中华肝脏病杂志最新文献

Objective: To establish a new method and platform for screening, identifying, and exploring a new strategy for anti-hepatitis B immunotherapy based on hepatitis B virus (HBV)-specific TCR. Methods: Peripheral blood mononuclear cells were isolated from patients with acute hepatitis B. CD3⁺CD8⁺CD137⁺T single cells were sorted out after stimulation with the HBsAg peptide library. The α and β chains in TCRs of single cells were amplified by PCR. TCR double-chain pairing and lentiviral packaging were performed through high-throughput sequencing. Re-infected Jurkat-76-NFAT-GFP cells and the cell lines stably expressing TCR were screened. HBsAg peptide library and immortalized B lymphocytes co-cultured with J76N-TCR were used to screen HBsAg-specific TCRs. K562 cell lines stably expressing HLA-A*24:02 were established to determine epitope peptide by screening A*24:02-restricted TCR. The screened TCRs were replaced with mouse C regions and packaged with lentiviruses. Functional validation was performed on healthy human CD4⁺T and CD8⁺T lymphocytes following infection. Results: Stable TCR-expressing cell lines were successfully prepared based on single-cell TCRαβ double-chain amplification and pairing technology. Twenty-one TCRs were screened using immortalized B lymphocytes, resulting in nine possible HLA-A*24:02-restricted HBsAg-specific TCRs. Further screening with K562-A2402 resulted in six A*24:02-restricted HBsAg-specific TCRs with identically recognized epitope peptide. The functional determination of the two TCR clones revealed their specific recognition function for target cells expressing HBsAg. Conclusion: HLA-A*24:02-restricted HBsAg-specific TCR with recognition function for target cells expressing HBsAg was successfully obtained based on the new experimental technology system, laying an important foundation for further exploration of antiviral immunotherapy based on HBV-specific TCR.

Childhood obesity has become a global public health issue. The incidence rate of non-alcoholic fatty liver disease (NAFLD) in children has rapidly increased with the increase in obesity. Thus, NAFLD has become one of the most common causes of chronic liver disease in children. Currently, there are no officially approved drugs for the treatment of NAFLD in children. Lifestyle changes, including dietary and exercise interventions, are first-line treatment options for NAFLD in children in the absence of effective drugs. This article reviews the latest progress of these years in dietary and exercise interventions in the prevention and treatment of NAFLD in obese children.

Hepatolenticular degeneration, also known as Wilson's disease, is a type of autosomal recessive genetic disorder of copper metabolism. The causative gene, ATP7B, is located on the long arm of chromosome 13 and encodes a P-type ATPase that is involved in copper transport. Pathogenic mutations in the ATP7B gene sequence lead to the diminished or lost function of the ATP7B protein, resulting in pathological copper deposition in organs such as the liver, brain, kidneys, and cornea. Currently, the treatment of Wilson's disease primarily involves oral medications to promote copper excretion or reduce copper absorption so as to alleviate the state of illness. However, pharmacological treatment has objective limitations, including the need for lifelong therapy and varying degrees of adverse drug reactions in some patients. Gene therapy can fully correct the genetic defect, restore ATP7B protein function, achieve a curative effect, and improve the patient's quality of life.

Objective: To investigate the correlation between the expression of the immunohistochemical marker cytokeratin (CK)-19 and the clinical characteristics and prognosis of dual-phenotype hepatocellular carcinoma (DPHCC). Methods: The data of patients diagnosed with hepatocellular carcinoma (HCC) who underwent surgical resection were collected. DPHCC cases were screened by immunohistochemistry, followed up, and grouped. The correlation between the expression of the immunohistochemical marker CK-19 and the clinical pathological characteristics and prognosis of DPHCC was analyzed by statistical methods. The enumeration data were compared using the χ² test or Fisher's exact probability method between groups. Results: The expression of CK19 was significantly correlated with factors such as the tumor size, histological grade, liver tissue cirrhosis surroundings, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA-199) levels in DPHCC, and the differences were statistically significant (P<0.05). There was no significant correlation between the expression of CK19 and the gender, age, tumor necrosis, multiple lesions, liver capsule invasion, serum alpha-fetoprotein (AFP), and immunohistochemical CK7 and mucin 1 (MUC-1) in DPHCC patients, and the differences were not statistically significant (P>0.05). The results of univariate analysis showed that immunohistochemical CK19 expression, MVI, number of lesions, tumor necrosis, tumor differentiation degree, serum AFP, and carbohydrate antigen 199 levels were related factors affecting the prognosis in DPHCC patients (P<0.05); while gender, age, capsule invasion, tumor size, and expression of immunohistochemical markers (vascular endothelial growth factor, CK7, MUC-1) were not significantly correlated with the prognosis in DPHCC patients (P>0.05). The results of multivariate analysis showed that tumor necrosis (P=0.042, 95%CI: 1.031-5.501) and serum AFP levels were independent risk factors affecting the prognosis in DPHCC patients (P<0.001, 95%CI: 2.581-24.075). Conclusions: The expression of CK19 is closely related to the prognosis of patients with DPHCC. Patients with high CK19 expression have faster disease progression than those with low CK19 expression. Furthermore, the overall survival rate of patients with high CK19 expression is significantly lower than that of patients with low CK19 expression, which is a risk factor for poor prognosis in patients with DPHCC.

Objective: To explore the distribution characteristics of HBsAg levels in treatment-naïve and treatment-experienced patients with chronic hepatitis B (CHB) in China. Methods: Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-naïve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean±SD, and M(Q₁, Q₃). Results: A total of 13 505 treatment-naïve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-naïve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-naïve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially. Conclusions: The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-naïve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

Liver failure is a severe clinical syndrome of liver disease with an extremely high mortality rate. Over the years, scholars worldwide have continuously investigated various aspects of liver failure, including its definition, etiology, classification, types, diagnosis and treatment, and prognostic assessment. Based on the latest advances in research, Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association along with Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association have conducted a comprehensive update on the Guidelines for diagnosis and treatment of liver failure (2018 version). This update aims to offer standardized protocols and evidence-based recommendations to guide the management of liver failure in clinical settings.

Ascites is the most common complication in the decompensated stage of cirrhosis, with approximately 5% to 10% progressing to refractory ascites (RA). The complex pathogenesis, difficult treatment, and poor prognosis are major challenges and difficulties in the clinical treatment of RA. Tolvaptan (TLV) is a kind of novel non-peptide, selective arginine vasopressin V2 receptor antagonist that can inhibit renal water reabsorption, promote free water excretion, and increase blood sodium levels, providing a new clinical option for the treatment of cirrhotic RA. This paper briefly summarizes the mechanism of action of TLV and introduces its effectiveness, safety, and predictive factors response in order to provide a reference for clinical application in the treatment of cirrhotic RA.

Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, aware-ness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.