Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

[Determination of the type and subtype of the hepatitis C virus in chronic viral hepatitis patients in Hungary]. / A magyarországi krónikus "C" vírushepatitises betegek vírustípus- és szubtípus-meghatározása.

The huge variability of hepatitis virus C is well-established. The geographical differences in its nucleotide sequence have important clinical significance by causing variant pathogenicities and affecting sensitivity to therapy. The authors pioneered the determination of the viral type and subtype in patients suffering from chronic viral hepatitis in Hungary. In this present work they report the applied methods and the results. In their virus serological laboratory was introduced the test "HCV Serotyping 1-6 Assay", which is based on the analysis of antibodies, in 1996. By this method they examined the samples of 127 patients and they found type 1 in 75.5%, type 4 in 25%, mixed types (type 1 + 2, 3, 4, 5, 6) in 9% and non-classifiable, non-reacting antibodies in 13% of the cases. Since 1999 they have used the combination of direct reverse-PCR of the viral antigen and reverse hybridization to type-specific specimens. These results, from 211 patients show that 6% belong to 1a, 85.5% to 1b, 3% to 1a + 1b, 1% to 1b + 2, 0.5% to 3 and 4% to mixed subtypes. Genotype 1b was associated with higher viremia. On the basis of the above they can conclude that 90% of the Hungarian population are infected by the most resistant 1b subtype of hepatitis virus C. It could explain the fact that only 20% of their patients with interferon monotherapy have become permanently virus-free. In view of these results they recommend combined, higher dose, long-lasting treatment in therapeutic protocols.

Hepatitis C virus infection: pathogenesis, diagnosis and treatment.

We discuss the basic questions concerning hepatitis C virus (HCV) infection and describe the molecular biological and epidemiological features of the causative agent HCV, as well as the pathogenetic mechanisms of the HCV-related hepatic and non-hepatic diseases. We then summarize the diagnostic and therapeutic procedures in accordance with the recent literature. All the problems are discussed from the point of view of Hungarian hepatologists who have given an account of the experiences and possibilities concerning these fields in Hungary.

[How great is the risk of personal contact in the transmission of hepatitis C virus infection?]. / Mekkora kockázattal jár a személyes kontaktus a C hepatitis vírus terjedésében?

The sexual, household and nosocomial transmission of Hepatitis C virus infection were studied in patients with HCV-RNA positive chronic active hepatitis, confirmed by PCR. Liver function tests and hepatitis C virus serology were performed in family members living in the same household of patients, sexual partners as well as members of the hospital environment in the Department of Hepatology. Fifty-three members of 27 families and 32 staff-members were examined. Quantitative HCR-RNA-PCR and virus serotype of anti-HCV (III.gen.) positive individuals were also identified. Two of the family members turned out to be anti-HCV positive. The husband in one of the married couples was treated for hepatitis of unidentified etiology in an Infectology Department four years ago. His wife was found to have chronic hepatitis C since two years. They both had C virus of serotype 1. The mother and daughter in another family suffered from von Willebrand factor deficiency syndrome. It was documented that they were infected by blood transfusion at different occasions. Their C virus serotypes were different. All the staff members of Hepatology Department were anti-HCV negative. These results confirmed the possibility of the non-parenteral transmission of hepatitis C virus, however, its incidence is very low.

[Effect of interferon-alpha2b therapy in chronic hepatitis C]. / Interferon-alpha 2B kezelés hatása chronicus C hepatitisben.

In chronic hepatitis C the interferon treatment given three times a week in a dosage of 3 million units (MU) normalizes the values of alanin-amino-transferase in a part of cases (25-40%), and produces bettering in the subjective complains of patients. In the short term therapy (3-6 months) the activity of ALT increases again after leaving the therapy, and the disease becomes active. The aim of this multicenter study in Hungary was to give newer data in the case of longterm efficacy with alpha-interferon. Ninety-one patients with chronic hepatitis C were selected into the open prospective clinical study in university and hospital departments. Treatment protocol was the following: Patients with chronic hepatitis C diagnosed by clinical and histological methods were treated with interferon-alpha 2B given 3 times a week in a dosage of 3 MU. Treatment period had lasted for one year and afterwards the patient had been on control for an other half a year. In non responder cases after 3 month treatment with interferon the dose of therapy was increased for 3 x 5 MU. In 37 cases (40.6%) out of 91 patients the authors found longterm sustained remission and in other 22 cases (24.2%) they observed a partial remission (among them 5 cases with late relapse). The rate of longterm sustained remission under 40 years was higher, than above 40. Higher rate was found when the treatment was started with a shorter chronicity of the disease. On te basis of the results the authors conclude: Interferon-alpha 2B is a good therapeutic modality for the treatment of patients with chronic hepatitis C. Efficacy of therapy is higher in younger patients and also in earlier application.

[Benign recurrent intrahepatic cholestasis]. / Benignus rekurráló intrahepaticus cholestasis.

The authors report the medical history of a 19-year-old male patient, who had been admitted to the department of infectious diseases three times with recurrent icterus of unknown origin, suspected of viral hepatitis before his internal examination. The clinical picture and the histological results of liver biopsy performed in acute phase proved the presence of a rare hyperbilirubinaemia syndrome, "the syndrome of benign recurrent, intrahepatic cholestasis". The authors briefly describe Summerskill-Walshe syndrome and its place in different hyperbilirubinaemia disorders.

[Clinical immunological features and interferon therapy in chronic hepatitis C]. / Klinikai immunológiai megfigyelések és interferon terápia krónikus C hepatitisben.

Clinical and immunological findings of 74 patients with chronic hepatitis C have been reported and experiences with interferon-alpha treatment of 31 patients are summarized. In addition, the first results of anti-HCV screening of blood donors are also briefly described. Transfusion in the history was noted in 69% of patients and the time, elapsed from the transfusion to the diagnosis was a mean of 7.15 +/- 8.1 years. Concerning the severity of the liver disease, chronic persistent hepatitis was established in 40%, active hepatitis in 45% and cirrhosis in 15% of the patients, respectively. Cholestasis was recorded in 32% of the cases. A significant elevation of serum immunoglobulin levels was noted in 83%, an antibody to liver specific protein (anti-LSP) has occurred in 80%, cryoglobulinaemia in 44% and circulating immune complexes in 33% of the patients. Natural killer cell activity of peripheral blood mononuclear cells significantly decreased. HLA B8 and DR3 antigens were found with elevated frequency (36.6% and 42.1%). Recombinant interferon-alpha at a weekly dose of 3MU thrice, for six months, has normalized serum alanine aminotransferase in 45% of patients and a sustained remission was found in 26%. The treatment resulted in the clearance of HCV-RNS from the serum in 40% of patients and that well correlated with the complete remission. In the good responders, a decrease in CD4+ cell count and a moderate decrease in CD8+ cell count as well as a transient rise in B cell count were seen during the treatment. Mitogen-induced lymphoproliferative response and natural killer cell activity increased. Predictors of response were as follows: female sex, shorter time elapsed from transfusion, absence of HLA, A1, B8, DR3 and serum anti-HBc negativity. Anti-HCV has been found in 0.33--0.38% of blood donors screened, and it is suggested, that a liver disease accompanied with elevated serum alanine aminotransferase, may be present in about 25-30% of anti-HCV positive symptom-free persons.