Hepatic Encephalopathy

The “gut-brain axis” is portrayed by complex bidirectional correspondence between the stomach and mind to keep up with gastrointestinal homeostasis and impact mental functions. Dysbiosis of the gastrointestinal microbiota adjusts the microenvironment of the colonic lumen, particularly the pH, which adds to enhanced production of ammonia from the stomach microbiota and enhanced absorption of ammonia from the colonic lumen to the blood. A few studies have affirmed that probiotics are successful and safe, are negligibly harmful, and have not much adverse impacts in the management of Minimal Hepatic Encephalopathy (MHE) ²² .

While comparing with lactulose, probiotics are linked with less side effects and are well tolerated. A recent study examined the effects of a probiotic mixture consisting of Bifidobacterium infantis and Clostridium butyricum on patients with MHE with the intention of developing a new clinically applicable adjuvant therapy for MHE ²³ .

Alcoholic Hepatitis

Despite the fact that alcohol is mainly metabolized in the liver and it is notable that alcohol ingestion causes gut lumen bacterial abundance and dysbiosis, digestive tract mucosal alterations, and enhanced gastrointestinal penetrability, prompting enhanced translocation of microbes and their by-products, endotoxin (chiefly lipopolysaccharide, LPS), into the portal circulation. Bacteria and their products accelerate the creation of ROS and proinflammatory cytokines and chemokines, lead harm to hepatocytes and the advancement of liver injury ²⁴ . Gut microscopic organisms determined endotoxin acts through certain pattern identified receptors, for example, toll like receptors (TLRs) which are communicated in liver occupant macrophages, Kupffer cells, as well as other tissue types in the liver. It has been generally shown that alcohol ingestion prompts endotoxemia ²⁵ . These perceptions recommend that gut microbes homeostasis, gastrointestinal barrier integrity, and hepatic TLRs are significant in the pathogenesis of ALD.

Non-Alcoholic Steato-Hepatitis

A wide range of pathological hepatic conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC), make up non-alcoholic fatty liver disease (NAFLD). Because of the high incidence of obesity, NAFLD is addressing a worldwide medical problem and the main source of liver injury around the world. Currently, there are no therapeutic interventions for the prevention and management of NAFLD, with the exception of lifestyle, diet, and exercise changes, which have disappointing results due to patients' poor compliance.

Numerous studies demonstrated that probiotics administration might attenuate NAFLD features in animal models ²⁶. The organization of VSL#3, a combination of three genera of microorganisms (a multistrain made by Streptococcus, Thermophilus and a few types of Bifidobacterium and Lactobacillus) for quite some time to Lep^ob/ob mice further developed insulin responsiveness, complete unsaturated fat substance, serum alanine aminotransferase (ALT) levels and the histological range of liver injury 26. The fact that Lep ^ob/ob mice exposed to VSL#3 had lower levels of uncoupling protein (UCP)-2 expression and less Jun N-terminal kinase (JNK) and NF-kB activation supported the hypothesis that intestinal bacteria may regulate the activation of host signalling pathways that interfere with hepatic insulin response and fat metabolism 26.

The impacts of probiotics as a mix of multistrain compounds have arrived at improved results in randomized trials. Most recently, Gao and collaborators showed that probiotics work on the clinical results of NAFLD patients, affecting insulin response and diminishing TNF-α. However, probiotics only reduced dyslipidemia in the Italian and Spanish populations, indicating that the effects of these molecules on HDL, LDL, and triglycerides may be influenced by ethnic background ²⁷ .

Potential Role in Sarcopenia and Frailty of Cirrhosis

Liver decompensation causes less nutritional consumption and metabolic changes characterized by accelerated calorie utilization, less glycogen storage, elevated starvation reaction, and protein catabolism, promoting wasting of fat and muscles ²⁸ . Sarcopenia represents a significant reduction of skeletal muscle volume and muscle function. Sarcopenia is linked with unfavourable outcomes in chronic liver disease (CLD). Sarcopenia is defined when the patient has less muscle mass and decreased HGS. Sarcopenia has great impact on activities of daily living, quality of life and functional abilities among older populations and in patients with liver diseases. Hence monitoring and assessment of level of nutrition and sarcopenia among cirrhosis patients is of utmost importance and special care has to be given to measure muscle mass and muscle strength ²⁹ . Sarcopenia in patients with liver cirrhosis (LC) has been drawing in much consideration these days as a result of linkage to unfavourable results. LC can be connected with sarcopenia because of protein metabolic issues and energy metabolic problems. LC is related with significant changes in gut microbiota and injure at various degrees of protective systems of the digestive tract.

Gut microbiota has a prominent role in liver ailment pathogenesis. Supplementation of probiotics can be a secure and cost effective approach in the liver disease management ³⁰ .

Role/Uses of immunonutrition in GI diseases

• Down regulation of pro-inflammatory cytokines and inflammatory responses

• Augments nutritional status

• Shortens length of hospital stay after surgery and liver transplantation

• Reduces post operative infectious complications

• Decreases morbidity and mortality

• Improves survival and clinical outcome

• Enhances immunity

• Improves liver function and decreases liver injury

• Enhances liver regeneration

• Improves gut epithelial barrier function

• Enhances wound healing and decreases surgical wound complications

In a recent study recommended the significance of early nutritional planning with nutritional counseling among patients with end stage liver disease patients waiting for liver transplant to improve the clinical outcomes and liver function and the use of immunonutrient didn’t show any statistically significant difference in liver function, but had showed some clinical improvement ³¹ .

Recommendation 1 - Nutritional status Assessment/Screening

Nutritional screening/assessment to be performed on all patients with Gastrointestinal disorders at the time of diagnosis or their visits during OPD and/ within 24 hours of admission and thereafter on a regular basis.

• Supporting findings

A recent study revealed that 45% of patients with GI diseases were malnourished. Hence, it is very essential to detect and manage malnutrition in patients with gastrointestinal disease as it will influence the patient’s clinical outcome and health care costs ³² .

Recommendation 2 - Use appropriate tools for malnutrition assessment

Global Leadership Initiative on Malnutrition [GLIM] in 2016 with ESPEN recommended ‘three phenotypic criteria’ (non-volitional weight loss, decreased body mass index, and less muscle mass) and ‘two etiologic criteria’ (less food intake, and inflammation or disease burden). The diagnostic criteria for malnutrition are the presence of at least one phenotypic and one etiologic criterion. Phenotypic criteria are used for assessing malnutrition as ‘stage 1 (moderate)’ and ‘stage 2 (severe)’. The etiologic criteria are intended for planning nutritional intervention and expected clinical outcomes ³³ . CLD patients have less capacity to bear protein and PEM is corresponded with lack of vitamin A, zinc and magnesium.

• Recommendation - 2a

  • Guidelines provided by ESPEN recommended to use the RFH-NPT (Royal Free Hospital-Nutritional Prioritizing tool) to detect risk of malnutrition among patients with hepatic diseases.

  • SGA (Subjective Global Assessment) was commonly used to assess level of nutrition specifically for CLD candidates waiting for liver transplant ^{34, 35 .}

  • The NRS-2002 (Nutrition Risk Screening) is a simple and well-validated tool, used most often in hospitals.

  • The Malnutrition Universal Screening Tool (MUST) used to identify malnourished individuals in all care settings.

Recommendation 3 - Use of Probiotics in GI diseases

• 3a- The World Gastroenterology Organization, 2011 guidelines for the use of probiotics in adults with level 1 evidence ¹⁸ .

  • Supporting findings

    • Act as a barrier by increasing epithelial barrier function ^{8, 9, 10 , 11, 12, 13 .}

    • Inhibit the pathogenic microorganisms ^{14 .}

    • Gastrointestinal immunity modulation ^{15, 16, 17 .}

    • Modification of gut microbiota & Regulation of intestinal microbiota ^{18, 19, 20 .}

• 3b – “Do not recommend the addition of glutamine, probiotics, or other supplemental nutrients to the diet in the aim of promoting the intestinal rehabilitation process (R39, Grade of evidence: low)” – ESPEN 2021 36 ^.

Probiotics have not been tested for use in SBS (short bowel syndrome) rehabilitation. A few articles have portrayed the utilization of probiotics in SBS for treating D-lactic acidosis ³⁷ .

Recommendation 4 - Use of Immunonutrition in GI diseases

• “Peri or at least postoperative administration of specific formula enriched with (arginine, omega-3-fatty acids, ribonucleotides) should be given in malnourished patients undergoing major cancer surgery (B). There is currently no clear evidence for the sole use of these formulas enriched with immunonutrients vs. standard oral nutritional supplements (ONS) in the preoperative period (0)”. ESPEN 2021 ^{38 .}

“Grade of recommendation B/0 e consensus (89% agreement)”

• “Immune modulating ONS including (arginine, omega-3 fatty acids, and nucleotides) can be preferred (0) and administered for five to seven days preoperatively (GPP).

Grade of recommendation 0/GPP e majority agreement, 64% agreement” ^{38 .}