Risk factors of unfavorable prognosis of chronic hepatitis C.

AIM: To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin's lymphoma. MATERIALS AND METHODS: This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. RESULTS: The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. CONCLUSION: Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.

[Antiviral therapy of chronic hepatitis C: 30 years success story].

Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90-95% of cases.

[Efficacy and safety of narlaprevir/ritonavir and daclatasvir non interferon combination in population of Russian patients with chronic hepatitis C].

AIM: Evaluate efficacy and safety of a combination of direct - acting antivirals narlaprevir/ritonavir with daclatasvir in patients with viral hepatitis C. MATERIALS AND METHODS: The study enrolled adult patients with HCV genotype 1b infection without demonstrated NS5A resistance - associated substitutions Y93C/H/N/S and/or L31F/M/V/I. Patients were treated with narlaprevir 200 mg QD, ritonavir 100 mg QD and daclatasvir 60 mg QD. Treatment duration was 12 weeks. Proportion of patients achieving sustained virological response 12 weeks after treatment (SVR12) was the primary efficacy endpoint. RESULTS AND DISCUSSION: In total, 105 (75.0%) patients were treatment with the study combination. Patients' age varied from 21 to 69 years, the mean age being 43.2±10.9 years. There were slightly more women (55.2%), and 69 patients (65.7%) had comorbidities. SVR 12 was 89.5% (95% CI 82.0-94.7%). In 10 of 11 patients with treatment failures NS5A resistance - associated substitutions in residues 31 and/or 93 were found, as well as less clinically relevant substitutions L28M, P58S, R30Q, Q62K. Adverse events (AEs) were found in less than one half of patients (45 patients, or 42.9% in the safety population). Almost all recorded AEs were mild to moderate. CONCLUSION: Efficacy of treatment with a combination of narlaprevir/ritonavir and daclatasvir in treatment - naïve patients with HCV genotype 1b was close to 90%. This combination was found to be safe and well - tolerated.

[Ways of improving adherence on telaprevir-based therapy in patients with chronic HCV infection].

AIM: To present the ways of improving adherence on telaprevir-based therapy in patients with chronic HCV infection. BACKGROUND: Telaprevir is a direct antiviral agent, registered in Russian Federation as a treatment for chronic hepatitis C genotype 1 patients in combination with pegylated interferon and ribavirin (PR). Phase III clinical trials showed a significant improvement in efficacy when adding telaprevir to pegylated interferon and ribavirin compare to the duel PR treatment along. Standard telaprevir regiment 750 mg 3 times per day is associated with difficulties in keeping adherence to the treatment. Here we present the results of administering telaprevir 1125 mg twice daily. CONCLUSION: Telaprevir-based 1125 mg twice daily regimen in combination with PR is comparable with telaprevir 750 mg every 8 hours treatment if looking at rates of SVR, relapse incidence, viralogical insufficiency, pharmacokinetics, safety, also taking in consideration higher treatment adherence even in HCV cirrhotic patients.

[Simeprevir in combination with pegylated interferon-α and ribavirin in the treatment of naïve patients with genotype 1 chronic hepatitis C].

Triple therapy with pegylated interferon-α, ribavirin, and simeprevir is now optimal among the antiviral treatment options available in the Russian Federation for patients with chronic hepatitis C (CHC), including inthe compensated stage of liver cirrhosis. The optimality of this combination is determined by its high efficacy--the given combination of antiviral agents allows one to predict that more than 90% of naïve patients with CHC will achieve a sustained virological response as 97-99% of the Russian population patients is infected with hepatitis C virus subgenotype 1b. The second important aspect that can recognize the triple therapy incorporating simeprevir to be most rational now is its safety similar to that of double therapy with pegylated interferon-α and ribavirin. In addition, the absolute advantages of the triple therapy including simeprevir are shorter treatment duration (for a total of 24 weeks) for all naïve patients with CHC, including those in the compensated stage of cirrhosis, and simeprevir taken as one capsule once daily.

[Successful treatment of severe HCV-cryoglobulinemic vasculitis with the use of CD20 monoclonalantibodies and antiviral agents].

This paper reports a case of successfuid treatment of severe HCV-cryoglobulinemic vasculitis with ulcerative necrotic skin lesions, digital necrosis, cryoglobulinemic glomnerulonephritis and sensorimotor neuropathy. Possibilities for the change of prognosis in the patients with HCV-cryoglobulinemic vasculitis are discussed along with the prospects for the improvement of antiviral and pathogenetic therapy.

[Systemic manifestations of primary sclerosing cholangitis].

Primary sclerosing cholangitis (PSC) is a chronic slowly developing cholestatic diseases of liver characterized by non-purulent destructive inflammation and fibrosis of bile ducts leading to secondary biliary cirrhosis. PSC etiology remains unknown and the disease is regarded as an autoimmune pathology. In 60-80% of the patients PSC combines with other autoimmune diseases (over 40 nosological forms). This paper deals with the diversity and prevalence of systemic manifestations of PSC in a group of 93 patients admitted to Tareev Nephrology Clinic. Autoimmune diseases were diagnosed in 79.6% of the patients. PSC was most frequently associated with ulcerative colitis (49.5%), Crohn's disease (17.2%), hemorrhagic vasculitis (8.6%) and autoimmune thyroiditis (7.59%). Nervous system, kidneys, lungs and eyes were affected less frequently. 20.3% of the patients had more than one (2-5) manifestations of PSC in different combinations. It is concluded that the knowledge of extrahepatic PSC symptoms will promote its early diagnosis in patients with cholestasis of uncertain origin.

[Congenital bile duct hypoplasia (Alagille-Watson syndrome)--a rare cause of biliary cirrhosis in adults].

A case of a rare hereditary disease, Alagille-Watson syndrome, is reported. It most frequently affects liver and cardiovascular system which leads to biliary cirrhosis and cardiovascular catastrophe in young patients. Pathogenesis and clinical variants of the disease are described.

[Significance of allelic variants of interleukin-28B gene in chronic hepatitis C].

Chronic hepatitis C remains one of the most urgent problems of today's medicine. The review unravels the current view of the role of a single nucleotide polymorphism of the interleukin-28B (IL-28B) gene in different aspects of hepatitis C virus infection. Major attention is paid to the discussion of the value of the allelic variants of IL-28B during standard double and current triple antiviral therapy for chronic hepatitis C. Furthermore, the paper covers the biological role of interferon-lambda, a product of IL-28A, B, and IL-29 gene expression, other associations of the allelic variants of the IL-28B gene with different clinical signs, as well as the possibilities of practical use of this genetic marker in chronic hepatitis C today and futures prospects.

[Possibilities provided by personalized therapy of chronic hepatitis C (case conference at E.M.Tareev Clinic of Nephrology, Internal and Occupational Diseases)].

The presented clinical case gave rise to discussion of the main mechanisms and factors behind the progress of chronic hepatitis C. Special emphasis is laid on the currently available possibilities of antiviral therapy and its future prospects. The efficacy of personalized treatment and approaches to its improvement are considered based on the proper preventive measures and correction of factors responsible for poor responsiveness to the treatment, in the first place metabolic disorders (obesity, hepatic steatosis).

[Primary sclerosing cholangitis: present views of its pathogenesis, diagnosis and treatment].

Primary sclerosing cholangitis (PSC) is a chronic slowly progressive cholestatic liver disease characterized by non-purulent destructive inflammation and sclerosis of the extra- and intrahepatic bile ducts, leading to secondary biliary cirrhosis. The etiology of the disease is unknown; however, bacterial and genetic factors are presumed to be implicated. In 66-84% of cases, PSC is accompanied by inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. The diagnosis of PSC is based on the clinical presentation of the disease and on the data of magnetic resonance imaging or endoscopic retrograde cholangiography. The treatment of PSC has not been developed; there is evidence that ursodeoxycholic acid reduces cholestasis. Orthotopic liver transplantation is indicated at the stage of decompensated liver cirrhosis.

[Hippocratic fingers: clinical importance and differential diagnosis].

Changing of the distant finger phalanges into the form of a drumstick or fingernails into the form of a watch-glass (hippocratic fingers--HF) presents a well-known clinical phenomenon that suggests the presence of various diseases, especially those associated with hypoxia, i.e. manifested by respiratory and/or heart failure, as well as malignant tumors and subacute infective endocarditis. At the same time, the fact that this clinical phenomenon can accompany other diseases (Crohn's disease, HIV-infection) should be taken into consideration as well. HF often appear ahead of more specific symptoms. In this connection, correct interpretation of this clinical sign, augmented with laboratory tests, allows for early and valid diagnosis.

[System manifestations of primary biliary cirrhosis].

Primary biliary cirrhosis (PBC) is characterized by high frequency of systemic extrahepatic manifestations (EHM), which often precede the development of full clinical picture of PBC and play the leading part in the clinical course of the disease, sometimes determining its prognosis. The examination of 145 PBC patients (including two men) found a frequency of EHM of 72. 4%. The majority of EHM were caused by delayed-type hypersensitivity reactions, such as Sjogren syndrome, fibrosing alveolitis, autoimmune thyroiditis, tubulointerstitial nephritis, pulmonary granulomatosis/sarcoidosis, systemic scleroderma, rheumatoid arthritis, and ulcerative colitis; immunocomplex pathology including vasculites involving blood vessels of different caliber and localization and polyneuropathy was rarer. In 24.1% of PBC patients, system EHM manifestations were the first clinical signs of the disease. In 62.8% of patients with EHM their different combinations were registered. The most frequent one was a combination of Sjogren syndrome, fibrosing alveolitis, and tubulointerstitial nephritis, which was found in 16.2% of the patients. 6 7% of the patients had a combination of four EHM - Sjogren syndrome, fibrosing alveolitis, tubulointerstitial nephritis, and autoimmune thyroiditis. A long duration of PBC (more than five years from the debut), stage IV of the disease, and the presence of the rheumatoid factor in blood serum, were risk factors of the development of system PBC manifestations. In 20% of EHM patients their symptoms prevailed in the clinical picture, thus determining the severity of the condition. Three patients died of system EHM of PBC (systemic scleroderma, pulmonary granulomatosis). Thus, PBC diagnostics must be performed with taking into account system EHM found in this category of patients.

[Kidney involvement and arterial hypertension in middle-aged and elderly subjects]. / Porazhenie pochek i arterial'naia gipertoniia u lits pozhilogo i starcheskogo vozrasta.

The examination covered 125 elderly and senile subjects (106 females and 19 males) which made up 90.6% of those living in the boarding house. Their mean age was 81.3 years. Arterial hypertension was detected in 61.6% of the examinees. 18.5% of the examinees had hyperuricemia. Concentration function of the kidneys was affected in all the examinees. Half of them exhibited a moderate rise in the level of blood creatinine. The authors discuss the relationship between high prevalence of arterial hypertension, its tendency to crises and involutional processes in the kidneys in the onset and development of renoprival condition.