Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome.

Autoantibodies in hepatitis C virus-infected patients may indicate autoimmune hepatitis or other immune-mediated diseases. This may impact safety and efficacy of interferon-based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched-pair analysis was performed matching one autoantibody-positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.

Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study.

In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P < or = 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b.

[Effectiveness of antiviral therapy in patients with chronic hepatitis C treated by private practice gastroenterologists]. / Effektivität der antiviralen Behandlung von Patienten mit chronischer Hepatitis C in der gastroenterologischen Facharztpraxis.

The standard treatment for patients with chronic hepatitis C consists of pegylated interferon (PegIFN) alpha in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral centre. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIF Nalpha 2a/ribavirin (n = 126) or PegIFNalpha2b/ribavirin (n = 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virological response was achieved in 54 % of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p < 0.0001), younger age (p < 0.0001), normal gamma-glutamyltransferase levels before initiation of treatment (p = 0.003), and absence of language communication problems (p = 0.023) were associated with a sustained virological response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p = 0.025). Patients infected with HCV genotype 1 in whom the PegIFNalpha dose was reduced had higher virological relapse rates (p = 0.049). With regard to the treating physician, sustained virological response rates ranged from 26 - 67 % in patients infected with HCV genotype 1. Our study shows that virological response rates similar to those in international randomised clinical trials can be achieved by private practice gastroenterologists. The presented network allows characterization of the treatment outcome in chronic hepatitis C not only with regard to virus- and host-related factors but also on an individual physician basis.

Localised form of spondylo-epiphyseal dysplasia congenita.

We report an unusual case of spondylo-epiphyseal dysplasia congenita which affected only the hips and the thoraco-lumbar spine. The epiphysis of the long bones are normal apart from the hips. Our child has a bilateral epiphyseal dysplasia of both proximal femoral epiphysis discovered incidentally at 11 months and confirmed later on at 8 years, associated with abnormalities of the superior margin of the vertebral bodies from T11 to L2. Very few similar cases have been reported anteriorly.

[Second malignancies after the therapy of Hodgkin's disease: the Freiburg collective 1940 to 1991]. / Zweitmalignome nach Therapie des Morbus Hodgkin: das Freiburger Kollektiv 1940 bis 1991.

AIM: To quantify the risk of second malignancies in patients with Hodgkin's disease treated at the Department of Radiotherapy, University Clinic Freiburg, with the object of comparing this risk with the international experience and as a contribution to the discussion about future treatment. PATIENTS AND METHODS: Second malignancies were reviewed in 1,588 patients treated for Hodgkin's disease between 1940 and 1991. Treatment consisted of involved or extended field radiotherapy as a single modality or in combination with chemotherapy. Before the early 1970's, chemotherapy used (sequential) monodrug regimens. The mean follow-up was 8.3 years. The cumulative risk was calculated using the Kaplan-Meier method and related to the risk of a normal population taken from epidemiological data of the National Cancer Institute. An estimate of radiation dose at the site of origin of the second malignancy was obtained from representative measurements employing an Alderson phantom. RESULTS: After 5, 10, 15 and 20 years the cumulative risk for all malignancies was 1.5%, 4.2%, 9.4% and 21%, respectively; for solid tumors it came to 1.2%, 3.1%, 7.9% and 19%; for non-Hodgkin lymphoma (NHL) the risk amounted to 0.1%, 0.9%, 1.4% and 1.9%; and for leukemia it was 0.1%, 0.3%, 0.6% and 0.6%. For the same time points the relative risk for all malignancies was calculated to be 1.1, 1.4, 1.8 and 2.5; for solid tumors it came to 1.0, 1.1, 1.6 and 2.5; for NHL it amounted to 3.3, 11.8, 9.3 and 8.0; and for leukemia it was 3.3, 3.1, 3.4 and 2.1. For combinations of radiotherapy and chemotherapy the risk for second malignancies was highest in patients receiving ABVD any time during their treatment. 51% of the second malignancies were located infield, 22% at the field border and 27% outfield. In those cases for which the cause of death was known, Hodgkin's disease accounted for 79% followed by second malignancies accounting for 8%. The results obtained in Freiburg fell within the range reported in international publications. CONCLUSION: The increased incidence of second malignancies in cured Hodgkin's patients is along-term risk making regular follow-up mandatory. Although part of the second malignancies are unrelated to therapy, there is a need to carefully collect the data from patients treated according to new protocols in order to detect any changes in the number or kind of second malignancies in due time. This may well lead to a reassessment of therapeutic concepts.