Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Hepatitis A and hepatitis A virus/HIV coinfection in men who have sex with men, Warsaw, Poland, September 2008 to September 2009.

We describe the epidemiology and characteristics of hepatitis A among men who have sex with men (MSM)who had been hospitalised due to the infection in Warsaw, Poland, from September 2008 to September 2009. A total of 50 men were analysed; their median age was 28 years (range: 17­43). None had travelled to hepatitis A-endemic regions during the six months before hospitalisation nor had they been vaccinated against hepatitis A. Of the 50 men, 40 had been tested before hospitalisation or on admission for the presence of anti-HIV antibodies: six were coinfected with HIV.The six HIV-positive MSM were significantly older than those who were HIV negative ­ median age: 37 years(range: 26­43) versus 28 years (range: 17­43); p=0.02.No difference in disease severity or the duration of hospitalisation was observed, however, between the two groups. Our study underlines the need to screen MSM for hepatitis A and to vaccinate them against hepatitis A. Given the ages of the MSM in our study,we recommend that this be carried out in Poland when the MSM are aged 20­35 years. This should apply not only to MSM with multiple casual partners but also to those in monogamous relationships.

Cigarette smoking and innate immunity.

Cigarette smoking is a worldwide epidemic and the most prevalent cause of many diseases leading to increased morbidity and mortality globally. The impact of smoking on pathogenesis of cancer is being extensively studied however cigarette smoke as an immunosuppressant is less well recognized. Here we review the immunosuppressive effects of cigarette smoke and the mechanisms by which smoking affects host innate immunity including structural and functional changes in the respiratory ciliary epithelium, lung surfactant protein, and immune cells such as alveolar macrophages, neutrophils, lymphocytes and natural killer (NK) cells. Thus smoking cessation should be emphasized not only for prevention of cancer and coronary artery disease but also for patients with recurrent infections and immunosuppressive states.