Demystifying the "golden hour" of antivirals: a critical moment in liver cancer prevention

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Case 1

CASES

Gao, male, 51 years old, was treated with entecavir 0.5mg/d antiviral for 3 years in April 2017 due to chronic hepatitis B. On January 4, 2020, due to the new crown epidemic, he stopped antiviral drugs for 3 years, and his liver and abdomen were uncomfortable for 7 days. On April 9, 2024, he came to our hospital for outpatient treatment and was admitted to the hospital with "chronic viral hepatitis B, liver cirrhosis, and liver tumor".

查体：神清，面晦，巩膜无黄染，肝区叩痛+，脾脏略大，双下肢不肿。 化验：血WBC 4.22×109//L、Hb 161g/L、PLT 92×109/L、ALT 70.1U/L、AST 78.4U/L、γ-GT 408U/L、LDH 343U/L、前白蛋白 124.6mg/L、TBA 20.9μmol/L、ADA 31U/L、CH 5.4mmol/L、CK同工酶 55.1U/L、α羟基丁酸脱氢酶 311U/L、HBsAg>250IU/ml、HBeAg 9.845IU/ml、AFP>1200ng/ml。

CT of the chest: small nodules in the anterior inner basal segment and outer basal segment of the left lower lobe, clear in the boundary, benign nodules considered, LungRADS class 2, punctate calcifications in the posterior segment of the right upper lobe, mild thickening of the pleura at the apex of both upper lungs, cirrhosis, hypodense nodules in the right lobe; Upper abdominal MRI scan and enhancement: left hepatic lobe mass, multiple nodules in the liver, fast-in and fast-out sample enhancement, liver cancer with multiple intrahepatic foci, portal vein cancer thrombus, portal vein cavernous degeneration, liver cirrhosis with diffuse regenerative nodules, splenomegaly, accessory spleen, cholecystitis, multiple lymph nodes in the hilar area and retroperitoneum. On the second day of hospitalization, he was transferred to the hospital for TACE treatment.

Disease 2

CASES

Tu, male, 74 years old, mother has a history of hepatitis B, started entecavir 0.5mg/d antiviral due to hepatitis B on May 4, 2016, HBV DNA continued to be less than 30IU/ml, (August 24, 2021) color ultrasound: mild fat deposition in the liver, cholesterol crystals in the gallbladder wall.

2023年3月28日：HBsAg 0.78IU/ml、HBeAb 72.9INH%、HBcAb 100.4INH%； TBIL 12.8μmol/L、ALT 28.1U/L、AST 31.6U/L、BUN 4.5mmol/L、UA 380.3μmol/L、Cr 71.2μmol/L、BG 6.21mmol/L、TG 2.82mmol/L、CH 5.76mmol/L、LDL-C 3.84mmol/L。

2023年12月：ESR 12mm/h、WBC 4.94×109/L、Hb 148g/L、PLT 115×109/L；尿隐血1+，大便隐血阴性；TG 1.84mmol/L、CH 5.64mmol/L、HA 79.09ng/ml、PT 11.5s、D-二聚体800μg/L、糖化血红蛋白5.9%、HBsAg 0.64IU/ml、HBsAb 7.6mIU/ml，甲功3项、HBV DNA、抗HCV、肝纤四项正常；彩超：肝脏体积正常，表面光整，回声稍增强细密，后方略伴衰减，边略钝，血管尚清晰，STE肝脏硬度值 7.41 kPa。

2024年4月11日：因肝区不适伴乏力10日入院，查血WBC 5.25×109/L、Hb 141g/L、PLT 141×109/L；HBsAg 36.673IU/ml、HBV DNA<30 IU/ml，CH 5.4mmol/L、LDL-C 3.86mmol/L、血淀粉酶22U/L、N端脑钠肽前体160.15pg/ml、AFP 8.22ng/ml，肝纤四项、甲功五项、肝肾功能、葡萄糖、电解质、心肌酶、凝血四项、D-二聚体正常。

Color ultrasound: the liver volume is normal, the surface is not smooth, the echo thickening is uneven, the edges are blunt, and the blood vessels are not clear. A 37×31mm heterogeneous hypoechoic piece of size can be seen in the right liver, with a clear border, regular morphology, and blood flow signals can be seen around it. STE liver stiffness value was 12.03kPa, and MRI of the upper abdomen was non-contrast and enhanced: the liver morphology was irregular, the posterior and lower part of the right lobe of the liver was 3.1cm×3.6cm abnormal signal mass, the boundary was clear, the signal was long T1 and long T2, the patchy liquid signal was seen inside, the DWI showed annular hyperintensity, the ADC value was reduced, the enhanced scan showed annular enhancement, and the tumor lesion was considered; Cholecystitis; Vascular ultrasound: bilateral carotid plaque, arteriosclerosis of both lower extremities with left plaque formation.

CASES

discuss

In 1992, the mainland began to vaccinate newborns with hepatitis B vaccine, and the mother-to-child transmission rate of pregnant women with hepatitis B "small three yang" was less than 20%, and the mother-to-child transmission rate of pregnant women with high level of hepatitis B virus replication was 70-90%. About 75% of hepatitis B infections in mainland China are transmitted from mother to child.

From 1992 to 2006, the mainland began to use "hepatitis B vaccine combined with hepatitis B immune globulin" for the "active and passive combined immunization" of neonates born to pregnant women with hepatitis B, and by 2014, the hepatitis B surface antigen carrying rate of children aged 1-4 years in the mainland was 0.32%, a decrease of 96.6% from 9.67% in 1992. The third stage of hepatitis B prevention in mainland China is neonatal combined immunization, and hepatitis B mothers start taking antiviral drugs at 24-28 weeks of pregnancy to achieve the effect of zero transmission of hepatitis B in newborns, also known as the "hepatitis B mother-to-child zero transmission project". The future of the next generation without hepatitis B is soon becoming a reality.

The existing hepatitis B patients are mainly mother-to-child transmission of hepatitis B patients born before 1992, at least 32 years old in 2024, if the first-line antiviral treatment of entecavir, tenofovir, tenofovir alafenol, and emitenovir is started from the age of 30 according to the latest guidelines, the effective antiviral time (defined as the time when the HBV DNA continues to be less than 20-30 IU/ml of the minimum detection line) is significantly less than the total infection time of HBV, which is the reason for the higher incidence of liver cirrhosis or liver cancer.

Case 1 Gao, who only started antiviral therapy for 3 years at the age of 45, stopped taking the drug for 3 years after the new crown came, developed liver cancer at the age of 51 and was diagnosed with advanced liver cancer, and could only undergo palliative treatment such as TACE and could not be cured by surgery; Case 2, mother-to-child transmission of hepatitis B, 66-year-old entecavir antiviral started, good compliance, effective antiviral time of 8 years, 74-year-old liver cancer was found in the early stage, there are surgical indications and can strive for radical cure, can be expected to achieve the average normal male life expectancy.

CASES

启示

1. For mother-to-child transmission of hepatitis B, the earlier the antiviral prevention of liver cirrhosis/liver cancer, the better the effect.

2. The longer the effective antiviral time, the better the effect of preventing liver cirrhosis and liver cancer.

3. The greater the ratio of effective antiviral time to total infection time, the better the effect of preventing liver cirrhosis and liver cancer.

4. With the increase of age, the interval between early screening of liver cancer in hepatitis B patients must be shortened, and case 2 was only 4 months, liver cancer grew from scratch to 3.1cm×3.6cm, and the AFP was only 8.22ng/ml, which was slightly increased.

5. Case 2: HBsAg grew from 0.64 IU/ml to 36.673 IU/ml in only 4 months, which reflected the decline of the patient's immune function from one side, and if the immune function was normal, there was a chance to achieve a clinical cure of hepatitis B.

6. To prevent liver cancer, we should adhere to the combination of antiviral and immune enhancement, pay attention to regular life, maintain a happy mood, ensure sleep and the nutritional needs of the body, and combine interferon therapy to further reduce the occurrence of liver cancer.

Since the first edition of the guidelines for the prevention and treatment of hepatitis B, experts have attached great importance to antiviral treatment, and as the task of eliminating the impact of hepatitis in 2030 is getting closer and closer, the antiviral indications for hepatitis B have been relaxed, the starting time of antiviral has been advanced, and efforts have been made in the direction of antiviral treatment as long as there is HBV DNA replication, and finally the goal of antiviral treatment for chronic hepatitis B is truly realized: long-term effective inhibition of viral replication, preventing the progression of hepatitis B inflammatory activity and fibrosis, and controlling the development of the disease. Improve the quality of life, prolong life, and reduce the complications of chronic hepatitis B complicated by cirrhosis and decompensation, ascites, hemorrhage, severe hepatitis, liver failure, liver cancer, etc.

Source: Liver Cancer Online