Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated administration of hepatotoxicants is usually accompanied by liver fibrosis. However, the difference in response as a result of repeated exposures of acetaminophen (APAP) compared to a single dose is not well-studied. Therefore, in the current study, the liver response after a second dose of APAP was investigated. Adult fasted Balb/C mice were exposed to two toxic doses of 300 mg/kg APAP, which were administered 72 h apart from each other. Subsequently, blood and liver from the treated mice were collected 24 h and 72 h after both APAP administrations. Liver transaminase, i.e. alanine amino transferase (ALT) and aspartate amino transferase (AST) levels revealed that the fulminant liver damage was reduced after the second APAP administration compared to that observed at the same time point after the first treatment. These results correlated with the necrotic areas as indicated by histological analyses. Surprisingly, Picro Sirius Red (PSR) staining showed that the accumulation of extracellular matrix after the second dose coincides with the upregulation of some fibrogenic signatures, e.g., alpha smooth muscle actin. Non-targeted liver tissue metabolic profiling indicates that most alterations occur 24 h after the first dose of APAP. However, the levels of most metabolites recover to basal values over time. This organ adaptation process is also confirmed by the upregulation of antioxidative systems like e.g. superoxide dismutase and catalase. From the results, it can be concluded that there is a different response of the liver to APAP toxic doses, if the liver has already been exposed to APAP. A necroinflammatory process followed by a liver regeneration was observed after the first APAP exposure. However, fibrogenesis through the accumulation of extracellular matrix is observed after a second challenge. Therefore, further studies are required to mechanistically understand the so called "liver memory".
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PMID:Second exposure to acetaminophen overdose is associated with liver fibrosis in mice. 3095 39

Background and aim: We aimed to evaluate the effectiveness of pegylated interferon (Peg-IFN) monotherapy (IFN group) and combination therapy with tenofovir (TDF) and Peg-IFN (IFN+TDF group) in chronic hepatitis B (CHB) patients. Patients and methods: Data of 143 CHB patients were analyzed in this study. All patients enrolled received liver biopsy. Virologic responses were defined as hepatitis B virus (HBV) DNA <100 IU/mL, biochemical responses were defined as normalization of alanine aminotransferse (ALT) levels, and HBeAg serological response was defined as HBeAg loss or HBeAg seroconversion to HBeAb. HBsAg serological response was defined as HBsAg loss or HBsAg seroconversion to HBsAb. Results: We observed that a total of 16.7% (11/66) and 33.8% (26/77) patients in IFN and IFN+TDF group achieved complete viral suppression after 48 weeks treatment (P=0.02). Although HBeAg levels in CHB patients in the IFN+TDF group decreased more rapidly during the 48-week treatment, we did not observe significant differences in HBeAg serological loss or seroconversion rates between the two groups at 24 and 48 weeks. HBsAg loss was observed in 13.0% (10/77) of CHB patients in the IFN+TDF group at 48 weeks, compared with only 3% (2/66) patients in the IFN group (P=0.032). No significant difference was observed in HBsAg seroconversion rate between the two groups during 48-week treatment. The biochemical response rate was also significantly higher in the IFN+TDF group than that in the IFN group at week 48 (P=0.015). Multivariate logistic analysis showed that IFN+TDF treatment (OR=4.41, P=0.003), severe baseline hepatic inflammation (OR=4.16, P<0.001), and lower baseline serum HBV DNA levels (OR=0.98, P=0.03) were strong predictors for the virological response. Younger age (OR=0.89, P=0.01), higher baseline ALT level (OR=1.01, P=0.038), and lower baseline HBeAg level (OR=0.99, P=0.008) were independent predictors for HBeAg sero-response after 48 weeks treatment. While only severe liver fibrosis (OR=1.69, P=0.028) and lower baseline HBsAg level (OR=0.22, P=0.005) were independent factors associated with HBsAg sero-response after 48 weeks treatment. Conclusion: Peg-IFN combined with TDF may increase the virological response rate, biochemical response rate, and HBsAg loss rate in patients with CHB infection. The combination treatment is more suitable for those patients who are likely to respond to the treatment.
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PMID:Comparison of pegylated interferon monotherapy and de novo pegylated interferon plus tenofovir combination therapy in patients with chronic hepatitis B. 3111 65

BACKGROUND Liver fibrosis, defined as the aberrant accumulation of extracellular matrix (ECM) proteins such as collagen in the liver, is a common feature of chronic liver disease, and often culminates in portal hypertension, liver cirrhosis, and hepatic failure. Though therapeutically manageable, fibrosis is not always successfully treated by conventional antifibrotic agents. While the traditional Chinese medicine (TCM) Alisma Shugan Decoction (ASD) has several health benefits, including anti-inflammation, anti-oxidation, and limitation of cardiovascular and respiratory disorders, it remains unclear if it has any hepato-protective potential. MATERIAL AND METHODS The present study examined the therapeutic effect of ASD in thioacetamide (TAA)-induced liver injury and fibrosis rat models. RESULTS We demonstrated that 50 mg/kg ASD significantly reversed TAA-induced elevation of alanine or aspartate transaminase levels, elicited no dyscrasia, and conferred a 40% (p<0.01) or 20% (p<0.05) survival advantage, compared to rats treated with TAA or TAA+ASD, respectively. Treatment with ASD reversed TAA-induced liver injury and fibrogenesis via repression of alpha-SMA protein and reduction of the collagen area and fibrosis score. Concurrently, ASD markedly suppressed the mRNA expression of fibrogenic procollagen, ICAM-1, MMP2, MMP9, and MMP13, and production of TIMP-1, ICAM-1, CXCL7, or CD62L cytokine in rat liver injury models. Interestingly, ASD-elicited reduction of liver injury and fibrogenesis was mediated by dysregulated p65/NrF-2/JunD signaling, with a resultant 3.18-fold (p<0.05) increase in GSH/GSSH ratio, and a 3.61-fold (p<0.01) or 1.51-fold (p<0.01) reduction in the 4-hydroxynonenal and malondialdehyde (MDA) levels, respectively, indicating reduced oxidative stress in the ASD-treated rats, and suggesting an hepato-protective role for ASD. CONCLUSIONS In conclusion, the present study provides supplementary evidence of the therapeutic benefit of ASD as an efficient treatment option in cases of liver injury and fibrosis. Further large-cohort validation of these findings is warranted.
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PMID:Alisma Shugan Decoction (ASD) Ameliorates Hepatotoxicity and Associated Liver Dysfunction by Inhibiting Oxidative Stress and p65/Nrf2/JunD Signaling Dysregulation In Vivo. 3267 53


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