中华肝脏病杂志最新文献

Molecular diagnosis is of enormous significance for the clinical diagnosis and treatment of hepatobiliary tumors. The expert group first released the "Expert Consensus for Clinical Application of Molecular Diagnosis on Hepatobiliary Tumors" in 2020. The introduction of this consensus has promoted the standardized application of molecular diagnostic technology in the clinical work of hepatobiliary tumors and improved the diagnosis and treatment capabilities of clinical physicians for hepatobiliary tumors. Research on hepatobiliary tumors has gradually been carried out in recent years, with the continuous publication of new research results. Hence, the expert group updated this consensus on the basis of the latest research progress, the original consensus, with a focus on the detection of molecular markers for targeted and immunotherapy of hepatobiliary tumors, in order to provide a reference for clinical physicians in treatment decisions and maximize the benefits for patients.

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated. Results: 666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m² were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion: CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective: To explore and analyze the clinical features of patients with immunoglobulin (Ig)G4-related hepatobiliary-pancreatic disease and the independent factors affecting the prognosis of IgG4-related sclerosing cholangitis (IgG4-SC). Methods: The clinical data of 179 adult cases diagnosed with IgG4-related hepato-pancreato-biliary disease in the Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2011 to December 2022 were retrospectively analyzed. Patients were divided into three groups: isolated IgG4-SC, IgG4-SC/type 1 autoimmune pancreatitis(type 1 AIP), and isolated AIP according to the clinical manifestations. Demographic characteristics, baseline biochemical immunological indexes, and imaging manifestations were analyzed. The treatment response rate and survival rate were compared. The COX proportional hazards model was used to analyze the independent factors related to prognosis. Results: The mean age of diagnosis of patients with IgG4-related hepatobiliary-pancreatic disease was 60.3±12.0 years. Males accounted for 74.9%, and the median follow-up time was 38 months. The 1-year clinical response rate of patients with isolated IgG4-SC was lower than that of IgG4-SC/AIP (67.9% vs. 91.7%, P=0.019), and the primary endpoint-free 5-year survival rate was significantly reduced (64.9% vs. 95.9%, P<0.001). COX regression analysis showed that having cirrhosis before treatment (HR=6.708, P=0.004) and poor response after half a year of treatment (HR=11.488, P=0.002) were independent risk factors associated with the occurrence of adverse events in hepatobiliary diseases among patients with IgG4-SC. Conclusions: The clinical response rate and survival rate of patients with isolated IgG4-SC are lower than those of patients with IgG4-SC/AIP. Patients with IgG4-SC who do not respond well at six months of treatment and who have progressed to cirrhosis before treatment are at significantly increased risk of adverse events.

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Thrombocytopenia in cirrhosis is causing puzzlement in clinical practice. Therefore, in order to help clinical practitioners grasp quickly and standardize the diagnosis and treatment of thrombocytopenia in cirrhosis, liver fibrosis, and portal hypertension, the Group of the Chinese Society of Hepatology of the Chinese Medical Association has organized relevant field experts to formulate the "Concise Guidelines for Clinical Management of Thrombocytopenia in Cirrhosis" with aim of providing guidance for the clinical diagnosis and treatment.

Chronic hepatitis B (CHB) mainly causes cirrhosis and hepatocellular carcinoma (HCC). Metabolic fatty liver disease (MAFLD) has become the most common chronic liver disease worldwide with the continuous changes in lifestyle and dietary patterns and the increase in the number of obese individuals. Consequently, the incidence rate of CHB combined with MAFLD is rapidly increasing. However, the pathogenesis, treatment, and clinical prognosis remain unclear due to the interaction between CHB and MAFLD. Notably, in the academic community, there are still controversies as to whether patients with CHB and MAFLD should immediately start antiviral treatment, whether MAFLD affects the antiviral efficacy in CHB patients, and whether nucleos(t)ide analogues (NAs) affect the body's metabolism. This article reviews the epidemiology, clinical prognosis, treatment management strategies (especially the antiviral efficacy of NAs drugs), and NAs drug effects on the body's metabolism in patients with CHB combined with MAFLD so as to provide diagnostic and therapeutic concept for clinicians.

Objective: To analyze and clarify the clinical and pathogenic gene variation and genetic etiology of polycystic liver disease. Methods: The proband clinical data and family history were collected. Whole-exome sequencing technology was used to detect the proband gene variations. Fluorescence quantitative PCR validation was performed on the proband and his family to screen out pathogenic gene variation. Results: A multiple liver cyst was found in an 18-year-old male proband during a physical examination. There were no abnormalities in his liver function, and both his father and grandfather had multiple liver cysts without any obvious discomfort or other special manifestations. Whole exome sequencing suggested a heterozygous deletion in exon 1 (Exon 1) of the SEC63 gene in the proband. Real-time fluorescence quantitative PCR confirmed that the heterozygous deletion variation of the SEC63 gene Exon 1 of the proband came from his father, and the same heterozygous deletion was detected in his grandfather. The gene variant had a pathogenic variation that had been rarely reported before and was in accordance with the the American college of Medical Genetics and Genomics (ACMG) guidelines. Conclusions: The genetic etiology of this autosomal dominant polycystic liver disease has been clarified, and the heterozygous deletion of Exon1 of the SEC63 gene is a newly discovered gene variation that broadens the variation spectrum of the SEC63 gene.

Objective: To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis. Methods: We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results: The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline (P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased (P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased (P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment (P＞0.05), and no serious adverse events were observed. Conclusions: For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.