Lege Artis Medicinae

[PREDICTORS OF RESPONSE TO TREATMENT IN CHRONIC VIRAL HEPATITIS]

PÁR Alajos

DECEMBER 19, 2008

Lege Artis Medicinae - 2008;18(12)

[As the results of antiviral therapy for hepatitis B and C infections are still suboptimal, attention has been given to the strategies to maximize the effectiveness of currently available therapeutic modalities. In this approach, individualized management - based on predictive factors that influence response to treatment - is a key component. The paper summarizes how predictors can assist in optimizing therapy of patients with chronic viral hepatitis. In chronic hepatitis B, a favorable response to interferon or nucleoside/ nucleotide therapy can be expected in young, HBeAg-positive patients with alanine aminotransferase (ALT) values >2-5× upper limit of normal, histological activity >4-10, HBV DNA <105 copies/ml (<20,000 IU/ml), and infection with HBV genotype A or B. Virological response at 12 and 24 weeks (>1 log10 decrease in HBV DNA titer or a titer of <400 IU/ml) may assist in decisions about treatment continuation or switching to another therapeutic option. In chronic hepatitis C, before interferon/ribavirin treatment, non-modifiable predictors are age, sex, race, cirrhosis, HCV genotype and HCV RNA titer. HCV1 genotype is an important negative predictor. Modifiable factors are body mass index, insulin resistance, diabetes, depression and cytopenias, which can be corrected in order to improve the chance of therapeutic success. During treatment, rapid (week 4), early (week 12), or slow (week 24) virological response may determine the duration of treatment (24, 48, or 72 weeks), and predict the likelihood of sustained virological response. Most important positive predictor is rapid response at week 4, similarly complete early response (at week 12) is also of value concerning the duration of therapy and even in the aspect of re-treatment. Body weight-adapted ribavirin dosing and patient adherence are important factors of therapeutic success, as well.]

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[SECONDARY MALIGNANCIES IN RHEUMATOID ARTHRITIS]

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[INTRODUCTION - Survival data for rheumatoid arthritis (RA) have improved during the past years. Due to longer life expectancy, more attention has to be paid to prevention and treatment of long-term sequelae, including secondary malignancies. Incidence of malignant lymphoproliferative diseases and bronchial cancer is higher in a number of rheumatic diseases including RA. Some drugs nowadays very rarely used in RA - primarily cyclophosphamide and azathioprine - may further increase cancer risk. According to several large meta-analyses, biological therapy may also increase the risk of lymphomas, however, as these agents are used for the treatment of active, refractory arthritis, benefit may override such risks. PATIENTS AND METHODS - Altogether 516 RA patients managed at our department were assessed for the incidence and type of secondary malignancies. Although the absolute number of RA patients with a tumor was relatively small, we compared our cohort to the Health for All database and calculated standard incidence ratios (SIR). RESULTS - We identified 13 cases of malignancy (11 females and 2 males) in 516 RA patients (2.5%). In two patients, cancer developed before the onset of RA. RA patients with malignancy had an even higher female predominance (5.5 to 1) than usual. Mean age at onset of RA was 51.4 years, while age at the diagnosis of malignancy was 61.8 years. Mean duration of RA at the time of cancer diagnosis was 11.2 years. Five patients died, 4 due to the underlying malignancy. In the fifth patient, the tumor was considered cured but the patient died of amyloidosis. Among the 8 surviving patients, mean survival is 7.3 years until now, while overall survival of all 13 cancer patients is 4.7 years. Regarding types of malignancies, there were 6 cases of bronchial cancer, 2 cases of follicular thyroid cancer, and one cutaneous B cell lymphoma, one breast cancer, one gall bladder cancer, one colorectal cancer, and one pancreatic cancer. In comparison to the Health for All database, the overall SIR of all malignancies in RA was 1.12 (CI 0,91-1,33), varying between 2.2 and 70.7 among different tumor types. Only one cancer patient received cyclophosphamide therapy and some received methotrexate or anti-TNF agents. CONCLUSION - We identified 13 cases of malignancy among our RA patients. In RA, secondary tumors including bronchial cancer and lymphomas are more common than in the general population. Adequate treatment and monitoring of these patients may help us to lower the risk of malignancies secondary to RA]

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