Hepatitis B virus (HBV) infection remains a serious issue in the dialysis population. Transmission of HBV through dialysis machines or other sources as well as seroconversion from HBV negative patients to positive ones is still not well understood. Seventy patients were selected from our chronic hemodialysis (HD) center. They were divided into two groups: Group (I) included 35 patients with negative hepatitis B surface antigen (HBsAg), while another 35 already known to have HBsAg positive were chosen as a control group (Group II). The aim of the study was to detect the presence of HBV DNA by analyzing the serum PCR of the negative (HBsAg) patients (Group I) then analyzing the viral sequencing of 5 of them in comparison to 5 of the known HBsAg positive. All patients received blood transfusions, were positive for HCV but negative for HDV and HIV. In group I, HBV DNA by PCR was detected in serum of 17/35 (48.5%) patients. Only 3 of them were positive for HBcAb. In group II, HBV DNA by PCR was detected in serum of 35/35 (100%) patients. The alanine transaminase enzyme (ALT) level was significantly higher than negative patients. Sequencing of the virus showed some mutated segments in 5 of the positive DNA by PCR compared to already positive HBsAg positive patients in Group II.
In conclusion, a high proportion of HBsAgnegative hemodialysis patients were found to have positive HBV DNA by PCR. Sequencing of the virus revealed some mutated segments of the DNA. These findings are of major importance for the planning of future screening of patients on hemodialysis. We recommend measuring HBV DNA of all negative HBsAg patients on HD as this can change the management and prognosis of this particular group on chronic HD.

BACKGROUND: There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and chronic liver disease.

METHODS: HBV genotypes were determined in 22 patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A type-specific primer based the nested-PCR method was employed in the HBV genotyping.

RESULTS: This study showed that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections. Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48(47.9%) v 3/22 (13.6%)].

CONCLUSION: These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients. Furthermore, our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects with CAH and a possible association of mixed infections with the severity of liver diseases.

Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (V) storage cells, they can be actively targeted by coupling liposomes to V. In this study, novel V-coupled imatinib-loaded liposomes (ILC) were prepared and optimized regarding V-coupling efficiency, imatinib entrapment efficiency, and particle size. Preferential accumulation of the selected formula in liver was proved by tracing intraperitoneally (i.p.)-injected V-coupled liposomes loaded with Nile Red (LCNR) to rats with CCl-induced liver fibrosis using live animal imaging. Co-localization of LCNR with immunofluorescently-labeled PDGFR-β in frozen liver tissue sections confirmed HSCs targeting. ILC bio-distribution, following single i.p. injection, revealed 13.5 folds higher hepatic accumulation than conventional imatinib in addition to limited bio-distribution to other organs including heart and lung reflecting diminished adverse effects. ILC therapy resulted in a potent inhibition of phosphorylated PDGFR-β expression when compared to conventional imatinib. Subsequently, there was a statistically significant improvement in liver function tests and reversal of hepatotoxicity along with liver fibrosis. Anti-fibrotic effect was evident from histopathologic Ishak score reduction as well as normalization of the level of profibrotic mediators (hydroxyproline, TGF-B and matrix metalloproteinase-2). Thus, HSC-targeted imatinib therapy shows outstanding anti-fibrotic effects with reduced cytotoxicity compared to conventional imatinib. It can represent a promising novel approach for liver fibrosis treatment.

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Juvenile systemic lupus erythematosus (JSLE) is a chronic autoimmune disease characterized by multisystem involvement and diverse clinical and serological manifestations. Clinically significant hepatic disease is generally regarded as unusual in JSLE, but many studies have showed that hepatic disease may be more common in SLE than was usually thought. Hepatic disease does not cause significant morbidity and mortality, but subclinical liver involvement is common. One of the hepatic disorders associated with JSLE is autoimmune hepatitis (AIH). The precise etiology of AIH and JSLE remains unknown, however both AIH and JSLE are associated with antinuclear antibody (ANA) and multisystem disease manifestations. A shared immunologic response and genetic predisposition were suggested. Recently, new approaches for treatment of SLE and recent patents that could develop into novel therapeutic agents in clinical management of SLE have been proposed. An array of promising new therapies is currently emerging or being developed including B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and present review, we will also report the case of a 12-year old girl who developed JSLE four years after her preliminary diagnosis with AIH.

Perinatal asphyxia (PA) is a major cause of morbidity and mortality in which dramatic transient impairment in liver functions occurs in some patients. We aimed to evaluate the state of the liver in cases of Perinatal asphyxia and to assess the severity of hepatic impairment in relation to different grades of HIE. This case-control study was conducted on 100 full-term newborns with perinatal asphyxia (Group I) and 50 healthy neonates served as controls (Group II). All biochemical parameters of liver function were measured on the 1st, 3rd, and 10th day after birth. These parameters include serum alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, serum albumin, serum bilirubin (total and direct), and international normalized ratio (INR), in both cases and controls. Among babies with PA, 25 (25%) had an Apgar score of 0 to 3 (severe PA), 43 (43%) had an Apgar score of 4 to 5 (moderate PA) and 32 (32%) had an Apgar score of 6 to 7 (mild PA) at 5 minutes of life. HIE was found in 39% among cases of PA and the remaining 61% were normal. Among babies with PA and HIE; 25.7% had stage I, 41% had stage II and 33.3% had stage III. Impaired liver function was reported in 48% of asphyxiated babies. On the first day of life, ALT, AST, ALP, LDH, PT, and INR were significantly higher in Group I compared to Group II. However, total protein and serum albumin were significantly lower in Group I compared to Group II. ALT and AST showed a positive correlation with the severity of HIE. On the third day of life, LDH rises as the stage of HIE progressed from stage 0 to stage 3. The difference in LDH among most stages of HIE was statistically significant. Liver enzymes can be used as an easy early diagnostic marker to differentiate between babies with asphyxia and those without asphyxia. Also, liver enzymes can be used for the detection of the severity of PA.

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy.

PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children.

RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy.

CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.