الفهرس 
ACKNOWLEDGEMENT
Structure and molecular virology of hepatitis B virusOnly 14 pages are availabe for public view
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Abstract
Hepatitis B virus infection represents a global health problem. A around two billions people are worldwide, of them 400 million suffer chronic infection with HBV. The prevalence of HBsAg in Egypt is of intermediate endemicity (2–8%).
Approximately, 15-40% of patients with chronic HBV will develop cirrhosis, end-stage liver failure or hepatocellular carcinoma (HCC) in their lifetime,
Progression rate with hepatitis B virus infection may be related to various factors like, age at infection, HBV genotype, increased alanine transaminases level and co-infection with other hepatitis viruses like HCV, HDV and HIV.
Alanine transaminases level is commonly used to assess activity of liver disease and to identify patients for antiviral therapy. Most international guidelines recommended treatment for CHB patients with persistent elevated enzymes, while those with normal transaminases should not be treated and follow up is recommended by ALT evaluation every 3 months. Liver biopsy may be my be advised but in especial situation.
However persistent normal enzymes are not always benign condition. Several studies revealed 12 % -40% of patients with chronic hepatitis B will develop serious complication during life time like cirrhosis, decompensated liver disease and hepatocellular carcinoma.
Our aim in this study was to assess the histopathological changes in chronic HBV patients with persistent normal transaminases and to evaluate the role of liver biopsy in implication for therapy in those patients with chronic HBV with normal transaminases.
A cross sectional studies included 93 Patients, who were recruited from Assuit Unit for Management of Viral Hepatitis. Patients included in the study have hepatitis B surface antigen positive for more than 6months, age more than 18 years, detectable HBV DNA by PCR and persistent normal ALT confirmed on 3 consecutive liver enzymes reading every 3 months. On the other hand, Patients with HCV coinfection, cirrhotic and undetectable HBV DNA were excluded from the study.
All participants were subjected to, Full history, clinical examination,
laboratory investigations, liver function tests, prothrombin time and concentration, blood picture, HBeAg, HBeAb , HBV DNA by PCR and abdominal U/S, liver biopsy was carried out in the usual standard manner for all patients.
Our results revealed, eighty two of our patients were males and 11were female, with mean age was 37 years (rang 20-58), HBeAg expression was negative in 77 patients, while 16 patients were HBeAg positive.
Considerable number of patients with persistently normal ALT were associated with significant histopathology finding on liver biopsy, 41/93 (44.1%) patients had significant fibrosis ≥ F2 and 33/93 (35.5%) patients were presented with moderate-to-severe Inflammation ≥ A2.
Comparing to HBeAg positive patients, HBeAg negative patients were significantly older in age (p=0.000), had a lower HBV DNA levels (p=0.003). Thirty eight 38/77(49.4%) HBeAg negative patients had significant hepatic fibrosis ≥ F2 (p=0.025), in comparison to 3/16 patients 18.2`% in case of HBeAg positive.
The baseline characteristics between the significant and non-significant fibrosis groups are compared. The significant fibrosis group was older, 23/33 (69.7) patients with age more than 40 years had moderate to severe fibrosis ≥ F2 (P=0.00). Also significant fibrosis was predominant in HB e Ag negative patients (p=0.025).
The significant fibrosis group had a lower mean platelet count and increased INR level than the non-significant histology group (p =0.000, 0.014) respectively.
Relationship between the significant liver pathology and HBV-DNA level was evaluated. We found that high HBV DNA viral load is significantly associated with necroinflamation ≥ A2 (P = 0.034).
In logistic regression analysis with significant fibrosis as the dependent variable; age, platelet, INR and HBeAg negative levels were independently associated with the risk for significant histology. The odds ratios for significant histology increased progressively according to decrease platelet levels and increased age, the odds ratio for significant histology was 2.93 (95% CI, 1.08–7.91) for patients aged ≥40 years, platelets level was associated with odds ratios (95% CI) for significant histology of 0.99 (95% CI, 0.98–99).
The proportion of patients who are became candidate to therapy after biopsy were 41/93(44.1%) patients represents 38/77 (49.4%) in HBeAg negative and 3/16 (18.8%) HBeAg positive cases.
When new cut off value for ALT was implicated (19 U for female and 30 U for male), 29 patients had persistent normal enzymes of them 11patients (37.9 %) had significant fibrosis ≥ F2, so even with application of new cut off value, we still have patients with significant fibrosis in the group of persistent low normal ALT, which support the need for liver biopsy with histopathology evaluation of that group of patients with PNALT.
Conclusion
• A considerable number of CHB patients with PNALT have significant histologic fibrosis.
• Age above 40 years and low platelet count could predict extensive liver damage.Liver biopsy should be considered in those patients with persistent normal ALT.More attention should be directed to future research for alternative noninvasive markers of liver damage in this group of patients.