BACKGROUND Chronic hepatitis delta virus (HDV) infection causes severe liver disease which often leads to cirrhosis and hepatocellular carcinoma (HCC). Aim of this study was to establish the disease severity and prognostic factors for disease outcome by analysing frequencies of clinical events and their correlation with baseline virological and biochemical parameters as well as interferon and nucleos(t)ide analogue treatment choice. METHODS We studied a single-centre cohort of 49 anti-HDAg-positive patients with HBsAg persistence for at least 6 months. Virological and biochemical parameters, interferon and nucleos(t)ide analogue treatment choice as well as clinical events during follow-up were analysed by retrospective chart review (mean follow-up time 3 years, range 0.25-7.67 years). RESULTS Severe clinical events occurred in 11/49 hepatitis D patients, including HCC (8/49), death (8/49) or liver transplantation (2/49). HCCs only occurred secondary to liver cirrhosis and their event rates in this cohort of hepatitis D patients did not differ from a matched HBV mono-infected cohort with comparable frequency of liver cirrhosis. A stepwise multivariate logistic regression revealed low platelet count (p = 0. 0290) and older age (p = 0.0337) correlating most strongly with overall clinical events, while serum HDV RNA positivity at baseline did not correlate with any clinical outcome. Interferon-free but not nucleos(t)ide analogue-free patient care correlated with the occurrence of HCC at logistic regression, although only 3/18 interferon-treated patients demonstrated repeatedly negative HDV PCR results post therapy. CONCLUSIONS Our data indicate that progressive liver disease at baseline plays a major role as predictive factor for overall clinical outcome of hepatitis D patients. In particular, HCC risk may not be underestimated in hepatitis D virus RNA negative hepatitis D patients with advanced liver fibrosis.

中文翻译：

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HBV / HDV合并感染患者的高肝硬化率和严重临床事件：德国队列的纵向分析。

背景技术慢性丙型肝炎三角洲病毒（HDV）感染引起严重的肝脏疾病，其通常导致肝硬化和肝细胞癌（HCC）。这项研究的目的是通过分析临床事件的频率及其与基线病毒学和生化参数以及干扰素和核苷酸类似物治疗选择的相关性，确定疾病严重程度和疾病预后的因素。方法我们研究了49名HBsAg持续存在至少6个月的抗HDAg阳性患者的单中心队列。通过回顾性图表回顾（平均随访时间3年，范围0.25-7.67年）分析了病毒学和生化参数，干扰素和核苷酸类似物的治疗选择以及随访期间的临床事件。结果11/49例D型肝炎患者发生了严重的临床事件，包括HCC（8/49），死亡（8/49）或肝移植（2/49）。HCC仅继发于肝硬化，并且在此D型肝炎患者队列中，其事件发生率与匹配的HBV单一感染队列和肝硬化发生频率相近。逐步多因素logistic回归显示，血小板计数低（p = 0. 0290）和老年（p = 0.0337）与整体临床事件密切相关，而基线时血清HDV RNA阳性与任何临床结局均不相关。尽管只有3/18干扰素治疗的患者在治疗后表现出反复阴性的HDV PCR结果，但无干扰素的护理却与无核苷酸类似物的护理与Logistic回归时HCC的发生有关。结论我们的数据表明，基线时进行性肝病在D型肝炎患者总体临床结局中起主要预测作用。特别是，在患有晚期肝纤维化的D型肝炎病毒RNA阴性D型肝炎患者中，可能不能低估HCC风险。