The first lecture: hepatitis B virus infection is not equal to chronic hepatitis B In China, about 10% of people are hepatitis B virus carriers, and although the carriage rate of hepatitis B virus has decreased in the past 20 years, it still reaches about 8%. Therefore, in a country like China, where hepatitis B is a major disease, whenever people talk about chronic hepatitis B, they are always “afraid of talking about liver”, and most of them are psychologically worried and cannot get rid of the psychology of helplessness, fear and worry, thinking that infection with hepatitis B virus is equivalent to having chronic hepatitis B, which is incurable and cannot be recovered. It is not possible to recover, let alone be cured. But is this worry necessary? Is chronic hepatitis B virus infection and chronic hepatitis B the same? The answer is of course no: chronic hepatitis B virus infection is not the same as chronic hepatitis B! Although the number of people infected is large, only a very small percentage actually become chronic hepatitis and cirrhosis and hepatocellular carcinoma; therefore, the fears and worries that most of us usually have are superfluous and totally unnecessary! This is because we do not really understand the hepatitis B virus and how it occurs and develops. To explain this, let’s first understand the different states that the hepatitis B virus infects humans in and the process that it goes through from infection to disease onset, because different states and processes of infection have completely different outcomes; it can be said that humans are constantly fighting against viruses in nature. However, chronic hepatitis B virus is probably the most diverse and complex virus in human beings after infection with various viruses; the disease spectrum and natural history of chronic HBV infection are diverse and variable, ranging from a stationary state of viral carriage to progressive and active chronic hepatitis, from a lifetime of never developing and “peaceful” virus The spectrum and natural history of the disease is diverse and variable, ranging from stationary carriage of the virus to progressive active chronic hepatitis, and from a lifetime of never developing the virus and being “peaceful” to the progressive development of cirrhosis and hepatocellular carcinoma (HCC) in a minority of individuals. Broadly speaking, there are five different manifestations of hepatitis B virus infection, which are expressed in medical terms as “HBV carrier state”, “immune tolerance stage”, “immune reactivity stage” and “HBEAG stage”. The medical terminology is “HBV carrier status”, “immune tolerance stage”, “immune reactivity stage”, “HBEAG negative chronic hepatitis B” and “HBSAG negative stage”. If we can clearly distinguish these four different states, we will have a comprehensive understanding of hepatitis B virus infection. The first, “quiescent HBV carrier state”: this is the most common state after infection with hepatitis B virus, and is often found to be serum HBSAG-positive during a physical examination, but the serum viral DNA is negative. Usually the transaminases are normal. Such a state is due to good immune control after infection, resulting in a relatively good long-term outcome for most patients, who almost rarely develop cirrhosis or liver cancer. A study in Taiwan found that in such a population, over a period of 25 years, about more than 40% will experience the disappearance of HBSAG and seroconversion to anti-HBS antibodies. The result of this seroconversion, in fact, represents the termination of the infection, or even self-healing; thus, it can be seen that hepatitis B virus infection, if only the virus carrier state, long-term inactivity of the disease, at least nearly half of the people, is able to heal on its own without any treatment! The second, “immune tolerance stage”: has several characteristics: HBEAG positive, high level of hepatitis B virus DNAV replication (in response to high level of serum HBVDNA), basically normal liver function, and extremely mild or slow progression of liver lesions. At this stage, the rate of natural disappearance of HBEAG is very low. In our country, most such individuals are infected at birth or within one year of age through a virus-carrying mother; because of the high level of virus replication in the body, such infections are highly contagious. If infected in adulthood, such people may spontaneously develop what is commonly referred to as seroconversion, or the disappearance of HBEAG, to a “quiescent HBV carrier state” over a period of years or decades without the need for treatment. However, there may be some triggers such as alcohol abuse, exertion, or severe mood swings that may lead to the “immune response phase” described below – the third state, the “immune response phase “This is the stage that requires the most attention and vigilance. Compared with the previous stage, this stage has the following major characteristics: negative or positive HBEAG, fluctuating HBV replication levels in response to high and low serum HBVDNA levels, and most importantly, elevated or fluctuating transaminase levels in response to liver function impairment, usually accompanied by moderate or severe necrotizing liver inflammation and rapidly progressive liver fibrosis. This phase can last from a few weeks to several years. Although the rate of spontaneous resolution of HBEAG increases during this stage, the potential for progression to cirrhosis and hepatocellular carcinoma also increases significantly if it persists for too long. Therefore, those infected at this stage should be treated aggressively with antiviral therapy to control the progression of the disease; fortunately, there are many treatment options available and effective, a subject we will elaborate on later. The fourth state, “HBEAG-negative chronic hepatitis B”: this stage refers specifically to those who are HBEAG-negative but have increased serum HBVDNA levels and the presence of viral replication; moreover, liver function tests reveal that transaminase levels are elevated or fluctuating, which is clearly different from the resting HBV carrier state we described above. Generally, it can be found only after the laboratory test in the hospital. Such a condition appears due to a small mutation of the virus in the body, and the result of this mutation can make the virus replicate without HBEAG secretion into the serum, thus the routine 2.5 test only indicates a “small triplet”, due to the existence of this state Active liver disease can progress rapidly to early cirrhosis, with a high risk of subsequent cirrhotic failure and HCC. Therefore, we must carefully assess the patient’s disease status and monitor serum transaminases and HBVDNA levels every 3 months. The fifth state, the “HBSAG negative stage”: the period after the disappearance of HBSAG, in general, hepatitis B virus DNA is undetectable in the serum, while anti-HBC antibodies, with or without anti-HBS, are detectable. The risk of cirrhosis, decompensation and hepatocellular carcinoma is reduced if HBSAG disappears before the age of 40 or before the onset of cirrhosis. The use of immunosuppressants during this period can lead to HBV reactivation if used for other reasons. If HBSAG is spontaneously negative or has progressed to cirrhosis after treatment, the patient remains at risk of progression to hepatocellular carcinoma and therefore must be monitored regularly for the development of hepatocellular carcinoma. It is thus clear that hepatitis B virus infection is a dynamic process. Only the latter two cases require treatment, while in the first and second cases, no treatment is needed. Not only that, but spontaneous viral clearance occurs in some people; therefore, not every person with hepatitis B virus infection is chronically hepatitis B, and even less does every infected person need treatment. It is important to note that these four stages are not necessarily consecutive. However, it is possible for some patients to have the four different states mentioned above transformed into each other for a variety of reasons, so what causes this disparate presentation and what causes the different states of the disease to transform into each other? This involves the different immune capabilities of each individual and the influence of a variety of external factors, which we will explain to you separately and carefully later.