癌旁肝组织活动指数与HBsAg、HCV抗原表达的相关性

目的对癌旁肝组织活动指数与HBsAg、HCV抗原表达进行相关性研究。方法采用免疫组织化学(SP)方法对100例肝癌组织及癌旁组织中的HBsAg、HCV抗原表达进行标记和分析,同时对其癌旁肝组织进行肝组织活动指数评分(HAI)。结果肝癌癌旁组织HAI在HBV、HCV双重感染组中分值最高(12.62±3.88),单独HBV感染组次之(9.80±2.97),都高于病毒全阴性病例(6.67±2.58)。肝癌组织、癌旁组织中HBsAg、HCV抗原表达与HAI明显相关(rs=0.39,P=0.0001)。HBsAg、HCV虽可在癌组织及癌旁组织表达,但有一定差异:HBsAg主要在癌旁组织表达(79%),高于癌组织表达(23%),而HCV在癌组织表达(15%)与癌旁组织表达(23%)水平相当。结论有病毒感染背景的肝癌,其癌旁肝组织活动指数明显地高于无病毒感染背景者。癌旁肝组织活动指数与HBsAg、HCV抗原表达明显相关,长期的病毒血症会加重肝脏组织病变。     

乙型肝炎患者胆囊黏膜中病毒抗原表达分析

目的通过对慢性乙型肝炎患者的胆囊组织进行HBsAg、HBcAg的检测,了解乙型肝炎病毒在胆囊黏膜组织中的定位及分布状况以及对胆囊功能的影响,探讨慢性乙型肝炎患者胆囊病变与乙肝病毒（HBV）感染的关系.方法以鼠抗-HBs单克隆抗体、兔抗-HBc多克隆抗体,采用免疫组化S-P（SP）法,检测胆囊黏膜组织中的HBsAg和HBcAg.血清乙型肝炎病毒感染标志物阳性患者石蜡包埋胆囊标本29例为研究对象,血清乙型肝炎病毒感染标志物检测阴性患者的胆囊标本12例为对照组.乙肝病毒血清学检查用ELISA法检测.结果（1）乙型肝炎患者胆囊黏膜中存在HBsAg和HBcAg,29例患者胆囊黏膜组织中HBsAg的检出率为37.9%（11/29）,HBcAg的检出率为20.68%（6/29）.对照组HBsAg和HBcAg各有1例阳性,阳性率为8.3%（1/12）,HBsAg主要呈弥漫胞浆型分布,光镜下呈棕黄色颗粒沉积,主要分布在胆囊黏膜上皮细胞中,HBcAg的分布呈胞浆型和核型两种形态,见于腺上皮细胞和成纤维细胞中;（2）HBV病毒抗原阳性组和阴性组均呈慢性炎症性改变,胆囊黏膜组织的病理改变无明显差异;（3）胆囊息肉与HBV病毒感染的关系密切,肝癌患者的癌旁组织和胆囊黏膜中病毒抗原表达明显.结论乙型肝炎病毒感染者的胆囊黏膜中存在HBV病毒抗原,提示乙型肝炎病毒在肝外组织胆囊黏膜中也存在感染.     

肝癌组织、癌旁组织中HBsAg、HCV抗原表达与T细胞亚群及NK活性的相关性研究

研究肝癌组织、癌旁组织中HBsAg、HCV抗原表达与T细胞亚群及NK活性的相关性。采用免疫组织化学方法(SP法)对肝癌组织及癌旁组织中的HBsAg、HCV抗原表达进行了标记和分析,同时对外周血T细胞亚群及 NK活性进行检测。肝癌患者中,CD4 细胞减少,CD8 细胞升高,CD4 ／CD8 比值及NK细胞的活性均比正常对照组明显降低,且HBsAg阳性、HCV抗原阳性者比阴性者下降更显著。肝癌组织、癌旁组织中HBsAg、HCV抗原表达与外周血T细胞亚群及NK活性Spearman相关性分析,与NK细胞、CD4 细胞、CD8 细胞、CD4 ／CD8 相关系数分别为-0．67,-0．28,0．35,-0．50(P<0．001)。肝癌患者出现免疫紊乱与乙肝、丙肝病毒感染有关,且混合感染者免疫功能紊乱较显著,提示抗病毒治疗可能改善肝癌患者的免疫功能。     

乙型肝炎相关性肝细胞癌HBV复制及其癌组织中HBsAg/HBcAg表达的研究

目的以慢性乙型肝炎(chronic hepatitisB,CHB)患者为对照,观察乙型肝炎相关性肝细胞癌(hepatocellular carcinoma,HCC)患者血清中HBVDNA水平的变化,以及HCC组织中HBsAg/HBcAg的表达情况,探讨HBV导致HCC的可能机制。方法 HCC组89例,CHB组120例。采用实时定量PCR法检测血清HBVDNA水平;分别留取肝脏穿刺组织标本(HCC组织均带有癌旁肝硬化组织),用免疫组化法检测组织中HBsAg/HBcAg的表达情况。结果 HCC组血清HBVDNA水平明显低于CHB组(P<0.05);在CHB组织、癌旁肝硬化组织和HCC组织中HBsAg表达阳性率分别为90%、51%和10%,HBcAg阳性率分别为78%、19%和3%,与CHB组织、癌旁肝硬化组织相比,HCC组织中2种抗原表达均明显较低(P均<0.05)。结论在HBV慢性感染不同疾病阶段,血清HBVDNA水平和HBsAg/HBcAg在肝组织内的表达具有显著差异;与CHB组相比,HCC组HBVDNA水平较低,HBsAg/HBcAg表达显著缺失,这可能与HCC患者HBVDNA复制水平降低有关,但也不排除其他因素导致HBsAg/HBcAg表达抑制。     

用基因重组丙型肝炎病毒抗原C11和C7对丙型肝炎进行分析

使用基因重组丙型肝炎病毒（ＨＣＶ）基因核心区所表达的抗原Ｃ１１及非结构区ＮＳ３区所表达的抗原Ｃ７，对北京地区慢性病毒性肝炎、肝硬化、原发性肝瘤４４２例进行了血清丙型肝炎病毒抗体（抗ＨＣＶ）检测。初步看出本地区乙型肝炎更多于丙型肝炎。肝硬变、原发性肝癌在病因学上与乙、丙型肝炎重叠感染的关系比单独乙型或单独丙型肝炎感染的关系更为密切。提示这些患者中乙型及丙型肝炎病毒之间有相互作用的可能性。     

慢性乙型肝炎患者肝组织HBsAg、HBcAg表达及临床意义

目的：探讨慢性乙型肝炎患者肝组织中HBsAg、HBcAg表达与血清乙肝病毒载量及肝组织损伤程度之间的关系。方法：对90例慢性乙型肝炎患者进行肝组织活检，进行病理诊断及乙肝病毒HBsAg、HBcAg免疫组化染色．同时荧光定量检测血清HBVDNA含量，并分析其相关性。结果：血清HBVDNA定量、肝组织炎症程度及纤维化程度与肝组织HBsAg表达强度无相关性，而与肝组织HBcAg表达强度有明显的关联性；血清HBVDNA定量与肝组织炎症程度及纤维化间无明显的相关性。结论：在慢性乙型肝炎的免疫损伤过程中，HBcAg是靶抗原，血清HBV DNA结合肝组织病毒抗原的表达可作为抗病毒治疗的指标。     

慢性病毒性肝炎肝细胞凋亡与Fas抗原和病毒表达的相互关系

为探讨病毒性肝炎肝细胞凋亡及其与病毒和Ｆａｓ抗原表达的关系，应用原位末端标记技术检测一组慢性乙、丙型肝炎患者肝组织中细胞凋亡状况，并以免疫组化方法检测病毒和Ｆａｓ抗原表达。结果３１例患者中，２５例肝组织中检出末端标记阳性细胞，散布于肝小叶和肝窦内，部分炎症坏死灶中和胆管上皮细胞也可检出阳性细胞；组织炎症活动度较大者和病毒抗原阳性者凋亡指数较高；凋亡细胞可为病毒抗原阳性和阴性；Ｆａｓ抗原阳性与阴性组间凋亡程度无显著差异。提示病毒性肝炎患者感染和未感染病毒的肝细胞均可发生凋亡，其机制有待进一步研究。     

慢性丙型肝炎患者肝组织中病毒和Fas抗原表达及其与干扰素应答的关系

目的 探讨丙型肝炎患者肝组织中HCV Ns5和Fas抗原表达及其与肝组织损伤和干扰素治疗反应的关系.方法 应用a干扰素对一组慢性丙型肝炎患者进行24周治疗,停药后随访6个月,以血清丙氨酸转氨酶(ALT)恢复正常及血清HCV RNA持续阴转为完全应答标准,采用免疫组化方法检测组织中病毒和Fas抗原表达状况.结果 29例慢性丙型肝炎患者肝组织中,HCV NS5和Fas抗原呈阳性者均为19例(65.5%),两者在肝组织中的表达显著相关;单因素相关分析时,两者均与组织病变程度有关,但多因素分析表明只有HCV NS5抗原表达水平与组织炎症活动度呈正相关.治疗和随访结束时分别有17例(58.6%)和15例(51.7%)患者表现为近期和远期完全应答.治疗前Fas表达水平与干扰素应答有关,但未见HCV NS5水平与干扰素应答有明显关系;5例随访结束时重复肝穿,3例完全应答者病毒表达显著受抑,但Fas抗原无明显改变,2例无应答者病毒表达无明显改变甚或增强,而Fas表达均增强.结论 慢性丙型肝炎肝组织中HCV Ns5表达在慢性丙型肝炎发病过程中有重要意义;Fas抗原表达水平与组织中病毒表达相关;治疗前肝组织Fas表达状况与干扰素治疗反应有一定联系.     

HBV感染血清学标志物的临床意义研究进展

感染乙型肝炎病毒(HBV)后血清中的乙型肝炎病毒标志物(HBVM)包括相应抗原(如HBsAg,HBeAg)和抗体(如抗-HBs,抗-HBe和抗-HBc),由于病毒感染状态及机体免疫应答水平的差异,血清中HBVM表达有多种组合方式。检测HB-     

慢性乙型肝炎患者血清HBV复制标志物与肝组织HBsAg和HBcAg抗原表达的相关性研究

目的探讨血清HBV复制标志物与肝组织HBsAg和HBcAg抗原表达的相关性。方法用免疫组化法检测肝组织HBsAg、HBcAg,与血清HBeAg和/或HBV DNA进行相关性比较。结果血清HBeAg阳性与阴性组中肝组织HBsAg阳性率无显著性差异,而血清HBeAg阳性者肝组织HBcAg阳性率显著高于HBeAg阴性者;血清HBV DNA阳性与阴性组中肝组织HBsAg阳性率无显著性差异,但血清HBV DNA阳性者肝组织HBcAg阳性率显著高于HBV DNA阴性者。结论血清HBeAg和HBV DNA水平与肝组织HBcAg阳性率呈正相关。     

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM： To investigate the correlation between hepatitis B virus surface antigen （HBsAg）, hepatitis C virus （HCV） expression in hepatocellular carcinoma （HCC）, the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein （AFP） level.
METHODS： The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immunohistochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index （HAIl score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups： patients positive for HBsAg （HBsAg group）, patients positive for HCV （HCV group）, patients negative for both HCV and HBsAg （NBNC group） and patients positive for both HBsAg and HCV （BC group）.
RESULTS： The BC group had significantly higher HAI scores than the other three groups. （BC 〉 HCV 〉 HBsAg 〉 NBNC）. HBV and HCV virus infection was positively correlated with HAI （rs = 0.39, P = 0.00011. The positive rate of AFP （85.7%） and the value of AFP （541.2 ng/mL） in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate （53.3%） of AFP and the value of AFP （ 53.3 ng/mL） in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP（rs = 0.38, P = 0.0001）.
CONCLUSION： The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The-serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman＇s rank correlation analysis, we can conclude that the severity of virally induced     

血清纤维化指标对肝纤维化诊断价值的研究

目的评价血清纤维化指标透明质酸（HA）、Ⅳ型胶原（CⅣ）、Ⅲ型前胶原肽（PⅢP）、层黏连蛋白（LN）对肝纤维化诊断的价值.方法对确诊的慢性乙型肝炎患者50例和健康人18例,测定血清纤维化指标水平,并进行肝组织纤维化分期.根据受试者工作特征曲线判别4项指标对于肝纤维化分期的诊断价值.结果血清HA、CⅣ、PⅢP和肝脏组织炎症分级呈较弱正相关（r分别为0.430、0.382和0.300,P＜0.05）.血清HA、CⅣ与肝脏组织纤维化分期呈中度正相关（r分别为0.614、0.708,P＜0.05）.血清HA、CⅣ水平随肝纤维化的进展程度而升高.血清HA诊断早期肝硬化（S4）的受试者工作特征曲线下面积（AUC）大于血清CⅣ、PⅢP和LN（AUC=0.967比0.932、0.659、0.403）.血清CⅣ诊断肝纤维化（S1～S4）的AUC大于血清HA、PⅢP和LN（AUC=0.853比0.680、0.536、0.487）.血清LN对于肝组织分级或分期均无统计学意义.联合HA＋CⅣ检测比单一指标有更高的特异度.结论血清纤维化指标对肝纤维化进程有一定的预测意义,但不能对肝纤维化精确分期,因此不能取代肝组织病理活检.联合多项指标检测可在一定程度上提高检测效率.寻找新的血清标志物和联合其他标志物是肝纤维化无创性研究的趋势所在.     

慢性病毒性肝炎肝组织病变的形态学特征

目的：探讨慢性病毒性肝炎肝组织炎症活动度,纤维化程度和肝细胞病变形态学特征的差异,方法：按1995年全国慢性肝炎诊断标准,对224例慢性肝炎患者的肝穿刺组织进行炎症活动度分级和纤维化分期;采用免疫组化法检测组织切片的乙型肝炎表面抗原（HBsAg),乙型肝炎核心抗原（HBcAg)及丙型肝炎病毒（HCV）核心抗原（CP10）,并据此将患者分为乙型肝炎病毒（HBV）组,HCV组及HBV＋HCV组,比较各组患者炎症活动度分级,纤维化分期,肝细胞脂肪变性,细胞内胆,嗜酸小体及毛玻璃样肝细胞的差异。结果：HCV组患者的炎症活动度,纤维化程度及肝细胞内淤胆均较HBV组重,HBV＋HCV组患者的炎症活动度及纤维化程度介于HVB和HCV组之间,而肝细胞内淤胆比单独感染组轻,毛玻璃样肝细胞仅出现于HBV感染者中,脂肪变性及嗜酸小体在各组间无显著差异。结论：HCV引起的肝脏炎症活动度及纤维化程度较HBV重,合并感染的病变不比单独感染重;肝细胞内淤胆可能是肝损伤加重的重要因素之一。     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

慢性乙型肝炎患者ALT、HBV DNA及血清肝纤维化标志物与肝纤维化程度的关系

目的探讨ALT、HBV DNA以及血清纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性乙型肝炎肝纤维化程度的关系。方法检测281例慢性乙型肝炎患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活检检测肝组织病理纤维化分期。结果 HBeAg阴性慢性乙型肝炎患者HBV DNA水平较低、纤维化程度较高。HBeAg阳性患者纤维化程度与HBV DNA呈负相关(r=-0.251,P<0.001),S≥3组水平最低。慢性乙型肝炎患者纤维化程度与PⅢP水平呈正相关,其水平随着纤维化程度的加重而明显升高。结论 PⅢP水平可能作为评估慢性乙型肝炎患者肝纤维化程度的血清学指标,血清HBV DNA与肝脏纤维化严重程度的关系仍需进一步深入探讨。     

Histomorphological characteristics of liver tissue in patients with chronic viral hepatitis

OBJECTIVE : Chronic viral hepatitis and cirrhosis caused by hepatitis B virus (HBV), hepatitis C virus (HBC) or both constitute the majority of cases of liver diseases in China. Pathologists often need to differentiate between the morphological features of HBV and HCV. The aim of this study was to explore the differences in inflammatory activity, fibrosis and morphological characteristics in various types of chronic viral hepatitis. METHODS : Inflammatory activity and degree of fibrosis in liver biopsies taken from 224 patients with chronic hepatitis were determined according to the Diagnostic Criteria of Chronic Hepatitis, China, 1995. Each of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and the hepatitis C virus nuclear core protein (CP₁₀) were detected on paraffin sections of the biopsies by using immunohistochemical methods. Patients were divided into HBV, HCV and HBV + HCV infection groups and the differences among these groups were assessed on the basis of histopathological characteristics including inflammatory activity, fibrosis, steatosis, intrahepatic cholestasis, Councilman bodies and ground‐glass hepatocytes. RESULTS : The HCV infection group had more severe inflammatory activity, fibrosis and intrahepatic cholestasis than did the HBV infection group. The degree of inflammatory activity and fibrosis in the HBV + HCV infection group was moderate, but the degree of intrahepatic cholestasis was the most severe of the three study groups. Ground‐glass hepatocytes were only noted in HBV‐infected specimens. There was no difference in the occurrences of steatosis and Councilman bodies among the three study groups. CONCLUSIONS : The degree of inflammatory activity and fibrosis induced by HCV in hepatocytes is more severe than that induced by HBV. The histological changes observed in liver infected by both HBV and HCV are no more severe than those observed in liver infected with either HBV or HCV. Intrahepatic cholestasis may play an important role in aggravating damage to hepatocytes.     

Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, the long-term clinical and histological outcomes following spontaneous hepatitis B surface antigen (HBsAg) seroclearance remain unclear. METHODS: Between 1984 and 2003, 49 (9.5%) out of 432 inactive HBsAg carriers had no detectable level of circulating HBsAg. Fifteen of 49 patients had undergone paired peritoneoscopic liver biopsies. RESULTS: During a mean follow-up period of 19.6 months after HBsAg seroclearance, 5 of 49 (10.2%) patients were noted to have HCC. Liver cirrhosis (P=0.040), a history of perinatal infection (P=0.005) and long-standing duration (at least 30 years) of HBsAg positivity (P=0.002) were associated with a significantly higher risk of developing HCC. Despite HBsAg seroclearance, HBV DNA was detected in the liver tissues from all 15 patients who underwent paired liver biopsies. Necroinflammation was significantly ameliorated (P<0.0001). On the other hand, amelioration of the fibrosis score did not reach a statistically significant level (P=0.072). Interestingly, aggravation of liver fibrosis was evident in 2 patients (13.3%) including one who had rapidly progressed to overt cirrhosis. CONCLUSIONS: In patients with spontaneous HBsAg seroclearance, necroinflammation was markedly improved and liver fibrosis was unchanged or regressed despite occult HBV infection. However, HCC developed in a minority of cases.     

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC)represents 90%of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV),hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.