RESUMO
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.
Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Tolerância Imunológica , Hepatite B/tratamento farmacológicoRESUMO
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.
Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Cirrose Hepática , Ácidos Graxos Voláteis/metabolismoRESUMO
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.
Assuntos
Antivirais , Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , China/epidemiologia , Antivirais/uso terapêutico , Interferon-alfa/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Polietilenoglicóis/uso terapêuticoRESUMO
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.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Vírus da Hepatite BRESUMO
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.
Assuntos
Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Antígenos E da Hepatite B , Antígenos de Superfície da Hepatite B , DNA Viral/análise , Adenina , Resultado do TratamentoRESUMO
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.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Complexo de Golgi , Humanos , Cirrose HepáticaRESUMO
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.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Consenso , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controleRESUMO
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.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite B Crônica , Neoplasias Hepáticas , Adulto , Humanos , Cirrose HepáticaRESUMO
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.
Assuntos
Colestase Intra-Hepática , Fígado Gorduroso , Hiperêmese Gravídica , Hepatopatias , Complicações na Gravidez , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/terapia , Feminino , Feto , Humanos , Hepatopatias/diagnóstico , Hepatopatias/terapia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapiaRESUMO
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 Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia
, Hipertireoidismo
, Neoplasias da Glândula Tireoide
, Adulto
, Idoso
, Antitireóideos/uso terapêutico
, Feminino
, Humanos
, Hipertireoidismo/complicações
, Hipertireoidismo/tratamento farmacológico
, Radioisótopos do Iodo
, Fígado
, Masculino
, Pessoa de Meia-Idade
, Estudos Retrospectivos
RESUMO
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.
Assuntos
Hepatite B Crônica , Alanina Transaminase , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática , NucleosídeosRESUMO
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.
Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
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.
Assuntos
Aldo-Ceto Redutases/metabolismo , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Aldo-Ceto Redutases/genética , Carcinoma Hepatocelular/genética , Pontos de Checagem do Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inativação Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Proteína do RetinoblastomaRESUMO
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.
Assuntos
Hepatite B/diagnóstico , Adulto , China/epidemiologia , DNA Viral , Hepatite B/epidemiologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Sangue OcultoRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Antivirais/administração & dosagem , DNA Viral , Feminino , Hepatite B Crônica/prevenção & controle , Humanos , Recém-Nascido , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/virologia , Carga ViralRESUMO
Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC) in China. The occurrence of HCC can significantly be reduced with effective long-term antiviral treatment. Since the widespread clinical use of nucleos(t)ide analogues, such as entecavir and tenofovir that has a strong potency and high genetic barrier to resistance; the detection rate of HBV DNA in serum of patients with chronic hepatitis B is no more than 85% ~ 95%, but HCC can still occur in a small number of patients. This article will review whether the timing and selection of NAs treatment differ to prevent and reduce the incidence of HCC.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Nucleotídeos/uso terapêutico , Carcinoma Hepatocelular/virologia , China , Tomada de Decisões , Humanos , Neoplasias Hepáticas/virologia , Fatores de TempoRESUMO
Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2-5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log(10) IU/ml and (3.95 + 0.40) log(10) IU/ml; t = 8.465, P < 0.001). Conclusion: Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.
Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Biomarcadores/sangue , DNA Viral , Feminino , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student's t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm(3)), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ(2) = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion: AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular , Linhagem Celular Tumoral/efeitos dos fármacos , Xenoenxertos , Neoplasias Hepáticas , Oxirredutases Atuantes sobre Doadores de Grupos Aldeído ou Oxo , Inibidores de Proteínas Quinases/farmacologia , Sorafenibe/farmacologia , Adulto , Aldo-Ceto Redutases , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To eliminate viral hepatitis as a public health threat, the World Health Organization has set the ambitious goal of reducing the prevalence of hepatitis B surface antigen (HBsAg) in children to 0.1% by 2030, and the key to this grand goal is cutting off hepatitis B virus (HBV) transmission from mother-to-child. Previously, national and international guidelines for the management of chronic hepatitis B recommended the use of hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) or combination of any in neonates and antiviral drugs for pregnant women with high viral load in late pregnancy. However, a recent study in Thailand found that the addition of antiviral drugs in pregnant women with high viral load in the third trimester did not significantly lower the incidence of mother-to-child HBV transmission, but no case of chronic HBV infection was seen with strict standards hepatitis B vaccine and HBIG combined immunoprophylaxis and the use of tenofovir disoproxil in pregnant women with high viral load in the third trimester. In addition, the incidence of mother -to- child transmission of HBV in the antiviral group was 0, while the incidence of HBV transmission in the placebo group was 2%. Therefore, it is not possible to deny the efficacy of adding antiviral drugs in treating pregnant women with high viral load in the third trimester with combined immunoprophylaxis. There is an urgent need for more real-world studies in clinical practice to further reveal the principles and existing problems of mother- to- child transmission of HBV.