Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
1.
J Viral Hepat ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048386

RESUMO

Not all treatment-naïve patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy can achieve complete virological response, and many factors may be related with the outcome of partial virological response. This study aimed to determine whether the manner of drug administration affects the antiviral efficacy of ETV/TDF monotherapy. All eligible patients were divided into complete or partial response cohorts based on their virological response following 24-week therapy. Factors related with partial response were evaluated. Patients with partial response were further grouped depending on whether they later adjusted the manner of drug administration, and the antiviral efficacy was compared between the two groups during prolonged treatment. A total of 518 patients were enrolled. Suboptimal drug administration (OR 77.511, P = .000), positive-HBeAg (OR 3.191, P = .000) and ETV treatment (OR 2.537, P = .001) were identified as independent risk factors for partial response. Among patients with partial response, 213 were in the adjusted group and 76 were in the unadjusted group. The percentages of patients with undetectable serum HBV DNA (78.9% vs 31.6%, P < .001) and with normal alanine aminotransferase (ALT) (88.7% vs 68.4%, P < .001) were both higher in the adjusted group than that in unadjusted group following a further 6-month therapy. In conclusion, the manner of drug administration is an important factor influencing the efficacy of ETV/TDF therapy, and optimal drug administration manner can help to increase antiviral efficacy and rescue patients with partial response.

2.
J Med Virol ; 92(3): 302-308, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31609007

RESUMO

AIMS: The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV. METHODS: CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization. The primary safety outcomes were changes in serum creatinine and serum phosphorus levels. RESULTS: A total of 143 patients were investigated, including 63 patients in the TDF monotherapy group and 80 patients in the TDF + ETV combination therapy group. Baseline demographics and clinical characteristics were comparable between groups. The median age of patients was 44.5 years, and 76.2% of them were male. The VR rate in TDF + ETV group was higher than that of the TDF group at 48 weeks (88.8% vs 71.4%; P = .009). At 48 weeks, the HBeAg seroconversion rate of TDF + ETV group was higher than that of the TDF group (30% vs 15.9%; P = .049). There was no significant difference in the proportion of patients with elevated ALT in the TDF group and TDF + ETV group at 48 weeks (9.5% vs 7.5%; P = .665). After adjusting the treatment regimen, serum creatinine levels increased slightly and serum phosphorus level decreased slightly in both groups. CONCLUSIONS: TDF + ETV combination therapy for 48 weeks had a higher VR rate than TDF monotherapy in CHB patients with PVR to ETV.

3.
Med Clin (Barc) ; 154(1): 7-12, 2020 Jan 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31133232

RESUMO

BACKGROUND: There is growing evidence that vitamin D is related to the development of a variety of diseases. The current study was performed to investigate the status of serum vitamin D distribution among adult Chinese people and reveal the influence of gender, age, seasonality and residential regions on serum vitamin D levels. METHOD: This cross-sectional study included 14,302 participants aged from 18 years old to 65 years old from six major cities in China. The basic demographic information and the levels of serum vitamin D (25(OH)D) and vitamin D3 (25(OH)D3) were collected from Jan 2, 2014 to Dec 25, 2017. RESULT: The prevalence of 25(OH)D3 concentration <30ng/mL reached up to 83%, in which the rate of vitamin D insufficiency (20-29ng/mL) was 32.7%, and vitamin D deficiency (10-19ng/mL) accounted for 41.9%, and vitamin D severe shortage (<10ng/mL) accounted for 8.4%. Women were more likely to have vitamin D3 deficiency and lower serum vitamin D3 concentration than men (both p<0.001). The mean concentration of serum 25(OH)D and 25(OH)D3 in summer and autumn were higher than that in spring and winter (p<0.001), and the mean concentration of serum 25(OH)D in people from Southern China was higher than that in people from other regions (p<0.001). Although the mean concentrations of serum 25(OH)D and 25(OH)D3 were both increased by age, the percentage of patients with serum 25(OH)D3 insufficiency was also increased. CONCLUSION: Serum vitamin D deficiency is very common in adults in China. The level of serum vitamin D may be associated with age, sex, seasonality and residential regions.

4.
J Clin Transl Hepatol ; 7(3): 232-237, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608215

RESUMO

Background and Aims: The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC. Methods: The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature. Meta-analysis with random-effects model was performed to combine the incidence rates of HCC after portal-systemic shunt. Finally, seven studies were included. In the present review, we mainly focused on 859 patients (365 in the transjugular intrahepatic portal-systemic shunt (TIPS) group and 494 in the non-TIPS group) from five studies to analyze incidence rates after TIPS. Results: At the end of follow-up, there were 66 (18%, 66/365) patients who developed HCC after TIPS intervention and 63 (13%, 63/494) patients who developed HCC after non-TIPS treatments. Pooled estimates with random-effects model did not demonstrate a significant increase of incidence of HCC after TIPS (risk ratio: 1.37 [confidence interval (CI): 0.96 to 1.97]; p = 0.08) compared with non-TIPS treatments. Subgroup analyses for those patients with transplanted liver also did not detect a significant difference between the TIPS group and non-TIPS group (risk ratio: 1.10 [CI: 0.59 to 2.07]; p = 0.75). Conclusions: Current evidence suggests that portal-systemic shunt is not associated with a higher risk of HCC development in cirrhotic patients.

5.
J Transl Med ; 17(1): 151, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077206

RESUMO

BACKGROUND: Fulminant liver failure (FHF) is a serious clinical problem and liver transplantation is the major intervention. But the overall survival rate of FHF is low owing to the donated organ shortage. Apolipoprotein A-V (ApoA5) is a regulator of triglyceride metabolism and has been reported to act as a predictor for remnant liver growth after preoperative portal vein embolization and liver surgery. This study aimed to investigate the therapeutic effect of ApoA5 on lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced fulminant liver failure in mice. METHODS: FHF mouse model was established using LPS/D-GalN and ApoA5 plasmid was injected by tail vein prior to LPS/D-GalN treatment. The expressions of ApoA5, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B p65 (NF-κBp65) were assessed by real-time PCR and western blotting. Serum alanine aminotransferase (ALT) and tumor necrosis factor-α (TNF-α) levels were measured using automatic biochemical analyzer. Histological assessment and immunohistochemical (IHC) staining were conducted. Survival rate after LPS/D-GalN administration was also determined with Kaplan-Meier curve. Meanwhile, the expression of ApoA5 in injured huh7 cells was tested. Cell apoptosis analysis was performed after huh7 cells were transfected with ApoA5 plasmid and stimulated with LPS. RESULTS: The expressions of ApoA5 decreased both in injured huh7 cells and FHF mice. ApoA5 overexpression reduced cell death rate using flow cytometry. ApoA5 not only decreased the serum ALT and TNF-α levels but also attenuated hepatic damage in hematoxylin-eosin (HE)-stained liver section. The protein expressions of TLR4, MyD88 and NF-κBp65 were inhibited when ApoA5 overexpressed. But the inhibitory effect would weaken with the increasing concentration of LPS in spite of ApoA5 overexpression. Besides, ApoA5 improved liver injury in a dose-dependent manner and the survival rate in FHF mice increased with increasing concentration of ApoA5. CONCLUSION: ApoA5 had a protective effect against LPS/D-GalN-induced fulminant liver failure in mice within a certain range by inhibiting TLR4-mediated NF-κB pathway.

7.
J Viral Hepat ; 26(5): 586-595, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30632235

RESUMO

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg-positive and HBeAg-negative CHB patients. In this study, 85 HBeAg-positive and 25 HBeAg-negative patients who have never received antiviral therapy were included. Among HBeAg-positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg-negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (ß = -0.563, P < 0.001), HBsAg (ß = -0.328, P < 0.001) and HBV RNA (ß = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg-positive patients, but only serum HBcrAg was associated with cccDNA level (ß = 0.774, P = 0.000) among HBeAg-negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg-positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg-positive and HBeAg-negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.

8.
Dig Liver Dis ; 51(3): 412-418, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30274791

RESUMO

AIMS: To analyze the role of serum miR-125b-5p in reflecting liver damage and predicting outcomes in chronic hepatitis B (CHB) patients with acute-on-chronic liver failure (ACLF). METHODS: CHB patients with normal hepatic function (n = 100), moderate-to-severe liver damage (n = 90), and ACLF (n = 136) were included. Among hepatitis B virus (HBV)-ACLF patients, 86 and 50 were in the training and validation cohorts, respectively. Serum miR-125b-5p level was measured by quantitative real-time PCR. RESULTS: Serum miR-125b-5p level increased with disease progression, and serum miR-125b-5p level was lower in surviving than in dead HBV-ACLF patients. Among HBV-ACLF patients, miR-125b-5p positively correlated with total bilirubin (TBil; r = 0.214, p < 0.05) and model for end-stage liver disease (MELD) score (r = 0.382, p < 0.001) and negatively correlated with prothrombin activity(PTA; r = -0.215, p < 0.05). MiR-122 showed a contrasting performance compared with miR-125b-5p. Cox regression analysis showed that miR-125b-5p, miR-122, and PTA were independent survival predictors for HBV-ACLF, and low miR-125b-5p and high miR-122 levels may predict a longer survival in HBV-ACLF. MiR-125b-5p (AUC = 0.814) had a higher performance for survival prediction in HBV-ACLF compared with miR-122 (AUC = 0.804), PTA (AUC = 0.762), MELD score (AUC = 0.799), and TBil (AUC = 0.670) alone; predictive effectiveness of miR-125b-5p was increased by combination with miR-122 (AUC = 0.898). MiR-125b-5p was an effective predictor of HBV-ACLF outcomes in the validation cohort. CONCLUSIONS: MiR-125b-5p increase is associated with severity of liver damage; high serum miR-125b-5p may serve as a predictor for poor outcomes in HBV-ACLF cases.


Assuntos
Insuficiência Hepática Crônica Agudizada/sangue , MicroRNA Circulante/sangue , Hepatite B Crônica/sangue , MicroRNAs/sangue , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Área Sob a Curva , Progressão da Doença , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Análise de Sobrevida
9.
J Viral Hepat ; 26(3): 316-322, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30380166

RESUMO

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment-naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF-based DAAs therapy, including SOF 400 mg plus daclatasvir (DCV) 60 mg daily or SOF 400 mg plus velpatasvir (VEL) 100 mg daily for 12 weeks. The sustained virological response 12 weeks after treatment (SVR12) was 100% (60/60) in treatment-naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P = 0.014) and week 24 (P < 0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P < 0.001). SOF-based therapy was well-tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment-naïve patients with HCV GT6 without liver cirrhosis.

10.
Eur J Gastroenterol Hepatol ; 31(3): 382-388, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30383554

RESUMO

BACKGROUND: A combination of sofosbuvir (SOF)+NS5A inhibitor therapies is the main treatment for patients with hepatitis C virus (HCV) genotype-2 (GT-2) chronic infection, but the data are rarely reported in China. This study aimed to investigate the virological response and liver fibrosis improvement among GT-2 patients receiving SOF+NS5A inhibitors. PATIENTS AND METHODS: In this retrospective study, patients who received SOF+NS5A inhibitors between March 2016 and July 2017 were recruited. The treatment duration was 12 weeks and the treatment strategies included SOF+daclatasvir, SOF/ledipasvir, and SOF/velpatasvir. The primary endpoint was a sustained virologic response (serum HCV RNA undetectable) at week 12 after the end of therapy and the secondary endpoint was the improvement in liver stiffness and scores of apartate aminotransferase to platelet ratio index and fibrosis-4. RESULTS: A total of 30 GT-2 patients were enrolled, with 13 (43.3%) patients in SOF+daclatasvir, 13 (43.3%) patients in SOF/ledipasvir, and four (13.3%) patients in SOF/velpatasvir. All patients [30/30 (100%)] achieved SVR, irrespective of treatment regimens and degree of liver fibrosis. After the treatment, liver fibrosis scores of apartate aminotransferase to platelet ratio index (2.27±2.14 vs. 0.89±0.77, P=0.003) and fibrosis-4 (1.17±1.22 vs. 0.42±0.25, P=0.013) were both significantly lower than those before treatment. CONCLUSION: SOF+NS5A inhibitor therapies may induce an excellent virological response and fibrosis improvement in HCV GT-2-infected patients.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Imidazóis/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Sofosbuvir/uso terapêutico , Uridina Monofosfato/análogos & derivados , Proteínas não Estruturais Virais/antagonistas & inibidores , Adulto , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Carbamatos/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Imidazóis/efeitos adversos , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Estudos Retrospectivos , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico , Carga Viral , Proteínas não Estruturais Virais/metabolismo
11.
Clin Res Hepatol Gastroenterol ; 43(3): 301-309, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30497844

RESUMO

AIM: This study aimed to investigate long-term kinetics of serum hepatitis B core-related antigen (HBcrAg) and its correlation with serum hepatitis B surface antigen (HBsAg) in a real-world cohort of patients who had received over 8 years of nucleos(t)ide analogs(NAs) therapy. METHODS: This was a retrospective study. All patients were recruited from our previous published study, who started therapy with NAs between 2007 and 2008. Serum HBcrAg and HBsAg levels were quantitatively measured at baseline, the sixth month and each year of follow-up, using the stored serum samples. RESULTS: Among the 94 patients, serum HBcrAg presented a gradually decreasing trend from baseline to year 8, either in HBeAg-negative or HBeAg-positive patients. After 8 years of NAs treatment, 21.3% of patients achieved serum HBcrAg < 3 log 10 U/mL, and only baseline HBcrAg was an independent predictor. Additionally, good correlation of HBcrAg and HBsAg was observed at baseline, but this correlation weakened remarkably during treatment. CONCLUSION: Serum HBcrAg is decreasing gradually with the duration of antiviral therapy, and baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection.

12.
Biomed Pharmacother ; 110: 641-645, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30544063

RESUMO

TNF-related apoptosis inducing ligand (TRAIL) is a potential antitumor protein known for its ability to selectively eliminate various types of tumor cells without exerting toxic effects in normal cells and tissues. TRAIL has recently been suggested as a potential therapeutic target in hepatocellular carcinoma (HCC) because it promotes apoptosis in cancer cells. Furthermore, studies on the role of TRAIL in liver injury have reported that TRAIL plays an essential role in viral hepatitis, fatty liver diseases, etc. However, several contradictory and confounding effects of TRAIL in these liver diseases have not been fully elucidated or placed into perspective. Hence, this review summarizes recent progress in studies on TRAIL, including its role in apoptotic signaling, potential therapeutic applications of TRAIL in HCC, hepatitis virus infection, and liver fibrosis and cirrhosis.


Assuntos
Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/agonistas , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ligante Indutor de Apoptose Relacionado a TNF/agonistas
14.
Virol J ; 15(1): 150, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285800

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) genotype (GT) 3 infection with advanced liver disease has emerged as a challenging to treat by direct-acting antivirals (DAAs), but the efficacy of DAAs in Chinese HCV-GT3 patients is rarely reported. This study aimed to analyze the efficacy of sofosbuvir (SOF)-based regimens in Chinese patients with HCV-GT3 and compensated liver disease. METHODS: This was a registered retrospective study. All patients had completed at least 12 weeks SOF-based regimens therapy (with or without RBV), and were followed up for at least 24 weeks after therapy discontinuation. The primary endpoint was sustained virological response 24 weeks after end of therapy (SVR24). RESULTS: A total of 102 patients who completed at least 12 weeks therapy were finally included, with 57 in SOF + Daclatasvir (SOF + DCV), 24 in SOF + DCV + ribavirin (RBV) and 21 in SOF/Velpatasvir (SOF/VEL). The total SVR24 rate was achieved in 90.20% (92/102), with 85.96% (49/57) in SOF + DCV, 91.67% (22/24) in SOF + DCV + RBV and 100.00% (21/21) in SOF/VEL. Among 10 relapsed patients (8 in SOF + DCV and 2 in SOF + DCV + RBV), the short course (12 weeks) of therapy and no RBV addition may be the leading cause. In this cohort, the SVR24 rate was not statistically different between patients with and without cirrhosis (81.82% [27/33] vs. 94.20% [65/69], P = 0.073). Additionally, both FIB-4 (4.03 vs. 2.08, P < 0.001) and APRI (2.15 vs. 0.68, P < 0.001) scores were significant improved from baseline to week 24 after completion of therapy, regardless of the presence of cirrhosis. CONCLUSION: SOF-based regimens are highly effective in viral clearance and fibrosis remission for Chinese patients with HCV-GT3 infection. If available, SOF/VEL should be first considered.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Adulto , Grupo com Ancestrais do Continente Asiático , Carbamatos/uso terapêutico , Feminino , Seguimentos , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento
15.
Stem Cell Res Ther ; 9(1): 227, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143052

RESUMO

Acute liver failure is a life-threatening clinical syndrome characterized by rapid development of hepatocellular necrosis leading to high mortality and resource costs. Numerous treatment strategies for acute liver failure simply prevent complications and decelerate disease progression. The only curative treatment for acute liver failure is liver transplantation, but there are many restrictions on the application of liver transplantation. In recent years, a growing number of studies have shown that stem cells can effectively treat acute liver failure. Several types of stem cells have been used to study liver diseases; mesenchymal stem cells are most commonly used because they are easy to obtain and present no ethical problems. The aims of this article are to review the current knowledge regarding therapeutic mechanisms of mesenchymal stem cells in acute liver failure, to discuss recent advancements in preclinical and clinical studies in the treatment of mesenchymal stem cells, and to summarize the methodological improvement of mesenchymal stem cell transplantation in treating liver failure.


Assuntos
Hepatócitos/citologia , Falência Hepática Aguda/terapia , Regeneração Hepática/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular , Ensaios Clínicos como Assunto , Meios de Cultivo Condicionados/farmacologia , Citocinas/genética , Citocinas/metabolismo , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Células-Tronco Mesenquimais/metabolismo
16.
Eur J Gastroenterol Hepatol ; 30(10): 1224-1229, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29727380

RESUMO

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a condition with high mortality. New strategies are urgently required. The present review aims to provide a comprehensive understanding of the efficacy and safety of mesenchymal stem cells (MSC) treatment in patients with ACLF associated with hepatitis B virus infection. MATERIALS AND METHODS: The MEDLINE, Embase, and Cochrane Library databases were searched for the relevant publications. If appropriate, a meta-analysis was carried out for the following outcomes: survival rate, model for end-stage liver disease score, and liver function. RESULTS: Three studies were eligible for the present systematic review. A total of 198 hepatitis B virus-ACLF patients were enrolled for this review. Ninety-one patients were treated with MSC and 107 patients were treated with standard medical therapy (SMT) as controls. Pooled results showed that MSC treatment could significantly reduce the mortality rate at week 12 [risk ratio: 0.50; 95% confidence interval (CI): 0.33, 0.76; P=0.00009] and the mortality rate at the final follow-up (risk ratio: 0.54; 95%CI: 0.37, 0.78; P=0.001) compared with the SMT group. Furthermore, pooled estimates showed that MSC treatment could significantly reduce the total bilirubin level at week 4 (mean difference: 58.89; 95%CI: 14.47, 103.32; P=0.009) compared with the SMT group. No severe complication associated with MSC treatment was observed. CONCLUSION: Our pooled results suggested that MSC treatment could significantly reduce the mortality rate, without increasing the incidence of severe complications.


Assuntos
Insuficiência Hepática Crônica Agudizada/fisiopatologia , Insuficiência Hepática Crônica Agudizada/terapia , Hepatite B Crônica/complicações , Transplante de Células-Tronco Mesenquimais , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Insuficiência Hepática Crônica Agudizada/virologia , Bilirrubina/sangue , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Taxa de Sobrevida
17.
Virol J ; 15(1): 61, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609638

RESUMO

BACKGROUND: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant. RESULTS: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg. Injection of L02 cells stable expressing truncated mutant HBsAg into the dorsal skin fold of nude mice resulted in increased primary tumor growth compared to L02 cells stable expressing wide-type and substituted mutant HBsAg. In HBV replication L02 cell lines, the key molecular involved in TGF-ß/Smad pathway was also investigated. We found that the mRNA and protein levels of Smad3/2, CREB and CyclinD1 were significantly higher and TGFBI level was significantly lower in cells stably expressing truncated mutant HBsAg as compared to cells stably expressing wide-type and substituted mutant HBsAg. Additionally, after administration of TGF-ß1 (increasing TGFBI level), the volume of tumor is obviously reduced in nude mice with injection of L02 cells stable expressing truncated HBsAg. CONCLUSIONS: The emergence of sW172* mutant may increase the tumorigenesis of HBV, and its mechanism may be associated with down-regulated expression of TGFBI in TGF-ß/Smad signaling pathway.


Assuntos
Transformação Celular Neoplásica , Expressão Gênica , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/virologia , Mutação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular , Transformação Celular Viral , Modelos Animais de Doenças , Feminino , Hepatite B/complicações , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais
18.
Infect Dis (Lond) ; 50(7): 522-530, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29463147

RESUMO

AIM: Recent studies revealed that both quantitative hepatitis B surface antigen (qHBsAg) and hepatitis B core-related antigen (qHBcrAg) could serve as a good marker for predicting treatment response and indirectly reflecting intrahepatic cccDNA levels. This study aimed to compare the value of qHBsAg and qHBcrAg in predicting HBeAg seroconversion among patients undergoing PEG-IFN therapy. METHODS: A total of 31 HBeAg-positive patients, who underwent PEG-IFN therapy for 12 months and follow-up for six months were retrospectively included in this study. The serum qHBsAg level was measured using Elecsys® HBsAg II Quant Assay and serum qHBcrAg level was measured using chemiluminescence enzyme immunoassay. RESULTS: During the 12-month treatment, the absolute levels of serum qHBsAg and qHBcrAg were both lower in patients with HBeAg seroconversion as compared to patients without HBeAg seroconversion, but only the difference in qHBcrAg was significant. During the 6-month follow-up period, both qHBsAg and qHBcrAg levels were rebounded significantly among patients without HBeAg seroconversion. Among patients with HBeAg seroconversion, no sustained significant decline of qHBsAg was observed, but serum qHBcrAg levels continued to decline significantly. The ROC curves analysis showed that both absolute qHBcrAg level and the extent of qHBcrAg decline at month 1 had better performance for the prediction of HBeAg seroconversion at month 6 after treatment, as compared to that of qHBsAg. CONCLUSION: Early on-treatment qHBcrAg may be a good biomarker for predicting off-treatment HBeAg seroconversion in patients receiving PEG-IFN therapy.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , DNA Viral/sangue , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/química , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Curva ROC , Estudos Retrospectivos , Soroconversão , Adulto Jovem
19.
Curr Stem Cell Res Ther ; 13(3): 193-201, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29303079

RESUMO

BACKGROUND: Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. OBJECTIVE: We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. RESULTS: Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. CONCLUSION: Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans.


Assuntos
Cirrose Hepática/terapia , Falência Hepática/terapia , Transplante de Células-Tronco , Animais , Humanos , Medicina Regenerativa
20.
World J Hepatol ; 10(12): 907-910, 2018 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-30631395

RESUMO

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer, liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety, mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA