Management of chronic hepatitis in drug addicts: a systematic review.

Injection drug users constitute the largest group of person at high risk for acquiring chronic hepatitis C, B and Delta. In particular viral, host and environmental factors all seem to favour rapid spread of these infections among drugs addicts. Host factors include behaviours that expose individuals to hepatitis virus such as the shared use of drug preparation, injection equipment and not protected sexual relationship with other drugs users. While in some clinical studies adherence to treatment regimens was often poor and to treat chronic hepatitis in injection drug users was stated as futile, in other controlled clinical studies adherence and sustained biological response to antiviral treatment was slightly lower or similar to that reported in other groups of patients. In this review we describe the epidemiology, diagnosis and treatment of chronic hepatitis C, B and Delta in intravenous drug users.

Pulmonary tuberculosis in HIV-infected patients presenting with normal chest radiograph and negative sputum smear.

BACKGROUND: HIV-infected patients with pulmonary tuberculosis exhibit atypical radiological presentation and negative sputum smear more frequently than their HIV-negative counterparts. PATIENTS AND METHODS: We performed a retrospective study based on a chart review of 146 HIV-infected patients with pulmonary symptoms and culture-proven pulmonary tuberculosis. We compared clinical characteristics and the outcome in 71 patients (49%) with positive sputum smear (SS+), 62 patients (42%) with negative sputum smear/abnormal chest X-ray (SS-/CXR+) and 13 patients (9%) with negative sputum smear/normal chest X-ray (SS-/CXR-). Patients were enrolled from January 1987 to December 1998, and were followed up until December 1999. RESULTS: On hospital admission the three groups of patients examined did not differ significantly in demographic characteristics, degree of immunosuppression or Mycobacterium tuberculosis drug-susceptibility pattern. SS-/CXR- patients were significantly Less LikeLy to present with prolonged fever and dyspnea. Median survival was shorter for SS-/CXR- patients (6.4 months vs 20.2 and 18.8 months in the other two groups). In multivariate analysis, SS-/CXR-patients had a significantly increased risk of death (hazard ratio 3.0, 95% confidence interval, 1.4 to 6.4, p = 0.004) compared to SS+ patients. This increase in risk was no longer statistically significant when initiation of antituberculous therapy within 8 weeks from the collection date of the first specimen yielding M. tuberculosis was included in the multivariate model. CONCLUSION: Decreased survival was observed in HIV-infected patients with pulmonary tuberculosis and with both negative sputum smear and normaL chest X-ray presentation. This may primarily be a resuLt of delayed tuberculosis diagnosis and initiation of antituberculous therapy. The latter delay may also lead to a faster progression of HIV infection in SS-/CXR patients, in whom diagnostic oversight may be common.

Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter, randomized trial.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. METHODS: One hundred and fifty-one patients were randomly assigned to receive either recombinant interferon alpha-2b (nine million units three times per week) and lamivudine (100 mg/daily per os) for 24 weeks or lamivudine alone (100 mg/daily per os) for 52 weeks. Patients were followed up for a further 48 weeks. RESULTS: Sustained HBeAg seroconversion with undetectable serum levels of HBV DNA was observed in 25 of 76 patients (33%) treated with the combination therapy and in 11 of 75 patients (15%) treated with monotherapy (P=0.014). Histological improvement defined as a reduction of at least two points in the inflammation score as compared with pretreatment score was observed in 35 of 76 patients (46%) treated with combination therapy and in 20 of 75 patients (27%) treated with monotherapy (P=0.021). Both therapeutic regimens were well tolerated. CONCLUSIONS: Six-month treatment with interferon alpha-2b and lamivudine in combination appeared to increase the rate of sustained HBeAg seroconversion compared to 1-year lamivudine monotherapy. However, the potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.

Endocarditis caused by Aspergillus species in injection drug users.

Aspergillus endocarditis is a rare event; a very few cases have been reported in injection drug users (IDUs) and patients infected with human immunodeficiency virus (HIV). We report 2 proven cases and 1 highly suggestive case of Aspergillus endocarditis in IDUs, 2 of whom were infected with HIV, and discuss some related clinical and pathogenic aspects.

Primary pulmonary hypertension in HIV patients: a systematic review.

The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.

Clinical manifestation of HIV-related pulmonary hypertension.

In recent years, much more thought has been given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH), which currently represents one of the most severe events during HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnea that will progress to the point of breathlessness at rest. The diagnosis of HRPH can be made only after all etiologies for pulmonary hypertension have been excluded. Echocardiography has been proven to be an extremely useful tool for diagnosing HRPH, and Doppler echocardiography can be used to estimate systolic pulmonary artery pressure and to monitor the effects of therapy. Assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension, since vasoconstriction is a determinant characteristic of this disease. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new, more efficient antiretroviral treatment are introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV+ patients in the future.

Pathogenesis of HIV-related pulmonary hypertension.

Human immunodeficiency virus (HIV)-related pulmonary hypertension (HRPR) is a cardiovascular complication of HIV infection that has been recognized in the last years with increasing frequency. The etiology of HRPH is unknown. All the attempts to isolate HIV on pulmonary vessels in HRPH patients failed, and an indirect role for HIV in this disease has been hypothesized. Current theories on the pathogenesis focus on abnormalities of endothelial and smooth muscle cells of pulmonary vasculature. Endothelial and smooth muscle cell injury could be due to a high production or to a reduced clearance of cytokines in these patients. In fact, in several studies high levels of ET-1, IL-1alpha, IL-6 and PDGF in primary pulmonary hypertension (PPH) and in HRPH have been found. HIV gp 120 could induce the production of these cytokines by a stimulation of monocytes/macrophages. A high alpha1-adrenoreceptors stimulation of pulmonary vessels could be also implicated in the pathogenesis of HRPH. Chronic hypoxia is observed with increased frequency in HIV patients, and this could induce a chronic stimulation of alpha1-receptors of pulmonary vasculature with typical pathological changes. However, only a small percentage of HIV- patients develop HRPH. This observation suggests the existence of an idiosyncratic susceptibility to the development of vascular disease. This susceptibility could have a genetic basis, and might be determined by particular major histocompatibility complex alleles.

Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase.

OBJECTIVE: To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). DESIGN: Prospective study. SETTING: University hospitals and AIDS centres. METHODS: 115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF). RESULTS: A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%). CONCLUSIONS: The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.

Left ventricular filling in young patients affected by insulin-dependent diabetes mellitus: a stress Doppler echocardiography study.

BACKGROUND: The purpose of this study was to analyze diastolic function in two different populations of young patients affected by insulin dependent diabetes mellitus (IDDM), with and without systemic diabetic complications, and to compare the results obtained at rest with those obtained during isometric exercise. METHODS: Forty-five IDDM diabetic patients were studied. On the basis of presence or absence of systemic diabetic complications (nephropathy and retinopathy) patients were divided into two groups. Group I (20 patients) without and Group II (25 patients) with diabetic complications. Diastolic function parameters were measured by Doppler echocardiography at rest and during isometric exercise. The two groups were similar regarding age, metabolic control and insulin dosage but there were significant differences in diastolic and systolic blood pressure and heart rate between the two groups, the patients with complications showing higher values (p < 0.001, p < 0.005, p < 0.01 respectively). RESULTS: Group II already presented at rest alterations of diastolic function parameters respect to Group I with a marked increase of: peak velocity of late left ventricular filling (peakA cm/sec), (60.1 +/- 13.4 versus 48.4 +/- 8.9, p < 0.01); late left ventricular filling integral (A area), (6.5 +/- 1.4 versus 5.0 +/- 0.8, p < 0.05); late left ventricular filling integral over total filling (A area/total area), (0.31 +/- 0.06 versus 0.26 +/- 0.06, p < 0.01). There was a decrease of E/A ratio in Group II versus Group I (1.5 +/- 0.32 versus 1.9 +/- 0.5, p < 0.05). During isometric exercise these changes became even more pronounced in patients with complications and in this group there was a marked decrease of flow integral of early left ventricular filling over total filling (E area/total area), (0.57 +/- 0.09 versus 0.68 +/- 0.07, p < 0.01). CONCLUSIONS: In conclusion, young IDDM patients with complications show an impairment of diastolic function more pronounced than those without. These changes are more evident during isometric exercise. Stress Doppler echocardiography is a reliable tool to detect early diastolic dysfunction in diabetic patients.

Negative predictors of survival in HIV-infected patients with culture-confirmed pulmonary tuberculosis.

We performed a retrospective study based on chart review of 118 HIV-infected patients with culture-confirmed pulmonary TB, in which M. tuberculosis isolates were tested for drug susceptibility. Patients were enrolled in the period January 1987 to December 1996 and followed until September 1997. The median survival for the entire cohort was 15.2 months with a 1-year survival rate of 57%. Prior AIDS-defining illness, low CD4 count (< 200/mm3), not having received antituberculous therapy with at least two drugs to which M. tuberculosis was susceptible in vitro, starting within four weeks of diagnosis, treatment duration of less than three weeks and multidrug resistant tuberculosis were each independently associated with decreased survival in multivariate analysis.

[Mycobacterium tuberculosis drug resistance in patients with HIV and pulmonary tuberculosis infections in Rome: 1987-1996]. / La farmaco-resistenza di Mycobacterium tuberculosis nei pazienti con infezione da HIV e tubercolosi polmonare in Roma: 1987-1996.

A retrospective chart review was performed on 118 HIV infected patients with pulmonary tuberculosis hospitalized between 1987 and 1996 in a tertiary care center for Infectious Diseases in Rome. The aims of this study were: a) to evaluate global prevalence of and risk factors for drug-resistant Mycobacterium tuberculosis and multidrug resistant tuberculosis; b) to assess trends in prevalence of drug-resistant tuberculosis over the 10-year study period. Prevalence of drug resistance of first Mycobacterium tuberculosis isolates was tested on Lowenstein-Jensen medium with the proportional method. Of the 118 patients studied, 83 had never been treated for tuberculosis and 35 had already been treated for at least 1 month. The overall prevalence of resistance to one or more drugs was 25% (17% in never treated patients vs 46% in already treated patients; p = 0.002). Five percent of isolates were resistant to both isoniazid and rifampin (1% in never treated patients vs 14% in already treated patients; p = 0.008). Resistance rates to individual drugs were: isoniazid 14%, rifampin 8%, ethambutol 0%, streptomycin 13%. During the study period no significant variations in prevalence of drug-resistant tuberculosis were found. In our area, empiric therapy should include 4 drugs: as well as isoniazid, rifampin and pyrazinamide, we recommend ethambutol. Surveillance of drug-resistant tuberculosis is needed. Directly observed therapy should be considered for HIV patients in order to prevent increases in drug resistance, relapses, and treatment failures.

Role of human immunodeficiency virus in primary pulmonary hypertension--case reports.

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

Left ventricular filling in young patients affected by insulin-dependent diabetes mellitus: a stress Doppler echocardiographic study.

BACKGROUND: The purpose of this study was to analyze diastolic function in two different populations of young patients affected by insulin dependent diabetes mellitus (IDDM), with and without systemic diabetic complications, and to compare the results obtained at rest with those obtained during isometric exercise. METHODS: Forty-five IDDM diabetic patients were studied. On the basis of presence or absence of systemic diabetic complications (nephropathy and retinopathy) patients were divided into two groups. Group I (20 patients) without and Group II (25 patients) with diabetic complications. Diastolic function parameters were measured by Doppler echocardiography at rest and during isometric exercise. The two groups were similar regarding age, metabolic control and insulin dosage but there were significant differences in diastolic and systolic blood pressure and heart rate between the two groups, the patients with complications showing higher values (p < 0.001, p < 0.005, p < 0.01 respectively). RESULTS: Group II already presented at rest alterations of diastolic function parameters respect to Group I with a marked increase of: peak velocity of late left ventricular filling (peakA cm/sec), (60.1 +/- 13.4 versus 48.4 +/- 8.9, p < 0.01); late left ventricular filling integral (A area), (6.5 +/- 1.4 versus 5.0 +/- 0.8, p < 0.05); late left ventricular filling integral over total filling (A area/total area), (0.31 +/- 0.06 versus 0.26 +/- 0.06, p < 0.01). There was a decrease of E/A ratio in Group II versus Group I (1.5 +/- 0.32 versus 1.9 +/- 0.5, p < 0.05). During isometric exercise these changes became even more pronounced in patients with complications and in this group there was a marked decrease of flow integral of early left ventricular filling over total filling (E area/total area), (0.57 +/- 0.09 versus 0.68 +/- 0.07, p < 0.01). CONCLUSIONS: In conclusion, young IDDM patients with complications show an impairment of diastolic function more pronounced than those without. These changes are more evident during isometric exercise. Stress Doppler echocardiography is a reliable tool to detect early diastolic dysfunction in diabetic patients.

Pulmonary cryptosporidiosis in patients with acquired immunodeficiency syndrome.

Several reports have showed Cryptosporidium species as a cause of intractable diarrhea and malabsorption in patients with acquired immunodeficiency syndrome (HIV). A case of chronic diarrhea in a drug addict woman associated with a symptomatic interstitial pulmonary infection due to Cryptosporidium parvum is described. This unusual C. parvum spread into the bronchial tree is underlined and a survey of the literature is made.

Alteration of left ventricular filling evaluated by Doppler echocardiography as a potential marker of acute rejection in orthotopic heart transplant.

To evaluate the changes in left ventricular (LV) filling associated with acute cardiac rejection, serial Doppler echocardiographic (ED) examination were performed on the same day as endomyocardial biopsy (EMB) in 40 patients who underwent orthotopic transplantation. The diameters and wall thickness of the left ventricle were measured. The indexes of LV filling in the following parameters were measured by pulsed Doppler: isovolumic relaxation time (IRT), peak early mitral flow velocity (V max E), and pressure half-time (PHT). The patients were classified into three groups on the basis of EMB: Group I (19 patients without rejection), Group II (11 patients with mild or moderate rejection), and Group III (10 patients with severe rejection). In Group III rejection was associated with a significant increase of posterior wall thickness (P < 0.05), with a decrease of IRT (P < 0.05), and an increase of V max E velocity (P < 0.01) in comparison with Group I. In Group II, Doppler indexes were not statistically significant in comparison with Groups I and II. In conclusion, in transplant patients, a diagnosis of acute rejection can be suspected in severe rejection by use of echocardiography when the diagnosis is based on a multiparametric evaluation of different ED indexes (m-mode and Doppler indexes). Doppler echocardiography is a method with an excellent specificity but insufficient sensitivity; this is due to the influence of recipient atrial contraction timing on Doppler indexes of LV filling.