Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.
Antiviral Agents/*therapeutic use ; DNA-Directed RNA Polymerases/antagonists & inhibitors/metabolism ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferons/therapeutic use ; Nucleotides/chemistry/therapeutic use ; Protease Inhibitors/*therapeutic use ; Viral Nonstructural Proteins/antagonists & inhibitors/metabolism ; Virus Internalization/drug effects

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.
Antiviral Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/etiology ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-alpha/adverse effects/therapeutic use ; Liver Cirrhosis/complications ; Liver Neoplasms/etiology ; Nucleotides/adverse effects/chemistry/therapeutic use ; Risk Factors

BACKGROUND/AIMS: This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients. METHODS: CHB patients treated with TDF monotherapy (300 mg/day) for > or =12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks. RESULTS: In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naive, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9+/-2.3 log IU/mL (mean+/-SD), and was higher in the NA-naive group than in the NA-exp and LAM-R groups (5.9+/-2.0 log IU/mL vs 3.9+/-2.0 log IU/mL vs 4.2+/-1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naive group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience. CONCLUSIONS: TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy ; Humans ; Lamivudine/therapeutic use ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; Nucleotides/*chemistry/therapeutic use ; Retrospective Studies ; Tenofovir/*therapeutic use ; Treatment Outcome