The phase IIb, double‐blind, placebo‐controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once‐daily (QD) with pegylated interferon (Peg‐IFN)‐α‐2a and ribavirin (RBV) in treatment‐naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg‐IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response‐guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg‐IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%‐86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%‐75.6% of SMV‐treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%‐86.1% of SMV‐treated patients completed treatment by week 24; 85.2%‐95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV. Conclusion: SMV QD in combination with Peg‐IFN and RBV significantly improves SVR rates, compared with Peg‐IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks. (Hepatology 2013; 58:1918–1929)

Up to 170 million people globally are currently infected with hepatitis C virus (HCV).¹ x 1 World Health Organization. WHO Fact Sheet 164-Hepatitis C. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed June 20, 2013. Google Scholar See all References In the United States and Europe, it is now associated with a mortality rate surpassing that of human immunodeficiency virus infection.² x 2 Casey, L.C. and Lee, W.M. Hepatitis C therapy update. Curr Opin Gastroenterol. 2012; 28: 188–192 Crossref | PubMed | Scopus (22) | Google Scholar See all References ^{, 3} x 3 Ly, K.N., Xing, J., Klevens, R.M. et al. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012; 156: 271–278 Crossref | PubMed | Scopus (493) | Google Scholar See all References ^{, 4} x 4 Muhlberger, N., Schwarzer, R., Lettmeier, B. et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health. 2009; 9: 34 Crossref | PubMed | Scopus (157) | Google Scholar See all References During the past decade, the standard of care treatment for chronic HCV infection has been a combination of peginterferon-α (PegIFN-α) and ribavirin (RBV) for 24−48 weeks.² x 2 Casey, L.C. and Lee, W.M. Hepatitis C therapy update. Curr Opin Gastroenterol. 2012; 28: 188–192 Crossref | PubMed | Scopus (22) | Google Scholar See all References ^{, 5} x 5 McHutchison, J.G., Lawitz, E.J., Shiffman, M.L. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009; 361: 580–593 Crossref | PubMed | Scopus (1022) | Google Scholar See all References The limitations of this therapeutic approach are well known, however, and include suboptimal response rates (approximately 40%−50%) in patients infected with HCV genotype 1,⁵ x 5 McHutchison, J.G., Lawitz, E.J., Shiffman, M.L. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009; 361: 580–593 Crossref | PubMed | Scopus (1022) | Google Scholar See all References ^{, 6} x 6 Hezode, C., Forestier, N., Dusheiko, G. et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009; 360: 1839–1850 Crossref | PubMed | Scopus (931) | Google Scholar See all References ^{, 7} x 7 McHutchison, J.G., Everson, G.T., Gordon, S.C. et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype-1 infection. N Engl J Med. 2009; 360: 1827–1838 Crossref | PubMed | Scopus (959) | Google Scholar See all References the most common genotype in the United States and Europe.⁸ x 8 Jacobson, I.M., Pawlotsky, J.M., Afdhal, N.H. et al. A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C. J Viral Hepat. 2012; 19: 1–26 Crossref | PubMed | Scopus (67) | Google Scholar See all References In addition, response rates in genotype-1−infected patients treated with PegIFN-α/RBV for a second time after initially failing to respond were 7%−22%.⁹ x 9 Jensen, D.M., Marcellin, P., Freilich, B. et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009; 150: 528–540 Crossref | PubMed | Scopus (172) | Google Scholar See all References ^{, 10} x 10 Poynard, T., Colombo, M., Bruix, J. et al. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology. 2009; 136: 1618–1628 Abstract | Full Text | Full Text PDF | PubMed | Scopus (201) | Google Scholar See all References

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug-drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug-drug interactions. Knowledge of pharmacokinetic profiles and concentration-effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.

Aim:present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points.Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion.Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

Cardiac amyloidosis (amyloid cardiomyopathy) is a disease damage to the heart caused by extracellular amyloid deposition. In some cases, there may be local damage to the structures of the heart, for example, the atria; more often, heart damage is part of a systemic (generalized) pathology. Depending on the amyloid precursor protein, 36 types of amyloidosis are described, among which hereditary and acquired forms are distinguished. Cardiac amyloidosis is diagnosed 1) in the case of the amyloid infiltration in the myocardial bioptates or 2) in the case of non-cardiac amyloid deposition and the left ventricular wall thickening >12 mm without arterial hypertension and other reasons. The heart is most often affected in AL-, ATTR-, AA-, AANF-types of amyloidosis. Cardiac amyloidosis should be considered in patients with a heart failure with an unclear etiology, especially with preserved left ventricular ejection fraction, refractory to treatment, with proteinuria and CKD 4-5, in patients with idiopathic atrial fibrillation and conduction disturbances, in patients with left ventricular wall thickening of unclear etiology, low ECG voltage, unexplained arterial hypotension and pulmonary hypertension. Screening for cardiac amyloidosis should include non-invasive methods such as electrophoresis and immunofixation of blood and urine proteins, the free light lambda and kappa chains of immunoglobulins, 99Tc-DPD scintigraphy, genetic testing (if hereditary variants of amyloidosis are suspected), as well as a histological examination of biopsy samples stained with Congo red and polarizing microscopy.