丙型肝炎病毒感染后的自然史

由于大多数丙型肝炎病毒(HCV)感染者在急性期及慢性感染早期症状隐匿，所以，确切的HCV感染后自然史很难评估。急性感染后的演变主要依赖动物实验或者对输血后丙型肝炎患者的前瞻性研究，慢性感染自然史则依赖于前瞻性研究和回顾性研究。     

输血后丙型肝炎患者的临床特点及自然病程

目的了解输血后丙型肝炎病毒感染者的临床特征及自然病程。方法采用回顾性调查与前瞻性研究相结合的方法,进行定期随访检查。结果在89例HCV感染者中输血时间主要集中在1987～1995年（67%）,其中以1990～1994年为最多（48%）,1995年以后输血后丙型肝炎感染率明显下降（0.9%）;在89例患者中输血原因分别为手术48例（54%）,外伤、车祸、骨折10例（11.2%）,重型肝炎2例（0.2%）;在89例患者中输血距离首次诊断时间为1年～21年,平均为11.5年;在89例患者中有70例诊断为慢性丙型肝炎,16例诊断为肝硬化,3例诊断为肝细胞癌,其中有16例给予普通干扰素治疗,除1例10年后发展为肝硬化外,其余病情稳定,无进展,有10例给予长效干扰素联合利巴韦林治疗,随访肝功能无异常。结论经输血感染丙型肝炎主要集中在1990～1994年,1995年以后发病率大幅度降低。     

丙型肝炎病毒感染家庭内传播的研究

对50例慢性丙型肝炎（丙肝）患者的121名家庭成员（配偶47名，子女74名）进行了血清抗-HCV的检测。结果47名配偶血清抗-HCV均阴性，74名子女中只有1名血清抗-NCV阳性。表明HCV感染家庭内日常生活接触及夫妻间性接触传播的危险性甚小。     

丙型肝炎病毒感染的自然经过和长期预后

本文综述了丙型肝炎病毒感染后不同临床类型的临床表现、肝功能和病毒标志物变化的自然经过，不同临床类型之间的相互关系和长期预后。     

丙型肝炎病毒感染与肝脏脂肪变性研究进展

1肝脏脂肪变性在慢性丙型肝炎患者中的发病情况 据文献报道,全世界1．7亿慢性丙型肝炎（chronic hepatitis C,CHC）患者中,大约一半的患者伴有肝细胞脂肪变,10％的儿童CHC患者并发非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）。在排除肥胖、     

丙型肝炎病毒感染与免疫

丙型肝炎病毒感染与免疫杨东亮郝连杰本文仅就ＨＣＶ感染与免疫的研究进展作一综述。一、ＨＣＶ基因组及其产物的多样性［１～３］１．ＨＣＶ基因组结构与变异ＨＣＶ基因组全长约１０Ｋｂ，由一个大的开放读框（ＯＲＦ）及其两端各一个非编码区组成。ＯＲＦ分为结构基因区...     

丙型肝炎病毒感染的血清学试验

丙型肝炎病(HCV)的分离和克隆，7年来对其感染的血清学诊断方面已有许多的进展，但当前国内试剂的质量不高、试验结果错误，给临床分析带来不少的困难；输血后丙型肝炎高发主要是试剂不灵敏使传染性病人的血清漏检。本文评述HCV感染血清学诊断，包括抗体检测和病毒扩增的已有成绩和问题。     

儿童丙型肝炎病毒感染84例分析

84例HCV感染儿中，63.1%有输血制品史；5例≤6月龄婴儿（1例有输血史）母亲HCV标志阳性；1例在其父患输血后丙肝21月后筛查发现血清HCV RNA和抗HCV阳性。除外原有其他肝病者，62例患儿临床上以急性无黄疸型（25.8%)、亚临床型（20.9%)和无症状感染（25.8%)多见。仅5例为急性黄疸型（8.1%)，慢性型占19.4%。并见HAV、HBV和HCV三重感染2例；HCV与HAV和HBV二重感染各6例和16例；与CMV混合感染3例。慢性和无症状HCV感染儿中混同HBV感染最多见（11／16，68.8%)，1例肝活检证实有肝硬变。血清HCV标志检测表明，HCV RNA在免疫发育不完善的婴儿、免疫抑制者及感染早期特异性抗体未能检出时更具诊断价值。9例接受α－干扰素辅以病毒唑治疗，近期病毒清理率达55.6%。     

The natural course of chronic hepatitis C: implications for clinical practice

Hepatitis C is an important public health problem with high rates of chronic infection ensuing after viral acquisition. The spectrum of the disease ranges from mild to severe chronic hepatitis, cirrhosis and hepatocellular carcinoma. Extra-hepatic manifestations may occur. The disease is complex and predictions about long-term prognosis for individual patients remain difficult. It is generally accepted that 10–20% of patients with chronic hepatitis C will develop cirrhosis within 10 years of first infection: identifying the group of patients at greatest risk remains a primary challenge for clinicians. Older age of infection, duration of infection, degree of liver inflammation at first biopsy and cofactors such as alcohol abuse, all appear to be predictors of a poorer prognosis. The following paper aims to identify some of the features of the natural history of hepatitis C most relevant to the clinician.     

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.     

The natural course of HCV infection and the need for treatment

Nowadays, hepatitis C infection has been identified as the main cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma in Western Countries. However, despite its large diffusion (with more than 150 million of people infected world-wide), the lack of symptoms during the acute phase, together with the indolent course of the disease over time, hampers the difficulties to assess the natural history of the disease, which still remains an interesting clinical dilemma. This complexity can also be argued from the large heterogeneity of disease complication's rate observed when different methodological approaches were used (retrospective cohort studies, prospective cohort studies, retrospective-prospective cohort studies). Moreover, the progression of the disease could also be dramatically affected by many variables related to the host, the virus and the environment. Finally, in the last few years, the long-term outcome of the infected subjects, has been deeply modified by the use of efficacy antiviral therapy, as shown by the better survival observed in patients who had achieved a sustained virological response after interferon treatment.     

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.     

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified.     

Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.     

Prevention of hepatitis C virus infection

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13-14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.     

丙型肝炎病毒感染的检测

丙型肝炎病毒（HCV）感染的检测包括血清学检测和核酸检测（NAT）,前者包括HCV抗体（抗-HCV）、核心抗原检测,后者包括定性/定量RNA检测和基因型/亚型检测。抗-HCV检测是应用最广的HCV感染筛查试验,操作简便、耗时短、成本低,但其缺点是窗口期较长,不能判别是活动性感染还是病毒已被清除,不适用于免疫缺陷人群。HCV RNA是病毒感染的直接证据,既往定性RNA检测灵敏度较高,但随着实时定量PCR技术的成熟,定量检测灵敏度不断提高,线性范围不断拓宽,适用于临床抗病毒治疗应答的监测,也正逐步取代定性检测用于血液制品的筛查。近年HCV抗原检测和抗原抗体联合检测试剂盒已用于HCV感染的筛查及治疗监测,但其灵敏度尚不及NAT。目前主流的HCV基因分型试剂检测基因型有较高的符合率,而检测亚型的结果存在较大差异,需要方法学上的改进。     

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...