Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children.

BACKGROUND: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. RESULTS: sFas was associated with fibrosis severity in pediatric (significant fibrosis p = 0.03, advanced fibrosis p = 0.01) and adult patients (advanced fibrosis p = 0.02). M30 levels were elevated in pediatric patients with severe steatosis (p = 0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p = 0.03) and they were associated with hepatitis severity (p = 0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). CONCLUSIONS: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

The role of serum biomarkers in predicting fibrosis progression in pediatric and adult hepatitis C virus chronic infection.

BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested. RESULTS: Significant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984) and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1. CONCLUSIONS: In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

Hepatitis b: historia natural: manejo del niño portador asintomático / Hepatitis b: natural history: management of asymptomatic carrier child

La hepatitis B es aún un problema de salud pública a nivel mundial. Según datos del CDC el 42% de las hepatitis B crónicas del adulto han sido adquiridas durante la infancia. La historia natural de la infección crónica por el VHB se caracteriza por tres fases: inicial de tolerancia inmune al virus; de “clearence” inmune de variable duración, y de remisión. Durante la infancia y sobre todo la adolescencia más del 80% de los pacientes con VHB seroconvierten a antiHBe. La historia natural de la infección crónica actualmente puede ser modificada por la indicación del tratamiento apropiado el que, en un porcentaje de pacientes, evita la progresión de la enfermedad y sus secuelas.

Hepatitis b is still a public health problem worldwide. According to the CDC for 42% of adult chronic hepatitis B have been acquired during childhood. The natural history of chronic HBV infection is characterized by three phases: initial immune tolerance to the virus; “clearance” immune of variable duration, and referral. During childhood and adolescence, especially more tan 80% of patients seroconverted to HBV antiHBe. The natural history of chronic infection can now be modified by appropiate treatment indicating that, in a proportion of patients, prevents the progression of the disease and its sequelae.

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied.

Hepatitis C virus infection in infants and children from Argentina.

Hepatitis C virus (HCV) infection is uncommon in children, and its natural history is still unknown. Our aim was to analyze exposure to HCV in 48 infants and children in Argentina and to evaluate consecutive samples in 26 of them to study the outcome of HCV infection in early stages. HCV viremia, as determined by reverse transcription-PCR (RT-PCR) from the 5' untranslated region, showed continuously positive, occasionally positive, and negative patterns during follow-up. Restriction fragment length polymorphism was performed on RT-PCR-positive samples to evaluate HCV genotype. Genotype 1 turned out to be predominant, and no patient displayed a genotype shift during the observation period. Perinatal HCV infection was predominantly observed in patients born to mothers coinfected with HCV and human immunodeficiency virus. HCV viral load was detected by means of the AMPLICOR MONITOR, version 2.0, kit. No correlation was observed between HCV viral load and alanine aminotransferase and aspartate aminotransferase levels, although we detected a trend towards higher levels among patients displaying consecutive positive HCV RT-PCR results. Our results demonstrate that pediatric HCV infection is characterized by high viral loads and diverse HCV viremia patterns, independent of both age and route of transmission in the population under study. Further research is necessary to determine whether the high rate of HCV replication is related to virus variability or to host immune response.