Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents.

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs ( e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

Alteration of the Total Nuclear DNA Ploidy in Different Histopathological Liver Tissues Negative and Positive for HCV RNA.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma (HCC). The molecular mechanisms of HCV-associated carcinogenesis are unknown. We aim to investigate the alteration of the total nuclear DNA content (ploidy) in different histopathological liver tissues infected with HCV and their relation to the seropositivity of HCV RNA. METHODS: Blood and liver tissues were collected from 26 patients. Diagnosis was carried out according to clinical and pathological examinations by specialized physicians. HCV RNA was detected in patients' sera and tissue samples by RT-PCR. To examine nuclear DNA ploidy, liver tissues were stained with blue Fulgen using the image analysis techniques. Finally, the patients' DNA content was examined by histochemical analysis depending on the optical density of DNA from liver biopsies using the grey image menu in each specimen. RESULTS: The HCV RT-PCR results demonstrated that 13/26 (50%) patients had detectable HCV RNA in their sera samples while 18/26 (69%) had detectable HCV RNA in liver tissues. The DNA content from those patients measured by image cytometry showed a high level of alteration of nuclear DNA ploidy and proliferation in liver tissues with HCC, less alteration of nuclear DNA ploidy in cirrhotic patients, and least proliferation nearly normal in liver fibrosis patients. Moreover, the results of histochemical analysis confirmed the DNA image cytometry results and showed that positive HCV RNA liver tissues had more DNA ploidy than negative HCV RNA liver tissues with statistical significance (p-value < 0.05). CONCLUSIONS: HCV positive liver tissue had alterations in DNA content (ploidy) which may lead to liver disease progression, malignant transformation of the liver cells and development of hepatocellular carcinoma.

Interrelation between peripheral platelet count and platelet activation during and after liver surgery in pigs.

The present work was designed to evaluate the functional and ultrastructural changes in platelets during and after major liver resection in healthy pigs as a trial to predict changes occurring in healthy liver donors. Measures to ensure the safety of the donor hepatectomy remain the main concern. Fifteen healthy pigs were prepared for liver resection by right trisegmentectomy. Blood samples were collected as such: one before the operation, two during the operation (one after the mobilization and other after the resection of the liver) and two after the operation (day 7 and day 14). Platelet count and markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were measured. Separated platelets from peripheral blood and the resected liver were examined by electron microscopy. Platelet count was significantly dropped after hepatic mobilization and resection [(P < 0.05) and (P < 0.01), respectively] in comparison to normal level. On day 7, it increased significantly (P < 0.05). On day 14, it increased to become nonsignificantly different from preoperative count. beta-Thromboglobulin and platelet factor 4 were significantly increased after hepatic mobilization and resection [(P < 0.05) and (P < 0.01), respectively]. On day 7, they decreased to become nonsignificantly different from normal level. On day 14, they significantly reincreased (P < 0.01). Electron microscopic examination of platelets revealed all signs of activation after hepatic mobilization and resection. These changes disappeared on day 7 and reobserved on day 14. Liver surgery causes an acute and profound drop in platelet count and an increase in platelet activation. It is necessary to give proper systemic coagulant therapy in addition to platelet transfusion at the end of surgery for 1 week in case of hepatic resection.