Recommendations of the Polish Group of Experts for HCV for the treatment of hepatitis C in 2020.

The recommendations set out the principles of diagnosis and treatment of hepatitis C virus (HCV) infections according to the most recent knowledge. The main goal of therapy for HCV infection is to eliminate the virus from the body, which consequently leads to arrest of progress or regression of changes in the liver. Current version of the recommendations prioritise pangenotypic regimens and provide guidelines in special populations of patients, such as children, cirrhotics, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfected, those with renal failure, hepatic decompensation and non-responders to previous therapies.

Recommendations for the treatment of hepatitis B in 2017.

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.

Recommendations for the treatment of hepatitis C in 2017.

The goals of treatment is to eliminate HCV infection, stop or reverse histological changes, reduce the risk of hepatocellular carcinoma development and transmission of the infection to other individuals. According to the recommendation of the Polish Group of Experts for HCV in 2017 all patients with chronic HCV infection should receive treatment, but it is not recommended in patients at high risk of short overall survival. If access to therapy is restricted, priority should be given to patients whose HCV infection can lead to an unfavourable outcome of the disease within a short time frame, particular to individuals with liver cirrhosis, rapidly progressing liver fibrosis, extrahepatic manifestations of HCV infection, chronic kidney diseases, patients before and after organ transplantation. Current recommendations of Polish Group of Experts for HCV provide guidelines to select optimal medication, assessment of liver fibrosis, treatment efficacy, dealing with resistance to direct acting antivirals, monitoring for hepatocellular carcinoma, management of HBV/HCV coinfection and drug interactions. It constains also advice on treatment of special patients populations such as renal failure, liver transplant and hepatic decompensation, as well as retreatment of patients which failed interferon free therapy. Moreover specific recommendations of management patients infected with different genotypes with currently reimbursed regimens or those expected to become available shortly in Poland are also included.

Prevalence and risk factors of HCV infection in Poland.

BACKGROUND: According to small studies carried out in preselected populations, the estimated prevalence of anti-hepatitis C virus (HCV) antibodies in Poland ranges from 0.6 to 2.1%. AIMS: The aim of this study was to evaluate the prevalence of anti-HCV and HCV RNA among patients and healthcare workers. METHODS: Anti-HCV antibodies were measured (Elecsys, Roche) in serum samples from 26,057 adults, consecutive patients or healthcare workers, from hospitals and out patient clinics not involved in the management of liver diseases. The majority of them (18,233) consented to fill out an anonymous questionnaire related to possible risk factors for HCV infection. Anti-HCV-positive samples were assessed for HCV RNA (Cobas Amplicor, Roche). A multivariate logistic regression model and the χ² test or the Fisher's exact test were applied. RESULTS: Anti-HCV antibodies were detected in 1.9% of individuals, and 31% of them demonstrated HCV RNA, which varied from 26% in hospitals to 66% in specialistic out-patient clinics. Prevalence of anti-HCV was significantly lower in healthcare workers (1.42%) than in patients (1.92%). Significant independent risk factors for anti-HCV positivity were as follows: male sex, more than three hospitalizations in a lifetime, blood transfusions before 1992, and intravenous drug use. The only significant risk factor for HCV RNA was intravenous drug use. An analysis carried out for multispecialistic hospitals demonstrated significantly lower prevalence of HCV RNA positivity in healthcare workers. CONCLUSION: Prevalence of anti-HCV in the Polish population studied was up to 1.9%, but active infection could be diagnosed in only 31% of them. Intravenous drug use, blood transfusions before 1992, multiple hospitalizations, and male sex increase the risk of HCV infection.

[Polish multicenter study on safety and efficacy of adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)]. / Wieloosrodkowe badanie bezpieczenstwa i skutecznosci preparatu dipiwoksyl adefowiru w leczeniu przewleklego wirusowego zapalenia watroby typu B u doroslych z opornoscia na lamiwudyne (HEP 2008).

Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.

C-reactive protein and chronic hepatitis C virus infection in diabetic patients.

INTRODUCTION: C-reactive protein (CRP) is one of the most widely used risk markers of cardiovascular disease in clinical practice. The contribution of hepatitis C virus (HCV) infection to low-grade inflammation in diabetic patients and its significance for cardiovascular risk scoring remain unclear. OBJECTIVES: The aim of the study was to investigate the relationship between HCV infection and CRP levels as one of the markers of cardiovascular risk in diabetic patients. PATIENTS AND METHODS: we compared patients with HCV infection and diabetes (n = 46) with HCV-negative type 1 (n = 56) or type 2 diabetic patients (n = 54), as well as HCV patients without diabetes (n = 54). RESULTS: CRP levels in diabetic HCV patients were lower than in type 2 diabetic patients (P <0.001), similar to those in the type 1 diabetic group (P = 0.747), and higher than in nondiabetic HCV subjects (P = 0.002). The median values were 1.07, 2.58, 0.91, and 0.45 mg/l, respectively. White blood cell count in diabetic HCV subjects was lower than in those with type 2 diabetes (P = 0.029) and similar to that found in type 1 diabetic (P = 0.064) and nondiabetic HCV patients (P = 0.279). There was difference in erythrocyte sedimentation rate between diabetic and nondiabetic HCV groups (P = 0.025); the respective medians were 10 and 5 mm/h. CONCLUSIONS: these findings indicate that HCV hepatitis may modulate chronic inflammatory state in diabetic patients. Moreover, these results suggest that screening for HCV should be considered prior to assessment of cardiovascular risk in diabetic patients, because the results may affect the cardiovascular risk scoring.

[Antiviral treatment of chronic B hepatitis; 2010 - therapeutic recommendations]. / Leczenie przeciwwirusowe przewleklego zapalenia watroby typu B--zalecenia terapeutyczne 2010.

The drugs currently approved for treatment of HBV infections are: interferon alpha2a and alpha2b, pegylated interferon (PeglFN-al-pha2a) natural interferons and nucleos(t)ide analogues (NA): adefovir, entecavir, lamivudine, telbivudine (currently not available in Poland) and tenofovir. The following questions are described: the primary goal of antiviral treatment, criteria in therapeutic decision-making (including extrahepatic manifestations, compensated and decompensated cirrhosis of the liver), treatment failure (including: drug resistance), management of patients with HBV-positive markers, in whom chemotherapy or other immunosuppressive therapy is planned. In treatment-naive patients with chronic hepatitis B the first line therapy should be PeglFN-alpha2a monotherapy, and the first-line should be entecavir or tenofovir (highest potential for HBV replication suppression and high genetic barrier to resistance). In drug resistance the patient should be switched to another, preferably high-potency NA (entecavir or tenofovir) or start PeglFN-alpha2a therapy.

p53 immunocytochemistry and TP53 gene mutations in patients with chronic hepatitis C virus (HCV) infection.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular carcinoma (HCC), mostly in patients with liver cirrhosis. Present study aimed at evaluation of cellular expression of p53 protein, genetic TP53 changes in liver samples and anti-p53 in serum of patients with chronic hepatitis C virus infection. The expression of p53 protein were analysed by immunocytochemistry in liver biopsies from adult patients with chronic, long-lasting hepatitis C. In order to detect TP53 mutations, PCR/SSCP and sequencing were performed. Antibodies against p53 in serum were determined using enzyme immunoassay (ELISA).In two out of 14 examined patients TP53 point mutations were detected in the liver samples. In the first patient, a substitution of C to T was demonstrated in position 1 of the codon 250, resulting in substitution of proline by serine. The other patient carried a substitution of C to G in position 13274 of the intron 6. The patient carrying mutation in the codon 250 demonstrated morphological traits of liver cirrhosis and had high number of p53-immunoreactive cell nuclei in tissue. None of the patients manifested elevated titres of serum anti-p53. In the liver, significant positive correlations were disclosed between expression of p53 on one hand and grading and staging on the other. A negative correlation was disclosed between cellular expression of p53 and duration time of infection. In conclusions, genetic changes in TP53 can be detected also in non-neoplastic lesions linked to chronic HCV infection.

Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C) in chronic, long lasting hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C) in liver biopsies from adults (n=19) with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex) technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05). At the level of electron microscopy, protein localization in endoplasmic reticulum (ER) membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT), serum level of HCV RNA or alpha-fetoprotein (AFP) on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging, proliferative activity of hepatocytes and serum AFP level represent more valuable indices of the disease progress than those provided by cellular expression of three potentially oncogenic HCV proteins in vivo.

[Bacterial endocarditis in the course of sepsis in 7th month of treatment with peginterferon alfa and ribavirin in patient with chronic hepatitis C]. / Bakteryjne zapalenie wsierdzia w przebiegu posocznicy w 7 miesiacu leczenia peginterferonem alfa I rybawiryna u pacjenta z przewleklym zapaleniem watroby typu C.

In the study we described severe adverse events such as sepsis and bacterial endocarditis in the patient treated because of chronic hepatitis C (CHC). A case of 57 year old man with CHC, with recurring increased aminotransferases up to 100 IU/l; histological result of liver biopsy--G3, S2, HCV-RNA positive, genotype--HCV1b. The therapy with peginterferon alfa and ribavirin was introduced. The negative result of HCV RNA was obtained in 12th week of treatment. In the 7th month the patient was admitted to the hospital because of sepsis due to Escherichia coli, acute renal insufficiency and right orchitis. In spite of the treatment and general clinical improvement, the patient was still febrile. The bacterial endocarditis was found after number of diagnostic procedures. The treatment of endocarditis lasted 6 weeks in the hospital. During the hospitalization and 6 months after the HCV-RNA were performed with the negative results. The therapy of CHC with peginterteron and ribavirin is save in most cases however requires increased clinical surveillance, especially in the second half-year.