The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis


THE PIVOTAL ROLE OF THE CLINICAL LABORATORY IN THE DIAGNOSIS AND MANAGEMENT OF VIRAL HEPATITIS

Hassan M. E. Azzazy, PhD, DABCC, FACB


Viral hepatitis is a major public health problem worldwide that leads to significant The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis morbidity and mortality due to complications of end stage liver disease. Chronic infections with hepatitis B and/or C viruses (HBV, HCV) are the major risk factors for the development of liver The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis cirrhosis and hepatocellular carcinoma (HCC). Several serologic and molecular assays may detect early viral hepatitis infections before other signs appear, differentiate acute from chronic infections, verify development of immunity, and response to therapy.

IgM The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis anti-HAV has been used, in different assay formats, as the primary marker of acute infection. The stability of HAV in the environment and its resistant to low pH and The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis heating facilitate its detection in contaminated environmental specimens using nucleic acid testing.

HBV can be diagnosed and staged using a complex combination of HBV antigens and antibodies. Three HBV-associated antigens The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis: HBsAg (surface), HBcAg (core), and HBeAg and their corresponding antibodies are assayed. The genotype and viral load of HBV DNA can be determined by molecular tests.

Acute HCV infection is usually subclinical and there are The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis no reliable predictive markers of chronic infection. The diagnosis of chronic HCV infection is established by detecting anti-HCV in serum using enzyme immunoassays followed by confirmatory determination of HCV The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis RNA. Several sensitive and specific assays are now available for quantifing and genotyping of HCV RNA.

This presentation will highlight the expanding role of the clinical laboratory in management of viral hepatitis. Current serologic The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis tests used to diagnose viral hepatitis such as biochemical indicators, enzyme immunoassay, and recombinant immunoassay will be presented. Key aspects and limitations of molecular assays used for viral genotyping and assessment The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis of viral replication will be summarized. Other tests used for screening for hepatocellular carcinoma, monitoring of immunosuppressive drugs and liver function after transplantation, as well as screening for coexisting liver diseases will The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis be presented. This presentation will also фокус on recent trends in laboratory management of viral hepatitis such as the utilization of FibroIndex as a non-invasive marker for assessing liver fibrosis, cost The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis-effective algorithms for diagnosis of viral hepatitis, and simultaneous detection of HBV and HCV using nanoparticle-based assays.


Biography:


Dr. Azzazy is an associate professor of Chemistry and a member of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis the Science & Technology Research Center, the American University In Cairo. He is certified as a diplomate of the American Board of Clinical Chemistry, Washington, DC, USA in two specializations: clinical chemistry The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis and molecular diagnostics. He is also certified as a Specialist in Clinical Chemistry (SC) by the Board of Registry, the American Society for Clinical Pathology (ASCP), Chicago, IL, USA. In addition, Dr The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis. Azzazy is a fellow of the National Academy of Clinical Biochemistry (FACB), Washington, DC. He is also an adjunct associate professor at the Graduate Biotechnology Program, University of Maryland University College, Adelphi The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, MD. Dr. Azzazy is a member of the editorial board of the Clinical Biochemistry journal and serves as a reviewer for several international journals including Clin Chimica Acta, Clinical Chemistry Laboratory Medicine, Canadian Medical Association The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis Journal, and International Journal of Biotechnology.

^ MANAGEMENT OF HEPATITIS C VIRUS INFECTION IN EGYPT

Abdel-Rahman El-Zayadi, MD


In Egypt, hepatitis C virus (HCV) infection is considered not merely a medical The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis problem but rather an economic, social and psychological problem. The prevalence of HCV infection - particularly genotype 4 - in Egypt is quite high compared to other Middle East countries. The primary step in The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis the management of chronic hepatitis C is to establish the diagnosis. Implementation of cost-effective and sensitive tests for both the diagnosis and follow-up of therapy is mandatory. Following establishment of the The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis diagnosis, segregation of patients into groups according to their clinico-pathological states is performed. It has been reported that better selection of patients for antiviral therapy is the milestone for a higher post The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis-therapy response. Furthermore, Control of comorbidities before embarking on antiviral therapy would improve the sustained virologic response.

Implementation of an affordable and effective therapy without major side effects is necessary. So The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis far, interferons particularly pegylated interferon combined with ribavirin considered the milestone of therapy of chronic hepatitis C patients. Continuous counseling and monitoring of the patients during therapy has been recommended to increase adherence of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis patients to therapy and to reduce the emergence of resistance to drugs. In the meantime, alternative options should be offered to the patients when the primary therapy is ineffective, intolerable The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, unaffordable or contraindicated.

The last but not the least is strong attention should be given to the supply source and storage of interferon to secure its efficacy and avoid expired drugs.


Biography:


Dr. El The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis-Zayadi is a professor of Hepatology and Gastroenterology, Ain Shams University and Cairo Liver Center. Dr. El-Zayadi has published 119 articles in the field of hepato-gastroenterology and endoscopy - which The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis cover hepatitis viruses (B, C, D, E, G), interferon trials for hepatitis C and B, hepatocellular carcinoma, portal hypertension, endoscopic sclerotherapy, schistosomiasis and toxic effects of smoking on the liver. He The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis is a member of the Editorial Board of the World Journal of Gastroenterology (WJG).

He was instrumental in establishing the African Association for the Study of Liver Disease (AAFSLD) in 1982. He served as The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis president of African Association for the Study of Liver Disease (1992 – 1994). He founded the Gastrointestinal Endoscopy Unit at Ain Shams University Hospital by personal efforts and contributions from industry and national banks (1975). Dr The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis. El-Zayadi was a member of the educational committee of the World Congress of Gastroenterology between 1986–1994 representing Middle East and Africa. He was the chief of Hepatology Division in the Pan Arab Association of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis Gastroenterology (1997-2001). He founded Cairo Liver Center on 1991 and after retirement, he devoted all his time for care of liver patients and conduction of scientific research at that center. He was included The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis in the World famous biography book (WHO’s WHO) as one of the most effective contributors to the field of hepatology. Recently, he has been nominated by the board of Ain Shams University The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis for State Award for Excellence in the advanced technologies of Medicine.

^ TOWARDS A SIMPLE ALGORITHM FOR THE TREATMENTS OF HEPATOCELLULAR CARCINOMA (HCC)

Amr Helmy, MD


Surgery - either resection or transplantation - remains the The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis gold standard treatment of HCC. Many patients are not fit for surgery upon discovering the disease due to the severity of the underlying liver disease, the location, volume and or number of HCC The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis lesion(s), vascular invasion or the presence of extra hepatic disorder increasing morbidity or mortality. Other therapeutic options commonly used nowadays aim at either ablation of the disease, cytoreduction The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis of the lesion or arrest of its growth.

Selective Transarterial Chemoembolization (TACE) has been widely used for more than 2 decades. The chemotherapeutic agent(s) is tagged to Lipiodol and together with the embolizing material The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis creeps into the lesion via its arterial supply. Percutaneous Intralesional Ethanol injection (PEI) and Radiofrequency Thermal Ablation technology (RFA) followed in the 1990s. They both puncture Glisson’s capsule, liver parenchyma and The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis the lesion itself and can be applied during open or laparoscopic surgery. More recently, Stereotactic Radiotherapy (SRT) appears to achieve some good results to ablate lesions of less than 4 cm The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis in diameter without radiation hepatitis and is non invasive.

With the use of integrated therapy, patients and even many lesions can be managed by more than one modality. In spite of all The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis these modalities, it remains that many patients with HCC still do not fit any of the inclusion criteria. For these, supportive, hormonal or systemic chemotherapy can be offered but with poor results. Immune modulating therapies The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, intralesional irradiation and gene therapies are future prospects.

This study offers an algorithm to help practitioners select the proper modality to treat an HCC lesion. It maps the sequence of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis using each in case of integrated therapy. The classification is based on the condition of the liver, the classical Child-Pugh grading in case of diseased liver, the size of the lesion The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, the affection of one lobe or both, the location of the lesion either peripheral or central and the presence or absence of portal vein thrombosis.


Biography:


Dr. Helmy is a professor of Surgery The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, The National Liver Institute, Menoufiya University Egypt. He is the current Chairman of the Department of Surgery, The National Liver Institute, Menoufiya University, Egypt. He served as the Dean of the The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis National Liver Institute, Menoufiya University, Egypt (1999-2002). He has supervised the initiation of the Adult-to-Adult Living Donor Liver Transplant Program at Dar El Fouad Hospital, Egypt and carried out the first Transplantation on The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis 21 September 2002. He also served as the Team Leader of the transplantation teams at Mahmoud Charity Hospital, Ahmed Maher Teaching Hospital, and the National Liver Institute. He is the chairman of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis the Egyptian Liver Transplantation Association and President of the Egyptian HPB Society. He has received numerous awards including Who’s Who 2003‏ for outstanding achievement and “Man of the Year 2003” (American Biographical The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis Institute) for achievement beyond the call of duty. He was recognized by several institutions as Best Doctor of the Year and received the Egyptian Medical Syndicate Award several times. He has published several The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis articles covering different aspects of liver disease.

^ IMPACT OF SCHISTOSOMAL INFECTION ON ETR TO INTERFERON THERAPY AMONG CHRONIC HEPATITIS C GENOTYPE 4 SUBJECTS

Gamal Esmat, MD


Hepatitis C virus (HCV) infection in Egypt is very common (9-24%); mainly The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis HCV genotype 4 (90%). Prevalence of schistosomaisis ranges between, 17-42 % leads to more advanced liver disease, higher HCV RNA titer , higher Histological activity index. It was shown that patients with concomitant HCV and The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis schistosomaisis were characterized by: inability to generate HCV specific CD(+)/Th1 T cell response which plays a role in the persistence and severity of HCV infection in patients with S. mansoni co The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis infection. Results: Rectal snip were positive for S. mansoni ova in 36/94 (38%). Living ova was present in 14/36 of studied patients. These patients received anti-schistosomal treatment before starting interferon therapy. Although a The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis lower ETR "End of treatment Response" was detected among those with positive rectal snip compared to those with negative rectal snip (HCV RNA negative 50% 18/36 versus 59% 34/58) this difference was not statistically significant. The response rates among The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis those with dead ova (50% 11/22) are the same as to those with living ova (50% 7/14) who received anti schistosomal treatment before starting interferon therapy. Conclusion: Our preliminary results suggest that previous exposure The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis to schistosomaisis does not seem to have significant impact on response to treatment with combined Interferon therapy.


Biography:


Dr. Esmat is a professor of Tropical Medicine at the Faculty of Medicine and director The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis of Hepatology Research Unit, Cairo University. He is the current and the first Arabic president of the International Association for the Study of the Liver (IASL). He published several articles The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis that cover viral hepatitis, schistosomiasis, ultrasonography and portal hypertension. He has received distinguished research grants from the National Institute of Health and Wellcome Trust Foundation to study epidemiology of HCV in Egyptian children and evaluate The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis protective, disease-associated & therapeutic immunity to HCV Infection, respectively. Dr. Esmat was awarded the Cairo Physician Excellency Award from the Egyptian Medical Syndicate.

^ ACUTE VIRAL HEPATITIS

Reda El-Wakil, MD


Acute viral hepatitis (AVH The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis) is a systemic infection predominantly affecting the liver. AVH is most often caused by viruses which are hepatotropic (hepatitis A, B, C, D and E). Other viral infections may The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, on occasion, affect the liver such as cytomegalovirus (CMV), herpes simplex, coxsackie virus, and adenovirus. Whereas hepatitis A and E are self-limiting, infection with hepatitis C and less so with hepatitis B mainly The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis become chronic.   Whereas most acute infections are asymptomatic, when symptoms are present they appear to be similar for all 5 virus varieties. It is important to establish the virus involved as risks of progression The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis differ. Hepatitis A infection is usually self limiting if it occurs during childhood, but there is a low risk of occurrence of acute fulminant hepatitis. There is a 1% fatality rate with an The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis age more than 40 yr. Hepatitis B infection is self limiting if the infection is acquired by an immuno-competent adult, chronic hepatitis is less than 5%, while chronic hepatitis may occur The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis in more than 95% if the infection is acquired perinatally or in the early childhood. Hepatitis C is a self limiting disease in less than 20% of cases. More than 80% of cases have a prolonged The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis course of chronic hepatitis that may last for decades and may lead to liver cirrhosis in 20% of cases. Hepatitis D virus is an incomplete virus that depends on HBV to complete its lifecycle The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis. The disease caused by HDV is self-limiting if the concomitant HBV infection is self-limiting. Hepatitis E is self-limiting. The overall case fatality in fulminant hepatic failure is The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis 1–3%, but in pregnant women this is 15–25%. Raised serum alanine transaminase (ALT) is the best indicator of acute hepatic injury but does not reflect disease severity (bilirubin and International Normalized Ratios (INR) are required The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis to assess severity). It is important to differentiate between acute infection and flare-up of a silent chronic infection. In almost every case it is best to do nothing (except to The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis stop medication such as oral contraceptives). There is no role for vitamins or restriction of proteins in uncomplicated acute hepatitis. Precautions should be taken to prevent transmission and including vaccination where appropriate The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis.


Biography:


Dr. El-Wakil is a professor of Tropical Medicine, Faculty of Medicine, Ain Shams University. He is the director of the Combined Endoscopy Unit Ain Shams University Hospital and head The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis of Hepatology, Gastroenterology and Endoscopy Department El-Sheikh Zayed Specialized Hospital. Dr. El-Wakil is the secretary general of the Egyptian Association for Study of Gastrointestinal and Liver Diseases (EASGLD), Treasurer of The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis the African Middle East Association for Gastroenterology (AMAGE), and a founding member of the African Association for Study of Liver Disease (AFASLD).

^ MOLECULAR CHARACTERIZATION PROVIDES EFFICIENT CONTROL OF CHRONIC HCV INFECTION

Mostafa K The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis. El Awady, PhD


Understanding the viral-cellular interactions in HCV infection allowed the molecular virologists to develop several laboratory methods to answer questions related to disease morbidity, intracellular viral replication, infection breakthrough, progression to chronic The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis infection and response to therapy. At the Biomedical Technology Department in the NRC, we developed molecular based technologies to answer these questions. The fact that HCV core protein plays active roles in The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis development of hepatic steatosis and hepatocellular carcinoma has encouraged us to develop, in house, core specific antibodies for assaying circulating core protein levels in patients with different states of chronic HCV The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis infections. These experiments demonstrated that core levels are more statistically correlated with hepatic enzymes and stages of chronic C infection but not with circulating viral loads. Also, our technical ability to detect The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis RNA minus strand of HCV allowed our investigators to evaluate the efficacy of antiviral treatment and permitted monitoring of viral response to therapy using peripheral blood mononuclear cells of patients as extrahepatic The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis reservoirs. These studies showed that assessment of intracellular HCV genomic replication may be helpful in predicting viral breakthroughs and achieving sustained virological response during and post termination of therapy. Furthermore, we recently developed a The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis molecular based technology to predict the response of HCV infection to interferon α2 therapy via knowing the mechanisms of virus/cell protein-protein interactions particularly those interferon inducible host proteins which The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis, in turn, accelerate viral RNA degradation machinery.

In conclusion the studies described herein post the significance of exploring intracellular pathways related to HCV infection and pave the way to develop more realistic The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis diagnostics, prognostics and novel anti HCV agents.


Biography:


Dr. El-Awady is the President of Division of Genetic Engineering and Biotechnology (DGEB) National Research Center, Cairo Egypt. He is also the Chairman The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis of Department of Biomedical Technology, National , Research Center, Cairo Egypt. He served as the dean of Genetic Engineering and Biotechnology Research Institute Mubarak City for Scientific Research and Technological Applications (2000-2001). He is the current The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis Scientific Consultant of The Egyptian Research Society for the study of Liver Diseases and Gastroenetrology. Dr. El-Awady is the recipient of Rockefeller's Biotechnology Career Award in Genetics The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis from the Rockefeller Foundation USA, NRC Award of scientific superiority in Chemical Sciences and its applications, and the State Award of scientific superiority in Basic Sciences. Dr. El-Awady has published over 70 articles The pivotal role of the clinical laboratory in the diagnosis and management of viral hepatitis in different fields including HCV, human genetics, cancer, schistosomiasis and tuberculosis.
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