Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

Lean Indian patients with non-alcoholic fatty liver disease (NAFLD) have less metabolic risk factors but similar liver disease severity as non-lean patients with NAFLD.

INTRODUCTION: Although most patients with NAFLD are obese or overweight, some are lean with normal BMI. Our aim was to assess differences in clinicopathological profile and liver disease severity among lean and non-lean NAFLD. METHODS: Data of 1040 NAFLD patients over last 10 years was analysed. BMI < 23 kg/m2 categorised lean patients. Non-invasive assessment of steatosis was done by ultrasound and controlled attenuation parameter (CAP) while fibrosis was assessed with FIB-4 and liver stiffness measurement (LSM). FibroScan-AST (FAST) score was used for non-invasive prediction of NASH with significant fibrosis. Histology was reported using NASH-CRN system. RESULTS: 149 (14.3%) patients were lean while 891 (85.7%) patients were non-lean. Diabetes mellitus [25 (16.7%) vs 152 (17.05%), p > 0.99], elevated triglycerides [81 (54.3%) vs 525 (58.9%), p = 0.33] and low HDL [71(47.6%) vs 479(53.7%), p = 0.18] were observed in a similar proportion. Lean patients were less likely to have central obesity [72 (48.3%) vs 788 (88.4%), p < 0.001], hypertension [16 (10.7%) vs 239(26.8%), p < 0.001] and metabolic syndrome [21 (14.09%) vs 290 (32.5%), p < 0.001]. No difference in steatosis assessment was noted using ultrasound (p = 0.55) or CAP (0.11). FAST [0.38 (0.18-0.66) vs 0.39 (0.27-0.73), p = 0.53], FIB-4 [1.08 (0.65-1.91) vs 1.09 (0.66-1.94), p = 0.94] and LSM [6.1 (4.8-7.9) vs 6.2 (4.7-8.6), p = 0.19) were similar. Liver biopsy was available in 149 patients [lean: 19 (12.7%), non-lean: 130 (87.3%)]. There was no difference in the number of patients with NASH [4 (21.05%) vs 20 (15.3%), p = 0.51], significant fibrosis [2 (10.5%) vs 32 (24.6%), p = 0.25] or advanced fibrosis [1 (5.26%) vs 18 (13.84%), p = 0.47]. CONCLUSION: Although metabolic co-morbidities are less common, there is no difference in liver disease severity among both groups.

Efficacy and safety of pan-genotypic sofosbuvir and velpatasvir in patients with hepatitis C and HIV coinfection on dolutegravir-based antiretroviral therapy.

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.

An Enigmatic Case of Jaundice and Photosensitivity in an Adolescent.

Erythropoietic protoporphyria (EPP) presents with nonblistering photosensitivity. Hepatobiliary manifestations are seen in around 5% cases and include cholelithiasis, elevations in liver enzymes, progressive jaundice, and end-stage liver disease. The diagnosis is suspected based on clinical features and elevated erythrocyte metal-free protoporphyrin and confirmed by genetic analysis showing loss-of-function mutations in the ferrochelatase (FECH) gene. We present an adolescent boy who presented with jaundice and photosensitivity with the liver biopsy showing deposition of brown pigments within the canaliculi and hepatocytes. This pigment showed Maltese cross birefringence on polarizing microscopy and Medusa-head appearance on electron microscopy. Genetic analysis revealed loss-of-function mutations in FECH. Introduction of EPP is an inborn error of heme biosynthesis caused by mutations in FECH with a prevalence of 1:75,000 to 1:200,000. We present a case of a 16-year-old adolescent boy with photosensitivity, abdominal pain, and jaundice with protoporphyrin deposition in the liver who was ultimately diagnosed with EPP based on genetic analysis.

Impact of anemia on the cardiovascular status in children with chronic kidney disease: A pilot study.

BACKGROUND & AIMS: Myocardial dysfunction is one of the common complications in children with chronic kidney disease which results in significant morbidity and mortality. We aimed to find the impact of anemia with cardiac changes in children with chronic kidney disease (CKD). METHODS: In this cross-sectional pilot study, 54 children (38 males) up to the age of 16 years with different stages of CKD, not on dialysis, were enrolled. Cardiovascular functions were evaluated using 2D-echocardiography using EPIC-7 (Philips) machine by an independent trained Pediatric Cardiologist. The M-mode measurements of the left ventricle were measured, indexed for body surface area and z-scores were calculated. They were divided into two groups i. e with and without anemia. RESULTS: Out of the 54 children with CKD, children with and without anemia were 34 and 20 respectively. The end-diastolic volume was significantly higher in patients with anemia when compared with those without anemia (46.43 ± 16.49 ml vs 32.51 ± 4.98 ml). The mean left ventricular mass (59.54 ± 23.99 vs 37.24 ± 7.88 g) and end-diastolic thickness of the interventricular septum (0.73 ± 0.14 vs 0.54 ± 0.05 cm) was significantly elevated in CKD children with anemia. CONCLUSIONS: Left ventricular hypertrophy along with left ventricular dimension and left ventricular diastolic dysfunction was found to be significantly correlating with the degree of anemia. CKD children with anemia should be screened for underlying cardiac dysfunction and appropriate dietary modification and nutritional rehabilitation for iron deficiency should be addressed.

Pediatric hypereosinophilia and toxoplasma: Peregrination beyond facileness.

Evaluation of pediatric hypereosinophilia (HE) is challenging, especially in the tropical developing countries, as appropriate diagnostic facilities may be lacking, parasitic/helminthic infections are common, and existing data on the etiology of severe eosinophilia are sparse. Second, data on long-term follow-up of these children including the temporal course of eosinophilia are also scarce. Besides, questions regarding the coexistence of multiple etiologies and their association with the severity of HE are largely unexplored. These challenges and questions often lead to diagnostic and therapeutic dilemmas. We highlight these difficulties utilizing a real-life clinical description. We emphasize the need for long-term follow-up of such children as HE may be the combinatorial effect of multiple etiologies, rather than a single cause. We also describe an unusual association of severe eosinophilia in a child with toxoplasmosis that was treated successfully with 8-week combination therapy with azithromycin and cotrimoxazole (sulfadiazine and pyrimethamine were not available).

Cardiac Abnormalities in Children with Pre-Dialysis Chronic Kidney Disease in a Resource-Limited Setting: A Cross-Sectional Observational Study.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in children with chronic kidney disease (CKD). We aim to estimate the prevalence of cardiac abnormalities in children up to age 16 years with CKD and their association with various risk factors. METHODS: This cross-sectional observational study was conducted on 107 CKD children. We assessed the systolic and diastolic function using 2D echocardiographic evaluation and M-mode measurements of the left ventricle (LV) indexed for BSA and z-scores were calculated. Results were compared with age, sex, stage of CKD, anaemia, estimated glomerular filtration rate (eGFR) and various laboratory parameters. RESULTS: LV diastolic dysfunction was seen in 88%, followed by increased LV dimensions in 33.6%, LV systolic dysfunction in 16%, right ventricle systolic dysfunction in 11.2% while increased pulmonary artery (PA) systolic pressure was seen in 9.3% of cases. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin levels. Left ventricular hypertrophy correlated directly with parathormone while inversely with eGFR, serum calcium and haemoglobin. Ejection fraction directly correlated to eGFR and serum calcium while inversely related to parathormone. Left PA pressure directly correlated with age and inversely with eGFR. Right ventricular systolic function assessed by tricuspid annular plane systolic excursion correlated inversely with haemoglobin. CONCLUSION: LV diastolic dysfunction and increased LV dimensions were the most common cardiac abnormality in children with CKD. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin. Diastolic dysfunction positively correlated with serum creatinine and parathormone levels.

A febrile child with a 'bunch of grapes' appearance on neck ultrasonography.

Kawasaki disease is a common childhood vasculitis. Fever and lymphadenopathy, at times, are the only clinical presentation of Kawasaki disease, which mimics infectious lymphadenitis, especially, when other features are yet to evolve. In such a scenario, ultrasonography of cervical lymph nodes can help to differentiate Kawasaki disease lymphadenitis from infectious lymphadenitis. We present one such patient who was initially diagnosed as having bacterial lymphadenitis; however, ultrasonography of the neck lymph nodes showed typical imaging features described with Kawasaki disease lymphadenitis.