Małgorzata Aniszewska

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 (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). 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 activity 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 11.5 ± 3.4 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 (P = 0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (P = 0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR] = 3.3, 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 (P = 0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (OR = 3.35, 95% CI: 1.01–11.07) and inversely associated with the duration of infection (OR = 0.74, 95% CI: 0.55–0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (OR = 3.62, 95% CI: 1.22–10.75) and stage of fibrosis (OR = 3.89, 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.

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.

BACKGROUND Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children. OBJECTIVES The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data. MATERIAL AND METHODS The 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. RESULTS A 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). CONCLUSIONS Children 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.

Fever in an 8-Month-Old Infant Following a Rat Bite

Rat-bite fever (RBF) is a zoonotic infection caused by Gram-negative microaerophilic Streptobacillus moniliformis and Spirillum minus. Rat-bite fever predominantly affects the population in areas of poor socioeconomic status. The disease has been reported in high-income countries where rats are commonly kept as pets. The case described below is that of an 8-month-old infant boy who was diagnosed with rat-bite fever.

872 Neonate Skin Laceration During Delivery as Iatrogenic Risk Factor of Mother-To-Child HCV Infection

HCV mother-to-child transmission occurs mainly in the peripartum period. Cesarean section delivery is not recommended as prevention of HCV neonate infection. Available data from professional centers are conflicting. There is no information about association between neonate laceration during delivery and HCV infection. The Aim of the study was to establish the rate of neonate injury during delivery and the role of this complication in the risk of mother-to-child HCV transmission. Methods We collected data of mode of delivery in the group of 392 children born to anti-HCV+ mothers: 34 HCV infected children and 358 without HCV infection. Results 235/392(60%) children were delivered vaginally, 157/392(40%) by cesarean section. Skin laceration was observed in 9(2.3%) children: 4/235(1.7%) delivered vaginally, 5/157(3.2%) by cesarean section. In the group of HCV infected children 25/34(74%) were delivered vaginally, 9/34(26%) by cesarean section. The rate of HCV infection among children delivered vaginally was 25/235 (10.6%), by cesarean section 9/157(5.7%). 5/9(55%) children with skin laceration were HCV infected. In the group of children without skin laceration HCV infection was diagnosed in 29/383(7.5%). There were 43 children delivered by elective cesarean section in 38Hbd and none of them was injured, none of them was HCV infected. Conclusions Iatrogenic exposure to HCV during delivery may increase the risk of HCV mother-to-child infection. There is a higher risk of skin laceration in emergency cesarean section than in vaginal delivery. No vertical HCV transmission was noted among children born by elective cesarean section without skin laceration.

884 The Variability in the Course of Hepatitis B in Children After Mother-To-Child Transmission as a Reason to Adjust Treatment

Background and Aims In Poland currently, despite obligatory hepatitis B vaccination we expect the occurence of mother-to-child infection. We present 3 different courses of the HBV mother-to-child infections as a basis to differentiation of the therapeutic models . Methods We investigated case reports of 3 children infected with HBV by their mothers HBsAg(+) HBeAg(+). Chronic hepatitis B was confirmed in mothers aged 18, 21 and 26 respectively. All children were vaccinated against hepatitis B at delivery: two of them three times, one two times. One of the children was administered HBIG in the first day of its life. Results Hepatitis B virus infection in 2 children was revealed in the 3rd year of life. Acute hepatitis with the Gianotti-Crosti syndrome was diagnosed in 1 child in the 6th month of life. Subsequently, all children were diagnosed with chronic hepatitis B and the course of the disease was different in each case. In the first child aged 1, the activity of alanine aminotransferase decreased to near normal level with the seroconversion of HBe antigen to antibodies anti-HBe. The second child in the fourth year of life has high level of HBV viral load and high activity of alanine aminotransferase. The third child (12 years old) has exacerbation of disease after failure of treatment (lamivudine, interferon twice). Conclusions 1. The course of chronic hepatitis B in children after maternal infection may be vary, therefore some adjustments in treatment should be taken into account.