制定未来慢性乙型肝炎抗病毒治疗指南之我见

慢性HBV感染是亚洲地区的重大疾病,对人群健康已造成严重危害。其一,全球有近4亿HBV携带者,在HBV感染的高流行区,HBV携带者占75%[1];其二,亚洲慢性乙型肝炎(CHB)患者ALT水平低的临床特点,反映具有长期病毒血症,极可能是亚洲CHB发展成肝硬化和肝细胞癌的危险因素[2]。     

肝硬化患者血清HBV DNA检测的临床意义

<正>我国慢性乙型肝炎(CHB)后肝硬化在肝硬化分类中占居首位[1]。CHB后肝硬化的发生与多种因素相关。2012年亚太地区CHB治疗共识中明确指出对HBeAg阳性的肝硬化患者及HBeAg阴性的肝硬化患者无论ALT水平高低只要检出HBV DNA者均建议抗病毒治疗[2]。由此可见抑制HBV复制在治疗和延缓肝硬化的形成中具有重大意义,因此本文对肝硬化患者进行免疫标志物及HBV DNA表达水平的测定旨在阐     

慢性乙型肝炎患者病毒学应答与临床终点事件

乙型肝炎病毒（hepatitis B virus,HBV）感染呈世界性流行,是导致肝衰竭、肝硬化和肝细胞癌（hepatocellular carcinoma,HCC）等终末期肝病发生的重要原因。及时有效地抗病毒治疗可改善慢性乙型病毒性肝炎（chronic hepatitis B,CHB）患者的临床结局。HBV DNA是目前应用最广泛的抗病毒疗效评价指标,国内外指南将实现完全病毒学应答（complete virological response,CVR）作为CHB的基本治疗终点。然而在临床实践中发现,即使是服用强效的一线核苷（酸）类似物,仍有20%～30%的CHB患者不能获得或者不能长期维持CVR。研究表明,血清HBV DNA的持续或间断存在是慢性肝炎向肝硬化和肝癌等终末期肝病进展的重要危险因素。不同病毒学应答模式与CHB相关性终末期肝病的发生风险高低密切相关,因此了解CHB患者不同病毒学应答的临床结局具有重要意义。     

儿童HBV感染：ALT水平正常患儿的抗病毒治疗

慢性乙型肝炎（CHB）是全球范围内的重大公共卫生问题,目前我国约有200万儿童HBV感染者。儿童感染HBV后更容易慢性化,成年后发生肝硬化以及肝癌的风险高。传统观点认为儿童HBV感染多数处于免疫耐受期,无需考虑抗病毒治疗,仅对免疫活动期和代偿期或失代偿期肝硬化的儿童CHB启动抗病毒治疗。越来越多的儿童CHB临床研究结果显示,儿童CHB抗病毒治疗（特别是以干扰素为基础的方案）应答率高,低龄儿童是临床治愈的优势人群,但对于ALT水平正常,特别是处于免疫耐受期的HBV感染的患儿是否接受抗病毒治疗仍然存在争议。本文针对儿童HBV感染的特点及ALT水平正常患儿抗病毒治疗必要性,特别是关于治疗时机等方面进行综述。     

陈建杰教授治疗低病毒载量慢性乙型肝炎经验总结

慢性乙型肝炎(CHB)是由乙型肝炎病毒(HBV)感染所引起的肝脏慢性炎症性疾病[1]。据流行病学调查显示全球约2.9亿人是HBV携带者,我国HBsAg阳性率约6.1%[2]。CHB如不及时治疗可进展为肝硬化、肝癌。对符合抗病毒指征的患者可选用干扰素(IFN)及核苷(酸)类似物(NAs)进行治疗[1]。因抗病毒适应证的限制,低病毒载量(HBV DNA阳性,定量<105 IU/ml)的CHB患者现代医学并无针对性治疗药物[3],而此类患者存在显著的肝组织损害[4],仍有发展为肝硬化及肝癌的风险[5,6]。     

关注慢性乙型肝炎特殊人群抗病毒治疗时机及治疗策略

慢性乙型肝炎（CHB）特殊人群要充分衡量肝硬化和肝癌家族史、年龄、疾病分期和抗病毒疗效等因素。CHB特殊人群选择合适抗病毒治疗时机并及时调整抗病毒策略,对于延缓疾病进展和降低肝硬化及肝细胞癌的发生起到重要的作用。本文将针对年龄≤30岁且ALT水平正常慢性HBV感染者、年龄>30岁且ALT水平正常慢性HBV感染孕妇、慢性HBV感染者儿童和HBeAg阳性低病毒血症经治CHB患者等特殊人群的抗病毒治疗时机和治疗策略进行阐述,帮助临床医生对CHB特殊人群选择更好的抗病毒治疗时机和优化治疗策略。     

乙型肝炎病毒相关肝硬化的临床诊断评估和抗病毒治疗的综合管理

HBV 相关肝硬化是慢性 HBV 感染的重要临床结局，病毒持续高载量与肝硬化累积的发生率密切相关，是发生肝硬化的高危因素，可作为预测肝硬化的独立因素。抑制 HBV 复制有助于改善肝纤维化，延缓代偿期肝硬化发展，降低门静脉高压等并发症的发生率。近年来，多项实验证实，有效的抗病毒治疗对改善患者预后具有重要意义，其为 HBV 相关肝硬化治疗方案的组成部分。多个国家肝病学会在乙型肝炎（CHB）诊治指南中提出，HBV相关肝硬化患者应积极进行抗病毒治疗。     

老年人慢性HBV感染的临床特点分析

目的探讨老年人慢性乙型肝炎病毒（HBV）感染的疾病谱及临床特点。方法比较53例老年慢性HBV感染者与相同例数的低年龄组慢性HBV感染者的性别、疾病谱、血清HBVDNA和ALT水平。结果老年组慢性HBV感染的疾病谱与低年龄组有显著不同,前者以非活动性HBsAg携带者为主（66.0%）,后者中HBeAg阳性慢性乙型肝炎患者较多（47.2%）。老年组慢性HBV感染者血清HBVDNA和ALT均明显低于低年龄组,差异有统计学意义（P〈0.05或P〈0.01）。两组总体性别组成差异无统计学意义。结论非活动性HBsAg携带者是老年慢性HBV感染的主要疾病谱,但HBeAg阳性或阴性慢性乙型肝炎（CHB）和乙型肝炎肝硬化的发生率仍较高,且存在HBV复制和肝脏病变。     

慢性乙型肝炎抗病毒及免疫调节治疗研究进展

<正>乙型肝炎病毒(hepatitis B virus,HBV)感染是危害人类健康的重要问题,持续HBV感染易导致肝炎、肝硬化和肝癌的发生。我国是乙型肝炎的高流行区,慢性HBV感染者约9 300万例,慢性乙型肝炎(chronic hepatitis B,CHB)患者约2 000万例[1]。CHB的治疗关键是抑制HBV。近十几年来,CHB的治疗研究取得了令人瞩目的进展,但目前面临着发展的"瓶颈",期待有新的突破。本文就     

不同临床类型HBV感染患者肝组织中单核细胞趋化蛋白-1的表达及意义

目的：研究乙肝病毒（HBV）携带者、慢性乙型肝炎（CHB）、乙型肝炎肝硬化患者肝组织中单核细胞趋化蛋白-1（MCP-1）的表达,并探讨其临床病理意义。方法：20例HBV携带者、18例CHB患者、13例乙型肝炎肝硬化患者肝组织经10%中性甲醛固定后制作石蜡包埋切片,并以两份正常人肝组织作为对照,采用免疫组织化学法（SP法）检测肝组织MCP-1的表达水平。结果：正常肝组织MCP-1无表达,HBV携带者、CHB、乙型肝炎肝硬化患者肝组织MCP-1表达阳性率依次为25%、77.78%、84.62%,差异均有显著性意义。结论：MCP-1在肝组织中的表达随肝脏炎症和纤维化的发展而升高,MCP-1可能在病毒性肝炎肝脏炎症和纤维化的病理过程中起重要作用。MCP-1的研究对乙型病毒性肝炎的病情诊断、发病机制探讨及治疗提供新思路。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.