Estimation of the risk of fibrosis in children with nonalcoholic fatty liver disease.

AIM OF THE STUDY: Assessment of liver fibrosis as a predictive factor of liver-related mortality in children with nonalcoholic fatty liver disease (NAFLD) is crucial. This study aims to estimate the risk of fibrosis using noninvasive markers. MATERIAL AND METHODS: The study group of 49 children with NAFLD (age range 3-16, mean 10.51 ±3.18 years) was created. The diagnosis was based on clinical picture, abdominal ultrasound, and laboratory tests; four children underwent liver biopsy. Then homeostatic model assessment (HOMA-IR) and noninvasive hepatic fibrosis scores were calculated, and patients were divided into four groups depending on body mass index (BMI, obese vs. lean) and aminotransferases. RESULTS: 71.43% of patients were obese, and 14.29% were overweight. We found that overweight children had lower mean corpuscular volume (MCV) than lean patients. In a group of patients with a high risk of fibrosis or significant fibrosis due to pediatric NAFLD fibrosis score (PNFS), higher alanine aminotransferase (ALT) to platelet ratio (APRI) values were observed. The highest values of APRI were found in a group of lean patients with elevated aminotransferases and the highest value of PNFS - among obese patients with elevated aminotransferases. A strong significant correlation between APRI and PNFS was found (r = 0.88). CONCLUSIONS: Apart from aminotransferase activity, complete blood count should be assessed looking for lower MCV caused by iron deficiency. In contrast to FIB-4 (fibrosis score), PNFS and APRI proved to be more accurate in our group. PNFS seems to be appropriate to evaluate fibrosis in a noninvasive diagnostic algorithm.

Skin lesions caused by Orthopoxvirus in children.

INTRODUCTION: The global eradication of smallpox and abandonment of mandatory smallpox vaccination has led to an increased proportion of the population who are immunologically naïve to infections caused by Orthopoxviruses (OPV). AIM: To present the different courses of OPV infection in children and to highlight the diagnostic difficulties in their differentiation from the other inflammatory processes. MATERIAL AND METHODS: We retrospectively evaluated the medical documentation of 5 children with OPV infection. Clinical diagnosis of OPV infection was based on evaluation of animal contact and skin symptoms, characterised by either a single ulcer or disseminated lesions. In all five cases, blood samples and skin swabs were collected from the lesion(s) to identify specific OPV DNA fragments (Vgf, b9R and D11L genes) using PCR. RESULTS: Two children presented with high fever, a single ulcer on the skin and local lymphadenopathy. The three other patients were in good general health and their skin lesions presented as a disseminated vesicular rash. Using the Vgf gene as the target for PCR, OPV infection was confirmed in material collected from skin lesions of all children and in blood samples of 4 children. The B9R and d11L genes tested positive in the skin material of 2 children and blood samples of 2 children. All analysed patients presented a history of ineffective antibiotic therapy. CONCLUSIONS: In the case of unclear necrotising skin lesions in children, the primary diagnosis always includes bacterial dermatitis. However, if the patient has come into contact with animals, diagnosis of OPV infection should also be considered.

Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disorder associated with a progressive deficiency of dystrophin that leads to skeletal muscle degeneration. In this study, we tested the hypothesis that a co-transplantation of two stem/progenitor cell populations, namely bone marrow-derived mesenchymal stem cells (BM-MSCs) and skeletal muscle-derived stem/progenitor cells (SM-SPCs), directly into the dystrophic muscle can improve the skeletal muscle function of DMD patients. Three patients diagnosed with DMD, confirmed by the dystrophin gene mutation, were enrolled into a study approved by the local Bioethics Committee (no. 79/2015). Stem/progenitor cells collected from bone marrow and skeletal muscles of related healthy donors, based on HLA matched antigens, were expanded in a closed MC3 cell culture system. A simultaneous co­transplantation of BM-MSCs and SM-SPCs was performed directly into the biceps brachii (two patients) and gastrocnemius (one patient). During a six­month follow­up, the patients were examined with electromyography (EMG) and monitored for blood kinase creatine level. Muscle biopsies were examined with histology and assessed for dystrophin at the mRNA and protein level. A panel of 27 cytokines was analysed with multiplex ELISA. We did not observe any adverse effects after the intramuscular administration of cells. The efficacy of BM­MSC and SM­SPC application was confirmed through an EMG assessment by an increase in motor unit parameters, especially in terms of duration, amplitude range, area, and size index. The beneficial effect of cellular therapy was confirmed by a decrease in creatine kinase levels and a normalised profile of pro-inflammatory cytokines. BM-MSCs may support the pro-regenerative potential of SM-SPCs thanks to their trophic, paracrine, and immunomodulatory activity. Both applied cell populations may fuse with degenerating skeletal muscle fibres in situ, facilitating skeletal muscle recovery. However, further studies are required to optimise the dose and timing of stem/progenitor cell delivery.

Epstein-Barr virus infection with acute acalculous cholecystitis in previously healthy children.

BACKGROUND: Acute acalculous cholecystitis (AAC), an inflammatory process of the gallbladder (GB) in the absence of gallstones, typically occurs in seriously ill patients. AAC can complicate primary Epstein-Barr virus (EBV) infection, but it is an atypical clinical presentation. AIM: The aim of our study was to analyse AAC occurrence in children with primary symptomatic EBV infection who had been admitted to the hospital. METHODS: We retrospectively evaluated the medical documentation of 181 children with EBV infection who were diagnosed based on the presence of viral capsid antigen IgM antibodies. All EBV-positive patients underwent transabdominal ultrasonography of the liver in the supine and right anterior oblique positions. Fifteen children who presented with AAC symptoms, including abdominal pain and a positive Murphy's sign, were analysed as a subsample and re-evaluated after 2-3 months. RESULTS: The incidence of AAC in children hospitalised with infectious mononucleosis (IM) was estimated at 8.3%. Analysis of the laboratory results confirmed that the C-reactive protein (CRP) concentration was the only parameter which was higher in children who presented with AAC symptoms. The mean number of leucocytes and monocytes and liver enzyme activities were not significantly higher. The radiological findings of AAC were evident: increased GB wall thickness, non-shadowing echogenic sludge and pericholecystic fluid collection. CONCLUSION: AAC during primary EBV infection appears to be a more common pathology than previously suspected. Its relatively mild nature and the lack of laboratory abnormalities mean that ultrasonographic examination is required for diagnosis. This might explain why the prevalence in children is underestimated.

Autoimmune encephalitis with GABAA receptor antibodies in a 10-year-old girl.

Recent studies have indicated that some cases of nonparaneoplastic autoimmune encephalitis in children can be caused by a systemic autoimmune disorder that generates autoantibodies to cell membrane proteins. We describe the clinical features of a 10-year-old girl with autoimmune encephalitis with autoantibodies against the GABAA receptor in whom type 1 diabetes mellitus developed during the course of the disease. The diagnosis was based on the progressive course of disease, pleocytosis in the cerebrospinal fluid (CSF), inflammatory changes in the brain and autoantibodies against the GABAA receptor detected in serum (absent in CSF). The treatment of encephalitis included intravenous immunoglobulins, intravenous methylprednisolone, oral prednisolone, cycles of plasmapheresis; this led to temporary remission. Finally, rituximab was applied as a second-line therapy with positive results.

Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C.

Treatment with pegylated interferon-α and ribavirin (PEG-IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG-IFN/RBV treatment response. Study included 26 children with CHC-13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG-IFNα-2b (60 µg/m2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.

Expression of Natural Killer Cell Inhibitory Receptors is Associated with Significant Liver Injury in Chronic Hepatitis C in Children.

INTRODUCTION AND AIM: Natural Killer (NK) cells play an important role in innate immune response to viral infections and their high proportion is situated in the liver. The aim of this study was to analyze possible relation between the expression of NK cell receptors and varied intensity of liver lesions in chronic hepatitis C (CHC) in children. MATERIAL AND METHODS: Study included 105 children with CHC - 54 boys and 51 girls, age 13.62 ± 3.48 years. Blood specimens were taken at the day of the liver biopsy. Histological evaluation was performed according to METAVIR scoring system. Circulating NK cells were evaluated by flow cytometry. The results were shown as a proportion of cells expressing evaluated receptor and its' mean fluorescent intensity (MFI). RESULTS: In 58 children with CHC (55.2%) significant liver fibrosis was observed ( ≥F2). Higher proportion of cells expressing CD158e inhibitory receptors was observed in the group of children with ALT > 2UNL (21.11 ± 14.60 vs. 12.22 ± 8.99%; p = 0.037). While higher proportion of cells expressing inhibitory CD158b receptor was observed in children with significant fibrosis (F ≥ 2) compared to minimal fibrosis (F < 2) - (34.14 ± 12.44 vs. 27.48 ± 8.71%; p = 0.049). Children with advanced fibrosis (F ≥ 3) had higher MFI of NK cell CD 158b receptor than children with fibrosis scored F < 3 - (5344.20 ± 3407.49 vs. 2979.67 ± 1190.64; p = 0.049). Proportion of NK cells expressing CD158b was found a predictor of significant fibrosis in univariate analysis - [OR 1.065; 95%CI (1.07-1.15); p = 0.046]. CONCLUSIONS: Higher proportion of NK cells expressing inhibitory CD158b and CD158e receptors is associated with significant liver injury.

Neurologic Complications Caused by Epstein-Barr Virus in Pediatric Patients.

We retrospectively analyzed the medical documentation of 194 children infected with Epstein-Barr virus. The diagnosis was based on clinical symptoms and the presence of the viral capsid antigen IgM antibody. Patients with severe neurologic complications also underwent neurologic examination, magnetic resonance imaging (MRI), and electroencephalography (EEG). There were 2 peaks in incidence of infection; the first one in young children aged 1 to 5 years represented 62.0% of cases. The second peak (24.6% of patients) occurred in teenagers. Febrile seizures were confirmed in 3.1% of affected children younger than 5 years and headaches in 24.2% patients, mostly older children. Ten children presented severe, neurologic complications: meningoencephalitis, acute encephalitis, acute cerebellitis, transverse myelitis, and myeloradiculitis. Our study identified a variety of Epstein-Barr virus-related neurologic complications. Epstein-Barr virus should be routinely tested for when a child presents with an apparent neuroinfection as it is a common pathogen that can induce a wide variety of signs and symptoms.

Successful outcome of therapy of acute hepatitis C following sexual and parenteral exposure - report of two cases.

Acute hepatitis C (AHC) remains difficult to diagnose due to its asymptomatic course. The manuscript presents two children with AHC after known sexual and parenteral exposure, which allowed for close monitoring. Both developed increased aminotransferase activity, though the viral load was significantly higher after parenteral exposure. Lack of hepatitis C virus (HCV) clearance led to therapy with recombinant interferon-α with good toleration and response. The conclusion is that treatment of AHC was effective and well tolerated.

The significance of Bartonella henselae bacterias for oncological diagnosis in children.

BACKGROUND: Cat-scratch disease (CSD) is a common infection in children; however, the wide spectrum of its clinical picture may lead to delayed diagnosis. An unusual presentation of CSD includes in the differential diagnosis malignant diseases, Epstein-Barr and cytomegalovirus infections, tuberculosis, and mycobacterioses. The diagnostic procedure is difficult, and it is important to consider CSD as the etiology of untypical lesion. PATIENTS AND METHOD: We present the analysis of 22 immunocompetent children treated with the clinical diagnosis of CSD in our hospital. Their ages were 2 to 16 years (mean 9.15 ± 2.2 years). Four of them presented classical papulas at admission time. Asymmetric, local lymphadenopathy was present in 16 patients. Five children, who presented an untypical course of CSD mimicking the oncological process, were analysed carefully. There were 3 patients with skull osteomyelitis, 1 with inflammation of the parotid gland, and 1 with an extra peripharyngeal mass. The diagnosis in these children was based on epidemiological, radiological, serological, and histological factors. RESULTS: About 25 % of children with bartonellosis present an untypical spectrum of symptoms, including the lack of documented cat contact, primary lesions, or peripheral lymphadenopathy. Radiological methods like USG, CT, MRI present the unspecific masses, but they are not enough to distinguish the Bartonella inflammatory and oncological process. The final diagnosis was based on a histological method with additional polymerase chain reaction test. CONCLUSION: CSD should be considered in differential diagnosis of any patient with untypical lesions located on the head, neck, and upper extremities.

Cat-scratch disease: a wide spectrum of clinical pictures.

The aim of this review is to present an emerging zoonotic disease caused by Bartonella henselae. The wide spectrum of diseases connected with these bacteria varies from asymptomatic cases, to skin inflammation, fever of unknown origin, lymphadenopathy, eye disorders, encephalitis and endocarditis. The reservoirs of B. henselae are domestic animals like cats, guinea pigs, rabbits and occasionally dogs. Diagnosis is most often based on a history of exposure to cats and a serologic test with high titres of the immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, however, azithromycin has been shown to speed recovery.

Pulmonary presentation of Toxocara sp. infection in children.

INTRODUCTION: The aim of this study was to investigate the associations between radiological findings, blood eosinophilia, hyperimmunoglobulinemia E and G and Toxocara seropositivity in Polish children with newly diagnosed pulmonary infiltration. MATERIAL AND METHODS: We retrospectively analyzed the documentation of 119 patients, aged 1 to 18 years (mean age: 7.21 ± 4.82), who were seropositive in Toxocara sp. antibodies. In all cases, peripheral blood eosinophils and leukocyte counts, serum total IgE, IgG levels and specific IgG antibodies against excretory and secretory Toxocara sp. antigens were measured at the first presentation. After the confirmation of seropositivity, all children had a routine radiological examination. RESULTS: In the documentation of 23 children (mean age 3.58 ± 2.63 years) we found abnormalities in the radiological examination of their lungs. Fifteen children who had abnormalities in radiological findings presented clinical respiratory complaints such as chronic cough, wheezing, asthma and haemoptysis. Eight children were asymptomatic. The analysis of peripheral eosinophils and leukocyte number, the level of IgE and specific anti-Toxocara IgG presented significantly higher values in children with radiological lesions than in children who had correct radiology. The concentrations of total IgG and gamma globulins were not significantly different. In 10 patients CT showed irregular round nodules with and without halo ranging from 1 to 13 mm. The number of nodules varied from a single lesion to multiple, disseminated ones. All nodules were located in peripheral areas of the lungs. None of them were found in the central areas. In 13 patients, CT images showed ground-glass opacities with ill-defined margins. None of the CT images presented lymphadenopathy and pleural effusion. CONCLUSION: The pulmonary lesions in small children with high eosinophilia and hyperimmunoglobulinemia E could be related to toxocariasis and for this reason they are eligible to undergo therapy with prolonged observation for several months, rather than start invasive malignancy investigations.

Transient lesion in the splenium of the corpus callosum due to rotavirus infection.

Transient signal changes in magnetic resonance imaging (MRI) of the splenium of the corpus callosum (SCC) can result from many different reasons, including encephalitis and encephalopathy caused by infection, seizures, metabolic disorders and asphyxia. We report a case of a 6-year-old Polish girl with rotavirus infection demonstrating a reversible SCC lesion on diffusion-weighted MRI images. She presented six episodes of generalized tonic seizures with mild acute gastroenteritis. Stool test for rotavirus antigen was positive. At the time of admission imaging showed the hyperintense region in T2-weighted and fluid-attenuated inversion-recovery MRI, a well-defined lesion in the splenium of the corpus callosum with restricted diffusion in diffusion-weighted MRI and no enhancement in post contrast T1-weighted imaging. Her first EEG showed slow brain activity in the posterior occipitotemporal portion, consisting mainly of theta waves with a frequency of 4.5-5.5 Hz and amplitude of 40 uV. The lesion had completely disappeared on follow-up MRI 10 days later. The patient recovered fully without any sequelae.

Alterations in NK cell phenotype in relation to liver steatosis in children with chronic hepatitis C.

NK cells were found to play an important role in liver fibrosis, a process commonly seen in a chronic liver disease such as chronic hepatitis C (CHC). The aim of this study was to evaluate potential differences in relation to coexisting liver steatosis in children with chronic hepatitis C. The study group consisted of 31 children with chronic hepatitis, aged 7-18 years (mean = 15 ± 2 years). Blood samples were taken prior to liver biopsy. The METAVIR scale was used for histological evaluation. Peripheral lymphocytes were subjected to monoclonal antibodies to CD56 antigen, KIRs and NKG2D antigens. Cells were assayed by flow cytometry for the ratio of positive cells and mean fluorescence intensity (MFI). Results were evaluated regarding the presence of liver steatosis. Significantly higher mean AST activity as well as higher AST-to-platelets ratio index (APRI) was observed in a group of children with coexisting liver steatosis. These children had significantly higher MFI for CD158e and lower MFI for NKG2D. All CHC patients had significantly higher MFI for NKG2D than the controls. The proportion of cells with expression of CD158i, KIR2D and APRI was found independent predictors of liver steatosis in univariate analysis and body mass index in logistic regression. The expression of NK cell receptors is altered in coexisting steatosis that may influence long-term prognosis in CHC.

Clinical condition and transmission of coinfections with human cytomegalovirus in infants of HIV-1 infected mothers in the era of mother-to-child-transmission prophylaxis.

BACKGROUND AND AIM: The aim of the study was to evaluate the clinical state and the risk of coinfections in infants of HIV-1-infected women receiving MTCT prophylaxis. METHODS: The study included 35 Polish infants of HIV-1-infected mothers diagnosed for congenital infections. Children were evaluated for HIV-1, HCMV and HCV infection by serological and molecular methods during following visits up to 18th month of life. None of the children received breast milk after birth. RESULTS: HIV-1 infection was found in one child not receiving MTCT prophylaxis, one HCV infection was detected in another infant. HCMV-DNA in the urine was present in 13/35 children (37.14%) in the 10th day and 24/35 children (68.57%) at 4th week of life. The group of children managed with full and incomplete MTCT regimen did not differ in most clinical parameters. Children receiving MTCT prophylaxis were born more frequently as first children (p=0.045) and by cesarean section (p=0.047). HCMV-positive children receiving MTCT prophylaxis were had lower gestational age (p=0.03) and smaller head circumference (p=0.02). They were born more frequently as premature (0.02) and with low birth weight (0.02). Maternal cART and the use of protease inhibitors were not significantly associated with perinatal complications. No differences in CD4+ and CD8+ counts were noted between the group receiving full and incomplete MTCT protocol. CONCLUSIONS: ARV used in MTCT preventive protocols is safe for infants although the risk of the transmission of HCMV coinfection is not reduced.

The influence of age on a clinical presentation of Toxocara spp. infection in children.

UNLABELLED: Toxocariasis is a helminthozoonosis due to the infestation of humans by roundworms, Toxocara spp. Actual informations indicate it the most common worm infection in many countries, typically connected with rural areas. The authors analyzed the documentation of 84 children with positive serology to this worm. An individual record was made and following data were restricted: anamnesis data, clinical symptoms, epidemiological data, eosinophils number, level of immunoglobulins G and E. The highest Toxocara spp. seropositivity frequency was found in the schoolchildren aged 7-10. The most frequent clinical findings in children infected Toxocara spp. were lymphadenopathy, hepatomegaly, arthralgia and arthritis. 15.5% of seropositive patients presented non-specific symptoms originating from the central nervous system: headaches, sleep and behavioural disorders, and hyperactivity. The mean eosinophilia in the peripheral blood was detected in the youngest children: 4,023 cell/µl, which is 15.55 times more than the limit value. Hyperimmunoglobulinemia E was detected in all age groups, and the youngest children presented a serum concentration of IgE that was 16.47 times higher than the limit value. CONCLUSIONS: 1. Toxocara spp. infection is detected in children at every age, but the most specific age group are schoolchildren, representing 38% of positive individuals. 2. The clinical spectrum of toxocariasis reflects various manifestations depending on the internal organs infected by the migrating worms and the intensity of infection. 3. Eosinophilia seems to be a good marker of infection in young children who have a more symptomatic course of the disease. 4. Hyperimmunoglobulinemia IgE can be the important element which distinguishes between current and past Toxocara infection, but its meaning is not connected with the age of infected children.

Human cytomegalovirus infection and clinical status of infants born to human immunodeficiency virus type 1 infected mothers.

OBJECTIVE: Human cytomegalovirus (HCMV) is one of the most common congenital infections worldwide and a frequent opportunistic infection that aggravates the condition of human immunodeficiency virus (HIV)-infected patients. The aim of the study was to evaluate the frequency and factors influencing HCMV infection among infants of HIV-positive women. METHODS: The study included 35 infants born to HIV-1-infected mothers examined for congenital infections. Children were evaluated for human immunodeficiency virus type 1 (HIV-1), HCMV, and HCV infection by serological and molecular methods. RESULTS: HIV-1 infection was found in one child whose mother did not receive antiretroviral treatment during pregnancy, and HCV infection in another infant. HCMV-DNA in the urine was present in 13/35 infants (37.14%) on the 10th day and 24/35 infants (68.57%) in the 4th week of life. The majority of HCMV-infected infants were asymptomatic, although they manifested microcephaly and low birth weight significantly more frequently (p = 0.006 and p = 0.02, respectively). Type HIV prophylaxis did not influence HCMV transmission. CONCLUSIONS: Although often asymptomatic, HCMV infection in infants born to HIV-infected mothers is frequent and may be associated with prematurity, low birth weight, and microcephaly. Diagnostic procedures in children of HIV-infected mothers should involve HCMV.

Factors influencing clinical course and histological findings in children with chronic hepatitis B.

INTRODUCTION: Although the clinical course of chronic hepatitis B (CHB) is relatively mild in a majority of children, a certain proportion of patients develops chronic liver disease that finally results in serious liver injury. Reports regarding clinical outcome of infection are scarce. OBJECTIVE: The aim of this study was to assess inflammatory activity, fibrosis, and their correlation to clinical data in children with CHB before antiviral treatment. MATERIALS AND METHODS: The study included 200 children, aged 1.5-18 years (mean 7.49+/-4.01 years), with CHB hospitalized before liver biopsy between 1992 and 2003. History and clinical data were analyzed. Histopathological assessment was based on the modified Knodell system. Statistical analysis was performed, and results with P<0.05 were considered significant. RESULTS: Necroinflammatory activity was found to be mild in 115 children and moderate in 44. Ninety-three children had minimal fibrosis (S1), 62 children - S2, and the remaining 8 - S3-S4. Alanine aminotransferase (ALT) activity was proportional to staging (Kruskall-Wallis test H=10.84, P=0.028) and was significantly higher in the children with staging >or=S2, P=0.0008. Spontaneous hepatitis B early antigen seroconversion occurred in 30/200 children (15%) and was related to the shorter length of infection, P=0.008. CONCLUSION: Intensity of liver injury in children with CHB varies from minimal to marked necroinflammatory activity and fibrosis varies from none to advanced. Progression of liver fibrosis seems to be proportional to the age at infection. ALT activity appears to be higher in the children with significant (S2-S4) fibrosis. Spontaneous hepatitis B early antigen seroconversion is apparently related to the shorter length of infection and higher ALT activity.