Herbal and dietary supplement induced liver injury leading to hepatitis-associated severe aplastic anemia: A case report.

Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use continues to increase. It is not only important to recognize HDS as etiology, but also for healthcare providers to carefully monitor these patients after resolution of liver injury for the development of HAAA.

Pediatric Acute Liver Failure Secondary to Autoimmune Hepatitis in an Infant With Thrombocytopenia-Absent Radius (TAR) Syndrome: A Case Report.

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal antibodies, and antibody-mediated rejection. Ultimately, these complications led to graft failure, severe sepsis, and death. This case highlights a new association of TAR syndrome with AIH and PALF and a potentially aggressive nature of AIH both pre- and post-transplant.

Nutritional Recovery of Children With HIV and Severe Acute Malnutrition Attending an Outpatient Therapeutic Care Program.

BACKGROUND: Despite significant morbidity and mortality from HIV and severe acute malnutrition (SAM) among children in sub-Saharan Africa, research is lacking in these children. We describe the proportion of children living with HIV with SAM achieving recovery, the factors associated with recovery, and time to recovery in an outpatient therapeutic care program. SETTING AND METHODS: This is a retrospective observational study of children with SAM and HIV on antiretroviral therapy (6 months-15 years), enrolled in outpatient therapeutic care from 2015 to 2017 at a pediatric HIV clinic in Kampala, Uganda. SAM diagnosis and recovery by 120 days after enrollment were determined per World Health Organization guidelines. Cox-proportional hazards models were used to determine predictors of recovery. RESULTS: Data from 166 patients were analyzed (mean age 5.4 years, SD 4.7). Outcomes showed 36.1% recovered, 15.6% were lost to follow-up, 2.4% died, and 45.8% failed. Average time to recovery was 59.9 days (SD 27.8). Patients 5 years or older were less likely to recover (crude hazard ratio [CHR] = 0.33, 95% CI: 0.18 to 0.58). In multivariate analysis, febrile patients were less likely to recover (adjusted hazard ratio = 0.53, 95% CI: 0.12 to 0.65). Patients with CD4 count of 200 or less at enrollment were less likely to recover (CHR = 0.46, 95% CI: 0.22 to 0.96). CONCLUSIONS: Despite treatment with antiretroviral therapy for children living with HIV, we observed poor rates of recovery from SAM, below the international target of >75%. Moreover, patients 5 years and older, fever, or low CD4 at diagnosis of SAM may require more intense therapy or closer monitoring than their counterparts.

A Liver Biopsy Validation Pilot Study of Shear Wave Elastography, APRI, FIB-4, and Novel Serum Biomarkers for Liver Fibrosis Staging in Children With Chronic Viral Hepatitis.

As liver biopsy in children poses inherent risks, noninvasive measures of liver fibrosis are needed. This was a cross-sectional, liver biopsy validation pilot study of 16 participants evaluating the ability of shear wave elastography, aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors, and novel serum biomarkers to stage liver fibrosis in children with chronic hepatitis B or C. There was very high intrasegmental shear wave speed variation in our participants and little correlation with fibrosis. APRI and monocyte chemoattractant protein (MCP-1) were higher in fibrosis stage F2-3 versus F0-1 (P = .02, P = .06, respectively). Soluble Fas (sFas) was lower in F2-3 versus F0-1 (P = .046). A logistic regression analysis calculated by (APRI × MCP-1)/sFas demonstrated an area under the receiver operating characteristic curve of 0.92 (P < .001), suggesting that this combination can differentiate fibrosis stage F0-1 from F2-3 in children with chronic viral hepatitis.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

OBJECTIVES: HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. METHODS: The study was a retrospective cohort study (study period 2004-2018). Cases of HIV + and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV + controls without SCD (HIV+/SCD-). RESULTS: Thirty-five HIV+/SCD + subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6 years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD + had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P = 0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD + and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD + cohort (P = 0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD + cohort showed a more rapid rise and higher total CD4 count (P = 0.012, regression analysis). CONCLUSION: The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD + achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

OBJECTIFS: Le VIH et la drépanocytose (SCD) sont des causes importantes de morbidité et de mortalité en Afrique subsaharienne. Compte tenu de leurs rôles distincts dans la dérégulation immunitaire, notre objectif était de caractériser l'impact du SCD sur la présentation et la progression du VIH pédiatrique. MÉTHODES: Etude de cohorte rétrospective (période d'étude 2004-2018). Les cas de patients VIH+ atteints de SCD (VIH+/SCD+) ont été obtenus par analyse des dossiers électroniques dans une clinique pédiatrique du VIH à Kampala, en Ouganda et appariés dans une proportion 1:3 avec des témoins VIH+ sans SCD (VIH+/SCD-). RÉSULTATS: 35 sujets VIH+/SCD+ et 95 témoins VIH+/SCD- ont été analysés (39% de femmes (51/130), 3,6 ans d'âge (SD3,9)). Au départ, le stade clinique de l'OMS (64% de la cohorte totale au stade III/IV) et l'état nutritionnel (9,4% de malnutrition aiguë sévère) étaient similaires pour les deux groupes, tandis que les VIH+/SCD+ avaient un nombre de CD4 de base plus élevé mais non significatif (1036 (DS, 713) vs 849 (DS, 638) cellules/microlitre, p = 0,20, test t bilatéral). Il y a eu 19 décès, 6 (17%) VIH+/SCD+ et 13 (14%) VIH+/SCD-, avec des modèles non ajustés/ajustés ne montrant aucune différence significative. La progression nutritionnelle et la progression du stade clinique n'ont montré aucune différence significative entre les groupes. L'analyse de Kaplan-Meier a montré un taux d'échecs de traitement plus lent dans la cohorte VIH+/SCD+ (p = 0,11, test de survie log-rank). L'analyse de la trajectoire a montré que dans la période analysée, la cohorte VIH+/SCD+ a montré une augmentation plus rapide et un nombre total de CD4 plus élevé (p = 0,012, analyse de régression). CONCLUSION: L'étude suggère que SCD n'affecte pas négativement la progression du VIH chez les patients sous ART. De plus, les patients VIH+/SCD+ ont atteint un nombre plus élevé de CD4 et moins d'échecs de traitement du VIH, ce qui suggère que les effets physiologiques dus à la SCD pourraient atténuer la progression du VIH.

Cryptococcal meningitis and immune reconstitution inflammatory syndrome in a pediatric patient with HIV after switching to second line antiretroviral therapy: a case report.

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.