[Acute hepatitis C infection: epidemiological and clinical aspects, and efficacy of interferon therapy]. / Epatite acuta C: aspetti epidemiologici, clinici e impatto della terapia interferonica.

Acute hepatitis C virus infection becomes chronic in 50-80% of patients; in recent years a number of studies on acute hepatitis C have shown that interferon treatment can solve more than 80% of cases. In this study we evaluated all cases of acute hepatitis C referred to our unit from 1998 to 2005 to study the epidemiological and clinical features and the efficacy of interferon therapy during the course of the disease. Forty-three patients (28 males, 15 females) were monitored: 22 were drug-addicts, 6 patients referred from recent surgery, in 3 cases a percutaneous exposure was described, 2 patients had had a colonoscopy, 4 were partners of subjects with chronic hepatitis C and in the remaining cases the transmission route was uncertain. All subjects were symptomatic, jaundice was evident in 20 out of 43 patients and in all cases hepatic protein synthesis was unaltered. Of the 21 patients who consented to interferon therapy, in 19 cases a sustained virological response was achieved while in 2 cases the follow-up period was too short for evaluation. Four of the 22 non-treated patients had a spontaneous resolution of the infection, in 13 cases the infection became chronic, and in 4 cases the follow-up was too short for an analysis. In our study all patients were young, in 58% of subjects a parenteral exposure was described and most patients were drug-addicts. All the treated patients obtained a sustained response, while in the majority of non-treated cases the infection became chronic.

[Alterations of bone metabolism in patients with chronic C virus hepatitis]. / Alterazioni del metabolismo osseo in pazienti con epatite cronica da virus C.

Patients affected with chronic hepatitis are prone to alterations in bone metabolism, osteoporosis and osteopoenia being the most common manifestations. Bone mineral densitometry is the method of choice for assessing bone mass; nevertheless, this is a static parameter whereas biochemical markers of bone remodelling reveal the dynamics of bone resorption and formation. With this study we used bone mineral densitometry and biochemical markers to evaluate bone metabolism in a group of male patients with chronic C virus hepatitis and in a group of healthy males. In the hepatitis group 56% of the patients proved osteopoenic or osteoporotic and bone depletion increased as the histological score of the disease increased. Crosslaps are a parameter of osteoclastic activity: their measurement showed alterations in all the age groups of the hepatitis patients studied, which goes to show that there is intense bone remodelling in these individuals due mainly to osteoclastic resorption. Hepatitis C is a risk factor for bone depletion: we believe that when this type of hepatitis is diagnosed it is useful to assess bone metabolism with bone mineral densitometry and with the crosslaps assay.

Patient-reported and physician-estimated adherence to HAART: social and clinic center-related factors are associated with discordance.

OBJECTIVES: To evaluate the rate of discordance between patients and physicians on adherence to highly active antiretroviral therapy (HAART) and identify factors related to discordance in these two assessments. DESIGN: Prospective, multicenter, cohort study (AdICONA) nested within the Italian Cohort Naive Antiretrovirals (ICONA) study. SETTING: Tertiary clinical centers. PARTICIPANTS: The patients filled out a 16-item self-administered questionnaire on adherence to HAART. At the same time, physicians estimated the current HAART adherence of their patient. MAIN OUTCOME MEASURE: Discordance between patient and physician on adherence to antiretroviral therapy. RESULTS: From May 1999 to March 2000, 320 paired patient-physician assessments were obtained. Patients had a mean plasma HIV RNA of 315 copies/ml (64% had undetectable HIV RNA) and a mean CD4+ cell count of 577 cells x 10(6)/L. Nonadherence was reported by 30.9% of patients and estimated by physicians in 45.0% cases. In 111 cases (34.7%), patients and physicians were discordant on adherence to HAART. Kappa statistics was 0.27. Using patient-assessed adherence as reference, sensitivity, specificity, positive predictive value, and negative predictive value of physician-estimated adherence were 64.7%, 66.6%, 81.2%, and 45.8%, respectively. On multivariable analysis, low education level, unemployment, absence of a social worker in the clinical center, and unavailability of afternoon visits were significantly correlated with patient-physician discordance on adherence to antiretrovirals. CONCLUSIONS: Physicians did not correctly estimate patient-reported adherence to HAART in more than one third of patients. Both social variables and factors related to the clinical center were important predictors of discordance between patients and physicians. Interventions to enhance adherence should include strategies addressed to improve patient-physician relationship.

Virologic correlates of adherence to antiretroviral medications and therapeutic failure.

Adherence to antiretroviral therapy affects the pharmacokinetics of antiviral drugs and activates a cascade of events ultimately leading to therapeutic success or failure. An optimal adherence usually affords minimal rounds of virus replication and rare spontaneous mutations, which are unable to be fixed in the genome because of the competition of wild-type (more fit) strains. Therefore, adherence-based therapeutic success is mostly accompanied by the prevalence of wild-type strains. In case of poor adherence, virus replication is substantial, and mutations randomly occurring tend to be fixed within the genome. Under these conditions, mutated-resistant strains will outgrow wild-type virus (sensitive to antivirals and thereby unable to compete enough with resistant strains for cellular targets): thus, therapeutic failure occurs, and mutated resistant strains are predominant. In the case of very low or absent adherence, virologic failure occurs, although wild-type virus (whose replication is not significantly affected by antivirals) is not outgrown by mutated strains randomly produced but unable to be fixed within the genome. Taken together, these events and their consequences strongly support the relevance of a tight and continuous monitoring of adherence to antiretroviral drugs to prevent the risk of development of mutated strains often cross-resistant to the majority of antiretroviral drugs currently available.