Raised Serum Transaminases Research Articles

Raziskovanje toksičnosti, ki jo povzroča trikloroocetna kislina na hepato-renalni sistem, in posredovanje prehrane, bogate z deviškim kokosovim oljem

Virgin coconut oil (VCO) is known for many beneficial health effects associated with its phenolic acids and flavonoid contents. We investigated the mechanisms underlying the antioxidative, anti-inflammatory, and anti-apoptotic mechanisms of Virgin Coconut oil-rich diet in treating trichloroacetic acid (TCA)-induced hepatic and renal damage in rats. Rats received TCA (250 mg/Kg b.wt, p.o) for ten days, followed by 5%, 10% or 15% VCO per gram feed for twenty-one days. Serum liver enzymes, urea, creatinine, tissue oxidative stress parameters, and inflammatory and apoptotic markers were then evaluated along with histological examination. TCA raised serum transaminases (ALT, AST), alkaline phosphatase (ALP), total bilirubin, urea and creatinine levels, which were abrogated by a VCO-rich diet dose-dependently. The activity of superoxide dismutase, catalase, glutathione peroxidase and nuclear factor erythroid 2-related factor 2 in the liver and kidney were enhanced, while malondialdehyde, tumour necrosis factor-α, interleukin-1β, nuclear factor-kB level hitherto increased by TCA were quashed by the VCO- rich diet (p<0.05). Similarly, the augmented level of Caspase-3 in the organs exposed to TCA was downregulated in favour of significantly increased BCl-2. Further, histomorphometry data validated the biochemical findings observed for the anti-inflammatory and anti-apoptotic potentials of VCO. Hepatocyte ballooning, pleomorphism and vascular congestion in the liver, loss of tubular architecture, tubular congestion and leukocyte infiltration in the kidney, all occasioned by TCA-intoxication, were evidently mitigated. Virgin coconut oil-rich diet could ameliorate liver and renal injury associated with trichloroacetic acid exposure via antioxidative, anti-inflammatory and anti-apoptotic mechanisms.

CLINICAL PROFILE OF EXPANDED DENGUE SYNDROME IN CHILDREN.

The objective is to study the clinical profile and outcome of expanded dengue syndrome (EDS) in children. We conducted a retrospective cohort study and enrolled consecutive children (1 month to 18 years) who presented with dengue fever for over 1 year. The diagnosis of dengue fever was confirmed by the presence of dengue NS1 antigen and/or dengue IgM positivity. Subsequently, we identified children exhibiting EDS according to the revised World Health Organization guidelines (2011). We compared the clinical and laboratory profiles of children diagnosed with EDS and those without EDS. Of 178 children with dengue fever, 33 (18.5%) had EDS [95% confidence interval (CI): 13.1%-25.0%]. In these 33 children, neurological involvement was the most common manifestation [n = 16/33 (49%, 95% CI: 32%-65%)], namely encephalopathy, febrile seizures and encephalitis, respectively. Gastrointestinal involvement was the second most common [n = 10/33 (30%, 95% CI: 17%-47%)], which included fulminant hepatic failure, acalculous cholecystitis and acute pancreatitis. Renal presentation [n = 7 (21%, 95% CI: 10%-37%)] was limited to acute kidney injury. Children with EDS were significantly anemic and had leukocytosis, hyperkalemia, azotemia, hyperbilirubinemia, raised serum transaminases and fluid-refractory shock than their non-EDS counterparts. Children with EDS had a trend toward higher mortality (P = 0.07) and the survivors had a longer duration of hospital stay (5 days vs. 4 days in non-EDS, P = 0.001). In conclusion, we observed a high prevalence (18.5%) of EDS among children hospitalized for dengue fever. The common manifestations of EDS include neurological, renal and gastrointestinal involvement. Children with EDS showed a trend toward higher mortality and longer duration of hospital stay than children without EDS.

Hepatic Transaminases in Patients with Type-2 Diabetes Mellitus: Cross-Sectional, Analytic Study

The risk of chronic liver disease is higher in patient with type 2 diabetes than general population. Raised serum transaminases levels are a sensitive indicator of liver cell injury. This study was performed to estimate the prevalence of elevated serum transaminases levels in type-2 diabetic patients and to identify the associated risk factors. In this cross-sectional type of analytic study, ninety-three purposively selected type-2 diabetic patients and equal number of healthy subjects were studied. Subjects who were taking hepatotoxic drugs and known to have any liver disease were excluded. Demographic data and anthropometric measurements were recorded from all participants. Liver function tests, fasting blood sugar, fasting lipid profile and ultrasonography of the HBS were performed. Raised levels of serum ALT, AST and ALP were found in 22.6%, 14.0% and 4.3% diabetic patients and in 4.3%, 3.2% and 3.2% healthy control. Mean serum ALT, AST and ALP levels were significantly higher in cases than controls (p < 0.05). Significant positive correlation observed between serum ALT level with fasting blood sugar, BMI and waist circumference but significant negative correlation observed between ALT level and age of the patient and duration of the diabetes. Study results were in accordance with previously reported high prevalence rates of abnormal liver enzymes in type-2 diabetic patients. Early detection of liver enzyme abnormality and intervention will help to prevent further progression to chronic liver disease. Screening of type-2 diabetic patients with serum ALT and AST is recommended.

Prolonged Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a type of fatty acid oxidation disorder in which long chain fatty acids cannot be transported into mitochondria for further processing and storage in our body. Typically, the patients present with lethargy, hypoglycemia, and raised serum transaminase levels before 2 years of age. Cholestatic jaundice as manifestation of this deficiency has been reported rarely; here, we report an adolescent male with CPT1A deficiency who developed prolonged cholestatic jaundice following a febrile illness.

EP438: Ethical issues related to gene therapy with onasemnogene abeparvovec for spinal muscular atrophy type 1 in a developing country

The 5-q linked spinal muscular atrophy (SMA) (OMIM#253300) or SMA type 1 is an autosomal recessive, neuromuscular degenerative disorder caused by deletion or variants of SMN1 gene. SMA type 1 had been the leading genetic cause of infant mortality and gene replacement therapy with onasemnogene abeparvovec (AVXS-101, Zolgensma) was approved by the Food and Drug Administration (FDA) in May 2019. We described our experience of the first four Malaysian patients with SMA type 1 who received compassionate treatment in University Malaya Medical Center (UMMC), Malaysia and explored the main ethical issue related to this therapy. In Malaysia, patients with SMA type 1 were offered compassionate care. Supportive therapy was provided and palliative treatment and genetic counselling were offered when it was available. In 2020, gene therapy with AVXS-101 zolgensma under Novartis global managed access program (GMAP) was offered on a compassionate basis for SMA type 1 patients under 2 years of age. Following multi-stakeholder meetings and discussion with parents of SMA patients, it was decided patients will be selected on the basis of the inclusion criteria involved. Four SMA type 1 patients who were on palliative care were selected and each patient has 0 copy of SMN1 gene with 2 or 3 copies of SMN2 gene, respectively. The parents were counselled and all consented to receive the therapy. The patients received the therapeutic dose of AVXS-101 therapy (1.1E14 vector genomes (vg)/kg) at 12-month, 15-month, 24-month and 19-month-old respectively. All 4 patients were negative for AAV-9 antibody and had normal liver function profile, serum troponin 1 levels and full blood counts. There were no complications during infusion. Post treatment, all patients showed raised serum transaminases and gamma-glutamyl transpeptidase (GGT), but none with clinical symptoms. Their liver function improved and normalized with a course of recommended dose of oral prednisolone. Asymptomatic thrombocytopenia occurred within 7 days post treatment and recovered without intervention. All patients experienced improvement in motor function with increase in CHOP-INTEND scores evaluated at 3 and 6-month post treatment. None of the patient was ventilator dependent although a patient received nocturnal non-invasive ventilatory support. With proper pre-treatment screening, immunization, respiratory and nutritional support, and post-gene transfer management, onasemnogene abeparvovec was safe and early efficacy was promising in 4 Malaysian children with SMA type 1. The future outcome and adverse effects could only be ascertained with long term follow-up and multi-disciplinary care. The main ethical issue relates to the high cost of the drug which is prohibitive in a developing country. Consequently, this had an impact regarding patient access to this drug and related life-saving orphan drugs in low and middle income countries. This will require further discussion with all stakeholders, support groups and governmental intervention to ensure equity of care and appropriate funding model for this severe neuromuscular condition.

EFFECT OF AN UNANI REGIMEN IN THE TREATMENT OF 'YARAQĀN' (JAUNDICE): A CASE REPORT

Jaundice due to hepatitis viruses is considered to be a most prevalent disease worldwide. In Unani literature, it is referred as 'yaraqān' which is caused by inflammatory diseases of liver, intra or extra-hepatic obstructions, and poisoning due to drugs or animals. Several Unani drugs including Ma'jun Dabid al-Ward, syrup Jigreen, Araq-iMako, Araq-i-Kasni, etc are frequently used for the treatment of jaundice and liver disorders including infective hepatitis. A 16 year old male patient suffering from yellowish discoloration of sclera, skin, mucous membranes and urine, nausea, vomiting, loss of appetite and fever for one week admitted in the male ward of RRIUM, Chennai. The laboratory investigations revealed severe hyperbilirubinemia, raised serum transaminases, alkaline phosphatase and negative HBsAg. On the basis of history, clinical observations and laboratory investigations, the patient was diagnosed as a case of 'yaraqān' (jaundice) which may be due to acute viral hepatitis. A Unani regimen comprising Ma'jun Dabid al-Ward (5 g twice a day), syrup Jigreen (10 ml twice a day), Araq-i-Mako (75 ml twice a day), Araq-iKasni (75 ml twice a day) for 25 days, Sharbat-i-Khaksi (10 ml twice a day for 7 days), and Habb-i-Tursh Mushtahi (1 g twice a day) for 15 days were given by oral route. The fever has subsided after 7 days and the appetite improved after 15 days of the treatment. The yellow discoloration of sclera and mucous membranes started to reduce gradually th from 7 day onwards. At the end of the treatment, the laboratory reports revealed that the total bilirubin, direct bilirubin, indirect bilirubin, SGOT, SGPT and ALP were within normal range. The core objective of this case report is to re-emphasize the effectiveness of Unani medicine particularly in the treatment of jaundice. Thus, this data may be helpful to increase awareness amongst the common people and scientific community for the popularity of Unani medicine in general and for the treatment of jaundice and liver disorders in particular.

Clinical, Hematological and Immunological Correlation in Children with Dengue Infection

Mortality rate caused by dengue in tropical urban life by a vector mosquito possess severe effects including children. This is an observational study carried out in a tertiary care hospital in Navi Mumbai, from June 2006 to August 2008 area which is endemic for vector borne diseases. The clinical signs, symptoms, hematological parameters and serological correlation in 100 serologically positive for IgM and IgG children confirmed by Mac ELISA were studied. Chi-square test of significance was applied between the selected laboratory and clinical parameters. The outcomes of the study were provided with a high incidence of infection was seen in the age group of 6-10 years (50%), with a male (63%) predominance affection. Fever (100%), along with Vomiting (89%), myalgia (45%) and abdominal pain (27%) are the most common symptoms associated with dengue. Other symptoms found in childrens affected by dengue shows hemorrhagic manifestation (25%), hepatomegaly (78%), as cites and effusion (50%), hem concentration (31%), leucopenia (38%), and raised serum transaminases (67%). These findings were correlated with the severity of the infection and the parameters which were statistically significant were hemorrhagic manifestation, plasma leakage with as cites and effusion, hepatomegaly, hem concentration and leucopenia. The findings would be useful in early detection and prompt management and referral of cases for preventing mortality rate in children.

Evaluation of the Impact of Ranolazine Treatment on Liver Function Tests in Patients With Coronary Heart Disease and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology in the developed world. Nonalcoholic fatty liver disease is associated with a higher risk of cardiovascular disease. We investigated the impact of ranolazine on liver tests in patients with NAFLD and coronary artery disease (CAD). Patients who had established CAD and NAFLD (as assessed by raised serum transaminase activity, sonographic criteria, and the absence of any other obvious liver disease) were allocated to "on ranolazine" (n = 40) or "not on ranolazine" (n = 35) groups. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in all patients at baseline and at the end of the study. After 6 months of ranolazine treatment, both ALT and AST activities were significantly lower in patients in the "on ranolazine" group compared with "not on ranolazine" patients (change from baseline: ALT, -11.0 ± 1.7 IU/L, P < .001; AST, -5.2 ± 1.9 IU/L, P =.009). In conclusion, the present study showed that treatment with ranolazine for 6 months led to a significant reduction in the activities of both serum aminotransferases in patients with stable CAD and NAFLD.

Updated View on Kidney Transplant from HCV-Infected Donors and DAAs.

Background: The discrepancy between the number of potential available kidneys and the number of patients listed for kidney transplant continues to widen all over the world. The transplant of kidneys from hepatitis C virus (HCV)-infected donors into HCV naïve recipients has grown recently because of persistent kidney shortage and the availability of direct-acting antiviral agents. This strategy has the potential to reduce both waiting times for transplant and the risk of mortality in dialysis. Aim: We made an extensive review of the scientific literature in order to review the efficacy and safety of kidney transplant from HCV-viremic donors into HCV naïve recipients who received early antiviral therapy with direct-acting antiviral agents (DAAs). Results: Evidence has been rapidly accumulated on this topic and some reports have been published (n = 11 studies, n = 201 patients) over the last three years. Various combinations of DAAs were administered—elbasvir/grazoprevir (n = 38), glecaprevir/pibrentasvir (n = 110), and sofosbuvir-based regimens (n = 53). DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT. The sustained virological response (SVR) rate was between 97.5% and 100%. A few severe adverse events (SAEs) were noted including fibrosing cholestatic hepatitis (n = 3), raised serum aminotransferase levels (n = 11), and acute rejection (n = 7). It remains unclear whether the AEs were related to the transmission of HCV, the use of DAAs, or kidney transplant per se. It appears that the frequency of AEs was greater in those studies where DAAs were not given in the very early post-kidney transplant phase. Conclusions: The evidence gathered to date encourages the expansion of the kidney donor pool with the adoption of HCV-infected donor organs. We suggest that kidney transplants from HCV-viremic kidneys into HCV-uninfected recipients should be made in the context of research protocols. Many of the studies reported above were externally funded and we need research generating “real-world” evidence. The recent availability of pangenotypic combinations of DAAs, which can be given even in patients with eGFR < 30/min/1.73 m2, will promote the notion that HCV-viremic donors are a significant resource for kidney transplant.

Correlation of severity of dengue with serum aminotransferase levels

Background: In dengue, association of fever (most common presenting symptom) with hepatic involvement can be relatively more serious. Such patients may have raised serum aminotransferase levels as well as can be more prone to bleeding due to deranged liver functions. Thus, the present study was conducted with an objective to correlate these enzyme levels with the severity of dengue fever.Methods: This prospective, observational study was carried out for 1.5 years at a tertiary care teaching hospital in southern Rajasthan after ethics committee approval. Those patients diagnosed with dengue, admitted at this tertiary centre, aged 18 years and above and willing to give consent for participation, were included in the study. Patients were assessed for clinical features of dengue along with both laboratory and radiological investigations. Severity of dengue was correlated with aminotransferase levels. Data analysis was carried out using appropriate statistical tests.Results: Total 200 patients were analysed. Mean age was 36.92±14 years while male: female ratio was 1.23:1 in the study population. All patients (100%) had fever whereas shock and bleeding tendency were noted in 16 (8%) and 4 (2%) patients respectively. Majority 130 (65%) patients had moderate dengue. Raised aminotransferase levels were noted in approximately 65% study patients out of which nearly 40% patients had moderate dengue. Correlation of raised aminotransferase levels with thrombocytopenia, shock, bleeding tendency were not statistically significant. Conclusions: Serum aminotransferase levels were elevated in moderate dengue patients. However, there was no significant correlation of raised enzyme levels with thrombocytopenia, presence of shock and bleeding tendency or as the severity of dengue increases. Thus, it is quite subjective whether to predict severity of dengue from raised enzyme levels or not.

Critical Level of Alanine Transaminase to Predict Foetomaternal Outcome in Intrahepatic Cholestasis of Pregnancy: A Case-control Study

Introduction: Intrahepatic Cholestasis of Pregnancy (IHCP) is a disorder of the second and third trimester causing pruritis without a rash in the women. To avoid the adversities, early delivery is indicated before serum bile acids levels of &gt;40 μmol/L is reached. In the settingswhere bile acid testing is not available, serum transaminases can be used for diagnosis and management of IHCP. Aim: To find out value of Alanine Transaminase (ALT) for the prediction of adverse outcomes. Materials and Methods: This case-control study was carried out from October 2018 to March 2020, enrolled 75 singleton women with IHCP and 75 controls in their third trimester. The diagnosis was based on the presence of pruritis without an identifiable dermatological cause along with raised serum transaminases. Serum ALT levels and the foetomaternal outcomes were noted. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Mann-Whitney test, Chi-square test and Fisher’s exact test were used to compare all variables. The p-value of &lt;0.05 was considered statistically significant. Results: The mean age of women in the IHCP and control groups was 24.81±4.2 and 25.95±5.13 years, respectively and the mean gestational age of women was 34±2.89 weeks. Women with IHCP had increased incidence of induction of labour (p=0.0003) and meconium staining of liquor (p=0.002) as compared to controls. Serum ALT levels showed a significant positive association with meconium staining of liquor (p=0.041), Intrauterine Death (p=0.01), and Neonatal Intensive Care Unit (NICU) admission (p=0.006) in women with IHCP. An ALT value of 133 U/L was found to be predictive of adverse foetal outcomes with sensitivity, specificity and likelihood ratio of 65.7%, 82.5% and 3.76, respectively. Conclusion: IHCP leads to adverse foetal outcomes. But pruritis is the only maternal distress. ALT &gt;133 U/L is predictive of adverse foetal outcome, therefore, termination of pregnancy can be advocated above this level.

Evaluation of Hepatotoxicity of Anti-Tuberculosis Regimens: A Prospective Study in Tribal Population of Central India

<!DOCTYPE html> <html> <head> </head> <body> <p style="text-align: justify;"><strong>Background: </strong>The magnitude of tuberculosis (TB) and associated risk factors for development of toxicity to anti-TB drugs in vulnerable tribal groups are useful indicators for understanding extent of TB transmission, effectiveness of TB therapy. Such studies help to gather information, helps in planning control and preventive strategies for TB in this special population. The study was carried out to evaluate incidence of hepatotoxicity, association between risk factors, anti-TB regimen and hepatotoxicity in selected vulnerable population. <strong>Materials and Methods:</strong> Prospective study in tribes (Gond, Halba, Kawar) of a district in central India diagnosed with pulmonary/ extrapulmonary/Multi drug resistant TB. These patients were on anti- TB regimen, monitored clinically and biochemically for hepatotoxicity at the end of 1, 3 and 6 months of anti-tubercular therapy. A specific criterion was set for diagnosing hepatotoxicity. <strong>Results: </strong>Incidence of hepatotoxicity was 9.23%. Raised serum transaminase, bilirubin level and symptoms of hepatotoxicity like nausea, anorexia, vomiting, malaise, jaundice, were observed. The onset of hepatotoxicity ranged from 25-180 days (median 65 days). Of various risk factors analyzed, high alcohol intake was associated with hepatotoxicity (odds ratio = 9.3, 95% confidence interval 1.8&ndash;47, p=0.003). Age, gender, extent of tuberculosis disease, malnutrition was not significantly associated with anti-tuberculosis treatment hepatotoxicity. Relative risk of developing hepatotoxicity in alcoholic addicted males was 14.117. <strong>Conclusion:</strong> Withdrawal of alcohol habit in selected tribes on anti- Tuberculosis regimen will cause a drop in developing hepatotoxicity by 93%. Mass education regarding same would curtail hepatotoxicity making therapy safe. <p style="text-align: justify;"><strong>Key words: </strong>Directly observed treatment shortcourse, Ethambutol, Isoniazid, Pyrazinamide, Rifampicin. </body> </html>

Study of hepatic profile in falciparum malaria in children of the age group of 1–10 years

Background: Severe falciparum malaria (FM) has more predilections to affect the liver resulting in raised serum transaminases. When the levels are more than 3 times the upper limit, it is known as malarial hepatopathy (MH). The liver function test is an important tool to predict complications and prognosis in patients with FM, which should be done at the earliest. Objective: The objective of the study was to study the patient characteristics, presenting features, and complications of malaria in patients with MH and to compare these with patients who had normal liver enzymes. Materials and Methods: This case–control study was carried out on 76 children of the age group of 1–10 years suffering from FM admitted in the department of pediatrics of a tertiary hospital of Bihar. All admitted children suffering from FM were divided into two groups based on the presence of MH as cases and controls. Various parameters were compared between these two groups and the results were interpreted. Data were collected and the results were analyzed by SPSS v23 software. Results: Baseline characteristics were comparable in both groups. Among cases, 90.9% had an altered level of consciousness and 72.7% had convulsions at admission, in comparison to 50.0% and 25.9% among controls. A total of 68.1% of cases of MH presented with icterus, compared to 3.7% of the controls (p&lt;0.0001). Patients of MH who suffered from renal failure were 18.1%, compared to 1.8% among controls (p=0.0321). Among cases, 36.3% suffered from hypoglycemia, compared to 12.9% among controls (p=0.0251). The mean hemoglobin (Hb) levels among cases were lower as compared to controls (p=0.0002). A total of 36.3% of cases and 12.9% of controls expired due to the disease (p=0.0251). Conclusion: MH is associated with a higher incidence of complications such as altered sensorium, seizures, icterus, raised bilirubin levels, renal failure, increased chances of hypoglycemia, and lower mean Hb levels and a poor outcome.

Association between HCV infection and the incidence of Diabetes Mellitus in Egyptians

The present work was planned to find a correlation between HCV infection and diabetes mellitus (DM) incidence in Egyptian patients by finding a possible relationship between HCV antibodies and both anti-insulin antibodies (AIAs) and pancreatic islet cell antibodies (PICAs). The screening results showed that the percentage of HCV patients out of 200 subjects were 35.5 and 14.5% in males and females, respectively. Also, the association between DM and HCV were 13.21 and 13.64% in men and women, respectively. The titers of antibodies in diabetic or non-diabetic patients ranged from 30 - 58 for AIAs and from 30 - 40 for PICAs, The percentage of patients with raised serum transaminases was significantly more in DM patients with positive HCV antibody (52.3%) than DM patients with negative HCV antibody (16.7%). Conclusion, it can be concluded that diabetic or non-diabetic patients with HCV might have a rise titer of the antibodies toward insulin or its secretory cells in pancreas or toward both. where are more susceptible to both HCV-infection and antibodies than women, indicating to here is a significant association between HCV infection and induction of diabetes in Egyptians.

Long-term outcome of liver transplantation in childhood: Astudy of 20-year survivors.

We report the results of a study of survival, liver and kidney functions, and growth with a median follow-up of 24 years following liver transplantation in childhood. From 1988 to 1993, 128 children underwent deceased donor liver transplantation (median age: 2.5 years). Twenty-year patient and graft survival rates were 79% and 64%, respectively. Raised serum aminotransferase and/or γ-glutamyl transferase activities were present in 42% of survivors after a single transplantation. Graft histology (35 patients) showed signs of chronic rejection in 11 and biliary obstruction in 5. Mean total fibrosis scores were 4.5/9 and 3/9 in patients with abnormal and normal serum liver tests, respectively. Glomerular filtration rate was <90mL·min-1 in 35 survivors, including 4 in end-stage renal disease who were undergoing dialysis or had undergone renal transplantation. Median final heights were 159cm for women and 172cm for men; final height was below the target height in 37 patients. Twenty-year survival after childhood liver transplantation may be close to 80%, and final height is within the normal range for most patients. However, chronic kidney disease or altered liver biochemistries are present in over one third of patients, which is a matter of concern for the future.

Clinical features and VPS33B mutations in a family affected by arthrogryposis, renal dysfunction, and cholestasis syndrome

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.

Clinical features and MYO5B mutations of a family affected by microvillus inclusion disease

Microvillus inclusion disease (MVID) is an autosomal recessive disorder caused by biallelic mutations in the MYO5B or STX3 gene. Refractory diarrhea and malabsorption are the main clinical manifestations. The aim of this study was to investigate the clinical features and MYO5B gene mutations of an infant with MVID. A 21-day-old female infant was referred to the hospital with the complaint of diarrhea for 20 days. On physical examination, growth retardation of the body weight and length was found along with moderately jaundiced skin and sclera. Breath sounds were clear in the two lungs and the heart sounds were normal. The abdomen was distended and the veins in the abdominal wall were observed. The liver and spleen were not palpable. Biochemical analysis revealed raised serum total bile acids, bilirubin, transaminases and γ-glutamyl transpeptidase while decreased levels of serum sodium, chloride, phosphate and magnesium. Blood gas analysis indicated metabolic acidosis. The preliminary diagnosis was congenital diarrhea, and thus parenteral nutrition was given along with other symptomatic and supportive measures. However, diarrhea, metabolic acidosis and electrolyte disturbance were intractable, and the cholestatic indices, including transaminases, γ-glutamyl transpeptidase, bilirubin and total bile acids, remained at increased levels. One month later, the patient was discharged and then lost contact. On genetic analysis, the infant was proved to be a compound heterozygote of the c.310+2Tdup and c.1966C>T(p.R656C) variants of the gene MYO5B, with c.310+2Tdup being a novel splice-site mutation. MVID was thus definitely diagnosed.

High Dose Methotrexate and Leucovorin Rescue Therapy in Childhood Malignancies: Experience in Resource-Limited Country

Background: Administration of high dose methotrexate (HDMTX) needs meticulous monitoring. Limitations in the availability of trained staff and adequate infrastructure often are great problems in the developing country like Bangladesh.Objective: The aim of this study was to evaluate the HDMTX toxicities by monitoring biochemical and serological markers where facility for serum MTX level in a tertiary care centre (Combined Military Hospital, Dhaka) of Bangladesh is available.Methods: An explorative study was done among twelve cases with a confirmed diagnosis of Pre-B &amp; T cell ALL, Burkitt’s lymphoma, T cell lymphoma and osteosarcoma. All of them received four cycles of HDMTX as part of their treatment. Demographic profile, details of HDMTX infusion and Leucovorin rescue and toxicities were collected and analyzed.Results: We evaluated and compared toxicity of repeated courses of high dose methotrexate (HDMTX) in five groups of pediatric patients. Neutropenia was observed in 83.3% case and vomiting in 70% during chemotherapy. Diarrhoea 12.5%, oral mucositis in 56.20% patients were noted. Low hemoglobin level, was observed in 14.58%, thrombocytopenia in 20.80% patients. Vomiting and diarrhea was most frequent in cycle 2&gt;1&gt;3&gt;4, whereas mucositis, fever was most frequent in Cycle 1&gt;2&gt;3&gt;4 and raised serum transaminase in cycle 3&gt;2&gt;1&gt;4. Two patients had &lt;100 creatinine clearance. There was significant relationship between neutropenia with toxicities like vomiting and mucositis (p&lt;0.05).Conclusion: The administration of HDMTX therapy was found to be safe without any life threatening adverse effect in a developing country like Bangladesh where there is lacking of lab support and adequate supportive management.Bangladesh J Child Health 2017; VOL 41 (1) :15-23

Raised Serum Transaminases during Treatment with Pegylated Interferon for Chronic Hepatitis C

Raised Serum Transaminases during Treatment with Pegylated Interferon for Chronic Hepatitis C

Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study

BackgroundAntituberculosis drugs cause hepatotoxicity in some individuals leading to acute liver failure, which results in death. Such phenomena limit the clinical use of drugs, contributing to treatment failure that possibly causes drug resistance. Furthermore, associated risk factors for the development of antituberculosis-drug-induced hepatotoxicity (anti-TB-DIH) are found to be controversial among different study findings. MethodsA prospective cohort study was conducted from May 2014 to October 2014 in Dawro Zone, Tercha District Hospital Laboratory, South Ethiopia. One hundred and twenty-four new tuberculosis-positive individuals available from Tercha Hospital and five health centers during data collection were consecutively included. The sociodemographic data and anthropometric measurement were obtained. Then, 5mL of venous blood was drawn from each individual, and the alanine transaminase, aspartate transaminase, and total bilirubin were measured photometrically at baseline, and then continuously monitored by measuring these liver enzymes every 2weeks for 2months. Data were analyzed with SPSS version 20 for Windows (SPSS Inc., Chicago, IL, USA). ResultsThe incidence of anti-TB-DIH was found to be 8% (10 patients out of 124). Raised serum transaminase and bilirubin level, as well as signs and symptoms of hepatotoxicity (nausea, anorexia, vomiting, malaise, and jaundice), were observed in the cases. The onset of hepatotoxicity ranged from 13days to 58days (median, 26days) after treatment was initiated. Of the various risk factors analyzed, only high alcohol intake was associated with the incidence of anti-TB-DIH (odds ratio=9.3, 95% confidence interval 1.8–47, p<.007). Age, gender, extent of tuberculosis disease, and malnutrition were not significantly associated with anti-TB-DIH. ConclusionThe incidence of anti-TB-DIH in Dawro Zone was high. The drug responsible for the hepatotoxicity was not known. However, chronic high alcohol intake was associated with the development of anti-TB-DIH.