Heterogeneous photocatalytic degradation of antiviral drug didanosine mediated by rose bengal and TiO2 nanoparticles.

There is a great concern among the researcher to remove the problem of the persistent organic pollutants in wastewater. Pharmaceutical agrochemical and personal care products are generally considered Persistent organic pollutants. Therefore, it is a matter of concern to develop new techniques how to remove these pollutants safely at low cost. This study mainly focuses on the commonly used antiviral drug didanosine and one most commonly used dye rose bengal. In this study, an organic dye rose bengal and TiO2 nanoparticles have been used in combination with UV light to achieve the photodegradation of selected pharmaceutical products and the dye was also degraded by using TiO2 Nanoparticles. The formation of three oxidation products was detected by using a very popular separation technique thin layer and column chromatography. The isolated photoproduct was characterized by using advanced characterization techniques like FTIR (Fourier transform infrared spectroscopy), UV Spectroscopy, and Proton and 13C NMR (Nuclear Magnetic Resonance spectroscopy). The role of singlet oxygen as an active species in this reaction was confirmed by using D2O as a reaction medium. The role of singlet oxygen in this photochemical reaction was also established by the addition of sodium azide. The TiO2 nanophotocatalyst efficiently degrade the didanosine and rose bengal in the presence of the UV light. In the TiO2-induced photocatalytic degradation of didanosine and dyes, the hydroxyl and superoxide radical anion play a prominent role. The finding of this manuscript is very useful to develop an efficient low-cost method for the treatment of wastewater contaminated by antiviral drugs, similar pharmaceutical products and dyes. This study was also very helpful to establish a plausible mechanism behind the phototoxicity of the didanosine.

Portal Hypertension Due to Hepatoportal Sclerosis in an HIV-Positive Patient Secondary to Didanosine Use.

Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an HIV-infected patient with portal hypertension due to hepatoportal sclerosis who presented with hematemesis at the emergency department (ED). CT angiography of the abdomen and pelvis with and without contrast revealed a diminutive portal vein with corresponding massive lower esophageal varices and superior mesenteric vein to the right gonadal vein varices. Esophagogastroduodenoscopy (EGD) revealed grade II varices were found in the lower third of the esophagus, for which the patient's symptoms improved with emergency endoscopic band ligation, octreotide and didanosine discontinuation. Our case demonstrates a rare complication that can occur with continued didanosine use in an HIV-positive patient. We highlight the need for a standard diagnostic upper gastrointestinal endoscopy to screen for portal hypertension and high-risk esophageal varices in patients with long-term didanosine use as seen in our patient.

Synthesis, in silico and in vitro anti-cancer studies of phosphorylated derivatives of didanosine targeting MDA-MB-231 breast cancer cell lines.

A series of new phosphorylated derivatives of didanosine were designed, synthesized and evaluated their anticancer effects on human breast cancer cells. Their binding affinities were evaluated against aromatase enzyme and the molecular docking studies demonstrated that 9a, 9h and 9i exhibited high binding interactions than the parent molecule (ddI) and other derivatives; evaluated the aromatase enzyme inhibition. The cell viability, cell proliferation, lactate dehydrogenase showed potential anti-proliferative in dose dependent manner, these results were well correlated with hoesch stain and DNA fragmentation on MDA-MB-231 breast cancer cell lines. Cytotoxicity results disclosed that tryptophan amino acid ester substituted derivative 9i showed potential cell death against MDA-MB-231 cancer cell lines. Furthermore, compound 9i has great potential significance for further investigations (in vivo).

Sustainable Protocol for the Synthesis of 2',3'-Dideoxynucleoside and 2',3'-Didehydro-2',3'-dideoxynucleoside Derivatives.

An improved protocol for the transformation of ribonucleosides into 2',3'-dideoxynucleoside and 2',3'-didehydro-2',3'-dideoxynucleoside derivatives, including the anti-HIV drugs stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), was established. The process involves radical deoxygenation of xanthate using environmentally friendly and low-cost reagents. Bromoethane or 3-bromopropanenitrile was the alkylating agent of choice to prepare the ribonucleoside 2',3'-bisxanthates. In the subsequent radical deoxygenation reaction, tris(trimethylsilyl)silane and 1,1'-azobis(cyclohexanecarbonitrile) were used to replace hazardous Bu3SnH and AIBN, respectively. In addition, TBAF was substituted for camphorsulfonic acid in the deprotection step of the 5'-O-silyl ether group, and an enzyme (adenosine deaminase) was used to transform 2',3'-dideoxyadenosine into 2',3'-dideoxyinosine (ddI) in excellent yield.

A Rare Case of Didanosine-Induced Mid-Peripheral Chorioretinal Atrophy Identified Incidentally 11 Years after the Drug Cessation.

Objective: This article aims to describe a unique case of didanosine-induced retinal degeneration that was discovered 11 years after the drug withdrawal. Case report: The patient is a 42-year-old woman with a medical history of HIV and hepatitis C virus since 2004. She has been prescribed antiretroviral therapy since then. For the first seven years (2004-2011), the patient was prescribed a combination therapy consisting of didanosine, efavirenz, and lamivudine. The protocol was changed to atripla (efavirenz, emtricitabine, and tenofovir) from 2011 to 2021. Recently (October 2021-January 2021), the patient was prescribed eviplera (rilpivirin, emtricitabine, and tenofovir). In addition, her past medical history revealed Gougerot-Sjogren syndrome and rheumatoid arthritis. She was prescribed hydroxychloroquine (HCQ) (2009-2021) at a dose of 400 mg daily. She had no vision complaint. Results: During her routine HCQ screening at the eye clinic, University Hospital Bretonneau, Tours, France, the widefield colour fundus photograph showed well-defined symmetric mid-peripheral areas of chorioretinal atrophy sparing the posterior pole of both eyes. Furthermore, the widefield fundus autofluorescence illustrated mid-peripheral round well-demarcation hypoautofluorescent areas of chorioretinal atrophy of both eyes. Conversely, the macular optical coherence tomography (OCT) was normal. Many of her drugs are known to be associated with retinopathy such as HCQ, tenofovir, efavirenz, and didanosine. Because our data corroborate peripheral retinal damage rather than posterior pole damage, this case report is compatible with didanosine-induced retinopathy rather than HCQ, efavirenz, or tenofovir retinal toxicity. Conclusions: All HIV patients who are presently or were previously on didanosine therapy should have their fundus examined utilising widefield fundus autofluorescence and photography.

Didanosine-Associated Retinal Toxicity in a Patient With a Mutation in the CRB1 Gene.

Purpose: This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene. Methods: Case report. Results: A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area. Conclusions: This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.

Didanosine-induced Retinopathy: New Insights with Long-term Follow-up.

INTRODUCTION: Didanosine is an adenosine analog, part of the nucleoside reverse-transcriptase inhibitor family. Since the description of didanosine-induced retinopathy in the early 1990s, little is known about the progression of this toxic retinopathy and the putative underlying mitochondrial defect. OBJECTIVES: We report long-term follow-up for cases of didanosine-induced retinopathy and discuss a new hypothesis for pathophysiology based on the alteration of endogenous adenosine on the photoreceptor outer segment turnover and phagocytosis by the retinal pigment epithelium. METHODS: Ophthalmic data from six cases (12 eyes) of didanosine-induced retinopathy from a single institution were retrospectively analyzed. RESULTS: All patients displayed bilateral retinal alterations in the mid-periphery. Despite didanosine discontinuation, patients with advanced areas of patchy chorioretinal atrophy appeared to have a faster progression than those with limited lesions. Full-field electroretinogram revealed generalized rod-cone dysfunction in most cases that remained stable over time. CONCLUSION: We propose new guidelines including early screening and long-term observations.

Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature.

Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients. Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms "HIV," "AIDS," "ritonavir," "didanosine," "maculopathy," "retinopathy," "visual loss," and "toxicity" to retrieve the appropriate literature on the subject. Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treatment. Patient 2: A 55-year-old man complained of slowly progressive peripheral visual field constriction for the past 5 years. History disclosed didanosine therapy for 13 years, however, stopped 4 years before the onset of visual symptoms. No alteration of therapy was offered to patient 2 as didanosine therapy was interrupted 9 years previously. Since 2011, 11 cases of ritonavir maculopathy have been reported in the literature. Relentless worsening of vision was reported in 3/7 patients despite cessation of ritonavir therapy. Didonasine peripheral retinopathy was first described in 1992, and a total of 24 patients have been reported since. Relentlessly progressive peripheral retinopathy was diagnosed despite the previous cessation of therapy in 14 patients. Conclusion: Ritonavir causes a slowly progressive atrophic maculopathy, and didanosine toxicity results in a relentlessly progressing peripheral atrophic retinopathy. The relentless progression of both toxic retinopathies reflects permanent alterations of the retinal metabolism by these medications. Both ritonavir and didanosine toxic retinopathies are rare events, but their clinical presentation is highly specific.

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist.

In vitro interaction of nucleoside reverse transcriptase inhibitor, didanosine with calf-thymus DNA: Insights from spectroscopic studies.

Many antivirals interact with DNA and alter their expression profile. Thus, it is necessary to understand the binding mode. Didanosine, a nucleoside reverse transcriptase inhibitor, is used to treat HIV infection in patients with or without acquired immunodeficiency syndrome. Understanding the mechanism of interaction of this nucleoside reverse transcriptase inhibitor with DNA can prove useful in the development of a rational drug designing system. In vitro studies (UV-vis, fluorescence, and viscometry techniques) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) show that didanosine drug interacts with calf-thymus DNA (ct-DNA) via partial intercalative binding mode. UV-visible spectroscopy confirmed the formation didanosine-DNA complex with a binding strength of about 1.5 × 105 M-1 thus indicating their biological worth. Dye displace experiments and viscometry confirmed that didanosine partially intercalates toward DNA molecules. Negative value of Gibb's-free energy change revealed that the process is spontaneous. The thermodynamic parameters such as enthalpy change (ΔH) and entropy change (ΔS) showed that the acting forces between didanosine and ct-DNA mainly included hydrophobic interactions.

The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds.

The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto's molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT < 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.

Design, synthesis and DNA interaction studies of new fluorescent platinum complex containing anti-HIV drug didanosine.

Forming coordination complexes with nucleoside analogues may be helpful in studying anti-tumour activity of them. Therefore, to improve the clinical efficacy of nucleoside analogue and design new ones, a new fluorescent platinum (Pt) complex with anti-human immunodeficiency virus drug didanosine (ddI); K[PtCl(OCH3)2(ddI)]; was synthesized and characterized. The ultraviolet-visible (UV-vis) spectroscopy, infrared, thermogravimetric analysis, mass assignments and elemental analysis confirmed the preparation of the complex. The molecular ion peaks seen at the positive mass spectrum of Pt complex confirm coordination of the drug to metal centre. The interaction of this complex with calf thymus DNA (ct-DNA) was studied using several spectroscopic techniques such as UV absorption, fluorescence spectroscopy and dynamic viscosity measurements. Hyperchromism of the band in the UV-vis spectra and the intrinsic binding constant (0.56 ± 0.25) × 104 M-1, decreasing in Hoechst-DNA fluorescence by adding Pt complex concentration and also relatively small changes in DNA viscosity indicated that this complex could interact as a groove-binder. According to the UV spectra and the fluorescence quenching of the complex in our case seems to be primarily caused by complex formation between the Pt complex and DNA. The thermodynamic parameters showed that hydrogen bond and van der Waals interactions play main roles in the binding of Pt complex to ct-DNA. The free energy values are negative, showing the spontaneity of the Pt complex-DNA binding. The docking simulation was performed and the results confirm a preference of groove site of synthesized complex on DNA helix. The knowledge gained from this study will be helpful to further understand the DNA binding mechanism and can also provide much fruitful information for designing a new type of anti-cancer drugs.Communicated by Ramaswamy H. Sarma.

Risk of cancer in children exposed to antiretroviral nucleoside analogues in utero: The french experience.

All nucleoside analogues for treating HIV infection, due to their capacity to integrate into and alter human DNA, are experimentally genotoxic to some extent. The long-term oncogenic risk after in utero exposure remains to be determined. Cancer incidence in uninfected children exposed to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) was evaluated, by cross-checking against the National Cancer Registry, in the French perinatal study of children born to HIV+ mothers. Twenty-one cancers were identified in 15,163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero between 1990 and 2014. Five of these children were exposed to zidovudine monotherapy, and 15 to various combinations, seven of which included didanosine. Overall, the total number of cases was not significantly different from that expected for the general population (SIR = 0.8[0.47-1.24]), but the number of cases after didanosine exposure was twice that expected (SIR = 2.5 [1.01-5.19]). Didanosine accounted for only 10% of prescriptions but was associated with one-third of cancers. In multivariate analysis, didanosine exposure was significantly associated with higher risk (HR = 3.0 [0.9-9.8]). This risk was specifically linked to first-trimester exposure (HR = 5.5 [2.1-14.4]). Three cases of pineoblastoma, a very rare cancer, were observed, whereas 0.03 were expected. Two were associated with didanosine exposure. Despite reassuring data overall, there is strong evidence to suggest that didanosine displays transplacental oncogenicity. These findings cannot be extrapolated to other NRTIs, but they highlight the need for comprehensive evaluations of the transplacental genotoxicity of this antiretroviral class. Environ. Mol. Mutagen., 60:404-409, 2019. © 2017 Wiley Periodicals, Inc.

Regulating the alky chain length of fatty acid-didanosine prodrugs and evaluating its role in albumin binding.

Rational design of prodrugs for efficient albumin binding shows distinct advantages in drug delivery in terms of drug availability, systemic circulation, and potential targeting effect. And fatty acids are good candidates due to their high affinity to albumin. However, how the alkyl chain length of fatty acids affects the binding dynamics between prodrugs and albumin, despite its importance, is still unclear. In the present study, three prodrugs of didanosine (DDI) and fatty acids were designed and synthesized to evaluate the effect of the alkyl chain length on prodrug-albumin binding process, including capric acid-didanosine (CA-DDI), myristic acid-didanosine (MA-DDI), and stearic acid-didanosine (SA-DDI). The binding dynamics between these prodrugs with bovine serum albumin (BSA) were studied by fluorometry, circular dichroism (CD), UV analysis, and molecular docking. It turned out that DDI itself showed poor binding affinity to BSA. In contrast, CA-DDI, MA-DDI, and SA-DDI demonstrated significantly improved binding affinity. Interestingly, the binding affinity between DDI prodrugs and BSA was correlated with the alkyl chain length of fatty acids, and the binding constant significantly increased with the extension of alkyl chain length (KCA-DDI = 5.86 × 103 M-1, KMA-DDI = 8.57 × 103 M-1, and KSA-DDI = 11.42 × 103 M-1 at 298 K).

Hipertensión portal no cirrótica por didanosina: Un caso infrecuente / Non-cirrhotic portal hypertension due to didanosina: A rare case

El compromiso hepático es usualmente visto en pacientes con infección por el virus de inmunodeficiencia humana (VIH), sobretodo en pacientes coinfectados con el virus de la hepatitis B o C, con el abuso de alcohol, etc. Sin embargo, existe un grupo de pacientes que desarrolla compromiso hepático e hipertensión portal de causa no específica. La hipertensión portal no cirrótica (HPNC) es un desorden hepático descrito recientemente, potencialmente grave, que ha sido reportado en pacientes infectados por el VIH con terapia antirretroviral de gran actividad (TARGA), específicamente didanosina (DDI). La fisiopatología involucra al agente infeccioso (VIH) y a su tratamiento (TARGA), pues ambas generan una venulopatía prehepática portal. Además, la infección por el VIH genera un estado protrombótico por deficiencia de proteína S conllevando a la obliteración de pequeñas vénulas hepáticas. Se ha postulado a la didanosina como un cofactor en la patogénesis del HPNC. Todo ello conlleva a que en muchas de las biopsias hepáticas se evidencie una hiperplasia nodular regenerativa. Se reporta el caso de una paciente con infección del VIH y en tratamiento con DDI de larga data que debuta con hemorragia digestiva alta (HDA) y ascitis como consecuencia de la HPNC, cuyo diagnóstico fue corroborado por biopsia. No existe reporte de casos del tema en nuestro país

Liver involvement is usually seen in patients infected with the human immunodeficiency virus (HIV), especially in patients coinfected with hepatitis B or C, in alcohol abuse, etc. However, there is a group of patients who develop liver involvement and portal hypertension of unspecified cause. Non-cirrhotic portal hypertension (NCPH) is a liver disorder recently described, but potentially serious. It has been reported in HIV-infected patients with highly active antiretroviral therapy (HAART), specifically didanosine (DDI). The pathophysiology involves the infectious agent (HIV) and its treatment (HAART), since both generate a pre-hepatic portal venulopathy. Similarly, HIV infection produces a prothrombotic state by protein S deficiency leading to the obliteration of small hepatic venules. It has been postulated that DDI as a cofactor in the pathogenesis of NCPH. All this leads that many of the liver biopsies show nodular regenerative hyperplasia. We present the case of a HIV-infected patient who was treated with a longstanding DDI. She developed upper gastrointestinal bleeding (UGB) and ascites due to NCPH, whose diagnosis was confirmed by biopsy. However, there is no similar study in our country

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.

Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken.

A series of novel phosphorylated derivatives of didanosine were designed and docking studies were performed with a fusion protein of the Newcastle disease virus (NDV), to develop antiviral compounds against NDV. Based on the docking scores and binding affinities, three derivatives were selected. These compounds were synthesized and characterized by IR, (1) H, (13) C, (31) P, and CHN analysis and mass spectra. They were assessed for their in vitro antiviral activity in DF-1 cells; DDI-10 showed better antiviral activity as evidenced by significant reduction in plaque formation and cytopathic effects. DDI-10 was further evaluated in NDV-infected chicken; the survival rates and antioxidant enzyme levels in brain, liver, and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised, and lipid peroxidation and HA titer levels were decreased upon treatment with 1.5 mg/kg body weight of DDI-10 than with 3 mg/kg body weight of DDI. Further histopathological alterations in NDV-infected tissues were restored in chicken treated with DDI-10. Thus, based on the results from in silico, in vitro, and in vivo assays, the novel phosphorylated DDI-10 might be considered as potent antiviral compound for NDV infection in chicken.

Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study.

AIM: To identify significant liver disease [including nodular regenerative hyperplasia (NRH)] in asymptomatic Didanosine (DDI) exposed human immunodeficiency virus (HIV) positive patients. METHODS: Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography (TE). Those with alanine transaminase (ALT) above upper limit normal and/or TE > 7.65 kPa underwent ultrasound scan (U/S). Patients with: (1) abnormal U/S; or (2) elevated ALT plus TE > 7.65 kPa; or (3) TE > 9.4 kPa were offered trans-jugular liver biopsy (TJLB) with hepatic venous pressure gradient (HVPG) assessment. RESULTS: Ninety-nine patients were recruited, median age 50 years (range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years (range 0.5-14.6). Eighty-one had a valid TE readings (interquartile range/score ratio < 0.3): 71 (88%) < 7.65 kPa, 6 (7%) 7.65-9.4 kPa and 4 (6%) > 9.4 kPa. Seventeen (17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mmHg. Commonest histological findings were steatosis (n = 6), normal architecture (n = 4) and NRH (n = 2), giving a prevalence of previously undiagnosed NRH of 2% (95%CI: 0.55%, 7.0%). CONCLUSION: A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.

Noncirrhotic portal hypertension in a human immunodeficiency virus (HIV) infected adolescent / Hipertensão portal não cirrótica em adolescente infectado pelo vírus da imunodeficiência humana (HIV)

OBJECTIVE: To alert the pediatrician who is following up HIV-infected patients about the possibility of non-cirrhotic portal hypertension (NCPH) in this period of life, in order to avoid the catastrophic consequences of this disease as bleeding esophageal varices. CASE DESCRIPTION: A 13 years old HIV-infected patient by vertical route was receiving didanosine (ddI) for 12 years. Although the HIV viral load had been undetectable for 12 years, this patient showed gradual decrease of CD4+ T cells, prolonged thrombocytopenia and high alkaline phosphatase. Physical examination detected splenomegaly, which triggered the investigation that led to the diagnosis of severe liver fibrosis by transient elastography, probably due to hepatic toxicity by prolonged use of ddI. COMMENTS: This is the first case of NCPH in HIV-infected adolescent described in Brazil. Although, the NCPH is a rare disease entity in seropositive patients in the pediatric age group, it should be investigated in patients on long-term ddI or presenting clinical and laboratories indicators of portal hypertension, as splenomegaly, thrombocytopenia and increased alkaline phosphatase.

OBJETIVO: Alertar o pediatra sobre a ocorrência de hipertensão portal não cirrótica (HPNC) na faixa etária pediátrica, no sentido de evitar as consequências catastróficas dessa doença, como o sangramento de varizes de esôfago. DESCRIÇÃO DO CASO: Paciente de 13 anos, infectado pelo HIV por via vertical, recebia esquema antirretroviral com didanosina (ddI) havia 12 anos. Apesar do controle adequado da replicação viral, com carga viral do HIV indetectável havia 12 anos, passou a apresentar diminuição gradativa dos linfócitos TCD4+, trombocitopenia prolongada e fosfatase alcalina elevada. O exame físico detectou esplenomegalia, que desencadeou o processo de investigação e culminou no diagnóstico de fibrose hepática acentuada pela elastografia, por provável toxicidade hepática devido ao uso prolongado de ddI. COMENTÁRIOS: Este é o primeiro caso de HPNC em adolescente infectado pelo HIV descrito no Brasil. Embora seja entidade mórbida rara em pacientes soropositivos para o HIV na faixa etária pediátrica, deve ser investigada nos pacientes em uso prolongado de ddI ou que apresentem indicadores clínicos e/ou laboratoriais de hipertensão portal, como esplenomegalia, trombocitopenia e aumento de fosfatase alcalina.

[Noncirrhotic portal hypertension in a human immunodeficiency virus (HIV) infected adolescent]. / Hipertensão portal não cirrótica em adolescente infectado pelo vírus da imunodeficiência humana (HIV).

OBJECTIVE: To alert the pediatrician who is following up HIV-infected patients about the possibility of non-cirrhotic portal hypertension (NCPH) in this period of life, in order to avoid the catastrophic consequences of this disease as bleeding esophageal varices. CASE DESCRIPTION: A 13 years old HIV-infected patient by vertical route was receiving didanosine (ddI) for 12 years. Although the HIV viral load had been undetectable for 12 years, this patient showed gradual decrease of CD4+ T cells, prolonged thrombocytopenia and high alkaline phosphatase. Physical examination detected splenomegaly, which triggered the investigation that led to the diagnosis of severe liver fibrosis by transient elastography, probably due to hepatic toxicity by prolonged use of ddI. COMMENTS: This is the first case of NCPH in HIV-infected adolescent described in Brazil. Although, the NCPH is a rare disease entity in seropositive patients in the pediatric age group, it should be investigated in patients on long-term ddI or presenting clinical and laboratories indicators of portal hypertension, as splenomegaly, thrombocytopenia and increased alkaline phosphatase.