Expert consensus opinion on the clinical diagnosis and treatment of occult hepatic encephalopathy in China

Source: Chinese Journal of Digestion, 2023,43(11) : 721-736.

Occult hepatic encephalopathy (CHE) is an important type of hepatic encephalopathy. In contrast to overt hepatic encephalopathy (OHE), patients with CHE do not have obvious clinical manifestations such as disorientation and asterixis, but they have neuropsychological and/or neurophysiological abnormalities, and some patients may have mild cognitive impairment, euphoria, or anxiety, and decreased attention and numeracy. CHE is not only prone to OHE, but also seriously affects patients' driving ability, fine operation ability and health-related quality of life, increases the risk of accidental injury, increases the burden on families and society, and shortens the survival time of patients with liver cirrhosis. In order to further improve the understanding of CHE and standardize the diagnosis and treatment of CHE, the Gastroenterology Branch of the Chinese Medical Association organized domestic experts in relevant fields to summarize the research results in related fields in recent years with reference to the recent relevant guidelines and consensus at home and abroad, and formulate this consensus opinion in combination with the actual situation in mainland China. This consensus opinion has formed 19 statements on the definition, epidemiology, etiology, triggers and pathogenesis, clinical manifestations, diagnosis and treatment, as well as prognosis and chronic disease management of CHE, in order to provide guidance for standardizing the diagnosis and treatment of CHE in China.

This article only elaborates on the recommendations of consensus, and interested readers can click https://rs.yiigle.com/cmaid/1489144 for in-depth reading.

1. Definitions

【Statement 1】Hepatic encephalopathy is a neuropsychiatric abnormality of varying degrees based on metabolic disorders caused by acute and chronic liver failure, liver cirrhosis and/or various portal vein-systemic shunts (hereinafter referred to as portosystemic shunts), and it is recommended to classify and grade hepatic encephalopathy according to the severity and duration of hepatic encephalopathy (level of evidence: level 1; level of recommendation: strong recommendation; statement agreement rate: 100%).

[Statement 2] According to the severity of the disease, hepatic encephalopathy is divided into OHE and CHE. CHE includes MHE and West-Haven grade 1 hepatic encephalopathy in patients with neuropsychological and/or neurophysiological abnormalities who may have no abnormal clinical manifestations or only mild cognitive impairment, euphoria or anxiety, decreased attention and numeracy, but no disorientation and asterixis (level of evidence: 1; level of recommendation: strong recommendation; agreement rate: 100%).

2. Epidemiology

【Statement 3】The prevalence of CHE in patients with liver cirrhosis is relatively high, which is closely related to the degree of liver impairment (level of evidence: 2; statement agreement rate: 96%).

3. Etiology, triggers and pathogenesis

[Statement 4] The underlying diseases that lead to CHE are similar to those of OHE, and common triggers include gastrointestinal bleeding, infection, electrolyte imbalances, surgery, constipation, and the use of sedatives and opioid analgesics (level of evidence: 1; statement agreement: 96%).

Fourth, the hazards of CHE

【Statement 6】CHE affects patients' ability to drive, work at height, and perform fine operations, increases the risk of accidental injury, reduces health-related quality of life, and increases the burden on families and society (level of evidence: 1; statement consent rate: 100%).

【Statement 7】CHE is prone to OHE and is closely related to the occurrence and progression of other complications of liver cirrhosis, and is an independent risk factor for death in patients with liver cirrhosis (level of evidence: 1; statement agreement rate: 100%).

5. Screening, diagnosis and differential diagnosis

【Statement 8】Once cirrhosis is confirmed, routine CHE screening is recommended, with particular emphasis on CHE screening in patients with high-risk occupational cirrhosis (level of evidence: level 1; level of recommendation: strong recommendation; statement agreement rate: 100%).

[Statement 9] Screening and diagnosis of CHE rely primarily on neuropsychological and/or neurophysiological testing. PHES is recommended as the preferred method for diagnosing CHE and the Stroop test is used for screening for CHE (level of evidence: 1; level of recommendation: strong recommendation; agreement with statements: 91%).

【Statement 10】Imaging tests such as conventional computed tomography (CT) and magnetic resonance imaging (MRI) have little value in the diagnosis of CHE screening, but they can be used to rule out organic lesions of the central nervous system (level of evidence: 2; level of recommendation: strong recommendation; statement agreement rate: 100%).

【Statement 11】There is a certain correlation between elevated blood ammonia and CHE, but it cannot be used as a basis for the diagnosis of CHE. Attention should be paid to the standardization of sampling, storage, transport and testing processes (level of evidence: 2; level of recommendation: strong recommendation; statement agreement rate: 100%).

【Statement 12】Other diseases that may cause cognitive impairment should be excluded in the diagnosis of CHE, and the investigation of other diseases should be paid more attention to when lactulose or rifaximin is not effective (level of evidence: 2; level of recommendation: strong recommendation; statement agreement rate: 96%).

6. Treatment

【Statement 13】Once CHE is diagnosed, active intervention should be performed, and treatment of the underlying disease and removal of the trigger are the basis of CHE treatment (level of evidence: 1; level of recommendation: strong recommendation; statement agreement rate: 100%).

【Statement 14】Adequate energy and protein supplementation improved HRQL in CHE patients without increasing the risk of OHE (level of evidence: 1; level of recommendation: strong recommendation; statement agreement rate: 96%).

【Statement 15】Lactulose can improve patients' cognitive performance and HRQL, and is recommended as a first-line treatment for CHE (level of evidence: 1; level of recommendation: strong recommendation; statement agreement rate: 100%).

【Statement 16】Rifaximin can significantly improve cognitive performance and HRQL in patients with CHE, and is also recommended as a first-line treatment for CHE (level of evidence: level 1; level of recommendation: weak recommendation; statement agreement rate: 100%).

【Statement 17】L-ornithine-L-aspartate (LOLA) can reduce blood ammonia levels, improve neuropsychological test results, and increase HRQL in patients with CHE, and can also be used for the treatment of CHE (level of evidence: 1; level of recommendation: weak recommendation; statement agreement rate: 100%).

【Statement 18】Probiotics can reduce blood ammonia and endotoxin levels and improve cognitive function in patients with CHE, and can be used as an adjuvant treatment for CHE (level of evidence: 2; level of recommendation: weak recommendation; statement agreement rate: 87%).

7. Prognosis and chronic disease management

【Statement 19】It is recommended that CHE should be included in the management of chronic diseases, health promotion and education should be strengthened, and standardized screening, treatment and good life care should be advocated to improve the HRQL and prognosis of patients (level of evidence: 2; level of recommendation: strong recommendation; statement agreement rate: 100%).