Growth Abnormalities in Children with Chronic Hepatitis B or C

Background. It has been suggested that chronic hepatitis B infection leads to growth impairment, but data are inconsistent and underlying factors are not defined. Methods. Children and adolescents with chronic hepatitis B (HBV) or C (HCV) were retrospectively evaluated for growth, weight, antiviral treatment, biochemical signs of liver inflammation, route of infection, and HBV DNA, respectively. Results. In all, 135 children (mean age 6.1 years, 81 male, 54 female) with HBV (n = 78) or HCV (n = 57) were studied. Route of infection was vertical in 50%, parenteral in 11%, and unknown in 39%. ALT levels were above 1.5 times above normal in 30% while 70% had normal/near normal transaminases. 80% were Caucasian, 14% Asian, 1% black, and 4% unknown. Mean baseline height measured in SDS was significantly lower in the study population than in noninfected children (boys −1.2, girls −0.4, P < 0.01). 28 children were below 2 standard deviations of the norm while 5 were above 2 standard deviations. SDS measures in relation to individual factors were as follows: elevated ALT: boys −1.4, females −0.5 (P < 0.01), ALT normal/near normal: boys +0.4, females +0.6; parenteral transmission: boys −3.3, girls −0.9 (P < 0.01), vertical transmission: boys −0.2, females −0.2. Antiviral treatment itself or HBV-DNA load did not reach statistically significant differences. Conclusions. Chronic HBV or HCV may lead to compromised growth which is mostly influenced by liver inflammation. Our data may argue for early antiviral treatment in children with significant ALT elevation

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling