Background and AimsTo evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).MethodsMononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation.ResultsOn clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments.ConclusionsIntraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.
Objective. To determine the efficacy and safety of direct-acting antiviral agents (DAA) in patients with chronic HCV infection and UGT1A1*28 polymorphism. Materials and Methods. An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n = 143) with chronic hepatitis C (CHC) and liver cirrhosis and UGT1A1*28 polymorphism was performed. A total of 139 patients with chronic HCV infection were included in the efficacy analysis (absence of HCV RNA in blood by PCR) by the rate of sustained virologic response at week 12 (SVR12). Results. The SVR12 rate in patients with CHC and HCV-CP was 92.5% and 87.9%, respectively (p = 0.508), regardless of the presence of UGT1A1*28 polymorphism. The SVR12 rate in patients with chronic HCV infection and (TA)7/(TA)7 was 84.8%, with (TA)6/(TA)7 – 92.2% compared with (TA)6/ (TA)6 – 90,5% (p = 0.518). The rate of SVR12 in patients with CHC and (TA)7/(TA)7 or (TA)6/(TA)7 was 80% and 95%, respectively, with (TA)6/(TA)6 – 95.2%. The rate of SVR12 in patients with liver cirrhosis and (TA)7/(TA)7 or (TA)6/(TA)7 was 92.3% and 87.5%, respectively, with (TA)6/(TA)6 – 85.7%. The rate of SVR12 in patients with 12- and 24-week treatment duration was 88.2% and 96.6%, respectively (p = 0.30). As many as 96.2% of patients with the previous treatment with interferon and ribavirin had SVR12 compared to 88.5% of patients who have not previously taken antiviral drugs (p = 0.486). Grade 1 adverse events (AE) occurred in 24% of patients with chronic HCV infection treated with DAA; two patients developed Grade 4 AE. Conclusions. The treatment with DAA was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.
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