Hepatitis B virus (HBV) infection is an important cause of liver cirrhosis. Studies have shown that effective inhibition of HBV replication can improve liver fibrosis, delay or stop the progression of compensated cirrhosis to decompensated stage, reduce further deterioration of decompensated patients, reduce the occurrence of portal hypertension and related complications, and prolong survival. Therefore, effective antiviral therapy is important for improving the clinical outcome of the disease and is an important component of the current overall treatment strategy for HBV-related cirrhosis.
In recent years, the updated guidelines or consensus on the diagnosis and treatment of chronic viral hepatitis B (CHB) by the hepatology societies in China, Asia Pacific, Europe and the United States have clearly stated that patients with HBV-related cirrhosis should be given aggressive and effective antiviral therapy. However, the current antiviral treatment opinions presented in the guidelines or consensus of each country are relatively simple and can hardly meet the needs of clinical practice completely.
For this reason, the joint project group of the 12th Five-Year Plan of the Ministry of Science and Technology organized relevant experts in China, systematically summarized the research progress at home and abroad, and formulated the “Comprehensive Management of Clinical Diagnosis, Evaluation and Antiviral Therapy for Hepatitis B-Related Cirrhosis” according to the principles of evidence-based medicine.
Consensus Opinions
Observation 1:Persistent high viral load independently predicts the development of cirrhosis. those with persistent positive HBeAg are at higher risk of cirrhosis. The association between HBV genotype and disease progression is controversial.
Observation 2: Compensated cirrhosis can occur through insidious progression or acute attacks of hepatitis leading to loss of compensation. The risk of decompensation is higher in those with high HBV load (or persistent replication) and in those with co-infection with other hepatophilic viruses.
Observation 3: Cirrhosis is the most important risk factor for the development of HCC. The role of baseline viral load and persistent viral replication in the development of HCC needs further elucidation.
Observation 4: The prerequisites for a clinical diagnosis of HBV-related cirrhosis include histologic or clinically confirmed evidence of cirrhosis, etiologic evidence of HBV infection, and a complete diagnosis including etiology, compensated/decompensated status, and comorbid conditions. Initial and subsequent complete clinical evaluation should include, at a minimum, viral replication status, liver function and compensability, comorbidities, and HCC screening.
Opinion 5: The diagnosis of cirrhosis needs to be based on a combination of clinical manifestations, laboratory tests, histology, imaging and other examinations, of which liver stiffness measurement can be used as a reference in the non-invasive diagnosis of cirrhosis. When a definitive diagnosis is needed, liver biopsy is the gold standard for clinical diagnosis of cirrhosis in the compensated stage.
Observation 6: HBV DNA should be tested once in 1~3 months after initial antiviral treatment, and monitored regularly every 3~6 months thereafter. If conditions permit, HBV DNA should be detected by internationally recognized assays with high sensitivity and large detection range as much as possible. Serological indicators can be tested at appropriate times, but not too often.
Observation 7: Monitoring biochemical indicators according to the condition and applying ICG, Child-Pugh classification and/or MELD score can help to accurately assess liver function and compensatory capacity and determine the risk of death.
Observation 8: The status of complications of cirrhosis can be assessed according to a 5-stage classification to determine disease progression and judge the risk of death; stages 1 and 2 are compensated cirrhosis and stages 3 to 5 are decompensated cirrhosis.
Observation 9: Patients with HBV-related cirrhosis should be screened for HCC even if HBVDNA is undetectable. in high-risk groups, HCC should be screened every 6 months with abdominal ultrasound and AFP. for AFP >400 μg/L without liver occupancy detected by ultrasound, CT and/or MRI should be performed. for AFP elevation not reaching diagnostic levels, dynamic changes in AFP should be monitored and 1 to 2 months If HCC is highly suspected, DSA hepatic artery iodine oil angiography can be considered.
Opinion 10: The primary goal of antiviral therapy for compensated cirrhosis is to stop or delay the occurrence of liver failure and HCC; the primary goal of antiviral therapy for decompensated cirrhosis is to maintain or improve residual liver function, reduce or delay the occurrence of complications and HCC, and reduce or delay the need for liver transplantation.
Observation 11: Early and long-term antiviral therapy can provide significant clinical benefit. HBV DNA level is the only factor that determines whether to initiate antiviral therapy in compensated patients. In patients with decompensated disease, early initiation of nucleic acid analog therapy is recommended on the basis of informed consent as long as HBV DNA is detectable; in cases where HBV DNA is undetectable, it is recommended that the presence of HBV replication be confirmed by internationally recognized highly sensitive methods of retesting.
Observation 12: In patients with compensated cirrhosis, the choice of IFN therapy is controversial and should be done with great caution, requiring a thorough risk/benefit assessment. IFNα is contraindicated in decompensated patients, and nucleoside (acid) analogs are indicated in both compensated and decompensated patients.
Observation 13: The selection of nucleoside (acid) analogs should be based on a combination of possible benefit, safety risk, resistance risk, and economic status. If conditions permit, it is recommended to prefer or prioritize monotherapy with potent and low resistance drugs such as ETV and TDF for long-term treatment.
Opinion 14: Regular close monitoring of CPK, renal function, blood phosphorus and amylase indicators, once there are serious myopathy, renal damage, osteoporosis, neuropathy and pancreatitis and other adverse reactions of nucleoside (acid) analogs mitochondrial toxicity, it is recommended to replace other nucleoside (acid) analogs. For patients with high MELD scores, the risk of lactic acidosis should be closely monitored, and the principles of safety monitoring and management of adverse reactions to IFN therapy are described in the Chinese “Guidelines for the Prevention and Treatment of CHB (2010 edition)”.
For LAM or LdT resistance, prioritize addition or switch to TDF; for ADV resistance, prioritize addition or switch to ETV; for ETV resistance, prioritize addition or switch to TDF; for TDF resistance, prioritize addition or switch to ETV (2b;B).
Observation 16: In patients with hepatic insufficiency, there is no evidence for dose adjustment of nucleoside (acid) analogs.
Observation 17: Dose or dosing interval adjustments should be made in those with renal insufficiency. In mildly impaired renal function, monitor serum muscle ration and blood phosphorus every 2 to 3 months; in moderately severely impaired patients, monitor once a month. If the creatinine level exceeds the baseline value by more than 0.5 mg/dL or the phosphorus level is lower than 2.0 mg/dL, it indicates the development of nephrotoxicity related to ADV or TDF, and if the renal function is impaired, priority should be given to switching to other nucleoside (acid) drugs, otherwise the dose or dosing interval should be adjusted according to the (estimated) glomerular filtration rate. The dose or dosing interval should be adjusted according to the estimated glomerular filtration rate.
Opinion 18: Antiviral therapy is an important part of the overall treatment of HBV-related cirrhosis, and the management of complications related to cirrhosis should be standardized on the basis of antiviral therapy with reference to the corresponding guidelines or consensus; those with liver transplantation indications should be promptly referred to liver transplantation centers.