Acute Liver Decompensation on Withdrawal of Cytotoxic Chemotherapy and Immunosuppressive Therapy in Hepatitis B Carriers

Five chronic carriers of hepatitis B virus developed a fulminanthepatitis-like picture when immunosuppression or cytotoxic treatment,given for unrelated disorders, was withdrawn. Viral replicationat the time of the final illness was confirmed in three of thefive cases by measurement of serum HBV DNA or the presence ofHBc antigen on liver biopsy. A cytoplasmic and nuclear patternof HBc was seen in histological material during life, but atpost-mortem was limited to a nuclear distribution, suggestinggreater destruction of hepatocytes containing cytoplasmic HBc. In two of the cases, chronic liver disease was found at post-mortem,there being no previous clinical or laboratory abnormality,but it is unlikely that this was a factor in the developmentof the superimposed fulminating hepatitis-like illness. Immunosuppressiveand cytotoxic agents must be used with extreme caution in anyhepatitis B carrier, as withdrawal can precipitate acute decompensationregardless of whether or not there is underlying chronic liverdisease.     

Wilson's disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients

An analysis has been made of presenting symptoms and course in 87 patients with predominantly hepatic Wilson's disease. In 30 patients, in whom the diagnosis was made relatively quickly, response to treatment was excellent and all recovered although two had severe haemolytic crises. Mean age of onset was 11 years (range five to 22). Nine patients suffered toxic reactions to penicillamine and were then treated with trientine. In 22 patients the diagnosis was made after neurological symptoms had supervened; in 20 the signs of hepatic damage had disappeared despite the lack of treatment but in two hepatic signs persisted until the central nervous system was affected. In the 20 patients in whom signs of liver disease resolved spontaneously there was a time interval of from one to eight years before neurological signs developed. All 22 patients in a third group died of hepatic disease without central nervous system involvement. In 19 cases duration of the illness was brief and the diagnosis was made very late or at post-mortem examination. One patient survived with chronic progressive liver damage for 20 years; diagnosis was also made at post-mortem examination. Mean age at death was 15 years. The diagnosis was made retrospectively in 13 patients who died. In two of these the diagnosis was confirmed by determination of the liver copper concentration on tissue saved at postmortem examination; in the other 11 the diagnosis is probable since other siblings developed a similar illness, proven to be Wilson's disease. Age range for these patients was eight to 13 years. Duration of the illness from onset to death was nine days to four years (mean 10 weeks). There was no example of primary carcinoma of the liver in this series.     

The immunological diagnosis of HBsAg liver disease by combined screening for thee system in the serum and the HB core and surface antigens in liver biopsy samples

Summary Serological screening for HBeAg and anti-HBe, combined with the immunohistochemical localization of the hepatitis B core and surface antigen in 110 HBsAg carriers, established different immunological profiles indicative of the liver status and prognostic of the future absence or progression of the disease. Intrahepatic HBcAg and serum HBeAg appeared the most sensitive indexes of chronic and progressive liver disease, anti-HBe and large amounts of cytoplasmic HBsAg suggest, instead, the asymptomatic carrier state without liver damage. Only the nuclear localization of HBcAg in immunohistochemical studies was a reliable prognostic indicator of transition to chronicity; absence or presence of serum HBeAg was of no help in predicting the outcome of acute HBsAg hepatitis.     

重庆市北碚区医疗机构病毒性肝炎诊断报告情况调查研究

目的 对重庆市北碚区医疗机构病毒性肝炎的诊断报告情况进行评价,探讨诊断报告中存在问题的原因,提出科学的防控建议。 方法 通过问卷调查了解可疑肝炎病例的临床表现,采集血液由疾控部门进行检验,对病例诊断进行判断,查询重庆市北碚区肝炎病例报告情况,对该地区医疗机构肝炎诊断报告情况进行分析,对医疗机构与疾控部门的实验室检测结果进行对比。 结果 共确诊病毒性肝炎217例,其中急性乙型病毒性肝炎(乙肝)116例,慢性乙肝88例,戊型病毒性肝炎(戊肝)5例,甲型病毒性肝炎(甲肝)3例。通过与医疗机构的网络报告进行对比,发现47例急性乙肝被医疗机构报告为慢性乙肝;医疗机构报告的慢性乙肝病例的阳性预测值仅为47%,而急性乙肝的阴性预测值也仅为52%,医疗机构仅对47%的可疑病例开展了抗乙肝病毒核心抗原抗体(抗-HBc IgM)检测,且其阳性率明显低于疾病预防控制中心(2=13.00,P0.01)。 结论 重庆市北碚区医疗机构病毒性肝炎诊断报告存在较大问题,建议临床医生更多运用抗-HBc IgM检测来辅助临床诊疗,并且要采取措施提高检测准确率,同时还要进一步提高医务人员传染病报告的意识,卫生行政部门也应加强督导检查。     

乙型肝炎病毒感染者肾移植前肝穿刺活检与预后分析

背景：乙肝病毒感染者肾移植手术国内有较多报道,但乙肝病毒感染者肾移植前肝穿刺活检观察有限。目的：对慢性肾功能衰竭合并不同程度慢性乙型病毒性肝炎患者进行肾移植前肝穿刺活检,移植后2年随访观察转归情况。方法：对接受肾移植的21例乙型肝炎病毒感染的尿毒症患者进行肝穿刺活检。根据肝活检组织病理学改变,分为轻度（n=9）、中度（n=7）、重度（n=5）3组。肾移植后随访观察2年。3组中各有2例进行重复肝活检组织病理学检查。结果与结论：轻度慢性乙型肝炎组在随访2年中各项观察指标均无明显变化。中度慢性乙型肝炎组从移植后3个月开始谷氨酰转肽酶活性明显高于正常水平,随访至终点时,2例重复肝活检病理显示已处于重度病变。重度慢性乙型肝炎组从移植后3个月开始谷氨酰转肽酶活性持续高于正常水平;18个月开始,血清白蛋白水平低于正常值,球蛋白水平高于正常值;随访至终点时,有4例呈肝硬化改变。提示不同程度的慢性乙型病毒性肝炎患者肾移植后预后不同,肝活检是评价肝脏病变程度的重要手段,具有指导肾移植选择的作用。     

乙型肝炎病毒感染者肾移植前肝穿刺活检与预后分析

背景:乙肝病毒感染者肾移植手术国内有较多报道,但乙肝病毒感染者肾移植前肝穿刺活检观察有限.目的:对慢性肾功能衰竭合并不同程度慢性乙型病毒性肝炎患者进行肾移植前肝穿刺活检,移植后2年随访观察转归情况.方法:对接受肾移植的21例乙型肝炎病毒感染的尿毒症患者进行肝穿刺活检.根据肝活检组织病理学改变,分为轻度(n=9)、中度(n=7)、重度(n=5)3组.肾移植后随访观察2年.3组中各有2例进行重复肝活检组织病理学检查.结果与结论:轻度慢性乙型肝炎组在随访2年中各项观察指标均无明显变化.中度慢性乙型肝炎组从移植后3个月开始谷氨酰转肽酶活性明显高于正常水平,随访至终点时,2例重复肝活检病理显示已处于重度病变.重度慢性乙型肝炎组从移植后3个月开始谷氨酰转肽酶活性持续高于正常水平;18个月开始,血清白蛋白水平低于正常值,球蛋白水平高于正常值;随访至终点时,有4例呈肝硬化改变.提示不同程度的慢性乙型病毒性肝炎患者肾移植后预后不同,肝活检是评价肝脏病变程度的重要手段,具有指导肾移植选择的作用.     

血清总胆汁酸在肝脏疾病诊治中的意义

目的 通过测定急、慢性病毒性肝炎、重型肝炎和肝硬化等不同肝病患者血清中总胆汁酸含量,探讨其在判定肝脏功能,指导临床治疗中的意义.方法 采集健康对照组(n=82)、急性病毒性肝炎(n=45)、慢性乙型病毒性肝炎(n=156)、重型肝炎(n=41)、肝硬化患者(n=104)清晨空腹静脉血,用自动生化分析仪测定.结果 急性病毒性肝炎组、慢性乙型病毒性肝炎组、重型肝炎组及肝硬化组血清TBA分别是健康对照组的42、15、66倍和9倍(P＜0.05);慢性乙型肝炎患者随着病情的加重,血清TBA水平也显著升高.结论 血清总胆汁酸含量的检测可了解肝细胞受损情况, 可作为肝功能检测的辅助指标, 对病毒性肝炎和肝硬化具有辅助诊断意义.     

421例乙肝病毒e抗原阴性及阳性慢性乙型肝炎及相关肝病临床和病毒学特点比较分析

目的：了解乙肝病毒e抗原（HBeAg）阴性和阳性慢性乙型肝炎及相关肝病患者临床和病毒学特点。方法：对421例慢性乙型肝炎及相关肝病患者进行回顾性调查,分析HBeAg阴性和阳性的乙肝患者流行病学、病例构成、肝功能、HBV-DNA载量及乙肝前S1抗体（PreS1Ag）等指标的差异。结果：HBeAg阴性组发病率高,占57.96%,高于HBeAg阳性组,其重型肝炎、肝硬化、肝癌构成及肝功能损害指标高于HBeAg阳性组,HBV-DNA载量、PreS1Ag阳性率低于HBeAg阳性组。结论：HBeAg阴性的慢性乙型肝炎及相关肝病发病率高,进展快,预后差,是今后防治慢性乙型肝炎的重点。     

Variations in codons 84-101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection.

Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in a small segment of 18 amino acids (codons 84-101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the five patients without mutations. These data suggest that the region with mutation clustering is the major target of CTL, and that the mutations evolve under the pressure of immune selection.     

A revised method for estimating hepatitis B virus transfusion residual risk based on antibody to hepatitis B core antigen incident cases

BACKGROUND: To take into account the transient nature of hepatitis B virus (HBV) antigenemia, the calculation of HBV residual risk (RR), based on the incidence/window period model, is adjusted by a correction factor that adds uncertainty to the RR estimates. STUDY DESIGN AND METHODS: This new method to estimate the RR for HBV is a weighted sum of the RR derived from hepatitis B surface antigen (HBsAg) incident cases and the one derived from antibody hepatitis B core antigen (HBc) incident cases. An anti‐HBc incident case was defined as a donation from a blood donor who had made at least one anti‐HBc–negative donation followed by a donation that was found positive with two different assays within a 3‐year period and positive for at least one of the following markers: 1) antibody to hepatitis B e antigen or hepatitis B e antigen, 2) anti‐HBc immunoglobulin M, 3) HBV DNA, 4) hepatitis B surface antibody without HBV vaccination history, or 5) HBV DNA retrospectively found in the previous donation. Five overlapping 3‐year study periods between 2000 and 2006 were analyzed. RESULTS: The HBV RR estimated with the classical method ranged from 1.51 (2000‐2002) to 0.69 per million donations in 2004 through 2006 with a decrease in 2002 through 2004 due to only two HBsAg incident cases reported in this period. By applying the revised model, the HBV RR ranged from 1.06 (2000‐2002) to 0.49 per million donations (2004‐2006), with a regular decrease. CONCLUSION: The new presented model provides HBV RR estimates that do not statistically differ from those obtained with the classical model; however, it provides more accurate data, especially in low endemic areas where the HBsAg incidence is low.     

Clinical Course of Chronic Lobular Hepatitis: REPORT OF FIVE CASES

The clinical course, and biochemical, immunological, and liverhistological changes in five patients with chronic lobular hepatitisare described. All were male (ages 17 to 44 years) and presentedwith an acute viral hepatitis-like illness. In two of thesepatients liver function tests have never returned entirely tonormal and in both prednisone has been necessary to maintaincontrol of the disease. In the other three the subsequent clinicalcourse has been characterized by remission and relapse. Up tofour relapses have occurred with a return of symptoms and strikinglyhigh serum aspartate aminotransferase concentrations (844 to2800 iu/l), and two of the three patients have required prednisoneto induce remission. The remissions appear to be complete andhave lasted for up to five years. During relapse the changesin liver histology on biopsy have invariably been indistinguishablefrom those of acute viral hepatitis, no case showing progressionto cirrhosis even after eight and a half years. All cases hadnon-organ specific auto-antibodies (antinuclear, antimitochondrial,or anti-smooth muscle) demonstrable in the serum and four hadhyperglobulinaemia (52 to 79 g/l). These findings together withthe initial presentation, the changes on liver biopsy, and therelapsing course would all be consistent with a persistent virusinfection.     

核不均一核糖核蛋白K(hnRNP K)在慢性肝病不同病理阶段的表达水平

目的:观察核不均一核糖核蛋白K(heterogeneous ribonucleoprotein K,hnRNP K)在健康体检者、慢性乙型病毒性肝炎、肝炎后肝硬化及乙肝相关性原发性肝癌患者血液和尿液中的表达差异,探讨hnRNP K在慢性肝病不同病理阶段表达水平及与乙肝相关性原发性肝癌的相关性。方法:选取2018年8月至2018年10月我院收治的健康体检者50例、慢性乙型病毒性肝炎患者43例、肝炎后肝硬化患者35例及乙肝相关性原发性肝癌患者53例,采集其空腹外周静脉血5 mL及清洁中段晨尿标本,利用ELISA分别检测hnRNP K在慢性肝病不同病理阶段血液和尿液中表达的含量,绘制ROC曲线评价hnRNP K在原发性肝癌诊断中的意义。结果:hnRNP K在慢性乙型病毒性肝炎、肝炎后肝硬化及乙肝相关性原发性肝癌患者血液、尿液中表达水平均高于健康体检者,差异有统计学意义(P<0.05)。乙型肝炎相关性原发性肝癌患者血清hnRNP K的ROC曲线AUC为0.775,敏感度和特异度分别为76.9%和64.3%;尿液hnRNP K的ROC曲线AUC为0.652,诊断乙肝相关性原发性肝癌的敏感度和特异度分别为100%和28.6%。结论:相较于健康体检者,慢性乙型病毒性肝炎、肝炎后肝硬化及乙肝相关性原发性肝癌患者的血清、尿液中hnRNP K表达水平上调,与乙肝相关性原发性肝癌具有相关性,提示hnRNP K可能是乙肝相关性原发性肝癌的潜在标志物,对原发性肝癌的诊断具有一定参考价值。     

Nucleoside analogue therapy following one-year course of hepatitis B immunoglobulin in preventing hepatitis B virus reactivation after living donor liver transplantation

The combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside analogue is well tolerated for the hepatitis B recipients after liver transplantation, but its cost is an important problem in these days. Here we report the efficacy of nucleoside analogue therapy following one-year course of HBIG plus nucleoside analogue after living donor liver transplantation (LDLT). Out of 103 LDLTs, we selected 14 recipients who received the post-transplant therapy against reactivation of hepatitis B virus for more than 30 months. Those were eight patients with chronic hepatitis B, three with fulminant hepatitis, and three whose donors were positive for antibody to HB core antigen (HBc). During two days after the operation, HBIG (40,000 units) was administered, and the serum level of antibody to HB surface antigen (HBs) was maintained at around 150 IU/L for one year by monthly administration of HBIG. After one year, HBIG was withdrawn. A nucleoside analogue was administered daily from just after LDLT, and it was continued up to the present. Among the 14 patients, two recipients had recurrence of hepatitis B. Three patients, including one patient with recurrence of hepatitis B, died due to hepatocellular carcinoma or its associated cirrhosis; namely, their deaths are unrelated to hepatitis B-related diseases. The remaining 11 patients are leading normal lives. In conclusion, nucleoside analogue therapy after one-year course of HBIG plus nucleoside analogue is feasible and cost-effective in preventing HBV reactivation. But the patients are still at risk of breakthrough and some patients may need continued prophylaxis with HBIG.     

血清甘胆酸水平在慢性肝病患者中的临床分析

目的探讨血清甘胆酸检测在慢性肝病患者诊断中的临床意义。方法将135例慢性肝病患者按病情程度分成慢性肝炎轻度组(32例)、中度组(18例)、重度组(8例),肝硬化组(62例),肝癌组(15例),同时选取20名健康体检者作为对照组。用放射免疫法检测各组对象血清甘胆酸的含量。结果慢性肝炎各组及肝硬化、肝癌组血清甘胆酸均高于对照组(P<0.01),血清甘胆酸水平在慢性肝炎各组患者之间差异有统计学意义(P<0.05)。结论慢性肝炎、肝硬化、肝癌患者血清甘胆酸较正常人升高,慢性肝炎患者随着病情加重血清甘胆酸升高。     

Fatal reactivation of chronic hepatitis B virus infection following withdrawal of chemotherapy in lymphoma patients

Four Chinese patients with non-Hodgkin's lymphoma and asymptomatic chronic hepatitis B infection developed fulminant hepatitis three to four weeks after two to five courses of chemotherapy. One was initially positive for hepatitis B e antigen and three were positive for antibody to HBeAg. They had normal initial serum aminotransferase levels. In all four patients, the hepatic illness appeared to be caused by reactivation of hepatitis B virus replication as evidenced by the appearance of HBV DNA in serum at the onset of hepatitis, seroreversion from anti-HBe to HBeAg positivity, and the absence of other incriminating drugs or viral markers. All died within three weeks after the onset of jaundice. Serum HBV DNA level dropped to undetectable level as the hepatitis progressed. We postulate that potent cytotoxic therapy reactivated HBV replication and permitted widespread infection of hepatocytes. Upon withdrawal of chemotherapy, the immunologic rebound resulted in rapid destruction of infected hepatocytes and massive liver necrosis. Several methods for the prevention of such hepatic reactivation are discussed.     

Hepatitis B virus. Update on the spectrum of clinical infections and on prophylaxis

Knowledge about hepatitis B virus (HBV) has expanded vastly over the past 20 years, elucidating not only the spectrum of clinical illnesses it causes but also its biologic characteristics. HBV is an important cause of both acute and chronic liver disease in the United States. The most serious outcome of hepatitis B infection is chronic liver disease, which can range from chronic hepatitis eventuating in cirrhosis to primary hepatocellular carcinoma. Molecular biologic studies have shown that HBV-DNA can be integrated into the genome of hepatocytes. This integration may be part of the natural history of chronic hepatitis B infection and may transform normal hepatocytes into neoplastic cells. Immunization with hepatitis B vaccine (Heptavax-B) of persons at high or intermediate risk is an essential means for preventing transmission of hepatitis B. Use of the vaccine after recent exposure to hepatitis B breaks the chain of transmission--an exciting capability. Postexposure immunization of neonates born of HBsAg-positive mothers is particularly important in preventing vertical, or perinatal, transmission of infection.     

声脉冲辐射力成像技术无创检测慢性肝纤维化的初步研究

目的探讨声脉冲辐射力成像技术（ARFI）检测慢性肝纤维化的价值。方法使用西门子超声的声脉冲辐射力成像技术检测320例受检者肝脏右叶,包括无肝病或脂肪肝的志愿者173例、乙肝病毒阳性而病理显示无肝硬化的患者84例和乙肝后病理证实肝硬化的患者63例,比较三组受检者的肝右叶感兴趣区的横向弹性参数值。结果 三组受检者的肝右叶感兴趣区弹性参数有显著差异（p〈0．001）,随着慢性肝病程度的加重,弹性参数值增加,两者有一定相关性。结论声脉冲辐射力成像技术可无创反映肝组织的弹性硬度,间接评估肝纤维化,具有潜在的临床应用价值.     

Failure of interferon to prevent recurrent hepatitis B infection in hepatic allograft

Chronic liver disease associated with hepatitis B virus infection is both common and serious; no satisfactory treatment currently exists. Orthotopic liver transplantation is an option for patients with end-stage liver disease associated with hepatitis B virus infection despite the risk of allograft reinfection. Passive immunoprophylaxis has been attempted perioperatively to prevent graft infection but has not been beneficial. Some patients with chronic type B hepatitis have benefited clinically from antiviral therapy and, in particular, interferon, but its use has not previously been reported as an approach to prevent allograft infection. We administered recombinant leukocyte A interferon perioperatively to a patient who underwent liver transplantation for type B chronic active hepatitis and cirrhosis. Circulating hepatitis B virus DNA was found postoperatively while the patient was receiving interferon, and stainable viral antigen subsequently reappeared in the transplanted liver. Thus, the drug failed to prevent viral replication and allograft infection. Thus far, no evidence of progression of the chronic hepatitis has been noted.     

HBV-DNA定量与HBV模式及肝功损害指标定量关系研究

目的探讨HBV-DNA定量与HBV模式及肝功损害指标定量关系。方法随机抽选369例乙肝或疑似乙肝病毒感染者,荧光定量聚合酶链反应(PCR)对患者血清HBV-DNA定量,酶联免疫吸附法测定乙型肝炎血清标志物模式(HBV-M),采用全自动生化仪进行天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、γ-谷氨酰基转移酶(γ-GPT)、总胆红素(TBIL)等肝功指标含量的检测。结果 HBV模式下HBs Ag+HBe Ag+HBc Ab(大三阳)患者的血清HBV-DNA阳性检出率(93.8%)及平均含量对数值(7.31±1.23)明显高于HBs Ag+HBe Ab+HBc Ab(小三阳)患者(P0.05);HBs Ag+HBe Ab+HBc Ab(小三阳)患者的血清HBV-DNA阳性检出率(41.0%)及平均含量对数值(5.03±1.31)低于HBs Ag+HBc Ab患者(P0.05),但均显著高于其他各HBV-M模式(P0.05)。HBV-DNA定量与AST、ALT等肝功损害指标呈正相关性(r=0.235,P=0.014;r=0.254,P=0.009)。结论 HBV-DNA定量与HBV-M模式关系密切,与ALT、AST呈正相关性,定期检测HBV-M和HBV-DNA能全面了解HBV感染、复制以及传染性状态。     

酒精性肝病与慢性病毒性肝炎的病理鉴别

本文对５４例单纯洒精性肝病（ＡＬＤ），６５例慢性乙型肝炎和１４例急慢性丙型肝炎的肝穿标本的病理变化进行了比较。在各型ＡＬＤ中常见的肝细胞变性，如肝脂变、小型肝细胞、巨大线粒体和麦氏小体，以及窦周纤维化，在病毒性肝炎中均少见，Ｐ值小于０．０５和０．０１。而病毒性肝炎中常见的汇管区及其周围炎、碎屑状坏死和桥接坏死以及肝窦内淋巴细胞渗出，在ＡＬＤ中少见，程度且轻。这对鉴别ＡＬＤ及病毒性肝炎有意义。