Introduction

The aim of this review article is to present current knowledge on hepatic encephalopathy with particular emphasis on its impact on cognitive function, nutritional aspects and patients’ quality of life. The paper discusses the pathophysiological mechanisms underlying the development of neurological impairment, current nutritional recommendations for the prevention and management of hepatic encephalopathy and the consequences of the disease for patients’ daily functioning. Special attention is given to the impact of hepatic encephalopathy on quality of life, highlighting the importance of early diagnosis and comprehensive therapeutic management. To provide a practical illustration of the issues discussed, a clinical case of a patient with hepatic encephalopathy is also presented.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome arising from liver dysfunction and/or portosystemic shunting, characterized by a broad continuum of clinical manifestations, ranging from subtle cognitive impairment to profound coma (American Association for the Study of Liver Diseases and European Association for the Study of the Liver, 2014).

Hepatic encephalopathy is classified into three types based on aetiology: type A – associated with acute liver failure, type B – resulting from portosystemic shunting without intrinsic liver disease, type C – occurring in the context of cirrhosis.

Overt HE is further categorized as recurrent when two or more episodes occur within a six-month period and as persistent when the patient fails to return to baseline neurological function between episodes (Montagnese et al. 2022). Hepatic encephalopathy may impair cognitive domains including memory, attention, concentration and executive function. Such deficits can significantly impact daily functioning, interfering with tasks such as financial management, appointment adherence and decision-making (Kanwal et al. 2009).

Malnutrition is frequently observed in individuals with end-stage liver disease and hepatic encephalopathy and is recognized as a critical prognostic factor influencing quality of life, clinical outcomes and overall survival (Bémeur et al. 2010). Therefore, it is crucial to implement appropriate nutritional management in neuropsychiatric disorders resulting from hepatic encephalopathy.

Methods – literature search strategy

The analysis utilized data from electronic databases, primarily PubMed/MEDLINE, as well as from scientific publishers’ databases such as Elsevier, Springer, Wiley, and Nature. Current guidelines from scientific societies, in particular the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), were also included. The literature review included publications from the past 5 years (2020-2025) and the following keywords: hepatic encephalopathy, nutrition, nutritional therapy, cognitive impairment, cognitive dysfunction, and quality of life. Original research articles, review papers, meta-analyses, and clinical guidelines concerning hepatic encephalopathy, cognitive disorders, nutritional management and quality of life in patients with chronic liver disease were included. Older publications were also considered as they contained essential definitions, fundamental diagnostic criteria and classifications of hepatic encephalopathy, which remain the basis for current scientific literature and clinical practice.

Etiopathogenesis and symptoms

Pathophysiology of cognitive impairment in hepatic encephalopathy

Figure 1 shows integrated mechanisms underlying cognitive dysfunction in hepatic encephalopathy (Bajaj 2019; Bémeur et al. 2010; Felipo et al. 2012). The diagram summarizes key pathophysiological pathways linking liver dysfunction with cognitive impairment in hepatic encephalopathy. Hyperammonaemia, systemic inflammation and gut–brain axis disturbances contribute to neuroinflammation, oxidative stress and neurotransmission imbalance. These processes lead to astrocyte swelling, mitochondrial dysfunction and cerebral metabolic disturbances. Collectively, these alterations underlie the clinical manifestations of cognitive impairment, psychomotor slowing and attention and memory deficits observed in patients with hepatic encephalopathy.

The role of neuroinflammation and oxidative stress

In patients with cirrhosis, HE is associated with mild cerebral oedema and enhanced oxidative/nitrosative stress within the central nervous system. These processes contribute to a range of functionally relevant alterations including post-translational protein modifications, oxidative damage to RNA, changes in gene expression and the induction of cellular senescence (Häussinger et al. 2021).

Inflammation caused by ammonia accumulation (Weissenborn 2019) plays a pivotal role in the progression of cirrhosis, acting both as a driver of disease and a regulator of pathophysiological pathways. Immune system activation occurs in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This response exacerbates endothelial and microvascular dysfunction, thereby facilitating the transition from compensation to decompensation and ultimately leading to tissue injury. Among the mediators, cytokines such as tumor necrosis factor α (TNF-α) are of particular importance, as they can activate cell death pathways (Engelmann et al. 2021). Moreover, disturbances in cellular metabolism further aggravate these mechanisms. While immune cells exhibit markedly increased energy demands, peripheral organs may experience insufficient energy supply. This imbalance frequently linked to mitochondrial dysfunction and enhanced oxidative stress contributes to global impairment of organ function. Consequently, the activation of specific disease-related pathways may precipitate a rapid deterioration of organ performance (Engelmann et al. 2021).

Symptoms of minimal and overt hepatic encephalopathy

Hepatic encephalopathy encompasses a broad spectrum of neuropsychiatric and motor manifestations including anxiety, depressive symptoms, sleep disturbances, cognitive impairment, motor dysfunction and, in advanced stages, coma. Cognitive decline is particularly evident in older patients with cirrhosis. According to the West Haven Criteria (WHC), HE is categorized into mild and severe forms (Table 1). The covert or minimal form (minimal or grade I) is characterized by subtle neurocognitive deficits that are often difficult to identify clinically. Nevertheless, covert HE may progress to overt HE (grades II-IV), which represents a major cause of hospitalization among cirrhotic patients (Cheon and Song 2021).

Minimal hepatic encephalopathy constitutes the mildest stage within the HE spectrum. Patients with MHE lack overt clinical symptoms, and diagnosis relies on psychometric or neuropsychological testing (NPTs). Depending on diagnostic criteria and study population, the reported prevalence of MHE ranges from 20% to 80%. Several practical tests such as the psychometric HE score, continuous reaction time and critical flicker frequency offer rapid assessment without requiring specialized psychological expertise. Despite these tools, the diagnosis of MHE remains challenging in routine clinical practice due to the absence of characteristic signs, the lack of universally accepted criteria and the associated need for financial and technical resources (Hanai et al. 2021; Bogdanowska-Charkiewicz et al. 2021). From a clinical perspective, assessing the risk of progression to overt HE is of particular importance. Preoperative risk stratification is essential to identify patients who may benefit from curative strategies such as transjugular intrahepatic portosystemic shunt (TIPS), as opposed to palliative treatment options (Yang et al. 2021).

Treatment of hepatic encephalopathy

General principles

The treatment of HE involves a twofold approach: identification and management of precipitating factors, reduction of ammonia and other neurotoxins that contribute to cerebral dysfunction.

The initial step in any episode of HE is to identify and correct potential triggers such as gastrointestinal bleeding, infection, electrolyte imbalance or excessive diuretic use.

Management of precipitating factors:

• Gastrointestinal bleeding – as it increases nitrogen load and ammonia production → it is recommended to quickly remove blood from the gastrointestinal tract (lactulose or mannitol via a nasogastric tube or lactulose enema) to prevent HE (Montagnese et al. 2022).

• Infections (spontaneous bacterial peritonitis, pneumonia, urinary tract infections) → require prompt antibiotic therapy and supportive care (Guimarães et al. 2023).

• Electrolyte disturbances (especially hypokalaemia, hyponatraemia) → should be corrected to improve ammonia metabolism (Guimarães et al. 2023).

• Constipation, dehydration, sedative use, excessive protein restriction or overdiuresis → should be addressed to restore metabolic balance (Pantham et al. 2017).

Pharmacological treatment:

• Lactulose and rifaximin:

– Lactulose remains the first-line therapy. It acidifies colonic content, reduces ammonia absorption and acts as a laxative.

– Rifaximin, a non-absorbable antibiotic, is recommended as adjunct therapy to prevent recurrent HE episodes (especially after a second episode) (Montagnese et al. 2022).

• L-ornithine L-aspartate (LOLA) enhances ammonia detoxification by stimulating urea cycle activity in the liver and glutamine synthesis in skeletal muscle. Clinical trials have demonstrated that LOLA improves mental status, reduces plasma ammonia levels and accelerates recovery in both overt and minimal HE (Butterworth and McPhail 2019).

Liver transplantation

In patients with recurrent or refractory HE despite optimal medical therapy, liver transplantation remains the definitive treatment. Cognitive function usually improves significantly after transplantation (Ahluwalia et al. 2016).

Nutritional management in hepatic encephalopathy

Patients with HE should maintain a daily energy intake of 30-35 kcal/kg body weight, and protein restriction is no longer recommended. On the contrary, an adequate protein intake of 1.2–1.5 g/kg body weight per day should be ensured to prevent or treat malnutrition and sarcopenia (Sobocki et al. 2025; Bischoff et al. 2020). Restricting protein intake can worsen malnutrition and sarcopenia, potentially exacerbating hyperammonaemia and hepatic encephalopathy (Singal et al. 2025; Sobocki et al. 2025). Plant-based proteins and proteins enriched with branched-chain amino acids (BCAAs) are preferred in the dietary management of hepatic encephalopathy. These protein sources are better tolerated by patients and may offer therapeutic benefits (Iqbal et al. 2021). BCAAs – leucine, isoleucine and valine – are essential amino acids that play a crucial role in protein metabolism and ammonia detoxification. Supplementation with BCAAs has been demonstrated to alleviate symptoms of hepatic encephalopathy, particularly in patients with cirrhosis and sarcopenia. This supplementation may enhance ammonia detoxification by providing substrates for glutamine synthesis in skeletal muscle, thereby reducing hyperammonaemia (Marrone et al. 2023).

Individualized nutritional strategies should be developed in consultation with healthcare professionals to optimize patient outcomes. Frequent small meals are advised with avoidance of prolonged fasting periods to prevent catabolic states. In cases where oral intake is insufficient to meet caloric and protein requirements, nutritional supplementation is recommended, preferably via the enteral route, including a late-evening carbohydrate snack, which may improve nutritional status and liver function. Deficiencies in micronutrients, such as zinc and vitamin D, should be monitored and corrected. In patients with non-alcoholic fatty liver disease (NAFLD) or steatohepatitis, supplementation with vitamin E may be beneficial. Regular coffee consumption may also confer health benefits in patients with liver disease. When oral intake is inadequate, enteral nutrition (EN) is preferred over parenteral nutrition (PN) to improve survival and reduce the risk of infections. Prevention of constipation is important, as it may exacerbate symptoms of hepatic encephalopathy. Early stages of hepatic encephalopathy are reversible with appropriately managed therapy (Bischoff et al. 2020).

Overweight or obese patients with chronic liver disease, including cirrhosis, are recommended to reduce weight. The minimum daily energy requirement for this group of patients can be determined according to individual needs, moderately hypocaloric (500-800 kcal/day), or based on body mass index (BMI) as follows:

• BMI < 30 kg/m² is 35 kcal/kg,

• BMI 30-40 kg/m² is 25-35 kcal/kg,

• BMI ≥ 40 kg/m² is 20-25 kcal/kg.

The daily protein requirement ranges from 1.2 to 1.5 g/kg of adjusted body weight/day, depending on cirrhosis compensation (compensated/decompensated), the presence of malnutrition, sarcopenia and weight reduction measures taken.

Patients with cirrhosis should be regularly assessed for nutritional status, ideally every 6-12 months for patients with compensated cirrhosis or every 2-3 months for patients with decompensated cirrhosis (due to the increased risk of electrolyte disturbances and the development of refeeding syndrome). The tools approved for assessing nutritional status in chronic liver diseases, including cirrhosis, are the Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) or the Liver Disease Undernutrition Screening Tool (LDUST). In cases of moderate or high risk of malnutrition, a more in-depth assessment of nutritional status, including an assessment of sarcopenia, should be performed. During follow-up visits, a physical examination should be performed, body weight should be measured and the results of the following laboratory tests should be evaluated: complete blood count, albumin concentration, creatinine concentration, C-reactive protein (CRP) concentration, international normalized ratio (INR) and 25-hydroxyvitamin D concentration. Additionally, in patients with decompensated cirrhosis, cirrhosis related to alcohol abuse or chronic cholestasis, the following tests should be ordered: vitamin A, B₁, B₁₂, E, magnesium, phosphorus, potassium, folic acid, zinc, selenium and iron studies.

The impact of hepatic encephalopathy on quality of life

An important aspect of hepatic encephalopathy is the impact on patients’ quality of life. The presence and severity of HE are associated with deterioration in overall well-being and health-related quality of life (HRQoL). Each form of HE is associated with varying degrees of cognitive and physical impairment, significantly affecting the daily functioning and independence of patients, including their earning capacity, work performance and ability to drive (Faccioli et al. 2022; Buckholz and Rosenblatt 2023; Sørensen et al. 2024). The cognitive functions that are impaired include primarily attention (including visual and auditory attention), alertness, sustained concentration, information processing, judgment and decision making; there is also a deterioration in working memory and impairment of psychomotor skills (slower reaction time, impaired coordination) and visuospatial skills (Faccioli et al. 2022; Buckholz and Rosenblatt 2023; Ghaemi 2025).

The changes discussed above mean that patients with a history of HE struggle with many problems. This condition adversely affects family and social life. It places a burden on informal caregivers (Bajaj et al. 2011; Sørensen et al. 2024) and causes patients to experience loneliness and stigmatization (Grønkjær and Lauridsen 2021). Hepatic encephalopathy also has a significant impact on socioeconomic status, making it difficult to maintain or find employment (Bajaj et al. 2011; Faccioli et al. 2022).

Malnutrition and sarcopenia are among the most significant factors affecting HRQoL in patients with cirrhosis. Sarcopenia has been shown to be an independent risk factor for the development of HE (Aamann et al. 2019). Malnutrition and protein deficiency – which frequently co-occur in patients cirrhosis – contribute to further muscle wasting and ammonia production (Sørensen et al. 2024). Loss of muscle mass and strength contributes to impaired extrahepatic ammonia detoxification, which directly exacerbates ammonia-mediated neurotoxicity and worsens cognitive function. At the same time, protein deficiency and caloric restriction lead to further deterioration of nutritional status, reduced physical performance and a lower quality of life. Diminished physical activity further accelerates the loss of muscle mass and strength. Patients with cirrhosis exhibit lower exercise tolerance (Aamann et al. 2019), which is further limited by complications of cirrhosis.

Therefore, maintaining adequate nutritional status, ensuring the recommended energy and protein intake and engaging in regular physical activity play a significant role, not only in preventing malnutrition but also in improving cognitive function and quality of life in patients. The impact of HE on quality of life is a multifaceted issue and is subject to numerous analyses. Early identification of patients at risk of HE, early diagnosis and treatment, including both pharmacotherapy and nutritional intervention aimed at preventing malnutrition and sarcopenia, may improve cognitive outcomes and health-related quality of life.

Case report

The 51-year-old man with a medical history of cirrhosis and its complications (ascites, oesophageal varices and previous episodes of HE), with obesity and insulin dependent type 2 diabetes, was admitted to the Gastroenterology Department due to disturbances of consciousness.

Physical examination revealed confusion, disorientation as to place and time, slurred speech, psychomotor retardation, lower extremities oedema and gynecomastia. Based on the medical history and clinical symptoms, the patient was diagnosed with overt hepatic encephalopathy, stage II according to the WHC.

A series of laboratory, microbiological (blood and urine cultures) and imaging (chest X-ray, abdominal ultrasound) tests were performed. No evidence of an infectious cause of decompensation of cirrhosis was identified. Laboratory tests revealed the following abnormalities, among others: increased AST activity, hyperbilirubinaemia, hyperammonaemia, hypoalbuminaemia, prolonged PT, mild normocytic anaemia and thrombocytopenia (Table 2).

The treatment included lactulose and ornithine aspartate, carvedilol, diuretic treatment with furosemide and spironolactone, and insulin therapy. Paracetamol, metamizole and captopril were administered as needed. Also, two attempts of paracentesis were made, but they were unsuccessful due to excessively developed subcutaneous tissue.

At admission, the patient’s body weight was 126 kg, and his height was 174 cm (BMI = 41.62 kg/m², class III obesity). The man was assessed for nutritional risk using the NRS 2002 scale, on which he scored 3 points, indicating the need for nutritional intervention. On the first day of hospitalization, due to electrolyte disturbances, oral intake was withheld (NPO), electrolyte deficiencies were replenished intravenously and a prophylactic dose of thiamine was administered to reduce the risk of refeeding syndrome. On the second day of hospitalization, due to persistent disturbances of consciousness and the associated increased risk of choking, it was decided to start enteral nutrition through a nasogastric tube. The patient’s caloric requirement (calculated excluding peritoneal fluid and peripheral oedema) was 3528 kcal/day. The diet used covered the protein requirement of 1.5 g/kg/day – a total of 151.2 g/day. Patients with cirrhosis are at risk of refeeding syndrome and B vitamin deficiency; therefore, the patient also received thiamine intravenously (Krutkyte et al. 2022)

Calculation of the basic caloric and protein requirements of patients with cirrhosis and ascites is presented in Table 3.

After a week of hospitalization, the patient’s condition improved. The disturbances of consciousness and psychomotor retardation described upon admission subsided. Minor peripheral oedema and mild ascites were still present. Laboratory results showed normalization of ammonia concentrations, as well as electrolytes. Upon discharge, the patient was advised to continue the prescribed pharmacological therapy and to perform daily self-monitoring of blood pressure, heart rate and blood glucose levels. Regular outpatient follow-up, including periodic assessment of serum electrolytes and renal function parameters with adjustment of diuretic therapy as clinically indicated, was recommended. The patient also received dietary counselling emphasizing frequent protein-rich meals, sodium restriction, vitamin D supplementation and gradual weight reduction. Complete abstinence from alcohol consumption and smoking cessation were strongly recommended. Furthermore, referral to a clinical dietitian was advised to establish individualized caloric and protein requirements and to provide comprehensive nutritional guidance.

Discussion

A limitation of this case is the lack of formal assessment of sarcopenia, which is increasingly recognized as an important contributor to hepatic encephalopathy and poor clinical outcomes. Despite this flaw, the case report illustrates several key issues discussed in this review.

Firstly, the patient presented with overt hepatic encephalopathy accompanied by typical cognitive and psychomotor manifestations. These symptoms reflect the spectrum of neurological dysfunction associated with HE and demonstrate the clinical relevance of cognitive impairment described in the literature.

Secondly, it highlights the importance of nutritional assessment in patients with decompensated cirrhosis. Although the patient had class III obesity, nutritional screening using the NRS-2002 identified a need for intervention. This observation is consistent with current evidence indicating that obesity does not exclude malnutrition and that patients with cirrhosis may simultaneously present with excess body weight, impaired nutritional status and a high risk of sarcopenia. The case demonstrates the practical application of contemporary nutritional recommendations, including energy and protein intake calculations. This approach reflects current evidence showing that inadequate protein intake may worsen malnutrition, sarcopenia and ammonia metabolism, thereby contributing to further neurological deterioration.

Finally, the favourable clinical outcome observed during hospitalization, including normalization of ammonia levels and improvement in cognitive status, emphasizes the importance of a multidisciplinary approach combining pharmacological treatment with individualized nutritional management. The case supports the concept that early nutritional risk assessment and nutritional therapy should be considered as an integral component of hepatic encephalopathy treatment rather than merely supportive care.

Conclusions

Hepatic encephalopathy is a major complication of liver diseases and represents a spectrum of neurocognitive impairment ranging from MHE to OHE, significantly affecting patient outcomes and quality of life. The present review demonstrates the multifactorial nature of OHE in decompensated cirrhosis and highlights the benefits of combining ammonia-lowering therapy, correction of metabolic disturbances and individualized nutritional support. Current management extends beyond ammonia reduction and includes addressing inflammation, malnutrition and sarcopenia. Adequate protein intake and early nutritional intervention are essential because preservation of skeletal muscle supports ammonia detoxification and reduces the risk of recurrence. Effective HE treatment therefore requires a comprehensive, multidisciplinary approach focused on long-term clinical and nutritional optimization.

Disclosures

This research received no external funding.

Institutional review board statement: Not applicable.

The authors declare no conflict of interest.

References