Microbiota, Sarcopenia, and Hepatic Encephalopathy Change in Cirrhotic Patients Before and After Rehabilitation

Microbiota, Sarcopenia, and Hepatic Encephalopathy Change in Cirrhotic Patients Before and After Rehabilitation

To Explore the Changes of Fecal Microbiota Before and After Treatment in Patients With Liver Cirrhosis Complicated With Hepatic Encephalopathy or Sarcopenia as a Reference for Future Fecal Microbiota Transplantation

Through this plan, it will provide many benefits to patients with liver cirrhosis complicated with sarcopenia and/or hepatic encephalopathy, their family members, and the government in Taiwan: To explore the changes of fecal microbiota before and after treatment such as resistance training rehabilitation in patients with liver cirrhosis complicated with sarcopenia and/or hepatic encephalopathy as a reference for future fecal microbiota transplantation; To measure the changes of sarcopenia level before and after rehabilitation; To measure the changes of hepatic encephalopathy level before and after rehabilitation. These study results will certainly bring updated diagnostic tool, latest treatment options, avoid serious sequelae and reduce medical expenditure.

Chronic liver disease is notorious as Taiwan's national disease and more than 4,000 patients died of liver cirrhosis each year in Taiwan. Hepatic encephalopathy (HE) manifests from minimal HE (MHE) to overt HE (OHE). The diagnosis of covert HE (CHE) requires psychometric tests or neurophysiological tools. However, psychometric testing for patients with CHE is often neglected in Taiwan. On the basis of the capability to detect all forms of HE, further investigation on the association of HE with fecal microbiota alterations is urgently needed. It is because HE is associated with dysregulation in the gut-liver-brain axis, which includes intestinal barrier dysfunction and gut microbial dysbiosis. However, despite current standard of care (SOC) therapy i.e., lactulose and rifaximin, there remains a subset of patients who continue to suffer recurrence, which leads to further cognitive impairment, sarcopenia and readmissions. There remain several factors that can influence the microbiota, such as demographics (geographic area, sex and diet), etiology, drugs, interventions, and finally the sampling compartment. These factors need to be controlled for and considered in the interpretation of future studies. The microbiome dynamic change during rehabilitation in cirrhotic patients with sarcopenia has never been studied and is worth exploring. Furthermore, from our previous study, the investigators have shown that one-year efficacy of rifaximin add-on to lactulose is superior to lactulose alone in patients with cirrhosis complicated with recurrent HE in Taiwan. The investigators also have preliminary data showing that rehabilitation could improve patient's sarcopenia. Further cohort validation is urgently required. Our innovative research purposes: To explore the changes of fecal microbiota before and after treatment such as resistance training rehabilitation as a reference for future fecal microbiota transplantation; To measure the changes of sarcopenia levels before and after rehabilitation

Handgrip strength is an assessment of muscle strength. The cutoff value of the handgrip is < 30 kg in men and < 20 kg in women.

Short Physical Performance Battery (SPPB) is an assessment of physical performance. The cut-off value of the Short Physical Performance Battery (SPPB) score for determining sarcopenia is ≤ 9.

Dual-energy X-ray absorptiometry (DXA) is the gold-standard technique in the analysis of body composition. The cut-off value of appendicular skeletal muscle mass (ASMI) score for determining sarcopenia is < 7.0 kg/m^2 in men and < 5.4 kg/m^2 in women.

Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. The cut-off value of Mini-Mental State Examination (MMSE) score is < 28.

The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). The cut-off value of the Psychometric Hepatic Encephalopathy Score (PHES) for determining minimal hepatic encephalopathy (MHE) is ≤ -4.

The animal naming test (ANT) is an easy tool for the assessment of hepatic encephalopathy (HE). The cut-off value of the Animal Naming Test (ANT) score for determining hepatic encephalopathy (HE) is ≤ 19.

Quantified EEG spectral analysis: Grade 0: Mean dominant frequency (MDF)> 6.8 Hz and no theta nor delta wave Grade 1: MDF > 6.8Hz and theta wave relative power ≧35% Grade 2: MDF≤ 6.8 Hz and delta wave relative power<49% Grade 3: MDF≤ 6.8 Hz and delta wave relative power≧49%

Inclusion Criteria: Patients with liver cirrhosis Exclusion Criteria: unstable vital sign such as shock, coma or intubation status Non-curative hepatocellular carcinoma (cannot receive operation, radiofrequency ablation, liver transplantation,etc Un-curative malignancies Poor-controlled diabetes mellitus (HbA1C≧8) Active alcoholism (male alcohol ≧40g/day, or ≧140g/week; female ≧ 30g/day, or ≧70g/week Psychiatric comorbidities Neurologic comorbidities like Alzheimer's, Parkinson's, stroke with neurological deficit Unable to speak Bed-ridden status Post- Liver transplantation.