RESUMEN
Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.
Asunto(s)
Antivirales , Hepatitis B Crónica , Humanos , Hepatitis B Crónica/tratamiento farmacológico , China/epidemiología , Antivirales/uso terapéutico , Interferón-alfa/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Polietilenglicoles/uso terapéuticoRESUMEN
Hepatitis B is mostly a chronic, progressive disease that, if not treated promptly and effectively, can slowly progress to cirrhosis, liver failure, or hepatocellular carcinoma. Therefore, antiviral therapy, i.e., a "complete therapy" strategy, should be started as long as the virus is positive. Immediate antiviral treatment is not recommended for infected patients who are only in the immune-tolerant phase, mainly because of the milder conditions and poor antiviral therapy efficacy, according to antiviral indications in China's Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version). The relevant issues of why hepatitis B virus infection in the immune-tolerant phase is the last mile of "complete therapy," with an emphasis on the disease's characteristics and antiviral treatment strategies, are discussed here.
Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Tolerancia Inmunológica , Hepatitis B/tratamiento farmacológicoRESUMEN
Short-chain fatty acids are metabolites of the intestinal flora and serve as the main energy source for intestinal epithelial cells. At the same time, as important signaling molecules, it regulate a variety of cellular inflammatory responses and homeostatic proliferation through receptor-dependent and independent pathways. Short-chain fatty acids regulate the gut-liver axis and thereby directly act on the liver, participating in the pathogenesis and transformation of various liver diseases, including alcoholic liver disease, metabolic dysfunction-related liver disease, autoimmune liver disease, liver fibrosis, and hepatocellular carcinoma. In addition, short-chain fatty acids can inhibit HBV DNA replication. This article reviews the research progress on the role of short-chain fatty acids in aspects of the pathogenesis and transformation of chronic liver diseases.
Asunto(s)
Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Cirrosis Hepática , Ácidos Grasos Volátiles/metabolismoAsunto(s)
Carcinoma Hepatocelular , Hepatopatías , Neoplasias Hepáticas , Humanos , Cirrosis HepáticaRESUMEN
Timely and effective antiviral therapy can prevent or delay the progression of the disease to cirrhosis, liver failure, or hepatocellular carcinoma in patients with chronic hepatitis B. Antiviral therapy indications are constantly expanding, and eventually it will be manageable to treat viral positives based on the new understanding of the disease progression and the changes in the definition of abnormal values in liver function tests.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Hepatitis B Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Virus de la Hepatitis BRESUMEN
Objective: To prospectively explore the treatment strategies for clinical difficulties in patients with hyperviremia HBeAg-positive chronic hepatitis B with incomplete response to first-line nucleos(t)ide analogues (NAs). Methods: Patients with hyperviremia HBeAg-positive chronic hepatitis B were treated with first-line NAs, including entecavir, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) for 48 weeks or more. Tenofovir amibufenamide (TMF) or TAF therapy was changed when HBV DNA remained positive and then divided into a TMF group and a TAF group. Clinical efficacy of treatment was evaluated at 24 and 48 weeks, including HBV DNA undetectable rates and virological and serological responses in both patient groups. Results: In the TMF group and the TAF groups, 30 and 26 cases completed 24-week follow-up, while 18 and 12 cases completed 48-week follow-up. There were no statistically significant differences in baseline HBV DNA, HBsAg, and HBeAg levels between the two groups before switching to TMF/TAF therapy (P > 0.05). At 24 weeks of treatment, 19 (19/30, 63.33%) cases in the TMF group had HBV DNA negative conversion, while 14 (14/26, 53.85%) cases in the TAF group had HBV DNA negative conversion (P > 0.05). Among the patients who completed 48 weeks of follow-up, 15 (15/18, 83.33%) cases in the TMF group and 7 (7/12, 58.33%) cases in the TAF group had negative HBV DNA tests (P > 0.05). The changes in HBsAg and HBeAg levels between the two groups of patients at 24 and 48 weeks of treatment were not statistically significant compared to baseline (P > 0.05). Conclusion: TMF is effective in treating patients with hyperviremia HBeAg-positive CHB with an incomplete response to first-line NAs treatment, but there is no significant difference compared to TAF.
Asunto(s)
Antivirales , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Antígenos e de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , ADN Viral/análisis , Adenina , Resultado del TratamientoAsunto(s)
Carcinoma Hepatocelular , Hepatopatías , Neoplasias Hepáticas , Humanos , Cirrosis HepáticaRESUMEN
Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Aparato de Golgi , Humanos , Cirrosis HepáticaRESUMEN
Clinically, chronic hepatitis B and C are the main common chronic liver diseases that lead to cirrhosis and liver cancer, followed by drug-induced liver injury, alcohol and metabolic-associated fatty liver disease, and autoimmune liver disease in adult, but, by contrast, some special liver diseases, including pregnancy-related liver disease, liver injury related to abnormal liver endocrine function, adult hereditary liver disease, and hepatitis caused by non-hepatotropic viruses are also gradually increasing. Early identification and diagnosis are the only accurate and timely manner treatment for these special liver diseases.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis B Crónica , Neoplasias Hepáticas , Adulto , Humanos , Cirrosis HepáticaRESUMEN
Pregnancy-related liver disease is a group of severe diseases that usually resulting in worsening clinical outcome in pregnant women and fetuses. Therefore, diagnosis and treatment at early-stage are essential. This paper reviews the early-stage clinical features, pathogenesis, diagnosis and treatment key points of common pregnancy-related liver diseases such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, hemolysis, elevated liver enzymes and low platelet syndrome, and acute fatty liver of pregnancy, in order to help clinicians, improve their understanding of pregnancy-related liver disease.
Asunto(s)
Colestasis Intrahepática , Hígado Graso , Hiperemesis Gravídica , Hepatopatías , Complicaciones del Embarazo , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/terapia , Femenino , Feto , Humanos , Hepatopatías/diagnóstico , Hepatopatías/terapia , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapiaRESUMEN
Objective: To analyze, explore and evaluate the clinical characteristics, abnormal thyroid function and follow-up of anti-hyperthyroidism treatment mode in patients with hyperthyroidism (commonly abbreviated as HT) combined with liver injury. Methods: The clinical data of patients with hyperthyroidism combined with liver injury were retrospectively analyzed, and then patients were divided into treated and untreated group according to whether they received anti-hyperthyroidism treatment before the consultation. Patients' thyroid and liver function test indicators at the time of treatment were analyzed to determine the main cause of liver injury. The characteristics of liver injury were analyzed in the treatment group. Patients with severe thyroid toxicity and hyperthyroidism combined with liver injury were followed-up with anti-hyperthyroid therapy, mainly low-dose methimazole (MMI) and radioactive iodine therapy to evaluate its efficacy and safety. The comparison between data groups was performed by t-test, rank sum test and χ( 2) test. Results: Among the 43 cases with hyperthyroidism combined with liver injury, 19 were males and 24 were females, aged 49.0 ± 14.6 years-old; 16 cases (16/43, 37.21%) aged 40 to≤60 years- old, and 15 cases (15/43, 34.88%) aged > 60 years-old. There were 22 untreated cases (untreated group, accounting for 51.16%), and 21 treated cases with anti-hyperthyroidism (treatment group, accounting for 48.84%) at the time of consultation. Thyroid function indicators (FT3, FT4, TSH) and liver function indicators (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, total bilirubin) of the two groups were compared, and the difference was not statistically significant (P > 0.05). The order of liver injury from mild to severe in patients with different treatment options were: methimazole (MMI) < propylthiouracil < radioactive iodine Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología
, Hipertiroidismo
, Neoplasias de la Tiroides
, Adulto
, Anciano
, Antitiroideos/uso terapéutico
, Femenino
, Humanos
, Hipertiroidismo/complicaciones
, Hipertiroidismo/tratamiento farmacológico
, Radioisótopos de Yodo
, Hígado
, Masculino
, Persona de Mediana Edad
, Estudios Retrospectivos
RESUMEN
Patients with chronic hepatitis B (CHB) who cannot receive effective antiviral therapy timely will eventually develop liver cirrhosis and/or hepatocellular carcinoma (HCC). Therefore, receiving nucleos(t)ide analogues (NAs) therapy can effectively inhibit hepatitis B virus (HBV) replication, improve liver tissue inflammation and fibrosis, prevent or delay the disease progression, and greatly reduce the occurrence of HBV-related HCC. However, it is often found in clinical practice that some patients treated with long-term NAs therapy can still develop HCC despite the effective inhibition of HBV replication. This phenomenon has attracted widespread concern and discussion. In this article, we focus on whether NAs can significantly reduce the occurrence of HCC while effectively inhibiting HBV replication, or HCC can still occur. Additionally, discuss the possible causes of HCC after NAs therapy, including the types of drugs, treatment timing, incomplete response, etc., in order to help clinicians implement antiviral treatment more accurately, and further reduce HBV-related HCC.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Consenso , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & controlRESUMEN
Objective: Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells. Methods: HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test. Results: AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 (P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion: AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.
Asunto(s)
Aldo-Ceto Reductasas/metabolismo , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Neoplasias Hepáticas/metabolismo , Transducción de Señal , Aldo-Ceto Reductasas/genética , Carcinoma Hepatocelular/genética , Puntos de Control del Ciclo Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Silenciador del Gen , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Proteína de RetinoblastomaAsunto(s)
Virus de la Hepatitis B , Hepatitis B , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Guías de Práctica Clínica como Asunto , Complicaciones Infecciosas del Embarazo , Antivirales , Niño , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Hepatitis B/transmisión , Antígenos de Superficie de la Hepatitis B , Vacunas contra Hepatitis B , Humanos , EmbarazoRESUMEN
Due to the difference in infection time and immune clearance ability, patients with chronic hepatitis B virus (HBV) infection may appear as virus carrier or chronic active hepatitis. Alanine aminotransferase (ALT) is the most sensitive biomarkers for evaluating liver inflammation. Current anti-HBV drugs, nucleoside analogues (NAs) and peginterferon α, can only achieve satisfactory results when liver inflammation is active. Therefore, international authoritative guidelines recommend HBV DNA positive and ALT > 2-fold the upper limit of normal (2×ULN) as indications for treatment. However, many studies have shown that some chronic HBV infected patients with normal ALT have insidious progression to liver cirrhosis or liver failure, because of not initiating antiviral therapy in time. Hence, the disease assessment and initiation indication for treatment have received more and more attention and become a hot topic in clinical research for chronic HBV infected patients with normal ALT.
Asunto(s)
Hepatitis B Crónica , Alanina Transaminasa , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática , NucleósidosRESUMEN
Objective: To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients. Methods: HBeAg-positive CHB-naïve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks. Results: As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group (P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log(10) S/CO (OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log(10) IU / ml (OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion: In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log(10) at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.
Asunto(s)
Antígenos e de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Resultado del TratamientoRESUMEN
Hepatitis B virus (HBV) infection remains to be a serious public health problem in China. There used to be a high prevalence of HBV infection in China, which resulted in a large number of HBV susceptible and post-infected population. Single anti-HBc positive usually indicates post HBV infection and its prevalence is particularly high among people over 40 years old, some of whom may be occult hepatitis B virus infection (OBI). The clinical diagnosis of OBI is difficult and easily missed. Since OBI may cause chronic liver disease progression and even lead to cirrhosis and hepatocellular carcinoma eventually, and more importantly, patients with OBI may leed to HBV reactivation when the immune function decreases or immunosuppressive therapy is performed, the accurate identify of OBI is of particular importance. Moreover, OBI is the potential source of HBV infection, which may transmit through blood transfusion, organ transplantation and mother-to-child transmission. In view of this situation, we reviewed the mechanism, prevalence and definition of OBI, and proposed a determination system for replication-competent HBV DNA based on our understanding of the updated OBI definition. It is expected to be beneficial for OBI diagnosis, treatment and management.
Asunto(s)
Hepatitis B/diagnóstico , Adulto , China/epidemiología , ADN Viral , Hepatitis B/epidemiología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Sangre OcultaRESUMEN
The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.