The continuous replication of hepatitis B virus in the liver is the main cause of the development of slow hepatitis B, cirrhosis, and liver cancer. In the panorama of hepatitis B treatment, cirrhosis and liver cancer are the final stages of hepatitis B development. For patients with slow hepatitis B, aggressive antiviral therapy is aimed at preventing disease progression to the cirrhosis or liver cancer stage; for patients with cirrhosis, the goal of treatment is to delay and reduce the onset of liver failure and the development of liver cancer. In the panorama of hepatitis B treatment, each stage of slow hepatitis B, cirrhosis and liver cancer needs to be treated step by step in order to have a long-lasting cure.
Difference 1-Treatment timing: If cirrhosis is found to be eligible for antiviral treatment, antiviral treatment should be given immediately.
The correct control of the timing of treatment can often achieve twice the result with half the effort. The timing of treatment for chronic hepatitis B and cirrhosis is different, and patients should not confuse the two.
Indications for treatment of chronic hepatitis B.
The 2010 Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B clearly states that antiviral treatment is required for HBeAg-positive patients with HBV DNA ≥105 copies/m l or HBeAg-negative patients with HBV-DNA ≥104 copies/m l and liver function tests with ALT ≥2 times the normal value; in addition, if the ALT is <2 times the normal value, but liver puncture tests reveal liver necrosis or fibrosis also need to be treated.
Indications for cirrhosis treatment.
Compared with slow hepatitis B, patients with cirrhosis have a thin “family base” and poor liver reserve function, which cannot withstand the stormy attack of hepatitis B virus, therefore, the threshold of antiviral treatment for cirrhosis is lower and the timing of treatment needs to be advanced. Professor Wang Yuming of the Department of Infection of Chongqing Southwest Hospital pointed out that “for patients with compensated cirrhosis (relatively light), as long as the HBV-DNA of HBeAg-positive patients is ≥104 copies/ml or HBV-DNA of HBeAg-negative patients is ≥103 copies/ml, antiviral treatment is required regardless of whether the liver function is normal or not. Patients with decompensated (more severe) cirrhosis require immediate antiviral therapy whenever they are tested for hepatitis B virus.”
Studies show that patients with hepatitis B cirrhosis who adhere to lamivudine antiviral therapy for 3 years can reduce the incidence of liver cancer by nearly half, and adherence to treatment for 10 years can lead to complete reversal of some early cirrhosis and remove the cap of cirrhosis; for patients with more severe cirrhosis, early initiation of antiviral therapy can alleviate the disease and reduce the proportion of liver transplants and extend survival time.
Difference 2-Treatment course: no definite time to stop drug for cirrhosis
Many hepatitis B patients ask their doctors, “When can I stop taking the medication before they start treatment? In fact, there are no shortcuts on the road to treatment for either slow hepatitis B or cirrhosis. Short-term treatment (less than 1 year) will lead to a high percentage of relapses after stopping the medication, so that patients are caught in a vicious cycle of “treatment-discontinuation-relapse”, and each relapse of hepatitis B will aggravate the fibrosis of the liver, and eventually get closer to cirrhosis and liver cancer.
Chronic hepatitis B course of treatment: 2010 “China slow hepatitis B prevention and treatment guidelines” pointed out that e antigen positive chronic hepatitis B patients after one year of treatment, if HBV-DNA is below the lower limit of detection, normal liver function and e antigen serological transformation, but also need to consolidate treatment for one year, the total course of treatment for at least two years before patients can stop the drug under the guidance of doctors. Many people mistakenly believe that “small triplets” (e antigen negative slow hepatitis B) are better treated than “large triplets” (e antigen positive slow hepatitis B), but in fact “small triplets” have a higher relapse rate and therefore require a longer treatment time. e antigen negative slow hepatitis B patients need to continue treatment for 1.5 years after one year of treatment, if the HBV-DNA is below the lower limit of detection and the liver function is normal, the total course of treatment needs to be at least 2.5 years. The total course of treatment should be at least 2.5 years. It can be seen that patients with slow hepatitis B can only be discontinued after a total course of treatment of at least 2-2.5 years after reaching the discontinuation test index.
The course of cirrhosis: Once the development of chronic hepatitis B has reached the stage of cirrhosis, whether compensated or decompensated, there is no clear indicator of drug discontinuation and long-term or even lifelong antiviral treatment is required. Experts have repeatedly stressed that “the danger of stopping medication in patients with cirrhosis is very great. Because their liver function is already very poor, if the virus rebound after stopping the drug, it may boom to trigger acute liver function loss, resulting in life-threatening.”
Consensus 1-Treatment strategy: optimize treatment
Currently, hepatitis B antiviral drugs are mainly divided into interferon and nucleoside (acid) analogues. Interferon must be used with caution in patients with compensated cirrhosis, while the use of interferon is strictly prohibited in decompensated cirrhosis. Patients with chronic hepatitis B may choose interferon or nucleoside (acid) analogs for antiviral therapy under the guidance of their physicians on a case-by-case basis.
In the treatment of cirrhosis and chronic hepatitis B with nucleoside (acid) analogs, the 2010 Chinese Guidelines for the Prevention and Treatment of Hepatitis B first recommended a strategy for optimal treatment. The critical time point is at six months (24 weeks) of treatment initiation. At this point, if the patient’s HBV-DNA is <103 copies/ml, the efficacy is satisfactory and monotherapy can be continued. However, if the HBV DNA is >103 copies/ml, it indicates that the efficacy is not very satisfactory and the possibility of drug resistance in the long term is high. In this case, the original monotherapy can be maintained on top of the combination therapy with a drug that does not have cross-resistance sites. More and more studies have found that it is better to add drugs than to change drugs to prevent and treat hepatitis B drug resistance. The expert consensus states that “the worst strategy for dealing with drug resistance is drug switching, which is now discarded in guidelines worldwide.” Because several nucleoside (acid) analogs have overlapping resistance sites, switching can lead to cross-resistance.
In addition to optimizing treatment, a national expert consensus also recommends initial combination in patients with cirrhosis, where treatment with two nucleoside (acid) analogs with different resistance sites is initiated at the start of antiviral therapy, with the same proven efficacy.
Consensus 2 – Regular monitoring: improving efficacy and reducing side effects
Starting antiviral therapy does not mean that you are in a “safe deposit box”. Both patients with chronic hepatitis B and cirrhosis need to be monitored regularly to understand the efficacy of drugs, adverse effects and disease progression through follow-up. Patients with cirrhosis need to pay special attention to the adverse drug reactions. The expert consensus states that “in patients with mild cirrhosis, all four nucleoside (acid) analogues can be used. However, in the severe stage of cirrhosis, patients need to be strictly monitored and safe drugs should be selected.”
In addition, various tests such as the five hepatitis B tests, HBV-DNA and liver function should be performed every 3-6 months for slow hepatitis B. The follow-up interval should be shortened if there are any changes in the condition during the follow-up. For patients with cirrhosis, especially those at high risk of liver cancer (>40 years old, male, alcoholic, incomplete liver function, etc.), in addition to the above routine examinations, AFP (alpha-fetoprotein) and abdominal ultrasound should be checked every 3-6 months for early detection of liver cancer.
In conclusion, both cirrhosis and chronic hepatitis B require long-term antiviral therapy, but the timing of treatment for cirrhosis should be as early as possible and there is no definite time to stop the medication. In addition to this, both groups of patients need to adhere to regular monitoring and optimize their treatment based on the results of hepatitis B virus testing.