中华肝脏病杂志最新文献

Hepatocellular carcinoma is one of the most common malignant tumors in the world, which is a serious threat to human health. HBV infection is one of the most common causes of hepatocellular carcinoma.The diagnosis of most hepatocellular carcinoma has progressed to the middle and late stage, and the prognosis is poor. Early detection, diagnosis and treatment are important supports to improve the clinical outcome of hepatocellular carcinoma. In recent years, scholars at home and abroad have established various hepatocellular carcinoma risk prediction models, which are conducive to improving the early diagnosis rate of hepatocellular carcinoma and reducing the mortality rate. This article reviews the risk factors and risk prediction models of chronic hepatitis B associated hepatocellular carcinoma, in order to provide reference for HBV-associated liver cancer risk monitoring and management decision.

Wilson's disease (WD) is a kind of inherited metabolic liver disease in which most patients need lifelong medication to maintain copper homeostasis in the body. Zinc is one of the most commonly used drugs for WD treatment. However, there are currently few high-quality, large-sample, and prospective clinical trials on zinc agent-treated WD. The selection and application of zinc agents are mainly based on patients' clinical phenotype, tolerance to zinc agents, and physicians' experience in treating WD. This article summarizes the application of zinc agents in WD.

Wilson's disease, also known as hepatolenticular degeneration, is an inherited disorder of copper metabolism caused by homozygous or compound heterozygous variants in the ATP7B gene, which is mainly clinically manifested as liver disease and/or neurological/psychological disorders, and Kayser-Fleischer ring in the peripheral cornea. Patients with Wilson's disease are currently treated with lifelong use of chelating agents that promote copper ion excretion and/or zinc agents that reduce copper absorption, but there is still an unmet clinical need because some patients who receive treatment have poor efficacy, disease progression, or serious adverse drug reactions. In recent years, new therapeutic drugs have been developed rapidly. This article will summarize the advances in drug treatment of Wilson's disease, shedding new light on the treatment of Wilson's disease.

Objective: To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis. Methods: 325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training (n=213) and validation (n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results: Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels (P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95%CI: 0.802-0.858) and 0.807 (95%CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95%CI: 0.796-0.858) and 0.811 (95%CI: 0.787-0.836), respectively. Conclusion: Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.

Professor Takeyori Saheki's team at Kagoshima University, Japan, published a paper in Nature Genetics in June 1999, pinpointing the pathogenic gene for adult-onset type Ⅱ citrullinemia as SLC25A13 and naming the protein product encoded by this gene as citrin. Over the past 25 years, the researches have made positive progress on the pathophysiological mechanism, clinical phenotype, molecular diagnosis, treatment, and prognosis of citrin deficiency (CD) as an autosomal recessive genetic disease. Currently, three age-dependent clinical phenotypes of CD have been found, namely neonatal intrahepatic cholestasis caused by citrin deficiency, failure to thrive and dyslipidemia caused by citrin deficiency, and adult-onset type Ⅱ citrullinemia. Although relevant internal medicine drugs are being researched and developed while liver transplantation has been used for the treatment of CD patients, scientific dietary therapy remains the foundation, core, and key for the management of this disease. Furthermore, CD management involves the full life cycle of patients, requiring the joint efforts of basic and clinical medicine as well as systematic articulation at multi-levels, such as the parents, family, and society. By full-cycle, multidisciplinary, and systematic management, it is an achievable goal for CD patients to learn, work, and live in a healthy manner.

Hereditary liver diseases are rare conditions characterized by a wide variety of types and very low incidence rate for each one. Their clinical manifestations are diverse, and diagnosis often requires specialized testing, posing a high likelihood of missed or misdiagnosis. Systemic learning the basic knowledge and classification of hereditary liver diseases, as well as an understanding of the clinical features, laboratory findings, imaging, and pathological features of the relatively common hereditary liver diseases in adults, such as Wilson's disease, hemochromatosis, and alpha-1 antitrypsin deficiency, is essential. Targeted genetic testing can aid in the timely identification and correct diagnosis of these diseases. Once the etiology is revealed, appropriate treatment can often improve the clinical outcomes and quality of life. Cell therapy and gene therapy represent future directions and may offer the chance of cure for certain conditions. Currently, for patients who have progressed to end-stage liver disease, liver transplantation remains the ultimate treatment option and mostly yield excellent long-term prognosis if the indication and timing are appropriate.

Hepatic encephalopathy (HE) is one of the severe complications of decompensated stage cirrhosis that causes cerebral dysfunction due to hepatic insufficiency and/or portosystemic shunts, and it usually manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. The pathogenesis of HE is complex, although ammonia toxicity, oxidative stress, inflammation, intestinal dysbiosis, and others among them mainly play an important role. The treatment for HE lacks specific drugs, and the current available drugs include non-absorbable disaccharides (lactulose), antibiotics (rifaximin), and other therapies (oral branched-chain amino acids, intravenous injection of L-ornithine-L-aspartic acid, probiotics). Recent research has shown that human albumin is a safe and effective treatment for HE, improving not only cognitive function but also enhancing patients' quality of life.

Progressive familial intrahepatic cholestasis (PFIC) is an important cause of liver-related death or transplantation in children. The PFIC spectrum is expanding, twelve types of PFIC are currently included in the Online Mendelian Inheritance in Man (OMIM) database. With the increase of PFIC types and the inconsistence of certain types in numbering, the current numbering classification of PFIC is confusing, so the experts in the field recommend using the corresponding mutant gene/ protein defect to name different type of PFIC except for PFIC type 1-3. The clarification of the genotype-phenotype relationship and/or the establishment of phenotypic predictors significantly improved the management of patients with PFIC. Odevixibat and maralixibat, inhibitors of the apical sodium ion-dependent bile acid transporter on the intestinal epithelial cells, were approved in European Union and the United States for the treatment of PFIC pruritus in 2021, expanding the treatment options for PFIC. Additionally, personalized treatments for specific mutations and novel gene therapy is promising.

Objective: To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis. Methods: One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ² test. Results: There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus (OR=2.958, 95%CI: 1.889-4.883, P<0.001), dispersion coefficient (OR=1.786, 95%CI: 1.424-2.292, P<0.001) and attenuation coefficient (OR=42.642, 95%CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose (OR=1.196, 95%CI: 1.048-1.392, P=0.011), alanine aminotransferase (OR=1.012, 95%CI: 1.006-1.019, P<0.001), aspartate aminotransferase (OR=1.027, 95%CI: 1.014-1.042, P<0.001), γ-glutamyl transferase (OR=1.008, 95%CI: 1.001-1.017, P=0.041) and HDL cholesterol (OR=0.087, 95%CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone (P=0.024, 0.027, 0.038 and <0.001). Conclusion: The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.