编者按：慢乙肝是严重威胁人类健康的疾病。在过去的十年中，慢性乙型肝炎的流行病学特征呈现出向“老龄化”以及“合并症”增多的变化趋势。在第70届美国肝脏病研究学会（AASLD）年会上，本刊特约专访了美国哈佛大学医学院Mindie H. Nguyen教授，就慢乙肝的“老龄化”与“合并症”问题进行了解读。

 

《国际肝病》：在过去的十年中，慢性乙型肝炎的流行病学特征呈现出怎样的变化?

 

Nguyen教授：我们对美国约4万名真实世界的患者数据进行分析的结果发现，在过去十年中慢性乙肝患者的中位年龄已从十年前的40多岁到2015年为50多岁。同样的，来自台湾、韩国以及日本的数据也得到相似的结果。除此之外，我们还发现随着年龄的增加，慢乙肝患者的合并症也显著增加了，其中最常见的是高血压、糖尿病和脂肪肝，还有相当一部分（大约15%）的患者合并了肾病，在美国人口中，轻度肾病的比例接近30%。骨病不太常见，但仍相当重要。

 

《国际肝病》：慢性乙肝患者常见的肝外合并疾病有哪些？对抗病毒治疗的选择有什么潜在影响？

 

Nguyen教授：基于这样一个流行病学特征，对于慢乙肝患者来说最重要的除了抗病毒药物的选择以外，还有肝癌的风险。因为患有代谢综合征，糖尿病的病人患肝癌的风险更高。因此对于这些患者，应该更密切地进行监测。

 

《国际肝病》：慢性乙肝患者合并NAFLD目前越来越常见，那么NAFLD对慢性乙肝的自然史有什么影响？

 

Nguyen教授：慢性乙肝患者合并NAFLD是一个非常重要，也是一个有争议的问题。研究表明，NAFLD和乙型肝炎的共患病率10%~30%不等，平均值约20%~25%。合并NAFLD对慢乙肝患者意味着什么呢？同时有两种疾病是不是会更糟？我们通常认为，如果同时患有两种严重的疾病，应该比仅仅有一种更严重。但是实际上，现有的数据存在矛盾。

 

有研究表明，肝纤维化（活检证实）和肝癌的风险更高，但这些人可能是特定人群。更大的一个队列——其中包括来自美国和中国台湾的包括4000-5000名患者，却得到了相反的结果。即如果只是普通的慢乙肝患者群体，而且只是合并了脂肪肝，这些患者实际上的肝癌和肝硬化风险更低，清除乙肝的几率更高。

 

总之，我们还不能确定合并NAFLD的慢性乙肝更好、更坏还是中性。这仍然是一个很有争议的问题。

 

We have looked at real world data in the United States, and this includes the analysis of about forty thousand patients. And we found that in the last ten years, the patients have aged with a median age in the early forties, now in the early fifties in 2015. So the patients have aged, definitely, and we saw the same thing. I have worked with investigators from Taiwan, Korea, Japan, and we saw really the same thing. Patients have aged over the years. And with this, the comorbidities have also increased, and quite remarkably so. And the most common ones are hypertension, diabetes, and fatty liver disease. And a substantial portion, about fifteen percent or so, also have some kidney disease. And mild kidney disease in the US population was close to thirty percent. The most common comorbidities are high blood pressure, hyperlipidemia, and diabetes. Kidney disease and bone disease are less common but are still quite significant. So I think the important things here are not just about antiviral medication choices, but also in the risk of liver cancer. Because patients with metabolic syndrome, with diabetes; they’re at higher risk for liver cancer. So these patients- that should be taken into consideration- whether they should be started on antiviral therapy or they should be monitored more closely. And patients who have kidney problems or bone problems, or are at high risk for it, then certainly we would not want to give them a medication that could make any of those conditions worse. Yeah, that is a very important question and also a controversial one. So, I believe that the prevalence of coexisting, NAFLD, and hepatitis B, ranges from ten to about thirty percent, in the literature, but the average is probably about twenty percent. Twenty to twenty five percent. Now, what does that mean to the patients with hepatitis B? So, if they have NAFLD, is it worse or not worse? So usually we think that if you have two bad diseases, it should be worse than just having one of them. And data is still very conflicting. So studies that have biopsy data show that fibrosis and liver cancer risk is higher. But these may be a selected population because these people must have something with them that requires liver biopsy so they may be sicker patients. But larger cohort- I am aware of one cohort from another country and one cohort from our group from the US and Taiwan, including four or five thousand patients, and we actually noticed the reverse. So if the patients have fibrosis already, then of course that’s bad. But if it’s just a general group of hepatitis B patients, and just have fatty liver, then actually some of those patients actually have lower risk of liver cancer and cirrhosis, and have higher chances of clearing the hepatitis B. So, I think that this is still a very controversial area and I don’t think we can tell for sure yet whether it is worse or better or neutral.