Recurrent elevated liver transaminases and acute liver failure in two siblings with novel bi-allelic mutations of NBAS

BackgroundAcute liver failure (ALF) in children can be life-threatening. Although many causes are known, ALF remains unexplained in about half of the cases. Recently, bi-allelic mutations in NBAS were reported to underlie recurrent episodes of elevated liver transaminases (ELT) and ALF in the context of diverse extrahepatic phenotypes.Methods and ResultsWe here describe two sisters, born to non-consanguineous Portuguese parents, who had short stature and presented with recurrent episodes of severe ELT triggered by febrile respiratory viral infections since early childhood. Patient 1 had mild facial dysmorphism and died during the second ELT crisis at 3–11/12 years of age. Patient 2, currently 9 years old, had multiple episodes of ELT (>30), twice with ALF, often accompanied by extensive urticaria and facial angioedema. Whole-exome and Sanger sequencing revealed that both patients carried previously undescribed compound heterozygous mutations of NBAS (NM_015909.3): c.680A > C (p.His227Pro), affecting an evolutionarily conserved residue, and c.1749G > A (p.Trp583*), causing a premature stop codon. Both mutations are predicted to be highly damaging. The parents and two younger siblings are healthy and heterozygous for one or another mutant allele.ConclusionThe multiplex kindred reported herein expands the genotypic and phenotypic spectrum of this recently described clinical syndrome due to autosomal recessive NBAS deficiency.     

HCV prevalence and co-infection with HIV among pregnant women in Saint Camille Medical Centre, Ouagadougou

Objective To determine hepatitis C virus (HCV) prevalence and the rate of HCV/human immunodeficiency virus (HIV) co‐infection in pregnant women attending Saint Camille medical centre (SCMC) in Ouagadougou. Methods A total of 607 pregnant women, 16–45 years old, with <32 weeks amenorrhoea were screened for HCV and HIV using rapid tests. The majority of the women included in the study were previously known as HIV infected, as the centre is a reference centre for the programme of prevention against mother‐to‐child HIV transmission in the country. HCV RNA was extracted and quantified using the cDNA polymerase chain reaction with the nested primers at the 5′ untranslated region. Transaminases were measured from plasma samples using spectrophotometric method. Results Of women, 62.27% were infected with HIV. The prevalence of HCV was 2.14% in the screened pregnant women: 1.75% in HIV‐negative women and 2.38% in HIV‐positive ones. This prevalence is not significantly different between HIV‐positive and HIV‐negative pregnant women (P = 0.81). HCV RNA was found in all women with anti‐HCV. A significant transaminase increase was noted in women infected with HCV (P = 0.01 and P < 0.01 for glutamic‐pyruvic transaminase and glutamic‐oxaloacetic transaminase, respectively). Risk factors significantly associated with HCV positivity in pregnant women included transfusion and genital excision. In addition, the infection was linked with the educational level of the women. Conclusion The issue of this study revealed that effort should be made to promote safe medical practices and fight against women genital excision that are found to be the main risk factors associated with the HCV infection.     

Serum transaminases as a prognostic factor in children post cardiac surgery

Background: Elevated serum transaminases that are often observed in critically ill children are frequently attributed to liver injury. Indeed, hypoperfused or hypoxemic livers will produce sudden and marked elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The aim of this study was to determine the frequency and consequences of elevated serum transaminases in children following cardiac surgery. Methods: Charts of all children admitted to the Pediatric Intensive Care Unit following cardiac surgery over a 10‐year period were retrospectively analyzed. Results: Of the 384 children studied, 46 (11.9%) had elevated transaminases. Extreme ALT and AST levels (≥20‐fold elevations over the upper limit of normal) were found in 3.4% and 4.7% of the children, respectively. Tetralogy of Fallot and double outlet right ventricle were significantly more common (P < 0.001) among the elevated transaminases group (26% and 13% vs 17% and 2.5%, respectively). A significant difference (P < 0.001) was noted between overall mortality among 384 patients studied: 15.8%, versus a mortality of 43.4% among children who manifested elevated transaminases levels following cardiac surgery. AST, ALT and lactate dehydrogenase peak levels were significantly higher in the group of children who died in comparison to the survivors (P < 0.05). Kaplan–Meier survival analysis demonstrated lower survival among the patients who had extreme ALT elevations (P < 0.05). Conclusions: Elevation of transaminases following cardiac surgery occurs more frequently than previously reported, particularly in the setting of right‐sided heart failure. Extreme elevation of ALT, AST and lactate dehydrogenase correlated with decreased postoperative survival and places these children in a high‐risk category, requiring closer, more stringent monitoring.     

Serum transaminase determined in the emergency room predicts outcomes in patients with acute ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention

Background

Elevated serum aspartate and alanine aminotransferase (AST and ALT) are often observed in patients with acute ST-segment elevation myocardial infarction (STEMI) and the condition is ascribed to liver hypoperfusion. We evaluated the prevalence and prognostic implication of hypoxic liver injury (HLI) in STEMI.

Methods

Patients with STEMI and no preexisting liver disease who underwent primary percutaneous coronary intervention (PCI) were enrolled. A blood test was performed at the time of presentation and transthoracic echocardiography was performed after the index PCI. We reviewed medical records and contacted families of the patients by telephone to assess outcomes.

Results

Of 456 patients (age 60 ± 13 years, 370 males), 31 patients (7%) died during follow-up (duration: 754 ± 540 days). Those patients were older (72 ± 10 vs. 59 ± 13 years), had higher AST (179 ± 224 vs. 64 ± 103 U/L), ALT (56 ± 79 vs. 35 ± 33 U/L), blood urea nitrogen (25 ± 15 vs. 17 ± 7 mg/dL), uric acid (6.9 ± 2.9 vs. 5.8 ± 1.6 mg/dL), creatine kinase-myocardial band isoenzyme (76 ± 104 vs. 41 ± 79 ng/mL), troponin I (19.9 ± 23.0 vs. 10.8 ± 19.1 ng/mL), and lower albumin (4.0 ± 0.5 vs. 4.2 ± 0.4 g/dL) at the time of presentation (p < 0.05 for all). Particularly, AST independently predicted all-cause mortality (per 10 U/L increase, hazard ratio: 1.06, 95% confidence interval: 1.02–1.10, p = 0.007), whereas cardiac markers did not. HLI (> 2-fold elevation of AST or ALT upper normal limits) showed close correlation with reduced left ventricular ejection fraction (β = − 0.12, p = 0.03) and patients with the condition (n = 100 [20%]) had poorer survival than the others (Log-Rank, p = 0.005).

Conclusion

The presence of HLI predicts mortality in patients with STEMI who undergo successful primary PCIs.     

Hypertransaminasemia in childhood as a marker of genetic liver disorders

Background The widespread use of routine biochemical assays has led to increased incidental findings of hypertransaminasemia. We aimed to evaluate the prevalence of different causes of raised aminotransferase levels in children referred to a university department of pediatrics.Methods We investigated 425 consecutive children (age range, 1–18 years) with isolated hypertransaminasemia. All patients had raised aminotransferase levels on at least two occasions in the last month before observation. Cases due to major hepatotropic viruses were excluded.Results During the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.Conclusions Genetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.     

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Biopsy‐proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal

Biopsy‐proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long‐term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open‐label and multicenter nature of most studies. Therefore, biopsy‐proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody‐mediated rejection require further investigation to determine their clinical role.     

The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment.     

Effects of Highly Consumed Dietary Oils on Several Hepatic Transaminases and Lipid Oxidation in Chick

The incidence of cardiovascular disease is well correlated with diets high in saturated fatty acids (such as butter). On the other hand, oils, which are rich in unsaturated fatty acids (e.g., sunflower oil and corn oils), reduce cholesterol synthesis and thus show protective effects against arteriosclerosis. However, sunflower oil and corn oil are also considered as risk factors for their sensitivities to free radical formation because of their high contents of polyunsaturated fatty acids (PUFAs). The aim of the present study described herein was to investigate the production of reactive oxygen metabolites (an indicator of oxidative stress) and the activities of several transaminases (markers of hepatic injury) in chick liver treated with highly consumed dietary oils (differing in the degree of saturation). The animals were randomly assigned to six groups of 29 and fed dietary butter, margarine, olive oil, sunflower oil, or corn oil for 2 months. The results indicated that the level of reactive oxygen metabolites (ROM) was lowest in the dietary butter-fed group but highest in the corn oil-fed group. Similarly, the activities of all transaminases measured were lowest in the butter group, and in the margarine-fed group only the Gama-glutamyl transaminase activity was lowest as compared to the control group. From these findings, it was concluded that the dietary butter was the most resistant oil to lipid oxidation, whereas corn oil was the most susceptible one, which may thus challenge the antioxidant defense system and increase the susceptibility of tissues to degradation products of lipid oxidation.