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Liver fibrosis is a chronic liver injury caused by various etiologies and a complex pathological change with the activation of hepatic stellate cells as the central link, and various signaling pathways are involved in the regulation of such complex lesions. It has the dual nature of repair and damage and may eventually progress to liver cirrhosis, liver failure, and even liver cancer. In recent years, rapid progress has been made in the basic research on the cell signal transduction pathways associated with liver fibrosis, and some achievements have been made in the research on the treatment strategy of liver fibrosis. This article briefly reviews the cell signaling pathways associated with the development of liver fibrosis, including the JAK/STAT signaling pathway, the NF-κB signaling pathway, the MAPK signaling pathway, the TGF-signaling 1/Smad signaling pathway, the Wnt signaling pathway, the Hedgehog signaling pathway, and the Notch signaling pathway, and also introduces the potential therapeutic strategies for liver fibrosis at present.
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Objective@#To explore the efficacy of glucocorticoid (GC) therapy on hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and the effectiveness and safety of voriconazole (VCZ) in preventing pulmonary Aspergillus infection in HBV-ACLF patients treated with GC.@*Methods@#Two hundred and thirty-two patients with HBV-ACLF were enrolled from January 2016 to December 2018 in the First Affiliated Hospital of Nanchang University. They were divided into non-GC group (104 cases), GC group (74 cases), and GC+ VCZ group (54 cases). The observation period was four months. The baseline liver function, the incidence of pulmonary Aspergillus infection, the survival rate during observation period, and the incidence of complications were compared among the three groups. The adverse reactions of VCZ were observed to identify the best dose for prevention. Quantitative data were analyzed by analysis of variance or rank sum test. Count data were analyzed by chi-square test or Fisher exact test.@*Results@#The baseline liver functions were not significantly different among the three groups (all P>0.05). The incidence of pulmonary Aspergillus infection in the GC group (22.97%(17/74)) was both higher than that in the non-GC group (5.77%(6/104)) and GC+ VCZ group (1.85%(1/54)), the differences were both statistically signifrcant (χ2=11.373 and 9.843, respectively, both P<0.01). The overall mortality rate of HBV-ACLF patients with pulmonary Aspergillus infection was 79.2%(19/24). The survival rate in non-GC group (37.5%(39/104)) showed no statistical difference with that in GC group (39.19%(29/74), χ2=0.052, P=0.819). The survival rate of GC+ VCZ group (66.67%(36/54)) was significantly higher than that in GC group and non-GC group (χ2 =12.126 and 9.431, respectively, both P<0.01). The blood concentrations of VCZ were randomly measured in 16 patients from the GC+ VCZ group, and the range was 0.82-5.38 mg/L, with no evident adverse reactions.@*Conclusions@#The GC treatment is effective in HBV-ACLF patients in early stage. The VCZ treatment effectively reduces the incidence of pulmonary Aspergillus infection in HBV-ACLF patients receiving GC treatment and increases the survival rate. Oral VCZ (200 mg/d) treatment has a stable blood concentration in HBV-ACLF patients, with rare adverse reactions and good safety.
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Objective To evaluate the clinical efficacy and safety of ritonavir-boosted danoprevir (DNVr) combined with daclatasvir (DCV) in the treatment of patients with genotype 1b chronic hepatitis C (CHC).Methods Thirty-three patients with genotype 1b CHC admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from August 2018 to February 2019 were enrolled.All the patients received DNVr +DCV antiviral treatment.HCV RNA levels were detected before and 2, 4, 12 weeks after treatment, and after drug withdrawal , respectively.Indicators of liver and kidney function and adverse events were observed.ANOVAV of repeated measurement was used to analyze the data. Results The baseline viral loads of 33 patients ranged from 1.12×104 to 1.76×107 IU／mL.Two weeks after treatment the viral loads of all patients were down to the lowest limit of detection (＜500 IU／mL). Serum ALT, AST and TBil levels returned to norml ( F＝58.26, 14.49 and 20.16, all P＜0.05) and sustained virologic response reached 100%12 weeks after drug withdrawal.Three cases had minor adverse reactions during the treatment.Conclusion DNVr combined with DCV can achieve a rapid and strong virological response in the treatment of patients with genotype 1b CHC with good safety.
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Objective To explore the efficacy of glucocorticoid (GC) therapy on hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF),and the effectiveness and safety of voriconazole (VCZ) in preventing pulmonary Aspergillus infection in HBV-ACLF patients treated with GC.Methods Two hundred and thirty-two patients with HBV-ACLF were enrolled from January 2016 to December 2018 in the First Affiliated Hospital of Nanchang University.They were divided into non-GC group (104 cases),GC group (74 cases),and GC + VCZ group (54 cases).The observation period was four months.The baseline liver function,the incidence of pulmonary Aspergillus infection,the survival rate during observation period,and the incidence of complications were compared among the three groups.The adverse reactions of VCZ were observed to identify the best dose for prevention.Quantitative data were analyzed by analysis of variance or rank sum test.Count data were analyzed by chi-square test or Fisher exact test.Results The baseline liver functions were not significantly different among the three groups (all P＞ 0.05).The incidence of pulmonary Aspergillus infection in the GC group (22.97％ (17/74)) was both higher than that in the non-GC group (5.77％ (6/104)) and GC + VCZ group (1.85％ (1/54)),the differences were both statistically signifrcant (x2=11.373 and 9.843,respectively,both P＜0.01).The overall mortality rate of HBV-ACLF patients with pulmonary Aspergillus infection was 79.2％ (19/24).The survival rate in non-GC group (37.5％ (39/104)) showed no statistical difference with that in GC group (39.19％ (29/74),x2=0.052,P =0.819).The survival rate of GC + VCZ group (66.67％ (36/54)) was significantly higher than that in GC group and non-GC group (x2 =12.126 and 9.431,respectively,both P ＜0.01).The blood concentrations of VCZ were randomly measured in 16 patients from the GC + VCZ group,and the range was 0.82-5.38 mg/L,with no evident adverse reactions.Conclusions The GC treatment is effective in HBV-ACLF patients in early stage.The VCZ treatment effectively reduces the incidence of pulmonary Aspergillus infection in HBV-ACLF patients receiving GC treatment and increases the survival rate.Oral VCZ (200 mg/d) treatment has a stable blood concentration in HBV-ACLF patients,with rare adverse reactions and good safety.
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Objective To observe the clinical effect of combination of Tongxiening granule and Mesalazine on treating mild and moderate ulcerative colitis(UC) .Methods Totally 380 patients with mild‐to‐moderate UC diagnosed through endoscopy were allocated to the control group (n=190) and observation group(n=190) .For the observation group ,patients were remedied with the combination of Tongxiening Granules and the Mesalazine by oral administration for eight weeks ,meanwhile the control group only received the Mesalazine for eight weeks .The total effective rate of the two groups were statistically analyzed ,and the levels of ser‐um MMP‐2 and MMP‐9 before and after treatment in the two groups were measured .The expression of S100A12 and RAGE were detected by immunohistochemistry SP method .Results The total effective rate of the observation group and the control group was 94 .74% and 89 .47% respectively ,and the difference was statistically significant(P<0 .01) .After treatment ,the expression levels of MMP‐2 and MMP‐9 in the two groups were decreased ,additionally the expression levels in the observation group was lower than those in the control group ,and the difference was statistically significant (P< 0 .01) .After treatment ,the expression levels of RAGE and S100A12 in the observation group were decreased ,and there was a significant difference when compared with the control group(P<0 .01) .Conclusion Combined application of Tongxiening Granules and Mesalazine in treating patients with mild‐to‐mod‐erate UC could better improve clinical symptoms and bring better therapeutic effect than single use of Mesalazine .
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Objective To analysis effect of Bifidobacterium tetravaccine tablets ( live ) combined with cefixime on C-reactive protein, ceruloplasmin, haptoglobin and α1-acid glycoprotein in patients with Bacterial enteritis.Methods 58 patients who were diagnosed with Bacterial enteritis were collected.All patients were randomly divided into experimental group and control group, 29 cases in each group, On the basis of conventional treatment, the control group was treated with cefixime, and the experimental group was treated with Bifidobacterium tetravaccine tablets ( live) on the basis of control group.After treatment, the serum levels of CRP, CER, HPT, AAG and clinical curative effect were detected in all patients.Results After treatment, CRP, CER, HPT, AAG levels were lower than before treatment (P<0.05),compared with control group, CRP, CER, HPT, AAG levels were lower than in the experimental group( P<0.05);the total effective rate was higher in the experimental group (χ2 =4.35, P<0.05).Conclusion Bifidobacterium tetravaccine tablets(live) combined with cefixime can significantly reduce the serum CRP, CER, HPT, AAG levels in patients with bacteria enteritis, improve the clinical efficacy, have guidance significance for clinic.
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Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.