L. Sollik

Eligibility and Safety of Triple Therapy for Hepatitis C: Lessons Learned from the First Experience in a Real World Setting

Background HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center. Methods All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12. Results 208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12. Conclusions P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options.

Improvement of liver function parameters in advanced HCV-associated liver cirrhosis by IFN-free antiviral therapies.

Successful antiviral treatment of decompensated hepatitis B with HBV polymerase inhibitors is associated with improvement of liver function. To what extent liver function also improves in cirrhotic patients with chronic hepatitis C receiving novel interferon‐free (IFN‐free) therapies is unknown.

Eligibility and safety of the first interferon-free therapy against hepatitis C in a real-world setting

Several real world data demonstrated that eligibility for and tolerability of triple therapy against hepatitis C virus (HCV) infection with a first‐wave protease inhibitor is limited. With the approval of sofosbuvir (SOF) effective treatment with and without pegylated interferon (PEG‐IFN) has become available for most genotypes. However, no data are available regarding the added benefit of an interferon‐free treatment concerning eligibility and tolerability in a real‐world scenario. We aimed to assess the eligibility and safety of SOF based therapies in patients with primarily advanced cirrhosis, including decompensated cirrhosis, in a real‐world setting.

The clinical significance of drug-drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C.

Drug–drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct‐acting anti‐virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P‐glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.

Frequent detection of HCV RNA and HCVcoreAg in stool of patients with chronic hepatitis C

BACKGROUND AND OBJECTIVE HCV is transmitted mainly by parenteral routes. However, unprotected anal intercourse has also been identified as a risk factor for HCV infection. HCV RNA can be detected in blood, saliva, and bile, but the presence of HCV in stool has not been investigated yet. STUDY DESIGN Therefore, stool samples of 98 patients were collected prospectively. Specific HCV primers were used to identify samples positive for HCV RNA. HCV RNA-positive samples were tested for HCVcoreAg with the Architect HCVAg assay (Abbott). Presence of occult blood was investigated by the hemoCARE guajak test. Viral stability and infectivity of recombinant HCV particles was investigated in vitro by incubation of genotype 2a chimeric virus Jc1 with bile and stool suspensions. RESULTS HCV RNA could be detected in 68 out of 98 stool samples from patients with chronic hepatitis C and 16 samples also tested positive for HCVcoreAg. Presence of HCV RNA in stool was more frequent in male than in female and in patients with low platelet counts but was not associated with the detection of occult blood. Stool suspensions and to a lesser extent bile reduced the in vitro infectivity of genotype 2a chimeric Jc1 virus even though infection of Huh7 cells was not completely abrogated. CONCLUSIONS In summary, this study shows for the first time that HCV can frequently be detected in stool samples of chronically infected patients irrespective of occult bleeding. We suggest that stool can be a potential source for HCV infection and thus unprotected anal intercourse should be avoided.