Liver Research最新文献

Background and aim

Methods

Results

Conclusions

Clinical trial number

Background and aim

Glucocorticoids are the only first-line drugs for severe alcoholic hepatitis (AH), with limited efficacy and various side effects on extrahepatic tissues. Liver-targeting glucocorticoid therapy may have multiple advantages over systemic glucocorticoid for AH. The aim of this study was to determine the role of hepatocellular glucocorticoid receptor (GR) in alcohol-associated steatosis (AS) and AH.

Materials and methods

AS was induced by a high-fat diet plus binge alcohol in adult male and female mice with liver-specific knockout (LKO) and heterozygote of GR. AH was induced by chronic-plus-binge in middle-aged male mice with liver-specific knockin of GR. Changes in hepatic mRNA and protein expression were determined by quantitative real-time polymerase chain reaction and Western blot.

Results

GR-LKO aggravated steatosis and decreased hepatic expression and circulating levels of albumin in both genders of AS mice but only increased markers of liver injury in male AS mice. Marked steatosis in GR-LKO mice was associated with induction of lipogenic genes and down-regulation of bile acid synthetic genes. Hepatic protein levels of GR, hepatocyte nuclear factor 4 alpha, and phosphorylated signal transducer and activator of transcription 3 were gene-dosage-dependently decreased, whereas that of lipogenic ATP citrate lyase was increased in male GR heterozygote and LKO mice. Interestingly, hepatic expression of estrogen receptor alpha (ERα) was induced, and the essential estrogen-inactivating enzyme sulfotransferase 1e1 was gene-dosage-dependently down-regulated in GR heterozygote and knockout AS mice, which was associated with induction of ERα-target genes. Liver-specific knockin of GR protected against liver injury and steatohepatitis in middle-aged AH mice.

Conclusions

Hepatic GR deficiency plays a crucial role in the pathogenesis of AS induced by high-fat diet plus binge, and liver-specific overexpression/activation of GR protects against chronic-plus-binge-induced AH in middle-aged mice. Hepatocellular GR is important for protection against AS and AH.

Hepatitis B virus (HBV) infection is a significant health problem that can result in progression to liver cirrhosis, decompensation, and the development of hepatocellular carcinoma (HCC). On a country level, the prevalence of chronic HBV infection varies between 0.1% and 35.0%, depending on the locality and the population being investigated. One-third of all liver cancer fatalities worldwide are attributable to HBV. The adoption of standard birth-dose immunization exerted the most significant impact on the decline of HBV prevalence. HCC incidence ranges from 0.01% to 1.40% in noncirrhotic patients and from 0.9% to 5.4% annually, in the settings of liver cirrhosis. Although antiviral therapy significantly reduces the risk of developing HBV-related HCC, studies have demonstrated that the risk persists, and that HCC screening is still essential. This review discusses the complex relationship between HBV infection and HCC, recent epidemiological data, different aspects of clinical disease characteristics, and the impact of antiviral therapy in this context.

Background and aims

Hepatocellular carcinoma (HCC), which is prevalent worldwide and has a high mortality rate, needs to be effectively diagnosed. We aimed to evaluate the significance of plasma microRNA-15a/16-1 (miR-15a/16) as a biomarker of hepatitis B virus-related HCC (HBV-HCC) using the machine learning model. This study was the first large-scale investigation of these two miRNAs in HCC plasma samples.

Methods

Using quantitative polymerase chain reaction, we measured the plasma miR-15a/16 levels in a total of 766 participants, including 74 healthy controls, 335 with chronic hepatitis B (CHB), 47 with compensated liver cirrhosis, and 310 with HBV-HCC. The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein (AFP). Lastly, to validate the diagnostic efficiency of miR-15a/16, we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.

Results

Plasma miR-15a/16 was significantly decreased in HCC than in all control groups (P < 0.05 for all). In the training cohort, the area under the receiver operating characteristic curve (AUC), sensitivity, and average precision (AP) for the detection of HCC were higher for miR-15a (AUC = 0.80, 67.3%, AP = 0.80) and miR-16 (AUC = 0.83, 79.0%, AP = 0.83) than for AFP (AUC = 0.74, 61.7%, AP = 0.72). Combining miR-15a/16 with AFP increased the AUC to 0.86 (sensitivity 85.9%) and the AP to 0.85 and was significantly superior to the other markers in this study (P < 0.05 for all), as further demonstrated by the detection error tradeoff curves. Moreover, miR-15a/16 impressively showed potent diagnostic power in early-stage, small-tumor, and AFP-negative HCC. A validation cohort confirmed these results. Lastly, the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.

Conclusions

We developed and validated a plasma miR-15a/16-based machine learning model, which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

Background and aim

Hepatitis B virus (HBV)-related gestational acute-on-chronic liver failure (ACLF) is a severe condition with limited treatment options. This study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy (CRRT) in managing pregnant women with HBV-related ACLF.

Methods

This study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and 2020. Patients admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol, which included more aggressive plasma exchange (PE) and CRRT strategies. All 19 pregnant women with hepatic encephalopathy (HE) were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three days. Our study had two primary objectives. Firstly, we aimed to evaluate the impact of PE and CRRT on puerperal survival. Secondly, we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with HE.

Results

The levels of total bilirubin on the second day postpartum (D3), the third day postpartum (D4), and the fifth day postpartum (D6) were significantly lower in the new treatment group compared to the conventional treatment group (P = 0.02, 0.01, and 0.02, respectively). The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group (P = 0.02). The incidence of HE overall increased from prenatal to postpartum D4, peaked on D4, and then gradually decreased from the fourth day postpartum (D5) （P = 0.027）. The first week after delivery revealed a significant difference in survival rate between the two groups, the conventional treatment group had statistically higher mortality rates compared to the new treatment group (P = 0.002). Similarly, the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment group (P = 0.002). Moreover, among all patients with HE, the non-early treatment group showed significantly higher puerperal mortality rates compared to the early treatment group (P = 0.006).

Conclusions

Early PE and CRRT conducted within three days post-childbirth, enhance puerperal prognosis for HBV-related gestational ACLF.

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.