Factors influencing and enhancing health-related quality of life in sarcopenia patients with liver cirrhosis: A comprehensive review

ABSTRACT

Patients with liver cirrhosis experience a significantly reduced health-related quality of life (HRQoL) due to a multifaceted interaction of physiological, psychological, and social factors. Identifying these key determinants is crucial for enhancing care strategies and treatment outcomes. This study systematically explored the factors influencing both negative and positive aspects of HRQoL in patients with liver cirrhosis. A comprehensive literature search was performed across PubMed, Scopus, Embase, and Google Scholar, focusing on original research published since January 1, 2021. Studies involving sarcopenia in cirrhosis and its impact on HRQoL, including various subgroups and influencing factors, were included to ensure a wide-ranging analysis. The review identified multiple significant risk factors associated with poor HRQoL in cirrhotic patients. These included advanced age, female gender, lower socioeconomic status, low body mass index, and the presence of comorbid conditions such as anxiety and depression. Additionally, complications like ascites, hepatic encephalopathy, abnormal endoscopic findings, higher disease severity scores, sarcopenia, disturbed sleep, impaired sexual function, muscle cramps, and elevated levels of bilirubin, prothrombin time, and albumin-bilirubin ratio were linked to diminished HRQoL. On the other hand, interventions such as increased physical activity, liver transplantation, stem cell therapy, mindfulness practices, and the use of probiotics, rifaximin, and lactulose showed positive effects on HRQoL. These insights underscore the importance of adopting a comprehensive management approach for liver cirrhosis that addresses not only physical health but also psychological and social well-being. Future research should aim at developing targeted interventions to reduce the burden of these risk factors and promote overall quality of life in this patient population.

Introduction

Cirrhosis, also known as hepatic cirrhosis or end-stage liver disease, is characterized by impaired liver function resulting from the formation of fibrotic scar tissue due to chronic liver damage. This progressive condition arises from a variety of etiological factors. Key causes include chronic viral infections such as hepatitis B or C, which lead to persistent liver inflammation and fibrosis. Excessive alcohol consumption is another significant contributor, causing alcoholic liver disease through mechanisms involving oxidative stress and hepatocyte apoptosis. Nonalcoholic fatty liver disease (NAFLD), including both simple steatosis and nonalcoholic steatohepatitis (NASH), is gaining greater recognition, especially in relation to metabolic syndrome. Inherited genetic disorders such as hemochromatosis, Wilson’s disease, galactosemia, cystic fibrosis, and alpha-1 antitrypsin deficiency also play a crucial role in the development of cirrhosis. Autoimmune conditions, where the immune system erroneously targets liver tissue, further contribute to cirrhosis. Additional factors include exposure to hepatotoxic substances, chronic schistosomiasis infection, and drug-induced liver injury from certain medications. The cumulative effect of these diverse causes leads to a progressive disruption of liver architecture and function, ultimately resulting in cirrhosis.[1] Cirrhosis of the liver can lead to several severe and potentially life-threatening complications. These include ascites, characterized by the accumulation of fluid in the abdominal cavity due to portal hypertension; variceal bleeding, which involves the rupture of dilated blood vessels in the esophagus or stomach, and spontaneous bacterial peritonitis, a bacterial infection of the ascitic fluid. In addition, cirrhosis can result in brittle bones or osteoporosis, increasing the risk of fractures, and hepatic encephalopathy, a condition where the accumulation of toxins such as ammonia impairs brain function, potentially leading to cognitive decline and coma. These complications underscore the critical need for vigilant management and monitoring in patients with cirrhosis.[1] Chronic diseases currently account for 7 of the top 10 major global causes of death.[2]

Sarcopenia, prevalent in 20–70% of cirrhosis patients, involves significant muscle mass and strength loss. It is linked to poor prognosis, increased complications, and elevated mortality rates.[3] According to a recent systematic review and meta-analysis, the incidence of sarcopenia in patients with cirrhosis was around 33%; however, this varied depending on diagnostic criteria and clinical features.[2] Sarcopenia in cirrhosis patients is more prevalent in men, correlating with higher rates of alcoholic liver disease (ALD) and severe liver dysfunction.[2,4] The pathophysiological mechanisms of sarcopenia in cirrhosis are multifaceted and not yet fully elucidated. Nonetheless, it primarily stems from an imbalance between protein synthesis and proteolytic breakdown. Sarcopenia is an independent predictor of longer hospital stays, decreased quality of life, and higher rates of morbidity and mortality in individuals with cirrhosis.[5] Therefore, early detection and accurate recognition of this condition are essential in clinical practice.

Sarcopenia in cirrhotic patients can be diagnosed through various imaging and measurement methods. Computed tomography (CT) is frequently used to calculate the skeletal muscle index and total psoas muscle thickness (TPMT) at the third lumbar vertebra, though it is often time-consuming and costly. Alternative methods for assessment include magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance analysis (BIA), each providing distinct advantages and limitations. Simpler screening tools such as mid-upper arm circumference (MUAC), skin-fold thickness, and calf circumference are also employed to estimate muscle mass and body fat. Although these anthropometric measures are generally reliable, they can be affected by factors such as human error, changes in skin elasticity, age, and variability in technique. Identifying factors associated with sarcopenia in patients with cirrhosis is crucial for improving clinical outcomes.

Chronic liver disease profoundly affects health-related quality of life (HRQoL) in patients, largely due to a range of complications such as gastrointestinal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. In addition, patients may experience significant negative effects including persistent fatigue, muscle and joint pain, sleep disturbances, diminished self-esteem, and impaired work capacity. The impact on HRQoL is further exacerbated by the disease management strategies, such as frequent paracentesis and band ligation, which can contribute to additional physical and emotional burdens.

Health, HRQoL, and quality of life (QoL) are terms frequently used interchangeably, but they encompass distinct aspects of well-being.[6,7] Although a universally accepted definition of QoL does not exist, a widely adopted definition has been established by the World Health Organization: “An individuals’ perception of their position in life in the context of their culture and value system in which they live and in relation to their goals, expectations, standards and concerns. It is a broad ranging concept affected in a complex way by the person’s physical health, psychological state, personal beliefs, social relationships and their relationship to salient features of their environment”.[8,9]

Several studies have explored the impact of disease severity on HRQoL.[10,11] Recent advancements in disease management have led to a significant improvement in long-term survival rates for patients with chronic liver disease (CLD). HRQoL now plays a crucial role in assessing patient outcomes beyond traditional clinical endpoints, such as mortality and complication rates. This systematic review was conducted to identify and analyze factors that influence and enhance HRQoL in patients with CLD.

Methodology

This systematic review was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement.[12]

Two reviewers independently conducted a comprehensive search of the PubMed, Scopus, and Web of Science databases from January 1, 2021, to the present to identify relevant studies examining factors associated with sarcopenia in patients with cirrhosis. The search was restricted to English-language publications and utilized a combination of Medical Subject Headings (MeSH) terms and related free-form keywords, including “sarcopenia,” “liver cirrhosis,” “health-related quality of life,” “HRQoL,” and “hepatic encephalopathy.” In addition, a manual review of the reference lists from included studies, as well as relevant systematic reviews and meta-analyses, was performed to ensure no pertinent studies were overlooked.

Studies were included in the review if they met the following criteria:

1. Population: Adult patients (≥18 years) diagnosed with cirrhosis through clinical evaluation, radiological imaging, or liver biopsy.

2. Factors: Identification of at least one factor associated with sarcopenia, such as age, BMI, sex, etiology, or cirrhosis complications, with each factor being assessed in more than two original studies.

3. Sarcopenia Definition: Clearly defined sarcopenia, characterized by loss of skeletal muscle mass and/or reduced muscle strength or function.

4. Study Design: Included cohort, case-control, prospective, and cross-sectional studies.

Two researchers independently extracted relevant data from the selected studies. The quality of the included studies was independently evaluated by two reviewers, with a third reviewer resolving any discrepancies or conflicts that arose during the assessment.

Results

Search strategy

There were 106 records found by the electronic searches [Figure 1]. 54 articles were included for full-text review after duplicates and ineligible titles and abstracts were eliminated. For the main analysis, a total of 54 studies were included.

Figure 1.

Study selection following PRISMA guidelines

Assessment of sarcopenia

Various modalities are available for assessing the components of sarcopenia, as summarized in Table 1. However, the field currently lacks a universally accepted, safe, and reproducible gold standard tool for defining sarcopenia.

Table 1.

Summary of tests used to assess sarcopenia (muscle mass, strength, function)

Category	Assessment Methods
Body Composition (Muscle Mass)	• Magnetic Resonance Imaging (MRI)
	• Computed Tomography (CT)
	• Dual-Energy X-ray Absorptiometry (DEXA)
	• Bioimpedance Analysis (BIA)
	• Mid-arm Muscle Circumference (MAMC)
	• Muscle Ultrasound
Muscle Function	• Short Physical Performance Battery (SPPB)
	• Liver Frailty Index (LFI)
	• Timed Get-Up-and-Go Test
	• Aerobic Exercise Capacity
	• Cardiopulmonary Exercise Testing (CPET)
	• 6-Minute Walk Distance (6MWD)
Muscle Strength	• Handgrip Strength (HGS)
	• Knee Flexion/Extension Peak Torque Strength
	• Liver Frailty Index (LFI)

Health-Related Quality of Life (HRQOL)

Several factors influence the HRQoL in patients with liver cirrhosis. The following Table 2 and Figure 2 summarizes the key factors affecting HRQoL in cirrhosis patients and their impact.

Table 2.

Factors affecting health-related quality of life in liver cirrhosis patients with sarcopenia

Reference	Study type	Sample size/Sarcopenia Prevalence	HRQoL tool	Outcomes
Demographic Factors and Etiology of Cirrhosis
Marchesini et al. (2001)[11]	Longitudinal	544	SF-36	All domains of HRQoL, except pain, were altered in cirrhosis (by 9%-42%), mainly in younger patients
Disease Severity Score
Nathiya et al. (2021)[14]	Cross Sectional	138	CLDQ	Significant association of CTP and MELD with HRQoL
Laboratory s
Nisshikawa et al. (2021)[15]	Retrospective	184	SF-36	• Decreased serum albumin levels, reduced muscle strength, and poor body composition may be associated with a decline in QOL.
Kok et al. (2020)[16]	Cohort	402	CLDQ	• Younger age, female sex, current smoking, lower serum albumin levels, frailty, and the presence of ascites were independently associated with lower CLDQ scores.
Systemic Symptoms and Activity
Shanavas et al. (2021)[13]	Cross Sectional	288/132	CLDQ	Systemic symptoms and activity were having a significant moderate negative correlation with HRQoL
Cirrhosis Complications
Lacob et al. (2022)[17]	Prospective	71	SarQoL	HE and ascites were the significant factors associated with lower SARQoL scores
Other factors
Nathiya et al. (2023)[19]	Cross Sectional	138	CLDQ	HRQoL shows a strong negative correlation with frailty, particularly in relation to scores for activities, emotional function, and fatigue.
Hu et al. (2022)[20]	Prospective	153	QLQ-C30	Preoperative sarcopenia reduces health-related quality of life in patients with HCC.
Chu et al. (2020)[21]	Cross Sectional	81	SF-36	Malnutrition is associated with lower HRQoL
Nishikawa et al. (2018)[23]	Prospective	410	SF-36	HGS seems to have a strong impact on H-QOL in patients with CLDs.
Labenz et al. (2019)[22]	Prospective	218	CLDQ	• In patients with Child-Pugh class A liver cirrhosis, the presence of CHE, female gender, active smoking, higher Clinical Frailty Scale (CFS) scores, and elevated serum levels of C-reactive protein (CRP) were independent predictors of impaired health-related quality of life (HRQoL) (all P<0.05). • In patients with Child-Pugh class B or C liver cirrhosis, female gender, a history of overt hepatic encephalopathy, and lower hemoglobin levels were independently associated with decreased HRQoL (all P<0.05)
Hui et al. (2014)[24]	Prospective observational study	355	EuroQol-5D (EQ-5D)	• Significant association between frailty and lower HRQoL scores
Comorbidities
Ando et al. (2019)[18]	Prospective	88	36-item Short-Form Health Survey version 2 questionnaire (SF-36 v2)	QOL scores were significantly lower on all eight domains (age, sex, BMI, etiology, HCC, albumin, total bilirubin, prothrombin, ascites, and diabetes mellitus) among cirrhotic patients with sarcopenia
Román et al. (2013)[25]	---	118	SF-36	Previous falls are associated with lower HRQoL in patients with cirrhosis
Zahed et al. (2020)[26]	Cross-sectional study	105	OHIP-14 (Oral Health Impact Profile) questionnaire and GOHAI (Geriatric Oral Health Assessment Index) questionnaire	Oral health significantly affects the QoL in patients with cirrhosis.

HRQoL=Health-related quality of life, CLDQ=Chronic liver disease questionnaire, CTP=Child-Turcotte-Pugh (score), MELD=Model for end-stage liver disease, SarQoL=Sarcopenia quality of life questionnaire, QLQ=Quality of life questionnaire, HCC=Hepatocellular carcinoma, HGS=Handgrip strength

Figure 2.

Factors Affecting Health-Related Quality of Life (HRQoL) in Sarcopenia Patients with Liver Cirrhosis

Demographic factors and etiology of cirrhosis

Few studies have reported the association between demographic factors (age, gender, education, BMI, and employment) and the etiology of cirrhosis in HRQoL in patients with liver cirrhosis.[11,13]

Disease severity score

In clinical practice, the severity of liver cirrhosis is commonly assessed using the Child-Turcotte-Pugh (CTP) score and the Model for End-Stage Liver Disease (MELD) score. However, the association between these severity scores and HRQoL in patients with liver cirrhosis has been explored in only a few studies. Notably, Nathiya et al. (2021)[14] demonstrated a significant and direct association between both the CTP and MELD scores and HRQoL in individuals with liver cirrhosis.

Laboratory values

Serological markers are routinely used to evaluate a patient’s overall health and well-being. However, only a limited number of studies have examined the influence of laboratory parameters on HRQoL in patients with liver cirrhosis. In CLD patients, Nisshikawa et al. (2021)[15] found that a drop in muscular strength, a low body composition, and a lower blood albumin level can all be linked to a decline in quality of life. Kok et al. (2020)[16] reported that younger age, female sex, current smoker, lower serum albumin, frailty, and ascites were independently associated with low chronic liver disease questionnaire (CLDQ).

Systemic symptoms and activity

Shanavas et al. (2021)[13] reported a moderate negative correlation with health related Quality of life as assessed by CLDQ particularly in relation with systemic symptoms and activity.

Cirrhosis complications

Over time, cirrhosis resulting from hepatic dysfunction can progress to portal hypertension. Either condition, alone or in combination, may lead to a range of complications, including ascites, hepatic encephalopathy, hepatocellular carcinoma, and coagulopathy. These complications not only worsen patient survival but also have a substantial negative effect on HRQoL. Lacob et al. (2022)[17] demonstrated that hepatic encephalopathy and ascites were significant factors associated with decreased scores in the Specific Assessment of Quality of Life (SARQoL).

Comorbidities

Ando et al. (2019)[18] showed that QOL scores were significantly lower on all eight domains (age, sex, BMI, etiology, HCC, albumin, total bilirubin, prothrombin, ascites, and diabetes mellitus) among cirrhotic patients with sarcopenia than in those without sarcopenia.

Other factors

In addition to the primary factors affecting HRQoL in liver cirrhosis patients, several secondary factors have been identified as contributing to a decline in HRQoL. These include malnutrition, which exacerbates overall health issues; sarcopenia, characterized by loss of muscle mass and strength; and sleep disturbances that impair daily functioning. Frailty, marked by increased vulnerability to stressors, and issues with sexual health further impact psychological and physical well-being. In addition, muscle cramps cause discomfort and interfere with daily activities. Addressing these secondary factors is essential for a comprehensive approach to improving HRQoL in this patient population. Nathiya et al. (2023)[19] reported a significant association between frailty, fatigue, scores of activity, and emotional function and decreased HRQoL scores. Hu et al. (2022)[20] reported that albumin levels and the interaction of sarcopenia and surgery were the independent factors influencing the short-term overall HRQOL after surgery. Chu et al. (2020)[21] noted that malnutrition is associated with lower HRQoL. Labenz et al. (2019)[22] reported that the presence of CHE, female gender, active smoking, higher CFS, and higher serum levels of C-reactive protein (CRP) were independent predictors of impaired HRQoL (all P < 0.05) in patients with CP A liver cirrhosis. In patients with Child-Pugh class B or C liver cirrhosis, female gender, a history of overt hepatic encephalopathy, and lower hemoglobin levels were independently associated with impaired HRQoL (all P < 0.05). Nishikawa et al. (2018)[23] found that hand grip strength (HGS) seems to have a strong impact on H-QOL in patients with CLDs. Hui et al. (2014)[24] showed significant association between frailty and lower HRQoL scores. Román et al. (2013)[25] reported that falls and cognitive dysfunction are independent factors associated with impaired HRQoL in patients with cirrhosis.

Zahed et al. (2020)[26] highlighted the significant impact of oral health on the quality of life of cirrhotic patients, emphasizing the need for professional care, self-care education, and oral health.

Factors promoting Health-Related Quality of Life (HRQoL)

Physical exercise

Many patients with chronic liver disease lead sedentary lifestyles, engage in limited physical activity, and experience malnutrition. As a result, individuals with cirrhosis are at heightened risk of developing frailty and sarcopenia—both of which are key indicators of increased morbidity and mortality. Recent studies have suggested that exercise may offer significant benefits for individuals with liver cirrhosis, potentially improving outcomes and overall quality of life. Aamann et al. (2020)[27] found that 12 weeks of supervised progressive resistance training increased muscle strength and size and had beneficial effects on general performance measures, compared with patients who did not change their daily activity routine (controls). Tandon et al. (2020)[28] reported that resistance training reduces risk of sarcopenia in patients with cirrhosis. Sirisunhirum et al. (2022)[29] noted that a 12-week moderate-intensity home-based exercise training program in compensated cirrhotic patients significantly improved the fatigue domain of the quality of life index without an increase in adverse events. Kappus et al. (2016)[30] mentioned that for individuals with cirrhosis of the liver, combining dietary changes, vitamin supplements, and a structured exercise regimen may help lessen or even reverse the consequences of sarcopenia. Exercise training and therapeutic diet are highly advised for managing sarcopenia in cirrhotic patients, according to Abdelbasset et al. (2021).[31] Yadav et al. (2015)[32] reported that physical Component Score (PCS) score correlated moderately with six-minute walk distance (6MWD), indicating a relationship between quality of life and functional status. Lee and Chung, (2021)[33] reported that adopting exercise and consuming fruits and vegetables did not impact on QOL. Various factors play a crucial role in enhancing the HRQoL of patients with liver cirrhosis. These factors help improve both physical and emotional well-being, promoting better disease management and overall quality of life. Table 3 below outlines these factors and their impact on HRQoL.

Table 3.

Factors Promoting HRQoL in Liver Cirrhosis Patients with Sarcopenia

Reference	Study Type	Sample Size	Intervention	Outcomes
Aamann et al. (2020)[27]	Prospective	---	12 weeks supervised progressive resistance training	Increased muscle strength and size; improved general performance measures.
Tandon et al. (2020)[28]	----	---	Resistance training	Reduced risk of sarcopenia in cirrhosis patients.
Sirisunhirum et al. (2022)[29]	Randomized Controlled	40	12-week moderate-intensity home-based exercise	Significantly improved fatigue domain of the quality of life index; no increase in adverse events.
Kappus et al. (2016)[30]	----	---	Dietary changes, vitamin supplements, exercise	May help lessen or reverse sarcopenia consequences.
Abdelbasset et al. (2021)[31]	----	---	Exercise and therapeutic nutrition	Recommended for managing sarcopenia in cirrhotic patients.
Yadav et al. (2015)[32]	----	213	Physical Component Score (PCS) analysis	PCS score moderately correlated with six-minute walk distance (6MWD), linking quality of life to functional status.
Lee and Chung (2021)[33]	Cross-sectional	98	Exercise and dietary changes	No significant impact on HRQoL.
Sato et al. (2020)[34]	Prospective	41	L-carnitine treatment	Potentially alleviates chronic fatigue and oxidative stress.

Sato et al. (2020)[34] noted that L-carnitine can potentially alleviate chronic fatigue, along with the increased BAP/d-ROM ratio, which were involved in increased oxidative stress in patients with cirrhosis.

Palliation in sarcopenia patients with liver cirrhosis

Palliative care is a specialized medical approach focused on improving the QoL for individuals with serious illnesses, such as liver disease. This type of care focuses on relieving symptoms, managing pain, and addressing stress and emotional challenges associated with the illness. By providing comprehensive support, palliative care aims to improve the overall well-being of both the patient and their family, ensuring a more compassionate and supportive experience throughout the course of the illness.[35] Table 4 below outlines Palliative Care Strategies for Sarcopenia Patients with Liver Cirrhosis.

Table 4.

Palliative Care Strategies for Sarcopenia Patients with Liver Cirrhosis

Symptom	Description	Treatment Options
Muscle Cramps	Muscle cramps in cirrhosis can cause persistent tenderness and swelling. They are independent of diuretic use and correlate with liver disease severity.	Medications: Orphenadrine, Methocarbamol, L-Carnitine, Baclofen, Quinidine, Furosemide, Zinc Sulphate, Taurine, Branched-chain amino acids, Eperisone hydrochloride.[36,37,38,40,47,49,50] Electroacupuncture: May improve muscular spasms.[51,52] Pregabalin: Reduces muscle cramps compared to placebo.[53] Pickle Brine: Improves cramp severity at onset.[46]
Itching (Pruritus)	Pruritus can significantly impact quality of life. It may be due to bile acid accumulation, opioid and histamine pathway alterations, or neuroimmune disruptions.	Medications: Bile salts, Rifampicin, Antipruritics, Opioid receptor antagonists, Antihistamines.[57,58,55,56] Nonpharmacological: Skin moisturizers, Bright-Light Therapy, Avoidance of skin irritants, Avoidance of hot environments.[59]
Sleep Disorders	Sleep-wake disturbances include insomnia, excessive daytime sleepiness, and sleep-wake inversion. They are often linked to hepatic encephalopathy.	Manage Hepatic Encephalopathy: Lactulose, Lactitol, Probiotics, L-ornithine L-aspartate.[60,61,63] Pharmacological Treatments: Antihistamines (e.g., Hydroxyzine), Benzodiazepines with safer profiles (e.g., Clonazepam, Zolpidem). Nonspecific Treatments: Hydroxyzine, Modafinil.[60]
Pain Management	Pain management is complicated by potential adverse effects of medications and requires careful dosing and monitoring.	First-Line Medications: Paracetamol (for moderate-severe pain). Avoid: Nonsteroidal anti-inflammatory agents (due to risks). Alternative Analgesics: Tramadol (safe for moderate-severe pain), Fentanyl and Hydromorphone (opioids with good safety profiles). Topical Treatments: Reduce oral drug consumption. Neuropathic Pain: Gabapentin (first-line treatment). Antidepressants: Amitriptyline (considered in some cases). Interventional Techniques: Reduce drug therapy and adverse effects. Multimodal Therapy: Incorporates psychological, physical, and rehabilitation approaches.[64]

Muscle cramps

Cirrhosis patients often experience muscle cramps, lasting for seconds to several minutes and causing persistent tenderness and swelling for up to 72 h. Konikoff and Theodor reported an 88% incidence of muscle cramps in cirrhosis patients, compared to 21% in a matched population without liver disease. They found no association between the incidence of muscle cramps and oedema, ascites, diuretic use, alcohol or any other cause of muscle cramps.[36] Abrams et al.[37] reported that the prevalence of muscle cramps in patients with Childs A or B cirrhosis was significantly higher (52%) than in those with chronic hepatitis (7.5%). They reported that muscle cramps in cirrhosis are independent of diuretic use and are correlated with the severity of liver disease and the progression of liver function deterioration. Treatments such as orphenadrine (an anticholinergic drug),[38] methocarbamol,[39] L-carnitine,[40] Baclofen,[41,42] quinidine,[43] furosemide,[44] Zinc Sulphate,[45] Taurine,[46,47,48] Branched-chain amino acids,[49] and Eperisone hydrochloride[50] may be beneficial. Lee et al. (2018)[51] and Seung-Mo et al. (2018)[52] reported that electroacupuncture therapy might improve muscular spasms in individuals with liver cirrhosis. Ahn et al. (2022)[53] reported favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients. Tapper et al. (2022)[46] reported that sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.

Itching

Pruritus can significantly impact the quality of life in patients with liver disease, making its management a crucial aspect of treatment. Although the precise pathogenesis of pruritus in chronic liver disease remains unclear, several hypotheses have been proposed. These include the accumulation of bile acids, which may act as pruritogens; alterations in opioid and histamine pathways; and disruptions in neuroimmune interactions. Understanding these mechanisms is essential for developing effective therapeutic strategies to alleviate pruritus and improve patient outcomes.

A considerable amount of research has been conducted to explore potential treatment options for pruritus in the context of chronic liver disease. These medical treatments range from bile salts, rifampicin,[54] antipruritic,[55,56] andopioid receptor antagonists[57,58] to antihistamines. In addition, nonpharmacological management such as skin moisturisers, Bright-Light Therapy,[59] avoidance of skin irritants, and avoiding hot environments can also prove to be very beneficial in reducing pruritus.

Sleep disorders

Liver cirrhosis often results in sleep-wake disturbances, which are closely linked to a decline in quality of life. The most common sleep abnormalities include insomnia (difficulty falling asleep, staying asleep, or experiencing unrefreshing sleep), excessive daytime sleepiness, and disruptions in circadian rhythms (such as sleep-wake inversion). The pathophysiological mechanisms behind these sleep disturbances are complex and may involve disrupted melatonin and glucose metabolism, alterations in thermoregulation, and changes in ghrelin secretion profiles. These sleep-wake abnormalities are commonly linked to the presence of HE, and improvements in sleep parameters are often observed with effective management of HE.[60] Lactulose and lactitol aim to decrease ammonia absorption from the gut and are effective for improving HE and QoL.[61] One retrospective study assessed sleep changes before and after liver transplant in 83 patients using questionnaires. Curiously, sleep quality improvement was excellent in patients with alcoholic liver disease but almost nonexistent in hepatitis C patients.[62] Probiotics and l-ornithine l-aspartate have been proven to improve HE and QoL.[63] However, no specific studies are currently focused on sleep disturbances. Sleep disorders should be treated by correcting HE, treating depression and anxiety, avoiding stimulants such as coffee and nicotine, and completely avoiding alcohol. Pharmacologic treatments include antihistamines such as hydroxyzine and controlled use of benzodiazepines with safer profiles such as clonazepam and zolpidem. A few nonspecific treatments for sleep-wake abnormalities have been tried, with encouraging results for hydroxyzine and modafinil.[60]

Pain management

Pain management in liver cirrhosis patients is challenging due to lack of efficacy and high adverse effects. Treatment focuses on acute or chronic pain and understanding its pathophysiological mechanism. Analgesics should be started with minimal effective dose and titrated slowly, avoiding polypharmacy. Adverse effects, such as sedation and constipation, must be monitored to prevent HE. Paracetamol is the first-line drug for managing moderate-severe pain, while nonsteroidal anti-inflammatory agents are contraindicated due to potential risks. Tramadol is safe for moderate-severe pain, while fentanyl and hydromorphone are the best opioids with a good safety profile. Topical treatment can reduce oral drug consumption, and gabapentin is the first-line treatment for neuropathic pain. Antidepressants such as amitriptyline can be considered in some cases. Interventional techniques can reduce drug therapy and adverse effects, and psychological, physical, and rehabilitation should be part of multimodal therapy.[64]

Conclusion

The HRQoL in patients with liver cirrhosis is multifaceted, influenced by a diverse array of factors including demographic variables, disease severity, laboratory values, systemic symptoms, complications, comorbidities, and secondary issues such as malnutrition and frailty. The association between these factors and HRQoL highlights the complexity of managing cirrhosis and underscores the need for a comprehensive and individualized approach to care.

Demographic factors such as age, gender, and employment status have been shown to impact HRQoL, though evidence remains limited and warrants further investigation. Disease severity scores, such as the CTP and MELD, are strongly correlated with HRQoL, suggesting that more severe disease stages are associated with a poorer quality of life. Laboratory values, including serum albumin levels and handgrip strength, also play a critical role, indicating that physical and biochemical markers of health are integral to HRQoL assessments.

Complications of cirrhosis, such as ascites and hepatic encephalopathy, significantly detract from HRQoL, emphasizing the importance of managing these complications effectively. Comorbidities, particularly sarcopenia and malnutrition, further exacerbate declines in quality of life. Notably, factors such as muscle cramps, pruritus, and sleep disturbances are prevalent and impact daily functioning, highlighting the need for targeted symptom management.

Conversely, there are several avenues for enhancing HRQoL. Physical exercise has demonstrated positive effects on muscle strength and overall performance, countering sarcopenia and frailty. Nutritional interventions and palliative care strategies also play critical roles in improving HRQoL. Palliative care, with its focus on symptom relief and emotional support, complements traditional medical treatments by addressing the broader aspects of well-being.

Despite the advances in understanding and managing HRQoL in cirrhosis, significant challenges remain. The variability in individual responses to treatments and the complex interplay between various factors necessitate ongoing research and tailored interventions. Future studies should aim to elucidate the mechanisms underlying HRQoL decline and develop integrated care models that address both the physiological and psychosocial aspects of liver cirrhosis.

In summary, improving HRQoL in liver cirrhosis requires a multidimensional approach that encompasses disease management, symptom control, and supportive care. By addressing the diverse factors that affect HRQoL and implementing effective interventions, it is possible to enhance the overall well-being and quality of life for patients with liver cirrhosis.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.