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发表于 2004-8-16 08:45
Hepatitis B Virus Infection
乙肝病毒感染
Hepatitis B Virus Infection -- Natural History and Clinical Consequences
Ganem D, Prince AM. Hepatitis B virus infection -- natural history and clinical consequences. N Engl J Med. 2004;350:1118-1129. This is a review article on hepatitis B virus (HBV).
乙肝病毒感染——自然病程和临床后果
这是关于乙肝病毒的评述文章
Natural History
May be symptomatic or asymptomatic; usually symptomatic, especially in young children.
More than 95% of cases are self-limited with clearance of virus and immunity to reinfection. Less than 5% develop persistent infection. Persistence is in 3 categories: (1) asymptomatic chronic HBV carriers -- normal alanine aminotransferase (ALT) and biopsy, (2) chronic hepatitis B -- elevated ALT and altered liver histology, and (3) cirrhosis -- develops in 20% with chronic hepatitis B.
自然病史
可能有症状或无症状，常见是有症状，特别是在幼儿中。
超过95%的病例是自限性清除病毒，并且对再次感染免疫。少于5%发展为持续感染。持续有
3种情况：（1）成为无症状慢性乙肝病毒携带者——谷丙转氨酶（ALT）和活组织检查正常，
（2）慢性乙肝——ALT升高，肝组织观察变化
（3）肝硬化——慢性乙肝有20%发展为肝硬化。
Primary Infection
Hepatitis B surface antigen (HBsAg) becomes detectable at 4-10 weeks followed by antibodies to the core antigen; viral titers reach 109-1010 c/mL; e antigen (eAg) is usually detectable, and animal studies suggest that 75% to 100% of hepatocytes are infected.
This is the period of greatest risk of vertical or horizontal transmission.
初期感染
可以检测测到乙肝表面抗原(HBsAg)，4——10周后检测到核心抗体，病毒浓度达到109-1010 c/mL，
通常可检测到核心抗原(eAg)，动物实验表明75%-100%的肝细胞被感染.
Liver injury is associated with T-cell-mediated immune response indicating immune-mediated liver injury.
In most cases, there is clearance of the virus with the disappearance of HBsAg and hepatitis B e antigen (HBeAg); anti-hepatitis B surface antibody (HBsAb) appears with little or no liver injury in most cases.
肝损伤同T细胞免疫反应相关，标志免疫反应造成肝损伤。
在多数情况，病毒会被清除，伴随表面抗原HbsA和核心抗原HbeAg消失；出现表面抗体HbsAb。多数情况，没有或有轻微肝损伤。
Persistent Infection
HBsAg persists, often in titers of 107-109 copies/mL, which are virons that are
replicating and transmissible. Titers are higher in the presence of HBeAg.
HBsAg usually remains detectable for life but titers of virus decline with time, and
this is often associated with HBeAg seroconversion at a rate of 5% to 10%/year.
持续感染
表面抗原HbsAg持续存在，通常滴度107-109 copies/mL，病毒在复制和传播；如果出现HbeAg病毒
表抗滴度会更高。HbsAg通常终生可检测到，但病毒滴度会随着时间减少，这通常会伴随HbeAg血清
转换，通常速率每年5%-8% 。
HBeAg-negative carriers usually have low levels of viremia, normal ALT, and a good
prognosis. In some areas, especially southern Europe and Asia, 15% to 20% have elevated ALT and high levels of viremia, and many of these carriers have a mutation that prevents the production of eAg.
Chronic HBV carries a risk of hepatocellular carcinoma that is 100 times higher than in noncarriers; this risk is highest with eAg, but is still a risk even with anti-HBeAg. This accounts for the recommendation for measuring serum alpha-fetoprotein and/or hepatic ultrasonography twice yearly with chronic HBV. This test is controversial -- there
is no agreement about when screening should start, and it has a poor positive predictive value estimated at 9% to 30%.
HbeAg阴性携带者通常病毒血水平低，ALT正常，预后良好。在一些地区，特别是南欧和亚洲，15%
到20%有ALT升高，病毒血水平高，很多这样的携带者有病毒变异，不能产生eAg抗原。
慢性HBV携带者的肝癌风险，比非携带者高100倍；该风险在有eAg时最高，但即使在有HbeAg抗体时仍存在。因此推荐，慢性HBV, 每年要两次检测血清α-甲胎蛋白和肝脏超声。该检测存在争议
——筛选的起点没有共识，估计有9%到30%的弱阳性值
Indications for Treatment
Chronic infection associated with HBeAg is an indication for treatment on the basis of risk for chronic active hepatitis and cirrhosis, and risk of carcinoma.
Chronic carriers that are HBeAg-negative with HBV-DNA levels less than 105 copies/mL and normal ALT levels have a favorable prognosis and are generally not treated.
Some eAg-negative patients have elevated ALT and high-level viremia; some favor treatment of this group as well.[8]
治疗指示
慢性感染伴随HbeAg，是治疗指示，是基于有慢性活动性肝炎和硬化，肝癌风险。
HbeAg阴性，HBVDNA水平小于105 copies/mL，ALT正常的慢性携带者预后良好，一般不治疗。
一些eAg阴性患者，ALT升高，病毒血浓度高，这些人群也应治疗。
Treatment
Seroconversion from HBeAg to anti-HBeAb and a reduction in levels of viremia are generally considered markers of successful treatment, because these are associated with
improved histology and the improvement may last for a prolonged duration.[9] Cure of
infection with the loss of HBsAg is achieved in only 1% to 5% of patients.
治疗
HbeAg血清转化为核心抗体anti-HbeAb，病毒血浓度减少，是一般认为的治疗成功标志，因为这与显微组织改善相关联，且改善会长期持续。表面抗原HbsAg消失，感染治愈的患者仅有1%到5% 。
Interferon: The standard dose is 5-10 million units subcutaneously 3 times weekly for
at least 3 months. Response rates are about 30% and the risk of hepatocellular carcinoma is reduced, but the side effects are serious.
干扰素 标准剂量为5—10百万单位，每周3次皮下注射，至少进行3个月。应答率大约30%，肝癌的风险减少，但副作用严重。
Lamivudine: Usually results in a 3-4 log10 decrease in viremia, often with HBe seroconversion. This treatment is well tolerated and has generally supplanted interferon. HBeAg seroconversion occurred in 65% of patients with an ALT exceeding 5 times the upper limits of normal (ULN), but only in 5% of those with an ALT of less than 2 times the ULN, which is the rate of spontaneous loss.[10] Drug resistance mediated by point mutations at the YMDD motif occurs with a frequency of 15% to 20% at 1 year, 40% at 2 years, and 67% by 4 years.[11] HBe seroconversion may occur even after the appearance of lamivudine resistance with a total rate of 40% to 50% at 4 years; therefore, some experts continue the drug even with resistant variants.
拉米夫定：通常有 3，4个数量级的病毒血浓度降低，经常伴随核心抗原血清转换。该治疗耐受性良好，一般可以代替干扰素。HbeAg转换在ALT超过正常值5倍的患者中，65%发生血清转换，但ALT高于正常两倍以下的只有5%发生血清转换,与自然转化相当.由YMDD遗传序列变异引起的抗药性发生率第一年15%到20%，第二年40%，第4年67%。核心抗体的血清转化，甚至在拉米抗药性出现后也会发生，第4年有40%到50%的概率；因此，一些专家在抗药性出现后仍持续给药。
Adefovir: This drug also is associated with a 3-4 log10 decrease in HBV viremia, an
increased frequency of HBe seroconversion, and histologic improvement.[12] This drug is active against lamivudine-resistant strains.
阿地福为：该药物也有3，4个数量级的病毒血浓度降低，核心抗体转换概率提高，预后改善。该药物对拉米抗药株有效。
Tenofovir: Another nucleotide that is associated with a 4 log10 decrease in HBV viremia and is active against lamivudine-resistant strains.
太诺夫为：另一种核苷类似物，有4个数量级的 HBV浓度降低，，对拉米抗药株有效。
Experimental drugs: These include entecavir (selective for HBV polymerase), emtricitabine (similar to lamivudine), and clevudine (another nucleoside).
正在试验中的药物：包括恩地卡为，（选择性HBV聚合酶），emtricitabine和拉米类似，clevudine，另一种核苷类似物。
[此贴子已经被作者于2004-8-15 19:47:05编辑过]
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