ABSTRACT
BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval of sofosbuvir and the expected approval of agents such as simeprevir and daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to serve as a guidance for the therapeutic management of chronic hepatitis C. METHODS: We performed a formal search through PubMed, Web of Science and ClinicalTrials.gov to identify all clinical trials that have been conducted with EMA-approved new agents in hepatitis C; for this version (April 2014) we focused on sofosbuvir. For each disease category, the evidence was reviewed and recommendations are based on GRADE. RESULTS: We identified 11 clinical trials with sofosbuvir and for each disease category recommendations for treatment are made. Not all disease categories were studied extensively and therefore in some cases we were unable to provide recommendations. CONCLUSION: The recent approval of sofosbuvir will most likely change the therapeutic landscape of chronic hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration of therapy, increase efficacy and result in less side effects, compared with standard of care. The efficacy relative to standard of care needs to be weighed against the increased costs of sofosbuvir. With future approval of the other direct-acting antivirals, the outcome of hepatitis C treatment will likely improve further and this guidance will be updated.
Subject(s)
Antiviral Agents/pharmacology , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/pharmacology , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Genotype , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Practice Guidelines as Topic , Protease Inhibitors/therapeutic use , Simeprevir , Sofosbuvir , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Uridine Monophosphate/analogs & derivatives , Uridine Monophosphate/pharmacology , Uridine Monophosphate/therapeutic useABSTRACT
In 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance.
Subject(s)
Adenine/analogs & derivatives , Drug Approval , Drug Resistance, Viral/drug effects , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Organophosphonates/therapeutic use , Practice Guidelines as Topic , Pregnancy Complications, Infectious/drug therapy , Adenine/administration & dosage , Adenine/standards , Adenine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/standards , Antiviral Agents/therapeutic use , Female , Guanine/administration & dosage , Guanine/standards , Guanine/therapeutic use , Hepatitis B, Chronic/complications , Humans , Infectious Disease Transmission, Vertical/prevention & control , Lamivudine/standards , Lamivudine/therapeutic use , Milk, Human/drug effects , Netherlands , Nucleosides/administration & dosage , Nucleosides/therapeutic use , Organophosphonates/administration & dosage , Organophosphonates/standards , Pregnancy , Renal Insufficiency/drug therapy , Renal Insufficiency/etiology , Telbivudine , Tenofovir , Thymidine/analogs & derivatives , Thymidine/standards , Thymidine/therapeutic useABSTRACT
BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) has an established effect on liver bio-chemistries in primary biliary cirrhosis (PBC). Few studies have evaluated long-term laboratory treatment effects and data beyond 6 years are not available. The aim of this study was to assess the long-term evolution of liver bio-chemistries during prolonged treatment with UDCA in biochemically non-advanced PBC. PATIENTS AND METHODS: Prospective multicenter cohort study of patients with PBC with pretreatment normal bilirubin and albumin, treated with UDCA 13-15 mg/kg/day. At yearly intervals, follow-up data including serum bilirubin, alkaline phosphatase (ALP), transaminases, albumin and IgM were collected. Data were analyzed with a repeated measurement model. RESULTS: Two hundred and twenty-five patients were included and followed during a median period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total biochemical improvement was achieved, the maximum response was observed after 3 years. After initial improvements, bilirubin and AST levels increased and albumin levels significantly decreased after 6-10 years. However, these changes were of limited magnitude. The beneficial effects on ALT and ALP were maintained while IgM continued to decrease. CONCLUSION: In non-advanced PBC the biochemical response to UDCA is maintained up to 15 years. The long-term evolution of bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level normalised and levels continued to decrease during the period of follow-up.
