. A number of marine-derived compounds are proven to improve lipid metabolism, modulate the gut microbiota, and possess anti-inflammatory, antioxidant, antibacterial, antiviral, and antitumor activities. With the increasing understanding of the molecular landscape underlying the pathogenesis of chronic liver diseases, interest has spiked in developing new therapeutic drugs and medicine food homology from marine sources for the prevention and treatment of liver diseases.