中华肝脏病杂志最新文献

Objective: To analyze the distribution of pathogenic microorganisms, drug resistance and influencing factors in patients with hepatitis B virus associated acute -on-chronic liver failure (HBV-ACLF) complicated with abdominal infection (IAI). Methods A retrospective analysis was conducted on 282 HBV-ACLF patients admitted to the Hepatobiliary Internal Medicine Department of Mengchao Hepatobiliary Hospital of Fujian Medical University, from May 2019 to December 2022, with 141 patients who had IAI and positive bacterial culture as the infected group; 141 non-infected patients admitted during the same period were used as the non-infected group. The clinical data, laboratory test results, pathogen species and drug sensitivity test results of the patients were collected, and the influencing factors of IAI in HBV-ACLF patients were analyzed by Logistic regression analysis. Results: A total of 204 pathogenic bacteria were detected in the infection group, including 115 Gram-negative bacteria (56.37%), 74 Gram-positive bacteria (36.28%) and 15 fungi (7.35%). The most frequently detected bacterial genera were Escherichia coli (21.57%, 44/204), Klebsiella pneumoniae (12.25%, 25/204), Enterococcus faecium (6.37%, 13/204), Staphylococcus aureus (5.39%, 11/204) and Staphylococcus epidermidis (4.90%, 10/204). The results of drug sensitivity tests showed that the resistance rates of Escherichia coli and Klebsiella pneumoniae to levofloxacin and ciprofloxacin were over 50% and 30% respectively; the resistance rate of Pseudomonas aeruginosa to carbapenems (meropenem and imipenem) was 60.00%; the resistance rates of Acinetobacter baumannii to meropenem and imipenem were 100% and 50.00% respectively; the resistance rates of Enterococcus faecium and Enterococcus faecalis to penicillin were 100% and 33.33% respectively; and the resistance rates of Staphylococcus aureus to penicillin (77.78%) and oxacillin (33.33%) were relatively high..The results of the multivariate unconditional logistic regression analysis showed that puncture and drainage (OR=17.90, 95% CI: 7.94~43.42, P< 0.001), procalcitonin (OR=3.23, 95% CI: 1.56~8.98, P=0.012), C-reactive protein (OR=1.05, 95% CI: 1.02~1.00, P=0.003), and age (OR=1.06, 95% CI: 1.02~1.10, P=0.001) were independent risk factors for IAI in patients with HBV-ACLF. Conclusions The pathogenic microorganisms of HBV-ACLF patients with IAI were mainly enterobacteriaceae bacteria and enterococcus. Puncture drainage, procalcitonin, C-reactive protein and age were independent risk factors for IAI in HBV-ACLF patients. Early intervention to avoid the increase of inflammatory in dicators is an effective measure to prevent abdominal infection in HBV-ACLF patients.

Although nucleotide analogs (NAs) and interferons are currently the primary treatments for chronic hepatitis B, they do not entirely remove cccDNA from hepatocytes. Antiviral therapy's desired outcome is the absence of hepatitis B surface antigen(HBsAg), often known as a clinical cure. Although interferon therapy has significantly higher HBsAg clearance and serologic conversion rates than NAs, combination or sequential therapy can improve HBsAg clearance and serologic conversion rates to some extent. Still, only a small proportion of patients will achieve clinical cure. As a result, it is critical to explore indications that might predict clinical cure before and during antiviral medication, allowing for early and prompt identification of patients more likely to achieve HBsAg clearance, improving clinical cure rates, and reducing treatment expenses. In this paper, we review the progress of recent studies on predictors of clinical cure in chronic hepatitis B, and discuss their value in predicting clinical cure to provide a reference for optimizing CHB treatment strategy.

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.

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.

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.

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.