Direct-acting antivirals (DAAs) can strongly inhibit the replication of hepatitis C virus (HCV) and effectively clear the infection, but it may cause hepatitis B virus (HBV) reactivation, leading to severe liver damage and fulminate hepatitis in patients with HCV/HBV coinfection. In this review, we summarized the different replication process of HCV and HBV in infected hepatocytes and consequent innate immune response, and then discussed the molecular mechanism and clinical significance of HBV reactivation, and put forward the clinical precaution.
Humans ; Hepatitis B virus ; Hepacivirus ; Antiviral Agents/pharmacology* ; Hepatitis C, Chronic/drug therapy* ; Virus Activation ; Hepatitis C/drug therapy* ; Coinfection/drug therapy* ; Hepatitis B/drug therapy*

Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
Antiviral Agents/therapeutic use* ; Hepatitis B/drug therapy* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Humans

Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C.
Antiviral Agents/therapeutic use ; Chemokines/*metabolism ; Hepatitis C/drug therapy/*immunology/*metabolism ; Hepatitis C, Chronic/drug therapy/*immunology/*metabolism ; Humans

Antiviral Agents ; therapeutic use ; Congresses as Topic ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans

Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferons ; therapeutic use ; Treatment Outcome

Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferons ; therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. METHODS: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. RESULTS: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. CONCLUSIONS: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.
Anemia ; Anemia, Hemolytic ; Carnitine ; Drug Therapy ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Hepatitis ; Hepatitis, Chronic ; Humans ; Hyperammonemia ; Liver Cirrhosis ; Liver Diseases ; Muscle Cramp ; Prospective Studies ; Ribavirin ; Sofosbuvir

OBJECTIVETo review the updated research on direct antiviral agents (DAAs)-including regimens for hepatitis C virus (HCV), and focus on "difficult-to-treat" HCV-infected patients.

DATA SOURCESThe literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.

STUDY SELECTIONData from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.

RESULTSIt was recognized that some "difficult-to-treat" patients would still exist, even though stronger treatments using such as DAAs, including telaprevir and boceprevir, which lead to higher sustained virological response rates, are available. Such patients include those with advanced fibrosis/cirrhosis, elderly persons, children, HCV-human immunodeficiency virus co-infected patients, HCV-infected recipients, and so on.

CONCLUSIONSCertain "difficult-to-treat" patients would still exist, even though stronger treatment is available. Although evidence from clinical trials is still lacking, interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.

Approved direct-acting antiviral agents (DAA ) in chronic hepatitis C were introduced. Metabolism and pharmacokinetics data of DAAs were analyzed. Comorbidity and concomitant medications of chronic hepatitis C (CHC) patients were extracted from Chinese Health Insurance database. Drug-drug interactions (DDIs) were calculated by integrated above data and confirmed by using Liverpool DDI website. Based on those data, experts propose consensus on management of drug-drug interaction with direct-acting antiviral agents in chronic hepatitis C, including pre-treatment, on-treatment, and post-treatment.
Antiviral Agents/therapeutic use* ; Consensus ; Databases, Factual ; Drug Interactions ; Hepatitis C, Chronic/drug therapy* ; Humans

Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Humans ; Liver Neoplasms/etiology* ; Sustained Virologic Response