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Section 6. Medical science
Egamova Intizor Normuhammadovna, Senior staff scientist at the Tashkent Institute of Advanced Medical
E-mail: evovision@bk.ru
Antiviral treatment of patients with liver cirrhosis of viral etiology (HCV-infection)
Abstract: The article analyzes the results of combination antiviral therapy in 100 patients with compensated liver cirrhosis (LC) caused by chronic HCV-infection. The duration of combination antiviral therapy (KPVT) was 24 or 48 weeks depending on the genotype of HCV. KPVT was discontinued due to ineffectiveness and/or the development of serious complications is almost 20 % of patients with liver cirrhosis. Although the overall efficiency KPVT was lower than the figures usually recorded in chronic viral hepatitis C (HCV) without the presence of liver cirrhosis, as a whole the percentage of sustained virologic response (SVR) when the CPU was quite high and amounted to 46.2 %. KPVT The efficiency was higher in patients with cirrhosis caused by genotype 3a HCV, as compared to the genotype 1b HCV. SVR was observed in this group, 52.3 % of patients compared with 40.8 % of patients infected by genotype 1b. Relapses with HCV genotype 3a met, on the other hand, slightly less (31.8 % vs. 36.7 %). Despite the lower efficiency and a higher percentage of complications, should be recognized KPVT in patients with compensated cirrhosis etiology of liver HCV-appropriate.
Keywords: ribavirin, pegylated interferon, antiviral therapy, liver cirrhosis, chronic viral hepatitis.
Relevance
In a world of 170 to 300 million people are infected with the hepatitis C virus. [5] As frequency hepatitis C virus is one of the first places among all infections transmitted through the blood [3; 4; 10]. Chronic hepatitis C virus (HCV) includes complications such as liver cirrhosis, hepatocellular carcinoma and liver failure [2, 4]. Approximately 25 % of all cases of cirrhosis and hepatocellular carcinoma develop due to chronic hepatitis C [2-4; 8; 10]. The most common cause of liver transplants in the world are severe liver damage resulting from chronic HCV. It is known that the frequency of HCV-infection serious complications increases due to slow disease progression [2; 8].
According to scientific literature, patients with liver fibrosis, cirrhosis, and especially in the greatest need of antiviral therapy, but the effectiveness of the treatment, which is estimated sustained virological response (SVR) is sufficiently low — approximately 30 %[1-4 ; 7; 9]. However, achieving SVR in these patients can significantly reduce the incidence of decompensated liver disease, complications and death [2; 6].
In connection with this important improvement in "difficult" antiviral therapy results in this patient group [2]. Consequently, information on the effectiveness of antiviral therapy of patients with viral cirrhosis very small.
Purpose of the study
Determination of the effectiveness of combined antiviral therapy (HTP) patients with cirrhosis ofviral etiology (HCV) infection.
Materials and methods
During the period of2007-2011, based BUZ "Regional Clinical Hospital of Infectious Diseases" of Voronezh were examined and treated 100 patients aged from 32 years to 58 years (56 males, 44 females) with a diagnosis of "cirrhosis of viral etiology (HCV) infection, compensation stage (Class A on the Child-Pugh). The diagnosis was established traditionally, according to generally accepted standards. Etiological diagnosis verification carried out based on the detection of serum HCV RNA by polymerase chain reaction (PCR). PCR diagnostics was carried out in real-time mode, the sensitivity of the test systems used (HCV RNA Am-pliSens) was 50 copies/mL. All the patients underwent genotyp-ing HCV. The most often detected genotype 1b infection — in 49 patients (49.0 %), genotype 3a met in 44 (44.0 %) patients. If necessary, carried out in patients with HCV RNA quantification in
blood. serum markers (a-HCV-IgG, and-HCV-IgM) were also determined using an enzyme immunoassay (EIA).
The diagnosis of liver cirrhosis (LC) was based on the ultrasound data ofthe abdominal cavity, where the signs ofportal hypertension, such as splenomegaly and expansion of the portal vein were detected. Also, all patients underwent endoscopy, which determines the dilated veins of the esophagus I-II degree. In all patients, the diagnosis was confirmed by the CPU via fibroelastometrii liver tissue Fibroscan FS-502 apparatus (Echosens, France) with the identification stage F4 fibrosis by Metavir scale. Besides this, 20.4 % of patients (19 persons) additionally hepatic biopsy by Mengini with morphological confirmation of the diagnosis of the CPU (F3-F4 on the Knodell) was carried out.
In addition to general clinical methods of examination, all patients performed a full serological examination for markers of viral hepatitis B, D, using ELISA and molecular diagnostics (PCR) was carried out determining the content of a-fetoprotein concentrations of iron and copper in the blood serum. Prior to the OEM serology ruled out the presence of autoimmune hepatitis and other autoimmune conditions.
Inclusion criteria were:
- A positive test for a-HCV-IgG, and-HCV-IgM;
- A positive analysis of HCV RNA PCR;
- An increased level of serum ALT;
- The results of liver biopsy and fibroelastometr, confirming the diagnosis of cirrhosis of the liver;
- The severity ofliver cirrhosis on the scale of Child-Turcotte-Pugh < 7 points.
Except for the criteria adopted:
- The patient's age (under 18 and over 65 years);
- Companion of HBV infection and HIV infection;
- The presence of concomitant liver disease (primary biliary cirrhosis, Wilson's disease, Budd-Chiari syndrome, hemochromatosis, autoimmune hepatitis, deficiency alpha-1 antitrypsin), or any disease of the liver in the stage of decompensation;
- Regular consumption of alcohol of more than 50 g/day in men and 25g/day for women in the last two years before the start of the OEM;
- The presence of previous antiviral treatment for HCV;
- The presence of any of the commonly accepted contraindications for OEM (severe thrombocytopenia less than 65 x 10 9/L, neutrophil count less than 1.5 x 10 9/L, severe heart disease,
Antiviral treatment of patients with liver cirrhosis of viral etiology (HCV-infection)
uncontrolled diabetes, autoimmune disorders, hemoglobin less than 80 g/l; increased creatinine above normal; a history of or existing at the time of the survey depression or mental disorders);
- The severity ofliver cirrhosis on the scale of Child-Turcotte-Pugh score 7 or greater.
All 100 patients were naive on HTP (previously none of them had received antiviral therapy for chronic hepatitis C). In all patients combined PVT was conducted. Patients received pegylated interferon alfa-2b (Peglntron) 120 mg. 1 once a week subcutaneously, or pegylated interferon alfa-2a (Pegasys) 180 mg. 1 time per week subcutaneously. Both regimens included in the complex therapy of ribavirin, which is administered in a daily dose of 1000 mg. for patients weighing < 75 kg. or 1200 mg/day of patient body weight at > 75 kg. orally in two divided doses. The duration of therapy was 24 weeks in patients infected with genotype 3a HCV-infection, and 48 weeks for patients infected with genotype 1b HCV-infection.
Achievement of SVR was assessed as the final indicator of the effectiveness of therapy. SVR — undetectable levels of HCV RNA in the serum 24 weeks after discontinuation of therapy [3].
All patients were randomized study groups on key clinical and laboratory parameters and body weight. In all the samples we tested the hypothesis of normality of distribution by Kolmogorov-Smirnov. To assess the reliability of the sample differences using nonparametric Mann-Whitney. All differences were considered significant at a value of P < 0.05.
Statistical analysis was performed using a standard Statistica for Windows software (version 13.0) from Statsoft Inc.
Results
In the course of antiviral therapy in 18 (18.0 %) patients with a diagnosis of "cirrhosis ofviral etiology (HCV) infection, stage of compensation", the treatment was stopped early for the following reasons:
- Lack ofvirologic response (10 patients);
- Developed in the course of treatment adverse reactions (8 patients), such as the expression of flu-like symptoms, anemia, leukopenia, thrombocytopenia.
The absence of response to therapy often recorded in patients infected with genotype 1b HCV-infection — 11 (22.5 %) patients than in patients infected with genotype 3a HCV-infection — 7 (15.9 %) patients.
Full OEM course completed 75 patients. Thus, in the total group of patients with CKD treated with HTP, SVR was recorded in 43 (46.2 %) patients, relapses were observed among the 32 (34.4 %) patients.
Analyzing the results of the OEM, depending on the HCV genotype, we obtained the following data. Patients infected with genotype 1b HCV, SVR recorded in 40.8 % of cases, relapse occurred in 36.7 % of patients. In patients infected with the HCV genotype 3a, SVR was recorded in 52.3 % of cases, relapses were observed in 31.8 % of patients.
Thus, among patients observed SVR was significantly higher in patients infected with genotype 3a HCV (52.3 %), compared to genotype 1b (40.8 %, P < 0.05). However, relapse rates for genotype 1b was slightly higher (36.7 % vs. 31.8 %, P > 0.05).
Conclusions
Thus, the combined antiviral therapy is effective in patients with cirrhosis ofviral etiology (HCV) infection. SVR in these patients in the future will allow to significantly reduce the frequency of decompensated liver disease, and hence the development of hepatocellular carcinoma.
Quite a high percentage of patients with genotype 1b, 3a and showed relapse after completion KPVT that is probably due to fibrosis of the liver, impairing effects of antiviral drugs and processes sanogenesis.
According to the findings, the optimal candidates for antiviral therapy are patients with compensated cirrhosis (Class A according to Child-Pugh) and not infected with genotype 1 HCV infection.
However, antiviral therapy is indicated in all patients with compensated HCV cirrhosis irrespective of achieving a sustained viro-logic response, because it reduces the rate ofprogression of the disease and the level of viremia.
References:
1. Бессонова Е. Н. Возможности противовирусной терапии у больных циррозом печени в исходе НС^инфекции//Российский журнал гастроэнтерологии, гепатологии, колопроктологии. - 2011. - № 4. - С. 43-51.
2. Бруно С. Эффективность и безопасность пэгинтерферона а-2а и рибавирина у больных выраженным фиброзом и циррозом, вызванными вирусом гепатита С//Клиническая гепатология. - 2010. - № 2. - С. 17-25.
3. Современные схемы лечения больных хроническим гепатитом С/В. Т. Ивашкин [и др.].//Российский журнал гастроэнтерологии, гепатологии, колопроктологии. - 2012. - № 1. - С. 36-44.
4. Целиковский А. В. Снижает ли стеатоз печени эффективность комбинированной противовирусной терапии хронического гепатита С?/А. В. Целиковский, Г. А. Усков//Материалы XVII Российского конгресса «Гепатология сегодня», 19-21 марта 2012. - М. - С. 26.
5. Шерлок Ш., Дули Дж. Заболевания печени и желчных путей: практическое руководство/пер. с англ. - М.: Гэотар Медицина, 2002. - С. 864.
6. Bruno S. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study 3/S. Bruno, T. Stroffolini, M. Colombo//J Hepatol. - 2007. - № 45. - Р. 579-587.
7. Heathcote E. Peginterferon alfa-2a in patients with chronic hepatitis С and cirrhosis//N Engl J Med. - 2000. - № 343. - Р. 1673-1680.
8. Perz J. The contributions of hepatitis B virus and hepatitis С virus infections to cirrhosis and primary liver cancer worldwide//J Hepatol. - 2006. - № 45. - Р. 529-538.
9. Salomon J. Empirically calibrated model of hepatitis С virus infection in the United States//Am. J. Epidemiol. - 2002. -№ 156. - Р. 761-773.
10. Shepard C. Global epidemiology of hepatitis С virus infection/C. Shepard, L. Finelli, M. Alter//Lancet Infect Dis. - 2005. - № 5. -Р. 558-567.
