Recent Advances in Protective Vaccines against Hepatitis Viruses: A Narrative Review.

Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.

Current situation of viral hepatitis in Egypt.

An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.

Changing Patterns of Hepatocellular Carcinoma after Treatment with Direct Antiviral Agents.

INTRODUCTION: The impact of direct antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial. One important aspect of this controversy is the changing pattern of HCC. OBJECTIVE: In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs. METHODS: A total of 51 HCC patients after DAA treatment and 54 HCC patients without DAA treatment were included. The diagnosis of HCC was based on typical dynamic CT and/or MRI criteria in both groups. Liver status was assessed by means of the fibrosis 4 index (Fib-4), Child-Pugh classification, and model for end-stage liver disease (MELD). HCC infiltrative pattern, portal vein thrombosis (PVT), local and distant metastases, and α-fetoprotein (AFP) level were compared in the 2 groups. The staging of HCC and treatment decisions were made in both groups following the Milan criteria, Barcelona Clinic Liver Cancer staging, tumor-node-metastasis staging, and Cancer of the Liver Italian Program categorization. RESULTS: The mean age of the HCC patients after DAA treatment (59.1± 7.4 years) was older than that of the HCC patients without DAA treatment. There was no significant difference between groups regarding sex distribution. The mean Fib-4 score (4.84 ± 3.53) was significantly lower in HCC patients after DAA treatment than in those without DAA treatment. The frequency of the infiltrative HCC pattern, PVT, and regional lymph node metastasis was significantly higher in HCC patients after DAA treatment than in those without DAA treatment (p ≤ 0.05); mean AFP level (5,085.2 ± 11,883.2 ng/mL) was also significantly higher. HCC patients after DAA treatment had significantly advanced stages and limited treatment options (p ≤ 0.05). CONCLUSION: The changing HCC pattern after DAA treatment may suggest the need for new HCC staging and treatment protocols.

Retreatment of Egyptian Chronic Hepatitis C Patients Not Responding to Pegylated Interferon and Ribavirin Dual Therapy.

In the current study, we aimed to assess the efficacy of different Sofosbuvir (SOF)-based antiviral regimens available in Egypt in the treatment of Pegylated interferon/Ribavirin (PEG-INF/RBV)-experienced chronic hepatitis C virus (HCV) patients. Two hundred fifty-eight patients experienced with PEG-INF/RBV, and 1,283 naive patients were included in the study. The patients received one of the following 3 regimens for 12 weeks; PEG-INF/SOF, Simeprevir/SOF (SIM/SOF), and Daclatasvir/SOF (DCV/SOF). The endpoint was a sustained virological response 12 weeks (SVR12) after the end of the treatment. SVR12, treatment failure, and relapse were assessed. Moreover, predictors of SVR12 were analyzed. The mean age of treatment-experienced and treatment-naive patients was 51.11 ± 5.84 years and 50.04 ± 5.97 years, respectively. Treatment-experienced patients included 132 (51.16%) males and 126 (48.83%) females. Treatment-naive patients included 709 (55.26%) males and 574 (44.73%) females. The SVR12, treatment failure and treatment relapse rates in treatment-experienced versus treatment-naive patients were 91.1% versus 96.8%, 0.8% versus 0.9%, and 8.9% versus 2.7%, respectively. The SIM/SOF regimen provoked a ubiquitous high SVR12 in both treatment-experienced and -naive patients. A SIM/SOF regimen provokes the highest SVR12 in PEG-INF/RBV-experienced chronic HCV patients. Retreatment with PEG-INF/SOF in PEG-INF/RBV-experienced chronic HCV patients has a high probability of treatment failure.

Hepatitis C Virus Exposure Rate among Health-care Workers in Rural Lower Egypt Governorates.

BACKGROUND AND OBJECTIVES: Studies on hepatitis C virus (HCV) in Egypt supported a strong role for various exposures in the health-care setting. In this study, we attempted to estimate the frequency of HCV exposure among Egyptian health-care workers (HCWs). METHODS: Five hundred and sixty-four (564) HCWs were included in this study. Two hundred and fifty-eight (45.74%) were health-care providers and 306 (54.25%) were non-health-care providers. All HCWs completed both the study questionnaire and provided a blood sample for anti-HCV testing by third-generation enzyme-linked immunosorbent assay. Subsequently, anti-HCV-positive samples were tested for HCV RNA using nested polymerase chain reaction (PCR). RESULTS: The mean age of included HCWs was 33.0 ± 9.8 years; of them, 319 (56.56%) were males and 245 (43.44%) were females. The mean duration of health-care work was 9.3 ± 6.7 years. The frequency of antibody against hepatitis C virus (anti-HCV) among included HCWs was 8.7% (n = 49). Old age and prolonged duration of health-care work were significantly associated with anti-HCV seropositivity. Forty (81.63%) of 49 with anti-HCV-positive HCWs had positive hepatitis C viremia. The frequency of HCV RNA positivity increased with age. The frequency of eradicated past infection among nurses (36.85%) was markedly higher than that (6.7%) detected in non-health-care providers. CONCLUSION: High rate of HCV infection is detected in Egyptian HCWs in rural Lower Egypt governorates. Health-care providers seem to eradicate HCV infection more frequently than non-health-care providers. National screening and treatment of infected HCWs are recommended.

Occult hepatitis B infection in Egyptian health care workers.

We tested the frequency of occult hepatitis B infection (OBI) among Egyptian healthcare workers (HCWs). We tested 132 HCWs for hepatitis B virus (HBV) DNA by nested polymerase chain reaction (PCR), and hepatitis C virus antibody (anti-HCV) by ELISA. HCV RNA was measured by nested PCR in anti-HCV-positive HCWs. HBV-DNA-positive HCWs were subjected to HBV genotyping. We included 132 HCWs who were negative for hepatitis B surface antigen and positive for hepatitis B core antibody (anti-HBc). OBI was detected in 7 male HCWs, and HBV E genotype was detected in 3, HBV D in 2 and HBV D and E in 2. Two OBI-positive HCWs had a history of neonatal hepatitis B vaccination. Anti-HCV seropositivity was detected in 17 HCWs who were positive for anti-HBc; 15 of whom were positive for HCV RNA by nested PCR. HCV infection was confirmed by anti-HCV and HCV RNA in 1 of 7 HCWs with OBI. In conclusion, Egyptian HCWs have a significant rate of OBI and HBV E genotype is prevalent.

Hepatitis B Virus Genotype E Infection among Egyptian Health Care Workers.

BACKGROUND AND OBJECTIVES: Health Care Workers (HCWs) are at a high risk of needle stick injuries and HBV infection in Egypt; this problem is further aggravated by low Hepatitis B (HB) vaccination coverage. Limited data are available on the prevalence of HBV infection in Egyptian HCWs. In this study, we aimed to assess the HBV infection rate and genotypes among Egyptian HCWs. METHODS: Five hundred and sixty-four (564) HCWs were included. Of them, 258 (45.74%) were health care providers and 306 (54.25%) were non-health care providers. All HCWs completed both the study questionnaires and provided a blood sample for HBV testing. Indeed, all HCWs were tested for Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B core antigen (anti-HBc), by enzyme-linked immunosorbent assay. HBVDNA was checked for HCWs who tested positive for HBsAg and/or anti-HBc, by nested Polymerase Chain Reaction (PCR). HBVDNA positive HCWs were further subjected to HBV genotyping. RESULTS: The mean age of included HCWs was 33.0 ± 9.8 years, of whom 319 (56.56%) were males. The mean duration of health care work was 9.3 ± 6.7 years. The frequency of HBsAg and anti-HBc were 1.4%, and 24.5%, respectively. Old age and prolonged duration of health care work were significantly associated with anti-HBc seropositivity. Among 140 HCWs positive for HBsAg and/or anti-HBc, 14 (10 %) had positive HBVDNA by PCR. HBV/E (n = 7), HBV/D (n = 3) and co-infection with E and D (n = 4) genotypes were detected. CONCLUSION: Egyptian HCWs have a significantly high rate of HBV exposure. The detection of HBV/E genotype among Egyptian HCWs suggests prevalent transmission of HBV/E among Egyptian populations.

Liver-specific Prox1 inactivation causes hepatic injury and glucose intolerance in mice.

Previous reports have revealed that Prospero-related homeobox 1 (Prox1) is required for the migration and differentiation of hepatoblasts during embryonic liver formation. However, the role of Prox1 in adults remains to be elucidated. We created liver-specific Prox1 knockout mice to verify the role of Prox1 in adult hepatocytes. The mutant mice exhibit hepatic injury and a nonobese, insulin-resistant diabetic phenotype in vivo. Hepatocyte injury is observed predominantly in the perivenous region and is characterized by the formation of vacuoles and emergence of round-shaped mitochondria, suggesting that the effect of Prox1 on the maintenance of adult hepatocytes is region dependent. Furthermore, glycolysis is suppressed, and both oxidative phosphorylation and autophagy are upregulated in the livers of Prox1 knockout mice, indicating that Prox1 has a role in regulating energy homeostasis in hepatocytes.

Occult hepatitis B virus infection in Egypt.

The emerging evidence of the potentially clinical importance of occult hepatitis B virus (HBV) infection (OBI) increases the interest in this topic. OBI may impact in several clinical contexts, which include the possible transmission of the infection, the contribution to liver disease progression, the development of hepatocellular carcinoma, and the risk of reactivation. There are several articles that have published on OBI in Egyptian populations. A review of MEDLINE database was undertaken for relevant articles to clarify the epidemiology of OBI in Egypt. HBV genotype D is the only detectable genotype among Egyptian OBI patients. Higher rates of OBI reported among Egyptian chronic HCV, hemodialysis, children with malignant disorders, and cryptogenic liver disease patients. There is an evidence of OBI reactivation after treatment with chemotherapy. The available data suggested that screening for OBI must be a routine practice in these groups of patients. Further studies needed for better understand of the epidemiology of OBI among Egyptian young generations after the era of hepatitis B vaccination.

Absence of occult hepatitis B virus infection in sera of diabetic children and adolescents following hepatitis B vaccination.

BACKGROUND: The prevalence of occult hepatitis B (HB) infection (OBI) in HB-vaccinated diabetic children has not yet been tested. Here, we aimed to determine the prevalence of OBI among HB-vaccinated children and adolescents with insulin-dependent diabetes mellitus (IDDM). RESULTS: Eighty-seven (51.2%) children had a titer for antibodies to HB surface antigen (anti-HBs) of <10 IU/L. These included 44 (70%) IDDM children and 43 (40.2%) healthy children. Eighty-three (48.8%) children had an anti-HBs titer of ≥10 IU/L; they included 19 (30%) with IDDM and 64 (59.8%) healthy children. None of the enrolled children (n = 170) were reactive for total antibody to HB core antigen (anti-HBc) as determined by enzyme-linked immunosorbent assay. HB virus DNA was not detected in HB-vaccinated IDDM or healthy children and adolescents. METHOD: An amount of 170 HBsAg-negative sera samples from HB-vaccinated children and adolescents was included. They were classified into the IDDM group (n = 63) and the healthy control group (n = 107). HBsAg, anti-HBc, and anti-HBs were tested by enzyme-linked immunosorbent assay, and HB virus DNA was tested by nested polymerase chain reaction using 3 pairs of surface, core, and X genes. IN CONCLUSION: Primary HB vaccination confers long-term protection against OBI in Egyptian diabetic children and adolescents. However, the number of cases tested in this study was relatively low, and further studies and long-term follow-up of large populations are needed to draw solid and convincing conclusions.

Antibody levels against hepatitis B virus after hepatitis B vaccination in Egyptian diabetic children and adolescents.

BACKGROUND: The remarkable effectiveness of universal infantile hepatitis B (HB) vaccination is well documented in many countries. Nevertheless, the influence of insulin-dependent diabetes mellitus (IDDM) on the sero-protective level of antibody to hepatitis B surface antigen (anti-HBs) after HB vaccination has not been investigated in Egyptian children. The aim of this study was to investigate long-term anti-HBs sero-protective levels after infantile HB vaccination in Egyptian IDDM children. RESULTS: The mean age of the healthy children was 10.86 ± 1.21 y (range, 5.5-15 y); 49 (45.8%) were boys and 58 (54.2%) were girls. The mean age of the IDDM children was 10.29 ± 3.04 y (range, 4-17 y); 32 (50.8%) were boys and 31 (49.2%) were girls. There were no significant differences between the healthy and IDDM children with respect to age and sex (p>0.05). Among the 107 healthy children, 43 (40%) did not have a protective anti-HBs level (anti-HBs<10 IU/L) and 64 (60%) had a protective level (anti-HBs ≥ 10 IU/L). In contrast, among the IDDM children, 44 (69.8%) and 19 (30.2%) did not and did have protective anti-HBs levels, respectively. This difference in anti-HBs concentration between healthy and diabetic children was highly significant (p<0.001). None of the vaccinated healthy or IDDM children was reactive to HBsAg or total anti-HBc. PATIENTS AND METHODS: A total of 170 children (81 boys, 89 girls) who had been routinely vaccinated against HB were included. Their mean age was 10 ± 2.1 y. The enrolled children were divided into healthy (n = 107) and IDDM (n = 63) cohorts. Body Mass Index and levels of hepatitis B surface antigen (HBsAg), total antibody to hepatitis B core antigen (anti-HBc), and anti-HBs were evaluated in all children. In addition, the duration of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) were measured in IDDM children. CONCLUSION: Our results are alarming. It appears that the majority of Egyptian diabetic children vaccinated against HB may not have sufficient anti-HBs levels to protect them from HB. Moreover, this study emphasizes the need for a population-based strategy for the management of patients without an anti-HBs protective level after HB vaccination and justifies the need to elucidate the heritability of those children.

High false-negative rate of anti-HCV among Egyptian patients on regular hemodialysis.

Routine serological testing for hepatitis C virus (HCV) infection among hemodialysis (HD) patients is currently recommended. A dilemma existed on the value of serology because some investigators reported a high rate of false-negative serologic testing. In this study, we aimed to detect the false-negative rate of anti-HCV among Egyptian HD patients. Seventy-eight HD patients, negative for anti-HCV, anti-HIV, and hepatitis B surface antigen, were tested for HCV RNA by reverse transcriptase polymerase chain reaction (RT-PCR). In the next step, the viral load was quantified by real-time PCR in RT-PCR-positive patients. Risk factors for HCV infection, as well as clinical and biochemical indicators of liver disease, were compared between false-negative and true-negative anti-HCV HD patients. The frequency of false-negative anti-HCV was 17.9%. Frequency of blood transfusion, duration of HD, dialysis at multiple centers, and diabetes mellitus were not identified as risk factors for HCV infection. The frequency of false-negative results had a linear relation to the prevalence of HCV infection in the HD units. Timely identification of HCV within dialysis units is needed in order to lower the risk of HCV spread within the HD units. The high false-negative rate of anti-HCV among HD patients in our study justifies testing of a large scale of patients for precious assessment of effectiveness of nucleic acid amplification technology testing in screening HD patient.

Regular arrangement of collecting venules: Does patient age affect its accuracy?

AIM: To address the diagnostic value of the regular arrangement of collecting venules (RAC) among old age patients. METHODS: A total of 390 consecutive patients whose Helicobacter pylori (H. pylori) status was known and who received upper gastrointestinal endoscopy, were retrospectively studied for the presence or absence of RAC as well as gastric mucosal atrophy. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RAC to detect normal gastric mucosa were assessed and were compared among two different age groups of patients. RESULTS: The mean age ± standard deviation (SD) of included patients (n = 390), was 62.9 ± 13 years. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RAC to detect normal gastric mucosa were 91.7%, 66.1%, 18.8%, 99% and 68.1% respectively. Although the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RAC among patients < 60 years (n = 139) was 94.7%, 71.2%, 46.2%, 98.1%and 76.1%, respectively, it was 80%, 64.3%, 5.1%, 93% and 64.6%, respectively, among patients ≥ 60 years (n = 251). Younger Patients (< 60 years), have highly significant rates of RAC sensitivity, positive predictive value, and accuracy (P ≤ 0.001, ≤ 0.001 and ≤ 0.02, respectively). Older patients had highly significant rates of H. pylori infection and gastric mucosal atrophy (P ≤ 0.01). CONCLUSION: Although RAC is a valuable sign for real-time identification of normal gastric mucosa, its accuracy seems to be affected by the patient's age.

Augmented damage of islets by impaired exocrine acinar cells undergoing apoptosis that is possibly converted to necrosis during isolation.

Islet damage attributed to impaired exocrine cells during pancreas preservation and isolation procedure remains elusive, although released exocrine enzymes could directly damage islets. The aim of this study is to investigate the cellular mechanisms associated with exocrine cells and their possible impact on the islet cell survival and function after isolation. Mouse pancreata were stored in cold University of Wisconsin preservation solution for 0, 24 and 48 h and incubated with or without collagenase at 37°C for 15 min. During preservation, the percentage of exocrine cells with necrosis, which means impaired cellular membrane that allows intracellular enzymes to be released, remains low (< 10%) regardless of preservation time; whereas the percentage of exocrine cells with apoptosis, which means impaired nucleus and possible intact cellular membrane, increases over time of preservation. After collagenase-free incubation, however, the percentage of exocrine cells with necrosis became higher in longer preservation time, and more than 60% of the necrotic exocrine cells contained apoptosis as well. Islet cells located in pancreata with intact structure are almost kept away either from necrotic or apoptotic changes even after 48 h preservation followed by collagenase-free incubation. However, when islets are isolated after collagenase-containing incubation, the percentage of islet cells with necrosis increases over time of preservation up to approximately 40%. This study suggests that exocrine cells with necrosis could cause damage of isolated islets when the pancreas is dissociated and that the necrosis in exocrine cells might be induced mainly as the conversion from apoptosis that has already existed during preservation.

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine.

The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.

Conventional narrow-band imaging has good correlation with histopathological severity of Helicobacter pylori gastritis.

BACKGROUND AND AIM: Narrow-band imaging (NBI) is an optical image enhancement technique that enhances the vessels and patterns of gastric mucosal surface. Here we aim to test the diagnostic role of conventional NBI (C-NBI) in identifying Helicobacter pylori (HP) infection, severity of gastritis, and gastric atrophy. METHODS: Initially, the endoscopic records of 300 patients were retrospectively searched for specific C-NBI gastric mucosal patterns, where five different C-NBI mucosal patterns were identified. In a second step, 20 patients with different C-NBI mucosal patterns were subjected to gastric mucosal biopsy for HP testing and histopathological assessment. RESULTS: Five different histopathological grades of HP gastritis, in terms of grade of gastric atrophy, intestinal metaplasia, infiltration by inflammatory cells, and density of HP infection, were recognized among the different C-NBI mucosal patterns. CONCLUSIONS: C-NBI seems to be a promising method for HP infection identification and gastric cancer risk stratification of patients.

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.

Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients.

PURPOSE: The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. METHODS: One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age +/- SD 48.8 +/- 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age +/- SD 46.6 +/- 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. RESULTS: Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. CONCLUSION: A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.

Chronic neutrophilic leukaemia: an Egyptian case.

Chronic neutrophilic leukaemia (CNL) is a rare myeloproliferative disorder of elderly patients characterised by sustained neutrophilia. The diagnosis of CNL requires the exclusion of BCR/ABL positive chronic myelogenous leukaemia and leukemoid reaction. We present here a case of a 61-year-old Egyptian man with CNL and 21 months of follow-up. The main symptom of our patient was purpura. Splenomegaly, hepatomegaly and lymph node enlargement were not detected at presentation or throughout the patient's course. Thrombocytopenia was a considerable problem in our patient, causing recurrent bleeding and affecting the hydroxyurea dose adjustment. While hydroxyurea decreased the total leucocytic count, it could not affect the fatal course of the disease. The survival course of our patient extended to 21 months after presentation. The cause of death was attributed to disease progression.