Maria Pokorska-Śpiewak

The influence of hepatitis B and C virus coinfection on liver histopathology in children.

AbstractThe influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell’s modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2u2009±u20093.0 vs. 4.2u2009±u20092.5, pu2009=u20090.04), but not control group B (pu2009=u20090.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (pu2009=u20090.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activityn Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.

Is liver biopsy still needed in children with chronic viral hepatitis

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

Liver steatosis in children with chronic hepatitis B and C: Prevalence, predictors, and impact on disease progression

Abstract Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5u200a±u200a3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (⩽5% hepatocytes affected), mild (6–33%), moderate (34–66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis. Steatosis was observed in 4/30 (13%) patients with CHB and 13/48 (27%) patients with CHC (Pu200a=u200a0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (Pu200a=u200a0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR]u200a=u200a3.3, 95% confidence interval [CI]: 1.02–10.64). In CHC, steatosis occurred more frequently in patients with hepatitis C virus genotype 3 compared with other genotypes (Pu200a=u200a0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (ORu200a=u200a3.35, 95% CI: 1.01–11.07) and inversely associated with the duration of infection (ORu200a=u200a0.74, 95% CI: 0.55–0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (ORu200a=u200a3.62, 95% CI: 1.22–10.75) and stage of fibrosis (ORu200a=u200a3.89, 95% CI: 1.05–14.47). Steatosis is a common finding in children with chronic viral hepatitis. It is associated with metabolic factors in CHB, whereas in patients with CHC, metabolic and viral factors may have a combined effect, leading to more advanced grades of steatosis in children with higher BMI z-scores. Moderate-to-severe steatosis is a predictor of advanced fibrosis in children with CHC.

Non-invasive evaluation of the liver disease severity in children with chronic viral hepatitis using FibroTest and ActiTest – comparison with histopathological assessment

Aim of the study Was to evaluate liver disease severity in children with chronic viral hepatitis using the FibroTest and ActiTest (FT/AT), and compare the results with the liver biopsy. Material and methods The study included 11 treatment-naïve children [mean age, 9.0 ± 3.0 years, 10 infected with hepatitis C virus (HCV), and 1 with hepatitis B virus (HBV)] who underwent an FT/AT. Ten of the children underwent a liver biopsy. The histopathological evaluation was based on the METAVIR scoring system. The FT/AT and METAVIR scores were considered concordant if the necroinflammatory activity or the fibrosis did not differ by more than one grade or stage. To analyze the agreement between the FT/AT and the histopathological evaluation, the inter-rater agreement (kappa) was used. Results In the histopathological evaluation, most children presented with mild necroinflammatory activity (METAVIR A1) and with minimal to mild fibrosis (METAVIR F1-2). Both the AT and FT values did not show any linear increases with advancing METAVIR scores A and F, respectively. A discordance between the FT and METAVIR scores was observed in 3/10 (30%) cases; concordance between the AT and METAVIR scores was found in 9/10 cases. The inter-rater agreement test showed poor agreement between the FT/AT and the histopathological evaluation (kappa for AT: 0.0667, and kappa for FT: 0.176). Conclusions The FT and AT values poorly correlate with histopathological evaluation. Further studies on non-invasive methods to evaluate liver disease severity in children with chronic viral hepatitis are needed.

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

BackgroundThere is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC.MethodsThirty children aged 9.4xa0±xa03.7xa0years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2xa0=xa0significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis.ResultsIn the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis.ConclusionsIncluding the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.

Prevalence and predictors of liver disease in HIV-infected children and adolescents

Liver disease in HIV-infected patients may result from the infection itself, antiretroviral treatment or comorbidities. In this study, we analysed liver disease in 79 HIV-infected children and adolescents aged 14.0u2009±u20095.1 years. All the patients were receiving combination antiretroviral therapy (cART), with a mean duration of 11.5u2009±u20094.7 years. Six patients (8%) had detectable HIV viral load, and 8/79 (10%) of the participants were coinfected with hepatitis B or C virus (HCV, 6/8 or HBV, 2/8). Liver disease was defined as an elevation of any of the following parameters: alanine or aspartate aminotransferase (ALT and AST), total bilirubin, and gamma glutamyl transferase (GGTP). For the noninvasive evaluation of liver fibrosis, the AST-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) were calculated. Liver disease was diagnosed in 20/79 (25%) of the patients, including 13/71 (18%) of participants without coinfection and 7/8 (88%) with coinfection (pu2009<u20090.0001). All of the liver markers except bilirubin were significantly higher in the coinfected group. APRI scores indicated significant fibrosis in 5/8 (63%) of patients with coinfection. HBV or HCV coinfection and detectable HIV viral load were independently positively associated with APRI (pu2009=u20090.0001, and pu2009=u20090.0001) and FIB-4 (pu2009=u20090.001, and pu2009=u20090.002, respectively). In conclusion, liver disease in HIV-infected children and adolescents results mainly from HBV or HCV coinfection. Effective antiretroviral treatment is protective against hepatic abnormalities.

Pruritic, Bizarre Tracks- A Vacation Souvenir

Cutaneous larva migrans (CLM) is an endemic parasitic disease in tropical and subtropical regions. However, cases acquired in other temperate climates, i. e. during holidays in the Mediterranean Basin, have been reported recently. Moreover, the number of autochthonous cases of CLM in non-endemic Europe is progressively increasing (Gutiérrez García-Rodrigo C et al., J Eur Acad Dermatology Venereol 2017; 31(1): e33–e35). Here we report the clinical findings of imported CLM in a teenager returning from a youth camp. The case highlights the methods of prevention and control of this emerging infection in returning travelers.

Clinical usefulness of new noninvasive serum biomarkers for the assessment of liver fibrosis and steatosis in children with chronic hepatitis C

Aim of the study Recently, novel serum markers modified by the body mass index z-score (BMI z-score) were proposed as a reliable noninvasive alternative for the detection of significant fibrosis and steatosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the clinical usefulness of these biomarkers. Material and methods Thirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC were included in this study. In all patients, histopathological evaluation of the liver fibrosis was performed using a 5-point METAVIR scoring system (≥ 2 points = significant fibrosis). Significant steatosis was diagnosed with > 33% of hepatocytes affected. The following noninvasive markers of liver disease were calculated: the modified aspartate transaminase (AST)-to-platelet ratio index (M-APRI: BMI z-score × APRI), the modified Fibrosis-4 index (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The clinically useful cut-offs for each marker were selected as simple round numbers, indicating significant fibrosis and steatosis. Results Significant fibrosis was detected in 7/30 (23%) cases, and significant steatosis was observed in 4 (13%) patients. Comparison with the histopathological evaluation revealed that B-AST < 0 excluded significant fibrosis, and < 100 excluded all patients with significant steatosis. For the M-APRI, < 0 excluded significant fibrosis, and < 0.5 excluded significant steatosis. For the M-FIB-4, < 0 excluded significant fibrosis and < 0.2 excluded significant steatosis. Conclusions Negative values of all three markers that included the BMI z-score excluded all patients with both significant fibrosis and significant steatosis.

Predictors of Liver Disease Severity in Children with Chronic Hepatitis B.

BACKGROUNDnEvaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children.nnnOBJECTIVESnThe aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data.nnnMATERIAL AND METHODSnThe study comprised 30 treatment-naïve children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score.nnnRESULTSnA histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01).nnnCONCLUSIONSnChildren with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury.