HCV and HGV infection, iron overload and liver disease in multitransfused patients with thalassaemia and persistently normal or abnormal transaminase levels

Prevalence and influence on liver disease of HCV and HGV infections, and HCV genotypes were studied in 28 HCV-Ab positive multitransfused thalassaemia patients with persistently normal ALT levels (group A) matched by sex and age with 28 patients with increased ALT levels (group B). Laboratory and virologic tests (all patients), liver biopsy (28 patients) and LIC by SQUID (30 patients) were performed. In group A, HCV-RNA was positive in 39%, genotype 2a was detected in 91%. In Group B, HCV-RNA was positive in 89%, prevalence of genotype 1b and 2a was 52% and 48% respectively; compared with group A, they had significantly increased values of gammaGT, AF, BA, TP, IgG, IgA, LIC (group B: 2,142 -/+ 1,524 microg/g liver; group A: 1,084 -/+ 610 microg/g liver). Overall prevalence of HGV-RNA was low (12.5%) and not significantly different between groups. Liver biopsies revealed no cirrhosis and severe fibrosis was found in 3 HCV viremic patients in group B. In 14 viremic patients examined both for LIC and liver histology, mild fibrosis was observed in 71%, in which iron overload was below 5 times the normal value. In conclusion, in patients with normal ALT levels, active HCV infection must be excluded by evaluation of HCV-RNA. Liver biopsy is indicated in HCV viremic patients, independent of ALT levels; in non-viremic patients, increased ALT levels may be due to iron overload and LIC measurement is indicated. Our data emphasise the crucial role of chelation therapy to maintain low LIC levels in order to prevent progression of fibrosis to cirrhosis in patients with HCV chronic hepatitis.     

Liver histology and alanine aminotransferase levels in children and adults with chronic hepatitis C infection

BACKGROUND: Chronic hepatitis C is often a mild disease in children, but whether this is related to younger age or shorter duration of infection is unclear. Histologic severity has been shown to correlate with duration of infection regardless of age. OBJECTIVES: We compared histologic findings in children and adults with chronic hepatitis C while controlling for sex, duration of infection, hepatitis C virus (HCV)-RNA level, and genotype. METHODS: Twenty-one children and 52 adults whose infection was less than 20 years in duration and who had undergone a liver biopsy were included. Two blinded liver pathologists reviewed the liver biopsies and scored inflammatory activity and fibrosis using the modified Knodell scoring system. RESULTS: The groups were the same with respect to HCV-RNA level (P=0.8), and genotype (P=0.6) but differed in duration of disease (P=0.01) and sex composition (P=0.005). Covariate analysis showed no influence of genotype, duration of infection, or HCV-RNA level on outcome. In controlling for sex, children had significantly milder liver disease and alanine aminotransferase (ALT) elevations. CONCLUSIONS: With equal duration of infection, HCV-RNA level, and genotype, children have lower serum ALT levels and less severe liver disease than adults infected with HCV.     

Virus genotype 1b and long-term response to interferon alpha monotherapy in children with chronic hepatitis C

Interferon alpha (IFN-) remains the basic modality in the treatment of chronic hepatitis C in children, but the effects of therapy are still unsatisfactory. The aim of this study was to evaluate parameters linked to IFN- response within a 2-year period. Human C virus (HCV) infected children (n=34) were subdivided into IFN-treated (n=20) and IFN-untreated (n=14 control) groups. The IFN-treated group received a dosage 3 MU of IFN- three times a week for 24 weeks. Liver biopsy was performed in all IFN-treated children and the HCV genotype was determined before the start of the study. Patients were sequentially screened for alanine transaminase (ALT) activity and tested for the presence of HCV-RNA in serum. All patients had either mild persistent or moderate active hepatitis, which was diagnosed from the liver biopsy. In the IFN-treated group ALT normalisation was observed by the end of treatment in 9/20 patients, but after 6 months 10 patients (50%) had sustained ALT normalisation and in 4 of them the virus was eliminated. They continued to show these features up to the end of the observation period (2 years). Eighteen out of 24 children tested had 1b genotype of virus. Out of 10 responders, all patients who were clear of HCV had the 1b genotype. The median age of responders (6.0, range 3.8–16) was significantly lower than non-responders (14.0, range 4–15) In the control group none of the children were clear of HCV-RNA. Conclusion: The negative predictive effect of HCV genotype 1b in the course of IFN- treatment may be not valid in children and other features have to be taken into account in the assessment of the efficacy of therapy.Abbreviations HCV human C virus - RNA ribonucleic acid - PCR polymerase chain reaction - ALT alanine aminotransferase - RBC red blood cells - HBsAg hepatitis B surface antigen - ELISA enzyme linked immunosorbent assay - CMV cytomegaly virus - IFN interferon - MU mega units - ETR end of treatment response - SR ALT sustained biochemical (ALT) response - HAI histological activity index - R responders - NR non-responders - U/l units per litter - CPH chronic persistent hepatitis - CAH chronic active hepatitis - APC antigen presenting cells - MHC major histocompatibility complex - ALL acute lymphoblastic leukaemia - CML chronic myelogenous leukaemia     

Lymphoblastoid interferon alfa treatment in chronic hepatitis C

Interferon is becoming the standard treatment in adults for chronic hepatitis C. Twenty one children with histologically proved chronic hepatitis C (10 boys, range 2.5-13 years), who were otherwise healthy, were enrolled in a randomised controlled study to test their response to interferon alfa. Eleven children were treated with lymphoblastoid interferon alfa (3 million units/m2) for 12 months; 10 children received no treatment. All had raised transaminases and positive antihepatitis C virus (HCV) antibodies and HCV-RNA. Alanine aminotransferase (ALT) serum levels became normal in five (45%) treated patients after a mean of three weeks (range 1-6 weeks) and no relapse had occurred by the end of follow up (30th month). Only one (10%) untreated patient had normal ALT serum levels from the 11th until the 30th month. Disappearance of serum HCV-RNA, persisting throughout the follow up period, was observed in the six children (five treated) whose ALT became normal. Biopsy specimens in treated patients showed a significant improvement in Knodell's score (median (SD) basal 9.0 (2.2); final 2.0 (0.4)). Interferon treatment was well tolerated in all. This study confirms the efficacy of interferon in children with chronic hepatitis C, not only by restoring normal ALT serum levels, but also viral clearance and histological amelioration of liver inflammation. Contrary to reports in adults no biochemical and virological relapses occurred in responder children.     

Lymphoblastoid interferon alfa treatment in chronic hepatitis C.

Interferon is becoming the standard treatment in adults for chronic hepatitis C. Twenty one children with histologically proved chronic hepatitis C (10 boys, range 2.5-13 years), who were otherwise healthy, were enrolled in a randomised controlled study to test their response to interferon alfa. Eleven children were treated with lymphoblastoid interferon alfa (3 million units/m2) for 12 months; 10 children received no treatment. All had raised transaminases and positive antihepatitis C virus (HCV) antibodies and HCV-RNA. Alanine aminotransferase (ALT) serum levels became normal in five (45%) treated patients after a mean of three weeks (range 1-6 weeks) and no relapse had occurred by the end of follow up (30th month). Only one (10%) untreated patient had normal ALT serum levels from the 11th until the 30th month. Disappearance of serum HCV-RNA, persisting throughout the follow up period, was observed in the six children (five treated) whose ALT became normal. Biopsy specimens in treated patients showed a significant improvement in Knodell''s score (median (SD) basal 9.0 (2.2); final 2.0 (0.4)). Interferon treatment was well tolerated in all. This study confirms the efficacy of interferon in children with chronic hepatitis C, not only by restoring normal ALT serum levels, but also viral clearance and histological amelioration of liver inflammation. Contrary to reports in adults no biochemical and virological relapses occurred in responder children.     

Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission

BACKGROUND: The studies on hepatitis C virus (HCV) vertical transmission, the effect of potential risk factors and the role of breast-feeding have reported conflicting results. PATIENTS AND METHODS: Seventy-three infants of 63 anti-HCV-positive and anti-HIV-negative mothers were studied from 1993 to 1999 in the south of Spain. The mean period of follow-up in children was 29.2 +/- 19 months (range, 8 to 76 months); 6 (8%) children were lost to follow-up. Breast milk was studied for HCV-RNA in 68 samples of 35 mothers. RESULTS: Alanine aminotransferase was high in 19 (26%) and HCV-RNA was positive in 46 (63%) pregnant woman. Breast milk HCV-RNA was negative in nonviremic mothers and positive in 20% of the viremic mothers. The overall rate of vertical HCV transmission was 11.9% (n = 8) (95% confidence interval, 6 to 23%) if HCV-RNA was positive one or more times, but only 1.5% (n = 1) (95% confidence interval, 0.1 to 9%) if HCV-RNA was permanently positive. Seven HCV-infected children did not develop antibodies to HCV, and they had a spontaneous clearance of the virus. A 10-month-old baby was HCV-RNA-positive from birth to the end of the follow-up. The genotype in each of the infants was consistent with that of their mother. The rate of HCV transmission was higher for infants of mothers with higher HCV viremia (P < 0.01) and also for infants whose mothers were HCV-RNA-positive in breast milk (P < 0.05). There were no statistically significant differences between other risk factors. CONCLUSION: The presence of transitory viremia without seroconversion indicates that the vertical transmission of HCV is not important. This could be related to the viral charge and ingestion of milk of HCV-RNA-positive mothers. However, to advise avoidance of maternal breast feeding, it would be necessary to conduct larger studies.     

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus

Objective: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV).Study design: Multicenter prospective-retrospective study in Italian children.Patients: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 ½ to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months.Methods: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up.Results: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis.Conclusions: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood. (J Pediatr 1997;130:990-3)     

Spontaneous remission of chronic hepatitis C in children

The clinical course of 48 children with chronic hepatitis C (33 boys, 15 girls; mean age: 12.2 years) was monitored for more than 3 years to clarify its natural course. All patients were positive for the second-generation antibody to hepatitis C virus (anti-HCV) and for serum hepatitis C virus (HCV) RNA. All but one patient had a history of blood transfusion. Serum levels of alanine aminotransferase (ALT) had been abnormal for more than 1.5 years. Spontaneous remission defined as a biochemical remission lasting more than 1 year in association with the disappearance of serum HCV RNA, occurred in 4 (8.3%), however, in 25%, HCV RNA was still detectable in the liver even after its disappearance from serum. In this patient, the level of antibody to HCV core antigen (anti-HCV core) did not decrease significantly and serum HCV RNA eventually reappeared. The serum titre of HCV RNA in the 4 children with spontaneous remission was lower than in the remaining 44 children. Spontaneous remission may occur in children with chronic hepatitis C in whom the serum titre of HCV RNA is low and serum level of anti-HCV core decreases significantly. Assessment of the intrahepatic HCV RNA is necessary to confirm complete remission. Conclusion A low serum titre of HCV RNA and a significant decrease in the serum titre of anti-HCV core were associated with spontaneous remission in children with chronic hepatitis C. Intrahepatic HCV RNA assessment is necessary to confirm complete remission. Received: 9 April 1996 and in revised form: 8 April 1997 / Accepted: 15 April 1997     

Natural history of vertically acquired HCV infection and associated autoimmune phenomena

The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9–15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. Conclusions: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.     

Serum alanine aminotransferase activity in obese children

To confirm the significance of the serum alanine aminotransferase (ALT) test for the diagnosis of fatty liver and to clarify the relationship between serum ALT activity and the duration of obesity, we analysed 310 obese young schoolchildren (195M, 115F), who were classified into three duration groups (1–3 y, 4–6 y, 7+ y), three age groups (6–7 y, 8–9 y, 10–11 y), and four obesity groups (weight excess; mild, 20–29%: moderate, 30–39%; severe. 40–49%; very severe. 50%). Seventy-seven patients with abnormal ALT test, >30 IU/1, and 27 patients with normal ALT test were examined by ultrasound study to identify the fatty-fibrotic pattern of the liver. Abnormal results of the serum ALT test were found in 24% of all patients. The fatty-fibrotic pattern was identified in 64/77 (83%) patients with abnormal ALT test and in 5/27 (18%) patients with normal ALT test. The serum ALT test has a sensitivity of 0.92 for detecting the fatty-fibrotic pattern proven by ultrasound study Frequencies of cases with abnormal serum ALT levels increased with the duration of obesity. In the shortest duration group, however, the frequencies of abnormal results in serum ALT test did not increase with advanced ages or the grades of obesity. In conclusion, the present study confirmed the usefulness of the serum ALT test for screening fatty liver, and showed that a longer duration of obesity is generally associated with the occurrence of fatty liver in a paediatric obese population. In young patients with mild obesity or a short duration of obesity, however, fatty liver or fatty fibrosis may develop. Early intervention should be made in the case of obese children.     

Hepatitis C virus infection and interferon therapy in patients with Down syndrome.

BACKGROUND: The clinical features of hepatitis C virus (HCV)-associated liver diseases, or the efficacy of interferon (IFN) therapy in children with Down syndrome (DS) remain to be elucidated. The purpose of the present paper was to survey the features of liver diseases in this subset of children and evaluate the efficacy of IFN treatment in those patients. METHODS: A questionnaire was sent to 41 members of the Japan Society of Pediatric Hepatology. Ten of them reported on 11 patients with DS who had concomitant chronic HCV infection, providing information on liver disease and the response to IFN treatment. RESULTS: Interferon therapy of 24 weeks duration using natural IFN-alpha was instituted in six of the 11 patients with DS, but none of the six patients cleared HCV-RNA from their serum. Among 12 age- and sex-matched control children who were treated with IFN using the same regimen against chronic HCV infection, half of them had a favorable response to IFN therapy with a sustained clearance of HCV-RNA from their serum. The major baseline features including alanine aminotransferase levels, HCV genotype and viral load were not apparently different between the six patients with DS and the 12 controls. CONCLUSIONS: IFN therapy for HCV infection in patients with DS may be unfavorable as compared with non-DS children.     

Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children

OBJECTIVE: To evaluate the clinical pattern and evolution of chronic hepatitis C in children with liver/kidney microsomal antibody type 1 autoantibodies (LKM1). STUDY DESIGN: A multicenter, retrospective study, including the following groups of children with hepatitis C virus infection: (1). 21 consecutive LKM1-positive patients, (2). 42 age- and sex- matched LKM1-negative patients, and (3). 4 interferon-induced LKM1-positive cases. LKM1 reactivity to human microsomes and recombinant cytochrome P450IID6 (CYP2D6) was assayed by immunoblotting. RESULTS: Clinical and biochemical features overlapped in LKM1-positive and LKM1-negative children, but a fibrosis score >3 (range 0-6) was significantly more frequent (P =.04) in the former. Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Five of 7 LKM1-positive children treated with interferon had an ALT exacerbation. CONCLUSIONS: LKM1-positive hepatitis C in children is characterized by a wide spectrum of biochemical, serologic, and histologic features. Whether autoimmunity may contribute to liver damage in a subgroup of patients with more severe liver disease, high LKM1 titers, and reactivity to CYP2D6 is a question deserving further investigation.     

Look-back study of Hepatitis C in teenagers after blood transfusions as neonates

AIM: To conduct a single-centre "look-back" study of the prevalence of hepatitis C in teenagers who had received blood products as newborns, prior to hepatitis C virus (HCV) blood donor screening. METHODS: Using blood bank records, we identified 732 surviving teenagers aged 14-18 years who had received blood products as neonates during 1986-1990. Letters recommending HCV antibody testing were sent to 732 surviving teenagers; 581 recipients were contacted and invited to undergo testing, and, of these, 429 consented (59% of the survivors). HCV antibody testing was performed on all and HCV-RNA was tested on those who were antibody positive. RESULTS: Three teenagers (0.7%, 95% CI 0.54-0.86) tested positive for HCV antibodies and all three were HCV-RNA positive. There were no cases in which antibodies were detected and polymerase chain reaction (PCR) was negative. Two of the three had mildly elevated liver enzymes and all three had mild inflammatory activity and low fibrosis scores on liver biopsy. CONCLUSIONS: The look-back process, even in a single centre with a stable urban population, is relatively inefficient in screening at-risk populations. Although the prevalence of hepatitis C in this sample was relatively low, paediatricians should offer screening to teenagers and young adults who received blood products in the neonatal period.     

Mother-to-infant transmission of hepatitis C virus

Anti-hepatitis C virus (HCV) antibodies and HCV-RNA were measured in the sera of 22 anti-HCV positive, HIV-1 negative mothers and their infants. ELISA and RIBA II were used for anti-HCV determination. HCV-RNA was measured by a nested polymerase chain reaction. HCV-RNA was found in 12 of 22 mothers. All 22 children were followed for 12 months. All were anti-HCV positive by the fourth month; 18 became anti-HCV negative between the 8th and 12th month. HCV-RNA was detected in 5 of 22 infants in the fourth month. They remained HCV-RNA positive. All children born to HCV-RNA negative mothers were HCV-RNA negative while 5 of 12 babies born to HCV-RNA positive mothers were infected. All five infected babies were born to mothers infected through transfusions or drug use. ALT levels in mothers seemed to have no effect on mother-to-infant transmission. Hence evidence for perinatal transmission of HCV from HCV-RNA positive mothers was demonstrated in the present study.     

儿童1b基因型丙型肝炎抗病毒治疗效果分析

目的了解儿童1b基因型丙型肝炎(丙肝)的临床特点,探讨聚乙二醇干扰素α(PEG-IFNα)或普通干扰素α(IFN-α)联合利巴韦林(RBV)的疗效和不良事件。方法收集复旦大学附属儿科医院感染传染科2011年11月至2014年12月收治的丙肝连续病例,截取其临床表现、治疗前基线、治疗期间HCV RNA等实验室指标和不良事件,行描述性分析。结果 10例1b型丙肝患儿进入分析,男8例,女2例;确诊时平均年龄37.1个月(8月龄至6.6岁)。10例均无明显临床症状,2例为母婴传播,8例非母婴传播(4例疑为输液器污染而感染,4例原因不明)。1治疗前9例HCV-Ab阳性,8例HCV RNA载量1×103IU·m L-1,5例ALT和AST轻度升高;7例行肝脏组织活检:1例提示肝脏轻度脂肪变性;炎症活动度2例G1级,3例G2级,1例G3级;纤维化程度分期1例S0期,3例S1期,2例S2期;27例接受了PEG-IFNα或IFN-α联合RBV治疗,6例治疗12周HCV RNA载量均1×103IU·m L-1,1例治疗4周HCV RNA载量1×103IU·m L-1,仍在治疗随访中;2例未接受抗病毒药物治疗,分别随访了16周和24周,HCV RNA持续1×103IU·m L-1,肝功能持续正常;1例母婴传播8月龄患儿未予抗病毒药物治疗,出院后失访;37例抗病毒治疗患儿均未观察到严重的不良事件,治疗初期均有发热,治疗4周1例出现WBC轻度降低,PLT出现3次一过性降低,Hb均无异常。结论 1b基因型丙肝患儿肝脏组织炎症和纤维化程度均较轻。PEG-IFNα或IFN-α联合RBV治疗儿童1b基因型丙肝反应良好,未见严重的不良事件。     

儿童慢性乙肝肝组织病理与相关标志物的研究

目的分析乙肝病毒核内共价闭合环状DNA（HBV cccDNA）、肝纤维化血清标志物、乙肝病毒基因型与肝脏纤维化和炎症活动度的相关性,以了解其在乙肝诊断中的价值,指导治疗和预后。方法2008年4月至2011年8月于甘肃省人民医院儿科和兰州大学第一医院感染科门诊就诊和住院的乙肝及HBV携带患儿为慢性乙肝组和HBV携带组,选择同期健康查体儿童为对照组。检测慢性乙肝组、HBV携带组和对照组血清HA、LN、PCⅢ和CⅣ。依据病情严重程度,慢性乙肝组进一步分为轻度、中度和重度亚组;慢性乙肝组和HBV携带组检测血清HBV cccDNA和HBV基因型;分析HBV cccDNA、肝纤维化血清标志物、HBV基因型与肝脏纤维化和炎症活动度的相关性。结果46例患儿进入分析,男34例,女12例,年龄1～16岁,平均年龄（11.8±3.7）岁。HBV携带组20例,慢性乙肝组26例（轻度13例、中度8例、重度5例）,对照组20例。①随乙肝临床分度加重,血清HA、LN、PCⅢ和CⅣ呈升高趋势,以重度乙肝亚组上升最为明显;②随肝组织纤维化程度与炎症活动度的增加,血清HA、LN、PCⅢ和CⅣ呈升高趋势;③ 血清HBV cccDNA阳性组与阴性组在肝组织炎症活动度     

Prolylhydroxylase and procollagen type III in long-term survivors of acute lymphoblastic leukemia (ALL): a biochemical approach to HCV-related liver disease

BACKGROUND: We examined two proteins, prolylhydroxylase (hPH) and procollagen type III (PIIIP), as possible non-invasive HCV-related markers of liver disease. The purpose of this study was to assess whether the measurement of these proteins could serve to monitor HCV related liver damage in acute lymphoblastic leukaemia (ALL) patients. PROCEDURE: A total of 34 ALL patients, 24 HCV-seropositive and 10 HCV-seronegative, who had had increased transaminase values (ALT) for almost 6 months were studied. Serum hPH concentrations were determined by an immuno-enzymatic assay kit. PIIIP was assayed by the radioimmunoassay method. RESULTS: Both hPH and PIIIP were increased in ALL patients with chronic hepatitis C. Serum hPH levels were significantly elevated in those with chronic hepatitis C with either normal or high transaminases when compared to those who never were HCV seropositive. The sensitivity and specificity of these protein measurements to evaluate hepatic fibrosis were not supported by histologic confirmation because only 6 out of 12 patients with chronic hepatitis had a liver biopsy. CONCLUSIONS: Our study suggests that PIIIP and hPH values are significantly higher in ALL patients with chronic HCV with either normal or high transaminases. This might suggest that the liver damage is more marked in patients with chronic hepatitis and that the liver damage is related to the HCV rather than chemotherapy. Future studies correlating histologic findings with the serum biochemical markers are required to establish the sensitivity and specificity of hPH and PIIIP in predicting hepatic fibrosis and to confirm this association.     

Autoimmune hepatitis

Autoimmune hepatitis is one of the causes of chronic progressive liver disease in childhood. Here we report 14 cases with clinical findings, therapeutic management and prognosis, in order to define the course of the disease. Diagnosis of autoimmune hepatitis was done with the presence of at least one of these autoantibodies; antinuclear antibody, smooth muscle antibody, liver-kidney microsomal type 1 antibody, and perinuclear antineutrophilic cytoplasmic antibody. Patients were seen every 3 to 6 months. After doing a complete physical examination, biochemical parameters and autoantibodies determined at each visit. Mean age at diagnosis was 10.9±2.6 years (range, 7–15.5 years) and female to male ratio was 1∶3. Thirteen patients had jaundice and all had high levels of ALT, AST and gammaglobulin. Hepatomegaly was found in 71.4% and splenomegaly in 64.3% of the patients. All patients were classified as type 1 autoimmune hepatitis. Liver biopsies revealed severe active hepatitis with mononuclear cell infiltration in portal areas, piecemeal necrosis. Drug therapy consisted of prednisone (2 mg/kg/day) per oral at the beginning, and addition of azathioprine (1.5 mg/kg/day) per oral at the 3rd-6th month with slow tapering of prednisone in 12 children. Both drugs were started together to two patients. Follow-up period was 30.7±15.6 months (range, 12–72 months). Sustained normalization of ALT could not be obtained with tapering doses of prednisone alone. Decrease in ALT levels did not correlate with disappearance of serum autoantibodies. None of the patients showed decompensation of liver disease. Azathioprine administration is necessary to decrease prednisone dose and to maintain a sustained normal transaminase values.     

Prevalence of hepatitis C virus (HCV) infection and its vertical transmission in Egyptian pregnant women and their newborns

We studied the prevalence of hepatitis C virus (HCV) antibody seropositivity using ELISA (Ortho Diagnostic system, 3rd generation test) polymerase chain reaction testing of HCV-RNA (PCR, Promega) and serum alanine transferase (ALT) level in 100 healthy, HIV-negative, pregnant women who delivered spontaneously at the Alexandria University Hospital, and their newborns. Some risk factors were studied using Fisher's exact test. Nineteen per cent of pregnant women were HCV seropositive and 14 of them (14/19) had circulating HCV-RNA, detected by PCR. Nine of the babies born to the 19 HCV seropositive females had circulating antibodies, whereas HCV-RNA was detected in five of them. This gives a vertical transmission risk of 5/14 (36 per cent) for mothers carrying the HCV-RNA and 5/19 (26 per cent) for those having circulating HCV antibodies. History of previous blood transfusion, elevated serum ALT level, and history of infection with schistosomiasis were significant risk factors for HCV infection in mothers. In addition to the previous factors, maternal history of jaundice, stillbirth and hepatomegaly were significant risk factors for neonatal infection. The occurrence of early jaundice and the presence of congenital anomalies in the newborns were non-significant risk factors. In conclusion, our data indicate a high prevalence of HCV seropositivity in Egyptian HIV-negative pregnant women with a significant high rate of vertical transmission of HCV.