Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis.

BACKGROUND: Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. METHODS: This cross-sectional study included 50 children, 5-18 years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. RESULTS: The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. CONCLUSION: APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

The adverse effects of interferon-free regimens in 149 816 chronic hepatitis C treated Egyptian patients.

BACKGROUND: Interferon-free regimens are associated with high sustained virological response; however, associated adverse effects have yet to be fully reported. AIM: To evaluate the adverse effects associated with the different direct-acting antiviral drug (DAA) regimens in Egyptian patients. METHODS: This multicenter retrospective study included all adverse effects during and after treatment with DAA regimens of 149 816 chronic hepatitis C treated Egyptian patients. Patients received sofosbuvir (SOF)/ribavirin (RBV) (n = 21 835), SOF/simeprevir (n = 24 215) SOF/daclatasvir (DCV) (n = 58 477), SOF/DCV/RBV (n = 45 188) and paritaprevir/ombitasvir/ritonavir/RBV (n = 101). The duration of treatment varied between 12 and 24 weeks. All changes in the treatment regimens, discontinuation, mortality, and serious side effects were reported. RESULTS: Adverse effects developed in 2475 (1.7%) (mean age [54 ± 9], male gender [53%]) patients. Serious side effects developed in 68% of these patients, and SOF/RBV was the most common causing regimen (73%, P < 0.001). Anaemia and hyperbilirubinemia were the most common side effects (731/149816, 0.5% and 463/149816, 0.3%, respectively) and SOF/RBV (588/21835, 3% and 353/21835, 1.6%, respectively) showed the highest incidence in the treated patients. Hepatocellular carcinoma and mortality were reported in 0.02% and 0.06% of all treated patients, respectively. Patients with liver cirrhosis showed higher incidence of serious side effects (Log rank P = 0.045) and mortality (Log rank P = 0.025) than patients without liver cirrhosis. Male gender (P = 0.012), lower haemoglobin (P < 0.001), platelets (P < 0.001) and albumin (P = 0.001), higher bilirubin (P = 0.002) and cirrhosis (P < 0.001) were factors associated with serious side effects development. CONCLUSION: Adverse effects associated with DAAs are few, anaemia being the most common. SOF/RBV regimen showed the highest rate of side effects while SOF/DCV showed the least.

Sofosbuvir-based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt.

BACKGROUND: Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Health's National Treatment Programme introduced sofosbuvir-based therapy in October 2014. AIM: To assess the clinical effectiveness and predictors of response to SOF-based treatment regimens, either dual therapy, with SOF/ribavirin (RBV) for 6 months or triple therapy with SOF/peg-IFN-alfa-2a/RBV for 3 months, in a cohort of patients treated in National Treatment Programme affiliated centres in Egypt. METHODS: Between October 2014 and end of 2014, patients who were eligible for treatment were classified according to their eligibility for interferon therapy: Group 1 (interferon eligible) were treated with triple therapy for 12 weeks and Group 2 (interferon ineligible) were treated with dual therapy for 24 weeks. Difficult to treat patients included those with F3-F4 on Metavir score, Fib-4 >3.25, albumin ≤3.5, total Bilirubin >1.2 mg/dL, INR >1.2 and platelet count <150 000 mm3 . RESULTS: Twelve weeks post-treatment data were available on 14 409 patients; 8742 in group 1 and 5667 in group 2. In group 1, the sustained virological response at week 12 (SVR12) was 94% and in group 2 the SVR12 was 78.7%. Multivariate logistic regression analysis in which treatment failure is the dependent variable was done. Male gender, being a difficult to treat patient and previous interferon therapy were significant predictors of nonresponse in both treatment groups. CONCLUSION: Results of sofosbuvir-based therapies in Egypt achieved similar rates of SVR12 as seen in phase III efficacy studies.

Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naïve and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis.

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4-infected patients with METAVIR F0-F4 fibrosis. Sixty-three patients (33 treatment-naïve and 30 peg-interferon/ribavirin (Peg-IFN/RBV)-experienced) enrolled in a partly randomized, open-label, multicentre, phase IIa study. Patients with F0-F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82-97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg-IFN/RBV null responders. The most commonly reported treatment-emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4-infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight- and 12-week regimens.

The future for the treatment of genotype 4 chronic hepatitis C.

Hepatitis C virus genotype 4 (HCV-4) is the most common type of hepatitis C virus (HCV) in the Middle East and Africa, in particular Egypt. Since the development of new protease inhibitors, the response of HCV-4 to the standard regimen of treatment (pegylated interferon/ribavirin) lags behind other genotypes and has become the most resistant type to treat. The development of therapeutic strategies for all patients with HCV-4 whether they are naïve, have experienced a virological breakthrough, are relapsers or non-responders is still a considerable challenge. New types of interferon (Consensus Interferon, Y-shaped, Albinterferon...) and new direct action antiviral drugs (Nitazoxanide, Vit.D, other) may improve the treatment of patients with HCV-4. The IL28B CC polymorphism may be associated with sustained virological response.

Anti-HCV prevalence among diabetic and non-diabetic Egyptian children.

Our aim was to determine the prevalence of the HCV infection among children with type 1 DM as compared to a group of non-diabetic children attending the general outpatient clinics of the same hospital and investigate the possible risk factors. The study was carried out on 692 children with type 1 DM attending the Pediatric Diabetes Unit at Cairo University Pediatric Hospital, Egypt, and 1042 non-diabetic children attending the general outpatient clinics of the same hospital. They were screened for HCV antibodies using third generation ELISA. Anti-HCV antibody prevalence in diabetic children below 9 years of age was comparable to that of non diabetic children (2.5% vs. 1.4%; p=0.25). Diabetic children had higher exposure to medical care (p=0.04); all diabetics were exposed to daily insulin injections and daily blood glucose monitoring. Non-diabetics had higher exposure to razors used by others (p=0.05) and higher rate of traditional hair cutting (p=0.05). To conclude, the prevalence of anti-HCV in diabetic children below 9 years of age was comparable to non diabetic children of the same age group. Application of standard precautions for infection control could successfully limit spread of HCV infection in our Pediatric Diabetes Unit, in a country with high HCV load as Egypt.

Clinicovirologic analysis of hepatitis C infection in transfusion-dependent beta-thalassemia major children.

Regular blood transfusion puts beta-thalassemia major patients at a higher risk of developing hepatic iron overload and hepatitis C virus (HCV) infection. The association between several transfusion-related factors and an increased risk of developing HCV viremia has been reported. The effect of HCV infection on liver damage in transfusion-dependent thalassemia patients has been poorly described. A sample of 100 Egyptian transfusion-dependent beta-thalassemia major children were studied. Individual patients underwent full history taking, clinical examination and a panel of laboratory tests including HCV ribonucleic acid polymerase chain reaction (HCV-PCR) in blood samples. Liver biopsy was performed for 24 patients. HCV-PCR was positive in 64% of patients. A statistically significant correlation was found between HCV-PCR positivity (HCV viremia) and shorter inter-transfusion interval. There was a significant positive correlation between mean serum ferritin level and mean levels of alanine aminotransferase and aspartase aminotransferase. Histopathologic features of both chronic hepatitis and siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in 41.67%. A higher risk of HCV viremia is noted with a shorter inter-transfusion interval. The reduced role of HCV infection in chronic liver injury in this group of patients may be surpassed by the associated effects of iron overload because of the chronic transfusion. However, the latter finding should be verified in larger studies.

Improvement of steatosis after interferon therapy in HCV genotype 4 is related to weight loss.

INTRODUCTION: Hepatic steatosis is common in patients with chronic hepatitis C virus (HCV) infection, and its occurrence may be related to both host and viral factors. Relationship between improvement in steatosis and response to anti-viral treatment remains unclear. This study assessed the factors associated with steatosis in patients infected with genotype 4 HCV, and to correlate degree of changes in steatosis with host factors and response to treatment. METHODS: Records of 175 patients with chronic genotype 4 HCV infection, who had received interferon and ribavirin combination therapy, were reviewed retrospectively to extract data on body mass index (BMI), presence of diabetes mellitus, and liver histology findings. Paired BMI data and liver biopsies (pre- and 24-weeks post-treatment) were available in 86 patients. Baseline steatosis and its changes (before and after treatment) were the dependent variables in a univariate and multivariate analyses. RESULTS: Steatosis was found in 88/175 (50.3%) of baseline biopsies. Its presence was related to baseline BMI (r=0.33, P<0.01), but not with viral load, or grade of liver inflammation or fibrosis. On follow up, improvement in steatosis was significantly associated with degree of weight loss but not with response to anti-viral treatment. CONCLUSION: Steatosis is common in genotype 4 HCV infection, and its presence appears to be related to high BMI, but not to viral load or degree of liver injury.

Cost-effectiveness of prescreening versus empirical vaccination for hepatitis A in Egyptian children with chronic liver disease.

The aim of the study was to determine the prevalence of anti-hepatitis A virus (anti-HAV) antibodies among 172 children with chronic liver disease, and to calculate the cost-effectiveness of prescreening prior to hepatitis A vaccination. Anti-HAV antibodies were positive in 85.1%. However, seroprevalence of anti-HAV antibodies was 62.1% in children < 5 years and 94.4% in children 5+ years. We conclude that while it is cost-effective to do prescreening before hepatitis A vaccination for children with chronic liver disease aged 5+ years, prescreening might not be cost-effective in those aged < 5 years.

Cost-effectiveness of prescreening versus empirical vaccination for hepatitis A in Egyptian children with chronic liver disease

The aim of the study was to determine the prevalence of anti-hepatitis A virus [anti-HAV] antibodies among 172 children with chronic liver disease, and to calculate the cost- effectiveness of prescreening prior to hepatitis A vaccination. Anti-HAV antibodies were positive in 85.1%. However, seroprevalence of anti-HAV antibodies was 62.1% in children < 5 years and 94.4% in children 5+ years. We conclude that while it is cost-effective to do prescreening before hepatitis A vaccination for children with chronic liver disease aged 5+ years, prescreening might not be cost-effective in those aged < 5 years

Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children.

AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver disease. RESULTS: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children.

Study of substance P, renin and aldosterone in chronic liver disease in Egyptian children.

UNLABELLED: Substance P is the most powerful endogenous vasodilator peptide produced by the enteric nervous system and partly cleared by the liver. Failure of the diseased liver to metabolize a vasodilator substance may be responsible for the rebound increased plasma level of vasoconstrictor intestinal peptide. AIM: To investigate the plasma level of Substance P and to study its relationship to aldosterone and plasma renin activity changes occurring in pediatric patients with chronic liver disease. METHODS: Forty patients with chronic liver disease and 10 healthy children were tested for AST, ALT, total and direct bilirubin, creatinine, aldosterone, plasma renin activity and plasma level of Substance P. RESULTS: The plasma level of Substance P was increased in all patients with chronic liver disease (119.5+/-68.2 pg/ml) compared to controls (16.2+/-4.6 pg/ml). The aldosterone concentration and plasma renin activity were significantly higher in patients [(84.1+/-38.3 ng/dl) and (11.1+/-7.3 ng/ml/h)] than controls [(8.2+/-3.9 ng/dl) and (2.0+/-1.1 ng/ml/h)]. The highest level of Substance P and aldosterone were observed in glycogen storage disease patients. CONCLUSION: Substance P was found to be increased in chronic liver disease patients; this increase was accompanied by an increase of aldosterone and plasma rennin activity. This correlation raises its potential use as a prognostic marker in chronic liver diseases.

Hepatitis C virus infection in Egyptian children: single centre experience.

The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti-HCV). The data of 105 anti-HCV-positive children presenting to the Pediatric Hepatology Unit, Cairo University Children's Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy-four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3-22 years, with a mean of 11.2 +/- 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti-HBc) were detected in 18 patients (24.3%). Twenty-six of the 43 HCV RNA-positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA-positive cases.