عفونت هپاتيت B: مقاله مروري

Hepatitis B infection: review article

هپاتيت B يك بيماري تهديد‌كننده حيات است كه كبد را تحت تاثير قرار مي‌دهد. تظاهرات باليني بيماري از فرم بدون علامت تا عوارض شديد مانند سرطان كبد و سيروز متفاوت است. باوجود در دسترس بودن واكسن و دارو، اين بيماري هنوز يك مشكل بزرگ براي سلامتي انسان در سرتاسر جهان باقي مانده است. هپاتيت B بسيار مسري بوده و از طريق خون و مايعات آلوده، مادر به جنين، استفاده از سوزن آلوده و تماس جنسي با فرد آلوده منتقل مي‌شود. ويروس هپاتيت B به‌كمك رسپتور سديم توروكولات كوترانسپورتينگ پلي‌پپتيد (NTCP) وارد هپاتوسيت‌ها شده و با تكثير در اين سلول‌ها باعث اختلال در عملكرد كبد مي‌شود. در واقع آسيب‌هاي كبدي نتيجه تكثير ويروس و فعال شدن سيستم ايمني به‌ويژه سلول‌هاي T سايتوتوكسيك اختصاصي ويروس است. سلول‌هاي CTL و CD4Th1 از طريق كشتن سلول‌هاي آلوده و تحريك توليد سايتوكين‌هاي ضد ويروسي تكثير ويروس را كنترل مي‌كنند. از طرفي عمكلرد اين سلول‌ها در افرادي كه به‌شكل موفق ويروس را حذف مي‌كنند بسيار قوي مي‌باشد، در مقابل در افراد مبتلا به عفونت‌هاي مزمن اين دسته از سلول‌ها تضعيف شده‌اند. بسياري از مطالعات نشان داده است كه چالش اصلي در حذف كامل ويروس مربوط به حضور Covalently closed circular DNA (cccDNA) است. اين ساختار در فرآيند سيكل تكثيري ويروس توليد شده و به‌مدت طولاني در داخل سلول ميزبان باقي مانده و به‌عنوان الگويي براي توليد Pre-genomic RNA و تكثير ويروس عمل مي‌كند. تاكنون هيچ داروي ضد ويروسي نتوانسته اين ساختار را از بين ببرد.

Hepatitis B virus (HBV) is an etiological agent of hepatitis B infection. Hepatitis B is a life-threatening disease that affects the liver. The clinical outcomes of the disease are varied from asymptomatic disease to serious complication such as cirrhosis and hepatocellular carcinoma (HCC). Despite availability of the vaccine and appropriate treatment, hepatitis B infection still remains a major public health problem worldwide. Based on WHO reports, over 887.000 people die annually from hepatitis B complication including cirrhosis and hepatocellular carcinoma. Hepatitis B is very contagious and spreads through infected blood, body fluids, mother to baby during birth, contaminated needle and between sexual partners. HBV uses sodium taurocholate cotransporting polypeptide (NTCP) receptor to enter hepatocytes and by replicating in these cells interferes with liver functions. In fact liver damage is as result of virus multiplication and activation of immune responses especially virus-specific cytotoxic T lymphocytes (CTLs) against infected cells. CTLs and CD4Th1 cells by killing infected cells and releasing antiviral cytokines control virus replication in infected individuals. Also, the functions of these cells in patients who successfully clear the infection are potentially strong. In contrast to acute self-limited HBV infection in persistent HBV infection, these cells are exhausted. Several studies have showed that the great challenge in clearance of the HBV infection is related to stability of covalently closed circular DNA (cccDNA). cccDNA produce in viral life cycle and remains inside the infected cells for a long time and act as a template for generating new pre-genomic RNA and virus propagation. So far, no antiviral treatment has been effective in the complete elimination of this structure. Prevention of the disease can be achieved by using effective vaccine. Previous studies indicated that neutralizing antibodies against surface antigen of the virus known as S antigen have protective properties. Therefore, a subunit vaccine containing S antigen is available. Currently S antigen is produced in recombinant form and WHO recommended the first dose should be given within a day of birth. Pegylated IFN-γ and nucleotide-nucleoside analogues are effective drugs against HBV infection, but they may have severe side effects. Ineffectiveness of the vaccine on premature infants and immunocompromised people and also drug side effects has made HBV infection a great trouble.