Aim:
to analyze the dynamics of fibrosis and steatosis of the liver according to fibroelastometry in patients with chronic hep-atitis C (CHC) after ≥ 6 months from transient elastometry (TE) ...achieving a sustained virologic response (SVR) to antiviral therapy.
Materials and methods.
At baseline, a prospective observational study included 628 CHC patients with known stage of liver fibrosis (F) before AVT, some of whom were phased out due to non-compliance with the inclusion criteria. The final analysis included 297 patients who had transient elastometry (TE) data with CAP™ technology on the severity of liver fibrosis (± steatosis) before treatment and after ≥ 6 months after reaching SVR (67 % – interferonfree regimens of therapy). Median follow-up from the moment SVR was confirmed was 3 years 2; 6.
Results.
At the end of the study, the average age of patients was 49 ± 12 years, of which 53 % were men. In the long-term period after reaching SVR, regression of liver fibrosis was diagnosed in 80 % of cases (including in patients with cirrhosis), and the progression of fibrosis was in 3 % of patient. At the same time, regression of liver steatosis was detected only in 31 % of the patient, worsening of the results was in 23 % (26 % of them had the appearance of steatosis (S) of the liver of 1–3 degrees in persons with no fatty liver before the start of AVT). In the group of patients with liver steatosis, the proportion of men was significantly higher (
p
= 0.004). Clinically significant stages of fibrosis F3–F4 were significantly more often recorded in patients with hepatic steatosis, both before treatment (46 % S1–S3 and 22 % S0,
p
< 0.001) and after ≥ 6 months after reaching SVR (19 % S1–S3 and 9 % S0,
p
= 0.023).
Conclusion.
In patients with chronic hepatitis C with SVR achieved in the long term, despite a significant regression of liver fibrosis, a high prevalence of hepatic steatosis remains. The data obtained indicate the feasibility of routine diagnosis of both fibrosis and steatosis of the liver in the management of patients with chronic HCV infection before and after successful antiviral therapy.
was to identify the most effective serum tumor markers for early diagnosis of hepatocellular carcinoma based on the combination of diagnostic characteristics and correlations.
There were observed 55 ...patients with chronic hepatitis C in the stage of liver cirrhosis with a verified diagnosis of hepatocellular carcinoma. The control group consisted of 55 patients with chronic hepatitis C at the stage of liver cirrhosis without hepatocellular carcinoma, comparable to the experimental group in terms of basic clinical profile. The following tumor markers were estimated in both groups: alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), annexin A2 (ANXA2), heparin-binding growth factor Midkine (MDK), glypican-3 (GPC3), des-gamma-carboxyprothrombin (DCP, PIVKA-II), dickkopf-related protein 1 (DKK-1), osteopontin (OPN), and Golgi protein 73 (GP73). There were also evaluated such indices as diagnostic sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio of a positive test, the possible correlation between alpha-fetoprotein and other tumor markers. The area under the ROC curve (AUC) was calculated at the 95% confidence interval.
The greatest sensitivity was revealed when using heparin-binding growth factor, annexin A2, osteopontin. Alpha-fetoprotein, alpha-fetoprotein-L3, glypican-3, des-gamma-carboxyprothrombin, dickkopf-related protein 1 had the best specificity. AUC>0.75 was found in annexin A2, heparin-binding growth factor, glypican-3, des-gamma-carboxyprothrombin, osteopontin, Golgi protein 73. The likelihood ratio of a positive test result was the highest for glypican-3. A significant correlation was found between alpha-fetoprotein and alpha-fetoprotein-L3, annexin A2, des-gamma-carboxyprothrombin.
According to the aggregate indicators of diagnostic efficiency, heparin-binding growth factor, glypican-3, and osteopontin are the most promising tumor markers of those studied. When they are used, integral AUC values are above the average, the level of these tumor markers in the blood of patients with hepatocellular cancer does not correlate with alpha-fetoprotein. They are applicable for diagnosing liver cancer in AFP-negative patients. The combined use of AFP + GPC3, AFP + OPN has already shown their advantages. However, the efficacy of the combination of AFP + MDK, GPC3 + OPN has not been determined yet; therefore, significance of the combined use of these tumor markers in the diagnosis of liver cancer should be investigated in the near future.
BACKGROUND:
The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion ...of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.
OBJECTIVE:
Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.
MATERIALS AND METHODS
: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.
RESULTS:
In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).
CONCLUSION:
For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective.
We evaluated the possibility of using an experimental model of hepatocellular carcinoma to study oncomarkers of primary liver cancer and compared the diagnostic efficacy of alpha-fetoprotein and ...osteopontin in the experiment and in clinical practice. Experimental studies were performed on a model of hepatocellular carcinoma induced by administration of diethyl nitrosamine to Fisher-344 rats. In addition, the levels of α-fetoprotein and osteopontin were determined in 35 patients with hepatocellular carcinoma detected at stages I-II according to TNM classification. The proposed model of liver cancer in rats reflects the sequence of stages characteristic of hepatocellular carcinoma in humans: liver fibrosis—cirrhosis—cancer. This model is applicable for the study of tumor markers at the early stage of tumor development. Osteopontin was found to have a more powerful diagnostic potential then alpha-fetoprotein.
Aim. To establish the main external and genetically determined risk factors for the development of hepatocellular cancer in the ethnic group of male Yakuts living in the Republic of Sakha (Yakutia) ...RS (Y) in the epidemiologically unfavorable conditions of the incidence of viral hepatitis. Materials and methods. A total of 97 male Yakuts were examined, including 44 people diagnosed with hepatocellular cancer and 53 people diagnosed with chronic viral hepatitis. HCC risk factors were identified by analyzing medical records and questioning patients. In the experimental and control groups, genetic studies of single nucleotide polymorphisms of genes mapped on the X-chromosome and involved in the activation of antiviral immunity along the TLR7 signaling pathway were performed. Results and discussion. In 100% of patients with hepatocellular cancer, infection with hepatitis B, C, D viruses or co - infection with these agents was detected. Every fourth patient with HCC in the RS (Y) was infected with hepatitis D. The course of hepatocellular cancer associated with HDV was characterized by rapid progression of liver cirrhosis, development of portal hypertension, bleeding from varicose veins of the stomach and esophagus (36.4%) and edematous ascitic syndrome (63.6%). In addition to viral agents, additional risk factors for liver cancer were identified, such as alcohol abuse, overweight, diabetes mellitus, and smoking. Among the studied variation sites of genes localized on the X-chromosome and encoding the reaction of innate antiviral immunity, no genetic marker was found with a sufficient degree of confidence determining the likelihood of hepatocellular cancer developing. Conclusions. The high incidence of hepatocellular carcinoma of the male population in the RS (Y) is due to the widespread prevalence of parenteral viral hepatitis, especially viral hepatitis D. Due to the introduction of mass vaccination of the population against hepatitis B in the Russian Federation in the foreseeable future in the RS (Y) we should see a decrease in the proportion of hepatocellular cancer associated with hepatitis B and D viruses, and therefore the focus should be on the treatment and prevention of hepatitis C virus and non - infectious risk factors.
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.
Аim:
diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic ...hepatitis C are presented.
Summary.
Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.
Conclusion.
Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
The review gives the data available in the literature in the efficiency of treatment in patients with chronic hepatitis C infected with hepatitis C virus.(HCV) recombinants, by applying various ...antiviral therapy regimens. The low efficiency of treatment with- pegylated interferons (PEG IFN) + ribavirin (RIB) and sofosburin (SOF) +RIB in this patient group (a sustained virologic response was achieved in 22 and 30.7%, respectively) compared with the efficiency of treatment (87-97 and 83-97%, respectively) inpatients infected with HCV genotype 2 does not allow the 2015 EASL HCV genotype 2 treatment regimens to be used in. such patients. In this connection, subtyping genotype 2 isolates by NS5B sequencing should be introduced into clinical laboratory practice to successfully detect recombinant HCVs and to enhance the efficiency of antiviral therapy.
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