Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. CONCLUSIONS: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

Prevalence of HCV genotypes in Poland - the EpiTer study.

THE AIM OF THE STUDY: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time. MATERIAL AND METHODS: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016. RESULTS: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%). CONCLUSIONS: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

HFE gene mutations in Polish patients with disturbances of iron metabolism: an initial assessment.

Hereditary hemochromatosis is one of the most frequent genetic disorders in Europeans, but its prevalence in Poland is still unknown. The aim of the study was an initial assessment of the prevalence of C282Y and H62D HFE gene mutations and their influence on the course of chronic hepatitis C. Forty-one patients were admitted to the Department of Infectious Diseases, Medical University of Gdansk in 2000-2004 because of chronic liver diseases with accompanying disturbances in iron metabolism. Genetic tests for the C282Y and H63D mutations were performed by PCR and restriction fragment length polymorphism (PCR-RFLP) analysis. The HFE gene mutations were confirmed in 24 of 41 (59%) cases with symptoms of chronic liver disease and iron overload, significantly more frequently in HCV-negative patients (12/14 vs. 12/27; chi2=8.28; p=0.05). The C282Y and H63D HFE gene mutations were detected in 16 of 41 (39%) and 9 of 41 (22%) cases, respectively. HCV-negative patients were C282Y carriers significantly more frequently than HCV-positive patients [9/14 vs. 2/27 C282Y homozygotes; 2/14 vs. 3/27 C282Y heterozygotes (p<0.0001)]. The carrier state of the H63D HFE gene mutation was not significantly more frequent in HCV-positive than HCV-negative patients. HCV infection seems to be a negative predictive marker of HFE gene mutations in patients with iron overload. The relationship of H63D HFE gene mutations with chronic hepatitis C and the possible influence of HCV infection on iron metabolism needs further analysis.

[Detection of HCV-RNA in liver tissue does not correlate with inflammatory process and fibrosis activity in chronic hepatitis C]. / Wykrycie HCV-RNA w tkance watroby nie koreluje z aktywnoscia i wlóknieniem watroby w przebiegu przewleklego zapalenia watroby typu C (wzw-C).

The significance of HCV-RNA presence in the liver tissue in chronic hepatitis C activity or prognosis has not yet been clearly explained. Therefore, we have examined the relationship between the presence of HCV-RNA in the liver and selected parameters of disease activity and liver damage. A group of 48 chronically HCV infected patients (7-63 years old, mean 39 years) was evaluated. In the patients we assessed the activity of transaminases (ALT, AST), gammaglutamyltransferase (GGTP), and alkaline phosphatase (ALP). The patients underwent routine liver biopsies and the liver tissue was examined histopathologically and in order to detect the presence of HCV-RNA, by means of a combined procedure joining a new method of HCV-RNA extraction from the liver tissue and HCV-RNA detection with RT-PCR automatic Cobas Amplicor Hepatitis C ver. 2.0 assay (Roche Diagnostics). At the time of the liver biopsy, 44 of the patients were identified as having detectable serum HCV-RNA (as examined by means of Cobas Amplicor Hepatitis C ver. 2.0 assay), 3 patients were negative, and 1 was not tested. The presence of HCV-RNA in the liver tissues was detected in 39 cases (81.2%). In the parameters examined we have not found any significant differences between currently liver HCV-RNA positive and negative patients. Presence of the detectable HCV-RNA in the liver bioptats from chronic hepatitis C patients does not correlate with disease activity or level of liver damage.

Disturbances of iron metabolism in chronic liver diseases.

BACKGROUND: Systematic biochemical and histopathological studies carried out in patients with diagnosed chronic liver diseases (cirrhosis, hepatocellular carcinoma) confirm the important pathogenetic role of commonly occurring accumulation of iron deposits, and not only in the classic form of hemochromatosis. The reports concern the pathologic role of iron storage in the liver often accompanying metabolic disturbance syndrome including obesity, type II diabetes and hypertension. The aim of the study was preliminary assessment of the incidence of iron metabolism disturbances in the population of patients with chronic liver diseases. MATERIAL/METHODS: Among 351 patients of the Department of Infectious Diseases who had histopathologic investigations of liver bioptates performed in 2000-2001, 99 subjects (28%) with morphological confirmation of iron deposition in the liver were selected. Retrospective analysis based on data from the patients' medical records took into consideration demographic information, results of laboratory tests (blood levels of hemoglobin, ALAT, iron, ferritin) and the ultimate diagnosis. The correlations between iron metabolism disturbances and the observed liver pathology were analyzed. RESULTS: The study group consisted of 99 subjects including 77 males (mean age 42.8 yrs) and 22 females (mean age 47.5 yrs). Most of them had been diagnosed with chronic hepatitis C, (N = 39). Liver damage due to hyperlipidemia was diagnosed in 12, and toxic liver damage in 11 patients. Subjects with chronic renal failure and after antitumor therapy accounted for 14%. In 7 patients, hemochromatosis was diagnosed or suspected. In that group, mean serum ferritin level amounted to 959.3 ng/ml. In 79% of cases, ALT values fell within the 41-500 IU/l range, whereas iron and ferritin levels exceeded the normal limits in 49% and 71% of cases, respectively. The preliminary analysis of pathologic iron accumulation in liver bioptates in relation to biochemical parameters of iron metabolism measured in the blood did not allow unequivocal confirmation of linear correlation between these phenomena. CONCLUSIONS: 1. Over 1/4 of patients diagnosed because of chronic liver diseases demonstrated excessive accumulation of iron in liver bioptates. 2. The analyzed group consisted predominantly of males with chronic hepatitis C. 3. Metabolic or toxic liver damage was diagnosed n 1/3 of cases. 4. No unequivocal confirmation of correlation between pathologic iron accumulation in the liver and values of iron metabolism parameters in blood was obtained.

Presence of HCV RNA in hepatic tissue and effectiveness of treatment with interferon and ribavirin.

BACKGROUND: The aim of the study was to assess the prognostic value of HCV RNA detection in hepatic tissue for the response to treatment with interferon alfa (IFN) and ribavirin (RIB) in patients with chronic hepatitis C. PATIENTS AND METHODS: A group of 55 patients infected with HCV was examined before the commencement of treatment with IFN and RIB. In all of them HCV RNA was detected in the serum. The presence of HCV RNA in hepatic tissue was confirmed using a technique combining a new method of HCV RNA extraction from hepatic tissue and detection of HCV RNA with RT-PCR Cobas Amplicor Roche tests. The group of 55 patients received IFN (3-6 MU, 3 times a week) and RIB (800-1200 mg daily) for 6 to 12 months. The response to treatment was assessed 6 months after completion of the therapy. Sustained response (SR) was defined as absence of HCV RNA in the serum and normalization of ALT levels. RESULTS: The presence of HCV RNA in hepatic tissue was confirmed in 48 patients (group A), and in 7 (group B) HCV RNA was not detected in the liver. SR was observed in 17 patients from group A and 6 from group B. Significant correlation (p < 0.05) was found between detection of HCV RNA in hepatic tissue and response to IFN + RIB therapy. CONCLUSIONS: As it follows from our results, the detection of HCV RNA in the hepatic tissue of a patient with chronic hepatitis C may be a negative prognostic factor for the patient's response to IFN + RIB therapy.

Assessment of correlation between histopathologic changes of gastric mucosa according to Whitehead's classification and extent of liver damage according to Knodell's scale in patients with chronic hepatopathy.

AIM OF THE STUDY: Patients with chronic liver damage often suffer from functional disturbances and pathologic changes in the stomach, including ulceration, erosions and chronic gastritis. It was attempted to establish whether there is a correlation between histopathologic abnormalities of the gastric mucosa and the extent of histopathologic changes in liver bioptates, i.e. inflammatory activity and fibrosis (Knodell's index) in patients with chronic hepatopathy. MATERIAL/METHODS: The study was carried out in 4 groups of patients: groups I--10 subjects with autoimmune hepatitis, group II--9 patients with chronic toxic liver damage, group III--11 patients with chronic hepatitis caused by HBV, and group IV--36 patients with chronic hepatitis caused by HCV. All the patients underwent gastroscopy with collection of gastric mucosa bioptates (from the antrum and the gastric body) as well as liver biopsy. RESULTS: The most frequent gastroscopy finding in all the studied groups were signs of gastritis: in group I--90%, in group II--78%, in group III--64% and in group IV--99%. Gastric mucosa histopathology assessed according to Whitehead's classification most frequently led to the diagnosis of gastritis chronica profunda (Group I--80%, Group II--78%, Group III--73% and Group IV--58%). No correlation was found between inflammatory activity in the liver assessed according to Knodell's scale and the extent of changes in histopathology of the gastric mucosa (p = 0.1). A negative correlation which, however, does not reach significance level (p = 0.054), is observed between the extent of fibrosis in liver bioptates and histopathologic abnormalities in the gastric mucous membrane. CONCLUSION: No statistically significant correlation between the extent of gastric mucosa damage and severity of inflammatory lesions and hepatic fibrosis was found.

Preliminary assessment of utility of radiofrequency ablation technique in treatment of primary hepatocellular carcinoma (HCC) in patients with hepatic cirrhosis.

BACKGROUND: Primary hepatocellular carcinoma very often develops in the cirrhotic liver. Surgical treatment of cirrhotic patients is associated with considerable risk. Even partial resection of the liver carries the risk of liver failure in such patients. Therefore, the thermoablation technique used in patients with liver tumors and cirrhosis, arouses considerable interest. The aim of the study was preliminary assessment of the value of radiofrequency (RFA) ablation in the treatment of HCC in patients with hepatic cirrhosis. MATERIAL/METHODS: From April 2001 to April 2002, 14 patients aged 30-79 with cirrhosis and focal lesions of primary liver tumor type (carcinoma hepatocellulare) were treated with transcutaneous thermoablation. Transcutaneous thermoablation with Cool Tip Equipment probe (Radionics) was performed under local anesthesia induced after intravenous sedation, or under general anesthesia with propofol (TIVA). In case of single lesions up to 3 cm in diameter, the exposure to thermal waves lasted 12 min, in case of larger lesions 2 to 4 sessions were used. The effects of RFA were assessed intraoperatively by means of USG, measuring the coagulation area, and then MRI was performed to confirm complete destruction of the lesions. The response to treatment was assessed by CT after 8 weeks. RESULTS: Among 8 patients with single focal lesions complete remission (CR) was obtained in 4, and partial remission (PR) in the remaining 4 cases. One subject with CR died 5 months later because of hemorrhage from esophageal varices. Among 6 patients with more than one HCC focus subjected to RFA, CR was obtained in 1, PR in 3, and one female patient who underwent the procedure in the period of non-compensated liver function, died 1.5 months later because of hepatic failure. Repeated thermoablation is considered in patients with PR. CONCLUSIONS: 1. Radiofrequency ablation is a safe method of treatment of HCC in patients with cirrhosis. 2. One of the advantages of RFA is that it can be performed repeatedly. 3. RFA can be combined with other methods.

Autoimmune hepatitis in the material of Department and Regional Hospital of Infectious Diseases in Gdansk.

BACKGROUND: The aim of the study was the analysis of patients with autoimmune hepatitis (AIH), with respect to diagnostics, clinical course and treatment, based on the material from the wards of infectious diseases. MATERIAL/METHODS: The study was carried out in the group of 106 AIH patients--95 females aged 11-81 (mean age 46 years) and 11 males aged 8-73 (mean age 35 years). The diagnosis of AIH was based on international criteria, including biochemical test results, autoantibodies, and liver tissue morphology. Serological test excluded hepatitis of viral etiology. Diagnostic procedures included also blood cell count, biochemical parameters of liver function with protein fractions, immunoassays (immunoglobulins, autoantibodies), according to commonly used methods. Liver biopsies were performed in 93 patients. RESULTS: The clinical presentation mimicked acute viral hepatitis in 75% of cases, in the remaining 25% corresponded to chronic viral hepatitis. 26% had other coincident disorders of autoimmune etiology. In 84% the initial stage of the disease was characterized with moderately severe course, in 11%--severe, 7% of the patients died--half of them at the initial stage of the disease. The following morphological patterns of hepatic abnormalities were observed: hepatitis chronica agresiva, fibrosis periportalis, hepatitis chronica agresiva in cirrhosim vertens, cirrhosis hepatis activa, hepatitis chronica persistence, hepatitis granulomatosa. Over 40% of patients demonstrated relapses of the disease due to discontinuation of treatment after obtaining clinical and biochemical remission. 51 patients were treated with glucocorticosteroid monotherapy, the same number with glucocorticosteroids combined with azathioprine, 1 female patient underwent liver transplantation. In nearly 30% of patients, the diagnosis of AIH was established after a period of persistence of pathologic symptoms of over a year. CONCLUSIONS: Late diagnoses of AIH indicate insufficient knowledge of the disease among physicians. The methods of treatment used in AIH are not sufficiently effective. Discontinuation of treatment should be preceded in each case by overall assessment of the pathologic process, including biochemical parameters, autoantibody level and liver histopathology.