Review

Principles of Nutritional Management in Patients with Liver

Dysfunction—A Narrative Review
Essam Mohamed Elsebaie 1, *, Alyaa Nasr Abdel-Fattah 2 , Nagwa Awad Bakr 2 , Kadry Mohamed Attalah 2
and Abdel-Hady Ahmed Aweas 2

1 Food Technology Department, Faculty of Agriculture, Kafrelsheikh University, Kafr El-Shiekh 33516, Egypt
2 Department of Food Industries Technology, Faculty of Technology of Industry and Energy,
Samannoud Technological University, Samanoud 31621, Egypt
* Correspondence: [email protected]; Tel.: +20-1556126015

Abstract: According to studies, the liver’s ability to perform its physiological functions in the body
determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to
metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about
diets and dietary supplements that manage liver dysfunctions nutritionally. Results: Malnutrition is
particularly prevalent in cirrhosis patients, according to clinical studies. Because malnutrition has
a significant negative impact on morbidity, mortality, and quality of life, it is crucial to evaluate all
cirrhosis patients, regardless of etiology or severity. A term of supplemental enteral nutrition may be
suggested for patients who do not achieve their nutritional objectives. A detailed nutritional and
exercise assessment will enable the development of an individualized treatment plan that includes
dietary and exercise plans. The dietary treatment should outline daily calorie targets with a focus
on high-quality protein and address any vitamin and micronutrient deficiencies, with a diet high in
those nutrients or supplements. Conclusions: While there is evidence to support the use of particular
restricted dietary plans and dietary supplements to manage liver diseases, these findings should be
regarded as preliminary until they are confirmed in larger randomized controlled clinical trials.

Citation: Elsebaie, E.M.; Keywords: hepatitis; cirrhosis; ascites; liver transplantation; hepatic encephalopathy; nutrition; diet;
Abdel-Fattah, A.N.; Bakr, N.A.; malnutrition; obesity
Attalah, K.M.; Aweas, A.-H.A.
Principles of Nutritional
Management in Patients with Liver
Dysfunction—A Narrative Review. 1. Introduction
Livers 2023, 3, 190–218. https://
doi.org/10.3390/livers3020013
As nutritional issues in patients with advanced liver dysfunctions are multifactorial,
treating malnutrition in these patients is difficult. To improve quality of life and prevent
Academic Editor: Giovanni medical complications linked to nutrition and improve nutritional status, such patients
Addolorato should have their nutritional status assessed right away [1]. All stages of chronic liver dis-
Received: 10 December 2022 eases are associated with the state of protein-energy malnutrition, and patients with chronic
Revised: 9 March 2023 liver diseases must consume a typical diet with the addition of supplements as required [2].
Accepted: 15 March 2023 For those patients to have a positive long-term outcome, it is critical to conduct an adequate
Published: 4 April 2023 assessment and nutritional therapy, ensuring a proper macronutrient, micronutrient, and
vitamin balance [3]. Due to the vital role that the liver plays in controlling nutritional
status and energy balance, patients with hepatic diseases are particularly susceptible to
developing malnutrition. Additionally, the presence of chronic liver dysfunctions may
Copyright: © 2023 by the authors. cause a decrease in appetite, which may affect the amount of nutrients consumed [4].
Licensee MDPI, Basel, Switzerland. Patients who have chronic liver diseases and those who are waiting for a liver transplant
This article is an open access article are almost always malnourished [4]. Patients with cirrhosis who are malnourished have
distributed under the terms and
higher rates of morbidity and mortality. Furthermore, problems and overall survival rates
conditions of the Creative Commons
following liver transplants are higher in individuals who are severely malnourished prior
Attribution (CC BY) license (https://
to the procedure [5], despite the crucial role that nutrition plays in the prognosis of persons
creativecommons.org/licenses/by/
with cirrhosis, and malnutrition frequently complicates the course of patients with the
4.0/).

Livers 2023, 3, 190–218. https://doi.org/10.3390/livers3020013 https://www.mdpi.com/journal/livers

Livers 2023, 3 191

disease and has complex causes. Despite the crucial role that nutrition plays in the prog-
nosis of those with cirrhosis, the ability to properly manage the patient’s nutrient needs
presents an additional set of challenges due to the catabolic nature of the disease process
and the common occurrence of anorexia and other symptoms that lead to a poor oral intake.
Malnutrition is a common complication in patients with cirrhosis and has a multifactorial
etiology [6], and, additionally, nutritional condition prior to liver transplantation is one of
the most significant factors that affects malnutrition and survival after liver transplantation.
Hepatic cholestasis increases the risk of protein-energy malnutrition and in particular
nutritional deficiencies [7]. Last but not least, malnutrition is a condition that may be
treatable and, when properly diagnosed and treated, can improve the results for people
with chronic liver dysfunctions [CLD] [8].

2. Materials and Methods

This monograph represents a narrative review of the evidence supporting the use
of diets and dietary supplements to manage chronic liver dysfunction and to discuss the
mechanisms through which food and the ingredients within foods and beverages might
affect malnutrition during liver diseases as well as the associations between being over-
weight, obesity, and liver disorders. A search through PubMed, MEDLINE, a Science Direct
database search, and Google Scholar was performed with the following search terms: “hep-
atitis A, hepatitis B, alcoholic hepatitis, cirrhosis, chronic liver diseases, ascites, liver failure,
liver transplantation, cholecysititis, gallstones, hepatic encephalopathy”. Each of these
search terms was then cross-referenced with “Nutrition, Diet, Malnutrition, and Obesity”
to identify relevant studies. Only studies that were written in English were included in
this review, in accordance with the goals of the current study, and the Bibliography and
citations of the selected studies were evaluated, with relevant articles, year of publica-
tion, irrelevancy, and animal studies as the exclusion criteria of the selected studies. The
aim of this study was to review the nutritional management of patients who have liver
complications.

3. Results
3.1. Role of Nutrition in Alcoholic Liver Disease (ALD)
Alcoholic liver disease (ALD) has different stages as it develops, and the severity of
ALD is correlated with malnutrition. The consumption of calories from alcohol instead of
calories from food results in poor nutrition, as does the malabsorption and maldigestion of
numerous nutrients linked to ALD. Alcohol abstinence is the only treatment for ALD that
has been proven effective. Infection-related problems linked with ALD may be effectively
decreased with enough nutritional replenishment and the right supportive treatment
techniques. In some malnourished patients, particularly, nutrition plays a substantial
beneficial role in the therapy of ALD [9], and given the frequency of malnutrition, especially
of the protein–calorie variety, it seems evident that diet contributes in some way to ALD.
Malnutrition typically correlates with the severity of ALD and is linked to the illnesses
that hospitalized patients experience. Abstinence from alcohol is the primary, validated
treatment for ALD. However, in general, good nutrition does not increase longevity. It does,
however, improve nitrogen balance, and it may boost liver tests and reduce hepatic fat
buildup. This implies that while appropriate diet is helpful when used in conjunction with
other forms of therapy, it is an insufficient therapy on its own. It has been hypothesized
that adequate nutritional replenishment along with other forms of therapy may be useful
in lowering ALD-related problems, notably infection [10,11]. Appropriate protein, calories,
and vitamins are necessary for optimal nutrition. The patient should, ideally, be given
enough food to eat orally or through a feeding tube. If this is the case, a nasogastric feeding
tube (also known as a nasogastric tube) or, if that is not possible, intravenous nutrition
may be needed [12]. In patients with severe AAH, morbidity and mortality rates are
substantial. Regrettably, there are still not many therapeutic approaches readily available.
As malnutrition has been linked to worse results, nutritional supplementation is a crucial
Livers 2023, 3 192

part of AAH treatment. In order to change clinical outcomes, the function of supplemental
nutritional assistance, such as enteral feeding and particular supplemental micronutrients,
needs to be more clearly defined [13].
The purpose of treatment is to decrease short-term morbidity and mortality through
the use of adjuvant pharmaceutical medicines and intensive supportive care. The cor-
nerstone of therapy, which is essential to long-term survival, is abstinence from alcohol.
Glucocorticoid therapy is currently the established pharmacological standard of care in
the treatment of severe AH, while the ideal length of therapy is still an unknown pe-
riod [14] Numerous randomised control trials (RCTs) have shown contradictory findings
in regards to the survival advantage. Short-term mortality at 28 days has been shown to
improve with the use of glucocorticoids, while long-term mortality advantages have not
been demonstrated [15,16]. There is no evidence to support pentoxifylline’s effectiveness
in reducing mortality [15]. The importance of getting enough calories and nutrients while
receiving extensive supportive care has caused this to be a priority area. Poor overall
nutritional status, which is frequently seen in individuals with AAH, is caused by a variety
of reasons. The fact that nutritional assistance is regarded as a crucial component of the
standard treatment for AH is largely due to these long-standing observations. Patients
with malnutrition are more likely to experience a slower recovery from AAH, which is not
surprising [17] as numerous studies have shown a link between severe AH patients who
are protein-calorie malnourished and increased rates of short- and long-term death [18,19].
The degree of protein–calorie malnutrition is closely related to mortality, with a rate that
reaches 80% in those patients who are classified as severely malnourished [19]. Numerous
investigations have demonstrated that low daily caloric intake is associated with higher
mortality in severe AH [20]. Reduced hepatic glycogen levels in patients with severe ALD
may cause hypoglycemia and rapid muscle catabolism to promote gluconeogenesis [21],
and this can tackled by reducing the amount of time spent without eating, with a focus on
having breakfast and a snack before bed as well as avoiding lengthy fasting while in the
hospital [21].
For a variety of causes, including delayed stomach emptying and longer small intesti-
nal transit durations that lead to early satiety, standard per oral food intake is frequently
impaired in these patients [22]. Additionally, ascites can affect stomach accommodation,
which might cause pain after meals [23]. Hepatic encephalopathy (HE), in addition to the
mental state changes that can be observed, limits the ability to eat. HE also contributes
to reduced appetite, and in certain more covert forms, results in an overall malnourished
state [24]. Last but not least, the use of lactulose (a non-absorbable but highly fermentable
synthetic sugar) in the treatment of encephalopathy might exacerbate bloating and discom-
fort feelings, further impairing oral intake [25]. Undernutrition is a danger for patients
who develop HE, and enteral access may be necessary [26,27]. Diets with a range of nor-
mal to high protein content are secure and do not raise the danger of encephalopathy in
alcoholic hepatitis. Enteral nutritional support should be started as soon as it is determined
that oral intake is impaired and should consist of 1.5 g of protein per kg of body weight
and 30 to 40 kcal per kg of body weight per day [28]. Given that complications such as
hypoalbuminemia, edoema, intravascular depletion, and ascites are frequently present in
this patient population and can conceal the patient’s true weight, the American Society
for Parenteral and Enteral Nutrition (ASPEN) recommends using an estimated euvolemic
weight or usual weight rather than the patient’s actual weight for these calculations in
patients with cirrhosis and hepatic failure. According to the American Gastroenterolog-
ical Association and ASPEN, EN is the preferred method for supplying nourishment to
individuals who are unable to tolerate oral ingestion [28,29]. The delivery of nutrition
to the gut enhances gut mucosal immunity and therefore reduces endotoxemia, which
may contribute to the pathophysiology of alcoholic hepatitis. In general, EN is also a less
expensive choice with far less consequences [30]. Nonabsorbable disaccharides, including
lactulose, should be used to treat patients with hepatic encephalopathy; rifaximin can be
given if this treatment is ineffective after 24–48 h [31]. Numerous micronutrient deficiencies,
Livers 2023, 3 193

including zinc, folate, thiamine, pyridoxine, vitamins A, B12, D, and E, have all been found
in patients with excessive alcohol consumption and ALD in addition to the high prevalence
of severe protein-calorie malnutrition [32,33]. These nutritional deficiencies are not just a
result of inadequate consumption; they are also a result of decreased absorption, which
increases the likelihood of developing alcohol-induced liver damage as well as osteoporosis,
myopathy, insulin resistance, and dyslipidemia in these patients. The inability of the liver
to produce carrier proteins, as well as the cholestasis that results in fat malabsorption,
reduces bile acid synthesis and small bowel delivery, which are all factors that contribute
to these deficiencies [34]. Through a number of mechanisms, including the enhancement of
intestinal barrier function, the reduction of proinflammatory cytokines, oxidative stress,
endotoxinemia, and the counterbalancing of hepatocyte apoptosis, zinc supplementation
may attenuate alcohol-induced liver injury and prevent hepatic encephalopathy [35,36].
Usually 50 mg of elemental zinc (220 mg of zinc sulphate) administered once daily with a
meal (to reduce potential nausea) is the suggested amount of zinc for treating liver disease.
Due to competition for absorption at the brush boundary, long-term zinc supplementation
has been linked to copper insufficiency. Further research is necessary to determine the
supplementation duration.

3.2. Role of Nutrition in Liver Cirrhosis

Malnutrition is a common consequence of liver cirrhosis and is linked to the progres-
sion of liver failure as well as a higher incidence of infections, hepatic encephalopathy,
and ascites. Cirrhosis instances linked to non-alcoholic steatohepatitis have increased in
recent years as a result of the rising incidence of obesity. Patients with liver cirrhosis may
have a worse prognosis and have a reduced chance of life due to malnutrition, obesity, and
sarcopenic obesity. Therefore, it is essential to assess and address nutrition in chronic liver
disease [37].
The physiology of rapid post-absorptive cirrhosis is one of accelerated hunger and is
characterised by a decline in the respiratory quotient [38,39]. The metabolic switch from
glucose to fatty acids as the predominant fuel is what causes the respiratory quotient to
decrease. Protein synthesis is reduced and gluconeogenesis from amino acids is elevated
during this state of accelerated hunger, which necessitates proteolysis and causes sarcope-
nia. Gluconeogenesis, an energy-demanding operation, could cause these patients’ resting
energy expenditure (REE) to rise even higher. Reduced nutritional intake caused by a vari-
ety of conditions, such as dysgeusia, anorexia from a chronic illness, salt-restricted cuisine
that is unappealing, and portal hypertension that affects gut motility and reduces nutrient
absorption all accelerate starving [40,41]. Inappropriate dietary protein restriction, hospital-
isation with periods of fasting for diagnostic and therapeutic procedures, encephalopathy,
and gastrointestinal bleeding are all additional reasons that lead to decreased nutritional
intake.
Total energy expenditure (TEE), which comprises REE, food-associated thermogenesis,
and energy expenditure related to physical activity, must be balanced by energy supply.
The optimal ways to evaluate TEE are in a respiratory chamber or with doubly-labeled
water; however, these are not practical in a clinical context. Physical activity is decreased
and practically nonexistent in people with decompensated cirrhosis. TEE ranges in cir-
rhotic individuals between 28 and 37.5 kcal/kg·BW/d [40,42–45]. Some research looked
at how REE was impacted by decompensated liver cirrhosis. According to a small longi-
tudinal research, ascites raises REE [46]. Nevertheless, cross-sectional research observed
no differences in REE between individuals with different degrees of fluid retention and
liver disease severity [47,48]. Hypermetabolism is the name for a condition where the
measured REE may be higher than expected. The severity and aetiology of liver cirrhosis,
the development of ascites, or clinical or laboratory parameters [49], however, cannot
identify hypermetabolism [50]. In advanced cirrhotic patients, REE can be predicted using
predictive equations, but they are erroneous, and, thus, it is always best to assess REE using
Livers 2023, 3 194

indirect calorimetry [38,39]. A patient’s daily caloric demands can be determined by using
the hand-held calorimeter that is available at the bedside [39].
Most dietary intervention trials for liver cirrhosis take the approach of providing at
least 35 kcal/kg·BW/d. It is deemed safe to use genuine BW that has been ascites-corrected.
Even if it is frequently challenging to attain this goal, the oral dietary intake may mostly
be tailored to achieve it. A recent retrospective study has highlighted the importance
of a nutrition support team by demonstrating how a nutritional intervention led by a
multidisciplinary team and involving cirrhotic patients in educational sessions about the
significance of proper nutrition in chronic liver disease was able to increase survival rates
and quality of life [51,52]. It has also been thoroughly investigated whether frequent
feeding can assist the prevention of increased hunger and the associated proteolysis. Since
the time between meals is at its longest at night, methods to reduce it by eating a late-night
snack have been investigated. These methods have improved metabolic profiles and quality
of life, while muscle mass did not demonstrate a consistent improvement. It is therefore
advised that cirrhotic patients adopt a breakfast that contains some proteins [53] and a
late-night snack to reduce the length of fasting.
The lowest amount of protein needed to maintain nitrogen balance is used to de-
termine protein requirements. Nitrogen equilibrium was attained in alcoholic cirrhosis
with intakes of 0.8 g/kg·BW/d [54]. In investigations where cirrhotic patients were given
meals with increasing protein content, this cut off was verified [45,55]. Additionally, these
investigations showed that individuals with cirrhosis can utilize up to 1.8 g/kg·BW/d
of protein [45]. There has previously been debate about whether HE patients should
temporarily restrict their protein intake in order to reduce the production of ammonium
and the conversion of protein to aromatic amino acids. However, HE is not precipitated
by a normal to high protein intake [56,57], and it may even benefit mental health [58,59].
1.2–1.5 g/kg.BW/d of protein is advised for patients with liver cirrhosis in order to avoid
muscle loss and reverse muscle loss in sarcopenic patients. As previously indicated, sar-
copenia does, in fact, negatively impact clinical outcomes, regardless of the severity of
liver disease [40]. The following section will go through sarcopenia therapy options. Short
dietary recommendations are given for use when managing cirrhotic patients at the bedside
or during an outpatient visit.
Any nutritional therapies are encouraged to adhere to the general guidelines listed
under “energy and protein requirements in cirrhotic patients.” In contrast, it can be chal-
lenging for malnourished sarcopenic individuals with severe liver disease to consume
enough calories and protein. Clinical investigations have used oral nutritional supplements
and branched chain amino acid (BCAA) supplements to address this issue [60,61], with
modest success.
Short-term enteral or parenteral nutrition should be utilised in patients with malnutri-
tion and cirrhosis who are unable to overcome the stage of underfeeding with the oral diet
(even with oral supplements).
Despite encouraging individual trials, thorough meta-analyses have not demonstrated
a significant survival benefit for enteral feeding in malnourished cirrhotic patients brought
to hospitals [62–64]. There is conflicting evidence regarding the advantages of parenteral
nutritional supplementation in cirrhotic patients, but this is likely to be helpful when oral in-
take is compromised for an extended period of time due to encephalopathy, gastrointestinal
bleeding, and impaired gut motility or ileus [65]. In a separate part, enteral and parenteral
nutrition in the perioperative period is covered. Even though there are currently no direct
studies on sarcopenia, there is some limited but consistent evidence that supplemental
nutrition enhances quality of life if it leads to an increase in lean body mass [66].

3.3. Malnutrition in Liver Cirrhosis

Malnutrition is a frequent cirrhosis consequence that worsens with increasing Child-
Turcotte-Pugh (CTP) scores and is linked to higher morbidity and mortality rates. Malnu-
trition is present but frequently goes unnoticed in up to 50% of patients with CTP class A
Livers 2023, 3 195

cirrhosis, despite the fact that it is readily apparent in chronically ill patients with CTP class
C cirrhosis. As a result, all patients with cirrhosis, regardless of aetiology or severity, should
be screened for malnutrition, although the diagnosis of malnutrition is rather ambiguous
in adults and is even more so in patients with hepatic failure, and a nutritional assessment
should be incorporated into the normal clinical care of patients with cirrhosis [67,68]. Loss
of skeletal muscle mass and strength (sarcopenia) in addition to other symptoms of mal-
nutrition are commonly used to describe cirrhosis in adults. Sarcopenia, immunological
dysfunction, and low body mass index (BMI) are all related to protein-calorie malnutri-
tion [69]. One of the key elements of frailty is sarcopenia, although the condition also
calls for performance loss in addition to skeletal mass reduction [70]. Malnutrition is more
common in cirrhotic individuals, with prevalence rates ranging from 50% to 90%, according
to the Pathophysiology of Malnutrition in Chronic Liver Disease. Malnutrition in cirrhosis
has a complex aetiology. Reduced oral intake, as well as malnutrition and malabsorption,
are contributing factors, especially in cholestasis patients [71,72]. Anorexia, zinc deficiency-
related dysgeusia, unappealing meals as a result of sodium restriction, and incorrect protein
restriction for patients with hepatic encephalopathy or chronic renal insufficiency are just
a few causes of decreased oral intake. Poor oral intake also happens frequently while in
the hospital due to procedures and/or hepatic encephalopathy. Additionally, patients with
decompensated cirrhosis and ascites feel early satiety as a result of the extrinsic constric-
tion of the gastrointestinal system by peritoneal fluid [72,73]. Fat malabsorption occurs
in cirrhotic patients as a result of lower luminal bile acids due to decreased production,
portosystemic shunting, and concomitant chronic pancreatitis in individuals who regularly
use alcohol [71]. Patients with prolonged lactulose use, intestinal dysbiosis, and/or portal
hypertensive gastropathy, and/or enteropathy may also experience malabsorption [72].
Patients with cirrhosis experience an altered metabolism due to a decreased hepatocyte
bulk, which causes a switch from glycogenolysis to gluconeogenesis as an energy source in
addition to decreased oral intake and malabsorption, following which gluconeogenesis,
lipopenia, and sarcopenia occur. Additionally, 15% to 34% of cirrhosis patients exhibit
hypermetabolism, which may be caused by sympathetic hyperactivity, gastrointestinal
bacterial translocation, and a proinflammatory phenotype [74,75]. Sarcopenia, which re-
sults from increased proteolysis and a decrease in protein synthesis, is one of the main
effects of malnutrition and is correlated with frailty. Cirrhosis causes the glycogen stores
to become depleted, which increases the dependence on gluconeogenesis as a source of
glucose. Gluconeogenesis mainly makes use of [72].

3.4. Micronutrient Deficiencies in Liver Cirrhosis

Due to malabsorption, decreased intake, and decreased generation of carrier proteins,
deficiencies in fat-soluble vitamins are frequent in individuals with severe cirrhosis, and
are particularly common in those with cholestatic liver disease [76,77]. Nyctalopia is a sign
of vitamin A insufficiency and can be detected by measuring serum retinol levels, which
are normal at 32.5–78.0 g/dL (night blindness). It is advised to replace lost vitamin A with
25,000 units per day for 4 to 8 weeks [76,78]. Vitamin D insufficiency is also frequent and
can cause osteopenia, osteoporosis, and osteomalacia. 2000 IU of vitamin D2 or D3 and
1200–150 mg of calcium should be consumed every day. An intake of 50,000 IU of vitamin D
is recommended for patients with vitamin D insufficiency (defined as a 25-hydroxyvitamin
D level below 20 ng/mL). Vitamin K insufficiency causes a prothrombin time prolongation
and an increased risk of bleeding, while vitamin E deficiency has been associated with
hemolytic anaemia, neuropathy, and creatinuria [76]. Because of the decreased clotting
factor synthesis in the context of hepatic dysfunction as well as prothrombotic variables that
occur in this state, the risk of bleeding is frequently difficult to estimate purely based on the
degree of prolongation. Treatment options for vitamin K shortage vary based on the clinical
situation, such as whether intramuscular or intravenous delivery is necessary for patients
with an active haemorrhage [73,76]. Patients with cirrhosis are also more likely to have
vitamin deficiencies that are water soluble. Both liver illnesses caused by alcohol and those
Livers 2023, 3 196

not caused by alcohol can have thiamine [vitamin B1] deficiency. Neurologic dysfunction,
such as Wernicke encephalopathy and Korsakoff psychosis, as well as high-output heart
failure, or “wet beriberi”, are some of its symptoms [73,76]. Although cirrhotic patients are
at risk due to decreased hepatic storage, pyridoxine (vitamin B6), folate (vitamin B9), and
cobalamin (vitamin B12) deficiencies are less frequent. Conversely, despite lower tissue
levels, blood vitamin B12 levels are increased in cirrhotic individuals due to the leakage of
inactive cobalamin mimics into the circulation [79]. Zinc deficiency is typical in cirrhotic
individuals and has been linked to dysgeusia, which may increase aversion to certain foods.
Acrodermatitis, glossitis, hypogonadism, and slowed wound healing are other symptoms.
Serum zinc levels may be deceptive because they do not fully reflect total body storage.
A once-daily dose of 50 mg of elemental zinc (220 mg of zinc sulphate) may be given if
deficiency is thought to exist; this dose has no negative effects on copper absorption [76,80].
Muscle cramps have been linked to a magnesium deficit, although serum magnesium
levels do not accurately reflect total body storage and do not predict cramping. In clinical
practice, supplementation with 400 mg of magnesium oxide is typical [81,82]. Patients with
cholestasis should not receive total parenteral nutrition because manganese and copper are
excreted in bile and may be higher in those with chronic liver disease [80,83].

3.5. Role of Nutrition in Management of Malnutrition and Sarcopenia in Liver Cirrhosis

Regarding macronutrient requirements, patients with compensated cirrhosis need 1.2
to 1.5 g/kg/day of protein to avoid or reverse sarcopenia and at least 35 kcal/kg/day of
their bodyweight as adjusted for ascites. Patients unable to meet these objectives might
benefit from enteral nutrition as a supplement. A high-protein diet (>1.5 g/kg/day)
combined with a hypocaloric diet (500–800 kcal below daily needs) is advised for obese
people to enhance weight loss without causing concurrent muscle loss [73]. Patients with
compensated cirrhosis need 1.2–1.5 g/kg/day of protein and 35–40 kcal/kg/day, whereas
those with hepatic encephalopathy need 1.2–1.5 g/kg/day [84]. The timing of meals is
crucial in reducing sarcopenia and malnutrition in addition to the overall number of calories
consumed and the makeup of the macronutrients. Patients with cirrhosis exhibit higher
fat oxidation, higher gluconeogenesis, and lower glycogenolysis following an overnight
fast, all of which resemble what happens in healthy persons after two to three days of
fasting [85]. When compared to using a caloric daytime supplement, a study found that
taking a nutritional supplement at night increased total body protein reserves. Importantly,
the subgroups with CTP classes B and C may have been underpowered, but this benefit
was only statistically significant in the cohort with CTP class A cirrhosis. This highlights
the necessity of treating all cirrhotic patients, not only those with more severe disease [86].
In contrast to individuals who had fasted, another trial showed that people with minor
hepatic encephalopathy had better cognitive function after eating breakfast [87].
Because of the contradictory evidence, oral BCAA use requires specific caution. Several
randomized, controlled trials (RCTs) have shown an increase in albumin synthesis, a
decrease in the risk of hepatic decompensating, and an increase in protein synthesis in
skeletal muscle. However, smaller studies have not revealed a meaningful benefit [88,89].
The suggested dose of oral BCAAs is 4 g per day, while the best time, method, and
preparation for administration are still up for debate [90]. Increasing physical activity has
been demonstrated to be crucial in avoiding and/or reversing sarcopenia in addition to
achieving the necessary protein–calorie energy goals and receiving enough vitamin and
mineral supplements [73]. Because of their sedentary lifestyles and poor baseline exercise
tolerance, patients with cirrhosis are more likely to experience muscle wasting [91,92].

3.6. Role of Nutrition in Management of Obesity in Patients with Liver Cirrhosis

Obesity is at least as prevalent in people with compensated cirrhosis as it is in the
general population, according to two studies [93,94]. Quality data are scarce, but because
there is a chance that weight reduction strategies could worsen sarcopenia, special attention
must be made to the amount of protein needed to preserve muscle mass. The ideal form of
Livers 2023, 3 197

physical activity (aerobic vs. anaerobic; endurance vs. resistance/strength training) and its
duration in this population are not well understood. Despite some evidence indicating that
resistance training is probably safe, it is prudent to avoid abdominal pressure in people
with portal hypertension [95]. Regardless of the cause of liver disease, exercise needs to be
customised to the patient’s abilities, starting with moderate intensity and lasting for a long
time from 20% to 35%. Obesity is found in the majority of instances of cirrhosis caused
by NASH. Additionally, cirrhosis patients have a high prevalence of sedentary lifestyles,
which may be considered a cofactor in this population’s increased BW. According to the
HALT-C experiment [94], the chance of histological progression or decompensating rose by
14% for every quartile point higher in BMI, and by 35% in patients whose BW increased
by more than 5% at 1 year. In a randomised controlled trial comparing the use of timolol
or a placebo to delay the onset of gastroesophageal varices, BMI was linked to clinical
decompensating in patients without varices and with a hepatic venous pressure gradient
of less than 6 mmHg, independent of portal hypertension and albumin [94]. Data from
much research implies that in obese patients with compensated cirrhosis, a decrease in
BW improves outcomes [94–96]. This was accomplished through a lifestyle intervention
programme that included supervised moderate intensity exercise and dietary therapy. For
patients included in the HALT-C trial, a weight loss of between 5% and 10% is regarded as
a sufficient target because it is linked to a slower rate of illness progression [94]. Dietary
intake should ensure a moderate calorie restriction and an appropriate intake of protein.

3.7. Role of Nutrition in Ascites

Patients with decompensated cirrhosis and refractory ascites who are malnourished
should be treated with supplemental continuous TF [97]. Patients with cirrhosis have a
deterioration of their nutritional condition along with progressive liver disease and dis-
turbance of the hepatic architecture [98]. In individuals with decompensated cirrhosis,
malnutrition is linked to an increase in decompensation-related symptoms including ascites,
hepatic encephalopathy, and the growth and progression of esophageal varices [99,100].
Between 40% and 70% of cirrhotic patients have sarcopenia [101], and, regardless of the
severity of the condition, it is linked to increased mortality [102]. Sarcopenia can occur
in cirrhotic people for a variety of reasons. Increased levels of inflammatory mediators,
dysbiosis, small bowel bacterial overgrowth, and elevated intra-abdominal pressure from
ascites all lead to a decline in liver function. Patients with cirrhosis have been proven to
develop sarcopenia when they consume insufficient amounts of protein and calories [101].
In patients with cirrhosis, determining nutritional status can be challenging and frequently
erroneous [8]. Poor indications of nutritional condition and muscle wasting in patients with
decompensated cirrhosis are some of the typical techniques used to measure nutritional sta-
tus, including whole bodyweight, unintentional weight loss, body mass index, and serum
proteins [103], with the presence of ascites, peripheral edema, and hepatic hydrothorax
frequently obscuring the degree of malnutrition using these criteria [104]. Thus, subjective
global assessment (SGA) of nutritional status [105], as well as hand grip strength, is part of
the standard nutritional evaluation of the patient with cirrhosis [106], along with adequate
oral intake, eating frequently, adjusting one’s appetite, tasting differently, feeling full sooner
than usual, and experiencing nausea. The contribution of ascites to the patient’s overall
dietary needs is still debatable, with some professionals arguing that it should be taken into
account when determining requirements [47]. It is known that the course of the disease
alters the macronutrient and micronutrient requirements of patients with decompensated
cirrhosis [104]. Evidence-based recommendations for the nutritional therapy of patients
with cirrhosis were released by the European Society for Enteral and Parenteral Nutrition
in 2006. These recommendations describe the elevated protein and energy needs for this
population as well as the use of oral sip supplements or tube feeding (TF) to help patients
fulfil these elevated disease-specific needs [107]. The practitioner, the patient, their careers,
and the healthcare system all face considerable challenges when trying to improve the
nutritional condition of patients with decompensated cirrhosis. The cost of liver illness
Livers 2023, 3 198

has an impact on many facets of life, including therapy compliance [108]. Any treatment
that lessens the symptoms and fragility of CLD patients can enhance their quality of life
and ease the financial burdens placed on them, their caregivers, and the healthcare sys-
tem. Ascites is one of the most prevalent signs of hepatic decompensating and frequently
co-exists with rising portal hypertension, but it is also influenced by starvation. Ascites
will appear in 50–60% of patients with decompensated cirrhosis [109]. Diuretic-resistant or
refractory ascites can also develop in up to 22% of ascites patients, which is associated with
a decreased 12-month survival rate [110]. In the case of resistant ascites, therapeutic para-
centesis, transjugular intrahepatic portosystemic shunts (TIPS), and liver transplantation
are the mainstays of standard ascites care [111].

3.8. Role of Nutrition in Management of Hepatic Encephalopathy (HE) in End-Stage Liver Failure
Patients with end-stage liver failure and hepatic encephalopathy frequently have
malnutrition, which is thought to be a significant prognostic factor affecting quality of life,
prognosis, and survival. Since liver illness may interact with biomarkers of malnutrition,
it can be challenging to identify patients who are at risk of malnutrition. In addition to
addressing calorie and protein needs, individuals with end-stage liver failure may benefit
from dietary supplements that include amino acids, antioxidants, vitamins, and probiotics.
This may improve their nutritional status, liver function, and hepatic encephalopathy [112].
It is plausible to infer that malnutrition affects all patients given the high prevalence of
malnutrition in cirrhotic patients and the absence of quick and effective procedures for
assessing malnutrition in this patient population. Depending on the particular clinical
circumstance, nutritional needs may change. The use of complex rather than simple
carbohydrates as a source of calories has been suggested for many [113,114], with little
feedings and an evening snack that is high in carbohydrates. Lipids may meet 20% to
40% of calorie requirements. It may be required to take nutritional supplements over
the long term to meet the recommended protein and calorie needs. To make specific
recommendations for nutrients such as zinc, selenium, and carnitine, more research is
required. Avoiding purposeful or unintentional weight loss and maintaining a nutrient-rich
diet should be the patient’s top priorities if they have end-stage liver failure. Patients
with liver cirrhosis may benefit from receiving 35–40 kcal/kg per day, according to some
research [115]. Long considered a cornerstone in the treatment of both HE and liver
disease is dietary protein restriction [116,117]. For example, it was discovered that protein
restriction (0–40 g protein/day) reduced the severity of encephalopathy in patients who
had had surgical construction of a portal–systemic shunt, the sole treatment for bleeding
varices at the time. Later, the protein restriction [0–40 g protein/day] was expanded to
all cirrhotic patients who experienced encephalopathy. Recent investigations, however,
have demonstrated that protein restriction in these patients has no effect on the severity of
encephalopathy and may significantly exacerbate their nutritional state [118]. The practice
of prolonged protein restriction in the management of HE has come under scrutiny due
to growing awareness of the steadily declining nutritional status in liver cirrhosis and a
better understanding of metabolic changes in the condition [119]. In actuality, cirrhotic
patients require more protein, and the majority of patients tolerate high-protein diets quite
well. Additionally, providing enough protein to malnourished patients with end-stage liver
failure generally results in a long-lasting improvement in their mental health. Protein also
aids in maintaining lean body mass, which is important for liver failure patients whose
skeletal muscles play a large role in ammonia elimination. Most experts agree that, except
for a small number of people with severe protein intolerance, protein intake should not
be restricted to less than 1.2 to 1.5 g per kg of bodyweight per day [120]. In patients with
severe protein intolerance, particularly those with grades III-IV HE, protein intake may be
temporarily restricted [121,122]. Vegetable proteins may be more tolerable in patients with
end-stage liver failure than animal proteins, a finding that has been attributed to either their
higher content in branched-chain amino acids or to their impact on intestinal transit [57,123].
According to one study, a diet high in vegetable protein [71 g/d] dramatically enhanced
Livers 2023, 3 199

the mental health of HE patients while boosting their nitrogen balance [124]. Vegetable
proteins may also speed up gastric transit time and raise intraluminal pH. Constipation
has been identified as an established triggering factor for HE in patients with cirrhosis,
and a high-dietary fibre diet has been advised to eliminate it [125,126]. In most patients,
a daily consumption of 30–40 g of vegetable protein has been found to be helpful [124].
Probiotics and antioxidants are being used more frequently to improve the nutritional
status of cirrhotic individuals. Patients with end-stage liver failure are advised to take
multivitamin supplements, with thiamine being a special recommendation. In patients
with end-stage liver failure, nutritional support with the goal of maximising the removal of
circulating ammonia, lowering pro-inflammatory mechanisms, and enhancing antioxidant
defences has the potential to slow the progression of liver dysfunction, treat HE, and
enhance quality of life [112].

3.9. Role of Nutrition in Liver Transplantation

Due to decreased food intake, HE in end-stage liver failure may cause malnutrition
during the waiting period before transplant [127]. Significant risk factors for both sur-
gical [128] and postsurgical [129] problems of liver transplantation include changes in
nutritional status markers, such as serum albumin. Additionally, non-absorbable disaccha-
rides (like lactulose) given to patients with end-stage liver failure for the treatment of HE
may cause intestinal malabsorption, which could have a negative impact on the success
of their transplant [130]. In early retrospective studies, it was noted that malnutrition
had a deleterious effect on liver transplantation [131]. Preoperative hypermetabolism and
body cell mass loss both had predictive significance for the success of transplantation [132].
Glycogen depletion, which is a known consequence of malnutrition, has been proposed to
increase the plasma lactate:pyruvate ratio during the hepatic phase and to trigger an aggra-
vated pro-inflammatory cytokine response, favouring the development of postoperative
systemic inflammatory response syndrome and multi organ failure in these patients [133].
As of now, there is not enough information about the pre-transplant period to provide
precise advice. Nutritional therapy in the post-transplant period enhances nitrogen balance,
lowers viral infection, and exhibits a tendency to shorten intensive care unit stays, thereby
lowering hospitalization costs [134,135].

3.10. Role of Nutrition in Gallbladder Diseases

The most frequent causes of gallstones and gallbladder inflammation are changing
lifestyle habits, reliance on fast food, lack of activity, and absence of a diet plan. Chole-
cystitis is a common disease in which the presence of gallstones is the primary cause of
infection [136]. High-fat, low-fiber diets are highly associated with gallstones. They are
uncommon in populations of Asian and African people who consume traditional, mostly
plant-based diets, and they become more prevalent as diets become more Westernized [137].
The main dietary risk factors for gallstone development appear to be an excess of animal
protein and fat, a deficiency in dietary fibre, and the consumption of saturated fat as
opposed to unsaturated fat.
Regarding vegetarian diets, gallstone development may be influenced by both animal
fat and animal protein. Since only 20% of gallstones contain more than 20% cholesterol, it is
possible that dietary adjustments (such as decreasing dietary saturated fat and cholesterol
and increasing soluble fibre) could lower the incidence of gallstones. Up to 90% of gallstones
are cholesterol stones [138]. Compared to non-vegetarian women, vegetarian women are
at a decreased risk of developing gallstones [139]. The majority of the fat in vegetarian
diets is in unsaturated forms, and they are frequently high in fibre. Consumption of fruits
and vegetables may contribute to some of this defence. A lower risk of cholecystectomy is
connected with eating a lot of fruits and vegetables [140]. The rate-limiting phase in the
breakdown of cholesterol to bile acids is affected by vitamin C, which is present in plants
but lacking in meat, and is inversely related to the incidence of gallstones in women [141].
According to research, women who consume the most plant protein have a 20–30% lower
Livers 2023, 3 200

risk than those who consume the least [142,143]. In a similar vein, men and women who get
most of their fat from plant sources have a lower risk of getting gallstones [144]. Trans fatty
acids, a type of partially hydrogenated vegetable oil commonly found in snack foods, are an
exception since they are linked to an increased risk of gallstones [145]. High LDL cholesterol
levels are linked to gallstone development in the general population, highlighting the
significance of a diet (high-fiber, low-fat) that maintains blood lipids in a healthy range [146].
Regarding substituting high-fiber diets for sugars and refined carbohydrates, refined
carbohydrate consumption is associated with a greater bile cholesterol saturation index,
which is known to increase the risk of gallstone formation [147,148]. Those who consume
the most refined carbs had a 60% higher chance of getting gallstones than those who
consume the least, according to a 12-year prospective cohort study among US men [149].
In contrast, a 1998 Italian cross-sectional research of men and women found that those
who consume the most fibre, especially insoluble fibre, have a 15% lower risk of gallstones
than those who consume the least [150,151]. Regarding avoiding excess bodyweight and
adopting a healthy weight-control strategy, compared to women with a BMI 25 kg/m2 ,
women with a BMI 30 kg/m2 had at least a double the risk of gallstone disease, Men
with a BMI of 25 kg/m2 or higher are at the same level of risk as those with a BMI of
22.5 kg/m2 . Risk increases as weight increases [152]. In a 1999 prospective cohort study of
47,153 women in 11 US states, the risk for cholecystectomy increased from 20% in “light”
cyclers (those who lost and regained 5 to 9 lbs) to 70% in “severe” cyclers (those who lost
and regained 20 pounds). Weight cycling is the practice of repeatedly losing weight and
unintentionally gaining it [153]. A similar tendency may be seen in a 2006 survey of US
men [154]. The risk of gallstones is increased by very low calorie diets (800 kcal/day), as
was already mentioned, but the reason why is as yet unknown. In calorie-restricted dieters,
a small quantity of fat (10 g/day) promotes maximum gallbladder emptying and inhibits
gallstone development [155]. Such findings support weight-management strategies based
on low-fat, plant-based diets, which often result in healthy and long-lasting weight control
as opposed to those based on formula diets with extremely low calorie intake.

3.11. Nonalcoholic Fatty Liver (NAFLD)

A clinic-pathologic condition called nonalcoholic fatty liver disease includes a number
of different clinical entities. Simple statuses, steatohepatitis, fibrosis, and end-stage liver
disease are all on the spectrum of disorders. The illness was initially identified in middle-
aged, obese, diabetic females who had liver histology that was compatible with alcoholic
hepatitis [156,157]. It is generally recognized that this condition affects slim people without
regard to gender as well as a rising proportion of obese youngsters [157,158].
This clinical entity has also been referred to by the labels alcohol-like hepatitis, pseu-
doalcoholic hepatitis, diabetic hepatitis, and steato-necrosis. Ludwig and colleagues first
used the term nonalcoholic steatohepatitis (NASH) to refer to those who fitted the profile
of an alcoholic hepatitis but have not engaged in heavy alcohol consumption [159]. Since
steatosis, steatohepatitis, fibrosis, and cirrhosis all fall under the umbrella of non-alcoholic
fatty liver disease (NAFLD), the word is more generally used to refer to the entire spectrum
of diseases. Patients with steatohepatitis and fibrosis are only allowed to receive NASH.
The most frequent reason for increased liver enzymes in the US is now understood
to be NAFLD. Although the precise cause of NAFLD is unknown, increasing oxidative
stress on the hepatocytes and insulin resistance may both contribute to it. The mainstay of
management for this illness is weight loss because no specific medicine has been licensed
for it [160].
The most common cause of liver disease worldwide is non-alcoholic fatty liver disease.
Its pathogenesis is thought to be complex and is governed by a wide range of mecha-
nisms, including variables from the environment, metabolism, genetics, and gut microbes.
Nonalcoholic fatty liver disease presents with vague and non-specific symptoms, making
diagnosis difficult [161].
Livers 2023, 3 201

3.12. Dietary Strategies in the Nutritional Management of (NAFLD)

In the onset, progression, and management of NAFLD and its metabolic-related
comorbidities, dietary habits and nutrients are crucial. An improper dietary pattern is
closely linked to the development of NAFLD. Numerous studies have demonstrated that
NAFLD patients share a common dietary pattern that is defined by a low consumption
of whole grains, cereals, fruits, and vegetables while consuming more red meat, viscera,
refined grains, and/or sugars than is advised [162–164].
These eating patterns are often associated with the Western pattern diet, which has
been linked to a number of metabolic disorders, including NAFLD [162–164]. Red meat
and soft drink consumption are linked to an increased risk of NAFLD, according to a
recent meta-analysis [165]. Similar to this, eating a lot of red meat is linked to insulin
resistance [164]. In fact, the Western diet is frequently characterised as having a high total
energy intake and a high proportion of refined carbohydrates and saturated fat. These
macronutrients have an impact on the metabolic processes that cause the buildup of liver
fat. As an illustration, a hyperenergetic diet that derived its surplus energy primarily
from saturated fatty acids increased intrahepatic triglycerides (55%) via inducing lipolysis
in adipose tissue. However, additional energy from simple carbohydrates was raised
through promoting lipolysis of adipose tissue. On the other hand, more energy from simple
carbohydrates boosted de novo lipogenesis, which led to an increase in liver triglycerides
(33%) [166]. Interestingly, we want to emphasise that despite the fact that saturated fats
have been associated with CVD for decades, mounting data suggests that this association
may be heavily skewed [167]. Together, these studies show that diet is a critical risk factor
that can be modified in the management of NAFLD because nutrition influences disease
risk in a significant way.
The most successful intervention for managing NAFLD was found to be exercise
plus diet, according to a network meta-analysis that comprised 19 randomized-controlled
studies [168]. Due to the high link between bodyweight reduction and improvements
in intrahepatic fat among other measures, the primary goal of lifestyle interventions in
NAFLD is to lower bodyweight. In a randomised clinical trial, both obese and non-obese
patients’ NAFLD remission was predicted by the amount of weight loss brought on by a
lifestyle modification. It is significant that cases without obesity required less weight loss
to reach remission (3–10%) than individuals with obesity (7–10%) [169].
When weight loss was greater (7–20%), improvements in steatosis, liver inflammation,
ballooning degeneration, and fibrosis were also seen in NASH [170–172]. In theory, the
best way to lose weight is by restricting your energy intake. However, for the majority of
patients, maintaining weight loss and maintenance while reducing energy is exceedingly
difficult, which limits long-term success. Notably, the number of meals per day has also
been a topic of discussion because eating more than three meals per day (including snacks)
results in more frequent insulin spikes, which may increase food cravings throughout the
day and interfere with the best diet compliance [173].
Therefore, a number of dietary strategies, such as the low-fat diet (LFD), low-carbohyd
rate diet (LCD), ketogenic diet (KD), Dietary Approaches to Stop Hypertension (DASH)
dietary pattern, and the Mediterranean dietary pattern (MedDiet) have been evaluated
in the NAFLD setting as alternatives to reducing overall energy intake. These dietary
methods pay close attention to both qualitative and quantitative nutritional characteristics.
In addition, the intermittent fasting (IF) strategy has gained popularity as an alternative to
conventional continuous energy-restricted diets for bodyweight management, and it has
drawn particular attention as a potentially innovative dietary therapy for NAFLD. There
is currently a lot of controversy over the best diet for people with NAFLD and how to
regulate their diet precisely [174].

3.13. Nutritional Therapy for Hepatocellular Carcinoma

The most prevalent primary liver cancer, hepatocellular carcinoma [HCC], typically
manifests as cirrhosis [175]. In addition to the more well-known risk factors for the devel-
Livers 2023, 3 202

opment of HCC, such as hepatitis B and C virus infection, age, and alcohol and tobacco
use, there are nutritional risk factors related to the development of HCC as well. These
include a high intake of saturated fats from red meat, the type of cooking (which produces
heterocyclic amines), and aflatoxins contaminating food [176–178]. Conversely, dietary
components that are protective include those high in fibre, fruits, vegetables, n-3 polyun-
saturated fatty acids, and coffee [179–181]. A special focus should be given to nutritional
support, including appropriate nutritional assessment and therapy by a multidisciplinary
team while the patient is being examined for staging and treatment of HCC. It must be
taken into account that these patients typically acquire HCC on top of chronic cirrhosis,
and, as a result, they may exhibit severe malnutrition. Complications from cirrhosis should
be adequately treated and taken into account for nutritional care. In addition to customary
techniques [182], among the most helpful tools for nutritional assessment are functional
testing, phase angle, and the skeletal muscle index-L3 generated from computed tomogra-
phy scans [183]. The dietary approach for hepatocellular carcinoma, according to Barcelona
Clinic Liver Cancer classification is presented in Figure 1 [184].The main goal of nutritional
therapy should be to supply enough protein and energy to meet the increased needs of
cirrhosis and cancer. Branched-chain amino acid supplementation is also advised since it
Livers 2023, 3, FOR PEER REVIEW enhances survival, nutritional status, and response to treatment. Lastly, physical activity 14
should be promoted and tailored to individual needs [184].

Figure1.1.Dietary
Figure Dietaryapproach
approachfor
forhepatocellular
hepatocellularcarcinoma,
carcinoma, according
according to to Barcelona
Barcelona Clinic
Clinic Liver
Liver Can-
Cancer
cer classification. BCAAs: Branched-chain amino acids; BCLC: Barcelona Clinic Liver Cancer;
classification. BCAAs: Branched-chain amino acids; BCLC: Barcelona Clinic Liver Cancer; TEE: Total TEE:
Total energy expenditure. Ref. [184].
energy expenditure. Ref. [184].

3.14.Hepatitis
3.14. HepatitisAAVirus
Virus (HAV)
(HAV)
Oneof
One ofthe
thewell-known
well-knownviruses
virusesthat
thatcauses
causeshepatitis
hepatitisglobally
globallyisisthethehepatitis
hepatitisAAvirus
virus
(HAV).Despite
(HAV). Despitethe thefact
factthat
thatthis
thisdisease
diseasehashasdeclined
declinedininindustrialised
industrialisednations
nationsasasaaresult
result
of
ofwidespread
widespreadvaccination,
vaccination,the
thevirus
viruscontinues
continuesto toplague
plagueaalarge
largenumber
numberof ofundeveloped
undeveloped
and
and underdeveloped nations [185].
underdeveloped nations [185].HAVHAV infection
infection cancan be disseminated
be disseminated through
through oral-
oral-fecal
fecal contact,
contact, and foodborne
and foodborne outbreaks
outbreaks are common
are common [186,187].
[186,187]. The prevalence
The prevalence of the
of the disease
disease has changed
has changed globallyglobally as a of
as a result result of improvements
improvements in socioeconomic
in socioeconomic and sanitary
and sanitary condi-
conditions
tions [188].[188]. Children
Children under under the of
the age agefive
of five are typically
are typically asymptomatic,
asymptomatic, but but as they
as they get
get older, the infection symptoms start to show. Fortunately, most patients
older, the infection symptoms start to show. Fortunately, most patients recover within 2 recover within
2months
monthsof ofinfection,
infection,while
while10–15%
10–15% of of patients
patients recur within the first
first 66 months
months and
andan
anacute
acute
infection may be self-limiting. Symptoms range from mild inflammation and jaundice to
abrupt liver failure in older people [189–193]. A virus hardly ever causes persistent in-
fection or liver damage, but undiagnosed chronic infections and the incorrect use of
therapeutic methods based on clinical standards are connected to a higher risk of cirrho-
sis, hepatocellular cancer, and mortality [194]. Supportive care is the cornerstone on
Livers 2023, 3 203

infection may be self-limiting. Symptoms range from mild inflammation and jaundice
to abrupt liver failure in older people [189–193]. A virus hardly ever causes persistent
infection or liver damage, but undiagnosed chronic infections and the incorrect use of
therapeutic methods based on clinical standards are connected to a higher risk of cirrhosis,
hepatocellular cancer, and mortality [194]. Supportive care is the cornerstone on which
therapy is founded. According to the Centers for Disease Control and Prevention and
the American Academy of Pediatrics, all children between the ages of 12 and 23 months
should receive routine vaccinations [195–197]. Antigen detection, monitoring liver enzyme
levels, and antibody screening are the three main components of the HAV laboratory
diagnosis [198–200]. A further benefit of polymerase chain reaction (PCR) technology is
that it has been used to confirm the presence of HAV in potential dietary sources [185].

3.15. Hepatitis B Virus (HBV)

The hepatitis B virus (HBV) has infected 2 billion individuals worldwide, 360 million of
them have a chronic infection, and 600,000 of them pass away each year from hepatocellular
carcinoma or liver illness associated with HBV [201].
The endemic hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma and
chronic liver damage in many parts of the world [202,203]. The treatment for HBV differs
depending on the stage of the illness. Liver transplantation is the best treatment choice for
patients with end-stage liver disease [204], although interferons or nucleoside analogues
are frequently used to treat HBV infection in chronic patients [205]. However, the majority
of HBV patients do not have access to treatment because of the barriers to care and the high
cost of antivirals [206]. These issues have prompted researchers to reevaluate therapeutic
modalities, such as nutritional therapy. According to recent research, hepatitis B patients
may benefit from resveratrol, vitamin E, lactoferrin, selenium, curcumin, luteolin-7-O-
glucoside, moringa extracts, chlorogenic acid, and epigallocatechin-3-gallate [207]. Most of
these nutrients have been examined in vitro and in animal models for their anti-HBV effects.
These nutrients have been linked to a variety of antiviral and hepatoprotective mechanisms,
including the induction of autophagosomes, regulation of metabolic homeostasis, epige-
netic control, activation of the p53 gene [208], inhibition of oncogenes, inhibition of virus
entry [209], and activation of antioxidant and anti-inflammatory pathways [210]. In conclu-
sion, scientific data suggests that nutrition can have a direct impact on HBV replication,
transcription, and expression of viral antigens. In the future, these nutrients might be taken
into account to create a suitable dietary treatment for hepatitis B patients [207].

3.16. Nutritional Considerations to Prevent and Manage Viral Hepatitis A and B

Patients with viral hepatitis, both acute and chronic, frequently have changed metabo
lisms that cause them to eat less and become malnourished. These patients may have higher
morbidity and mortality rates if they are suffering from protein and calorie deficiencies.
Malnutrition’s prognosis and overall survival are improved by early detection and timely
treatment [211].
Sanitation and hygiene: International travellers are more likely to contract hepatitis A
(HAV) through handling or consuming contaminated raw fruits and vegetables. HAV must
be rendered inactive by boiling or heating food and water for 1 min at 85 ◦ C [185 ◦ F] [212].
Avoiding game foods and tainted seafood is important, as the majority of acute HAV
infections are brought on by eating infected seafood [212].
The microbial pathogens in saltwater can concentrate when shellfish are harvested
from waters that have been polluted by sewage. Clams and oysters, for example, that have
been harvested from the coastline are especially likely to be pathogenic. Animal products,
particularly wild game and contaminated pig, as well as tainted seafood and produce, have
all been found to contain hepatitis E (HEV) [213,214].
Avoiding iron supplements and foods strong in iron is also important, as patients’
hepatitis C progresses as a result of faster hepatic iron intake and the oxidative stress
Livers 2023, 3 204

brought on by free radical generation stimulated by iron. A low-iron diet and phlebotomy
help these individuals’ risk of developing hepatocellular carcinoma (HCC) [215].
Supplemental nutrition might also be necessary. Weight loss has been documented
in 11–29% of treated patients who receive interferon treatment. Treatment with interferon
can cause digestive symptoms, which can then lead to a decrease in appetite and food
consumption [216].
A diet with reduced fat and cholesterol may be beneficial. Hepatic steatosis risk is
increased by chronic hepatitis C (CHC) infection [212,216]. This issue is exacerbated by a
larger dietary cholesterol intake, which is also linked to the advancement of liver disease
brought on by hepatitis C. Patients with CHC who followed a diet low in fat (23 percent of
calories) and cholesterol (185 mg/day) saw a decline in liver enzyme elevations as well as
an improvement in immunological abnormalities [TH17/Treg balance], which are known
to contribute to liver inflammation [217].
Adequate vitamin D status is important as patients with chronic liver illness frequently
have vitamin D shortage and may have a harder time converting vitamin D to its active
form [218]. In patients with CHC, vitamin D levels and viral load appear to be inversely
correlated. Vitamin D supplementation increases the likelihood that a patient will respond
to treatment, but deficiency dramatically reduces the likelihood of a sustained virological
response to pegylated interferon and ribavirin [218,219].
Avoiding B12 status extremes is useful because patients with hepatitis C are better able
to eliminate the virus from their systems when their B12 levels are adequate. However, very
high serum B12 levels have been linked to hepatitis C RNA levels and may also promote
viral replication [220].
Chronic hepatitis C and coffee intake are associated because drinking coffee may be
beneficial as it decreases oxidative DNA damage, increases the death of virus-infected
cells, stabilises chromosomes, and decreases fibrosis [221]. For people with nonalcoholic
fatty liver disease (NAFLD), a feasible addition to therapy is a moderate daily intake of
unsweetened coffee [222].
We can summarize the information about all mentioned diseases in Table 1, which
describes the nutrition dysregulated and the nutrition management required for each
disease.

Table 1. Describing the nutrition dysregulated and the nutrition management required.

Hepatic Dysfunction Required Dietary Modifications N. Reference

Patients with (ALF: acute liver failure,
ASH: alcoholic steatohepatitis) and REE is usually increased (REE, resting energy expenditure) [222]
cirrhosis
patients with NAFLD (non-alcoholic fatty
Normal REE [222]
liver disease)
Malnutrition can impair the whole spectrum of hepatic
Malnutrition and sarcopenia metabolic-functions, and malnutrition alone can cause severe fatty [223]
liver but is not known to cause chronic liver disease
Patients with chronic liver diseases and
Should receive a total energy supply of 1.3*REE [224]
have a sedentary life style
Livers 2023, 3 205

Table 1. Cont.

Hepatic Dysfunction Required Dietary Modifications N. Reference

A severe disorder of carbohydrate, protein, and lipid metabolism
should be expected in ALF due to subtotal loss of hepatocellular
Acute Liver
function and ensuing multi-organ failure. This disorder is
Failure [72]
characterised by impaired hepatic glucose production and lactate
(ALF)
clearance as well as protein catabolism linked to
hyper-aminoacidemia and hyper-ammonemia
Acute Liver In ALF patients, obesity is associated with an increased risk of death
Failure or need for transplantation and increased mortality ofter [225]
(ALF) transplantation
In patients with mild hepatic ONS “oral nutritional supplements” should be used when feeding
[226]
encephalopathy goals cannot be attained by oral nutrition alone
In patients with severe hyper-acute
Nutritional protein support can be deferred for 24–48 h until
disease with hepatic
hyper-ammonemia is controlled. When protein administration is
encephalopathy and highly elevated [227]
commenced, arterial ammonia should be monitored to ensure no
arterial ammonia who are at risk of
pathological elevation occurs.
cerebral edema
Acute Liver
Should receive EN via nasogastric
Failure [228]
Inaso-jejunal tube
(ALF) who cannot be fed orally
ALF patients without malnutrition should be provided with
EN: enteral nutrition in Acute Liver
nutritional support (preferentially EN) when they are considered [72]
Failure (ALF)
unlikely to resume normal oral nutrition within the next 5 to 7 days
EN: enteral nutrition in Acute Liver Standard enteral formulas can be given, as there are no data
[229]
Failure (ALF) regarding the value of a disease specific composition
In malnourished ALF patients, EN and/or PN should be initiated
PN: parenteral nutrition in Acute Liver
promptly, PN should be used as second-line treatment in patients [228]
Failure (ALF)
who cannot be fed adequately by oral and/or EN
Individualized nutrition counselling should be used in order to
Alcoholic Steatohepatitis (ASH) [230]
improve food intake
ONS should be used when patients with severe ASH cannot meet
Alcoholic Steatohepatitis (ASH) their caloric requirements through normal food in order to improve [231]
survival:
1. In order to increase survival and reduce morbidity in patients
with severe ASH who are unable to meet their caloric needs
through conventional diet and/or ONS, EN should be utilised
2. EN can be used in people with severe ASH to make sure they 1. [231]
EN: enteral nutrition in Alcoholic get enough protein and energy without raising their risk of 2. [232]
Steatohepatitis (ASH) developing hepatic encephalopathy 3. [233]
3. Standard formulae, preferably those with high energy density
(1.5 kcal/mL), should be utilised for ONS or EN in patients
with severe ASH

1. Patients with severe ASH who are moderately or severely

malnourished and who are unable to receive enough nutrition
through oral and/or enteral routes must start receiving PN
PN: parenteral nutrition in Alcoholic 1. [234]
right away
Steatohepatitis (ASH) 2. [235]
2. Daily administration of electrolytes, trace minerals, and water-
and fat-soluble vitamins, starting at the start of PN, is required
to meet needs
Livers 2023, 3 206

Table 1. Cont.

Hepatic Dysfunction Required Dietary Modifications N. Reference

1. Patients with NAFL/NASH who are overweight or obese must

adhere to a weight-loss plan to lower their risk of comorbidity
and to improve their liver enzyme levels and histology
(necroinflammation)
2. To improve steatosis and liver biochemistry in overweight or
obese NAFL INASH patients, a weight loss of 7–10% should be 1. [236]
the goal; a loss of more than 10% should be the goal to improve 2. [237]
Non-alcoholic Steatohepatitis (NASH) fibrosis 3. [238]
3. Regardless of the macronutrient composition, a hypocoloric 4. [239]
diet must be followed in order to lose weight, according to
current obesity guidelines
4. After weight loss diets and extensive lifestyle therapies have
failed in otherwise eligible obese NAFL INASH patients
without cirrhosis, bariatric surgery should be suggested

1. To improve liver enzymes and histology in nondiabetic persons

with histologically proven NASH, vitamin E (800 /U
a-tocopherol daily) should be administered
2. Antioxidants, such as those found in vitamins (resveratrol,
anthocyanin, and bayberries), cannot be advised for the
treatment of NAFL or NASH until more information on their
1. [240]
efficacy is known.
2. [241]
3. Until more information on their effectiveness is available,
Non-alcoholic Steatohepatitis (NASH) 3. [242]
omega3 fatty acids cannot be advised for the treatment of
4. [243]
NAFL or NASH
5. [244]
4. Patients with NAFL or NASH may benefit from nutritional
supplements, including specific probiotics or synbiotics to boost
their liver enzymes
5. Patients with intercurrent illnesses who are obese and receiving
EN or PN should have a target energy intake of 25 kcal/kg
IBW/d and a higher target protein intake of 2.0–2.5 g/kg IBW

1. It should be expected that individuals with cirrhosis will have a

high prevalence of malnutrition, protein depletion, and trace
element deficit
2. To improve patients’ long-term outcome/survival, specific 1. [245]
dietary counselling should be applied to cirrhotic patients 2. [246]
employing a multidisciplinary team 3. [247]
3. To improve the status of total body protein, a late-night snack 4. [247]
should be encouraged. This will help to shorten periods of 5. [248]
famine 6. [249]
4. Patients with cirrhosis who are malnourished or experience 7. [249]
Liver Cirrhosis (LC) higher energy consumption (such as acute complications or 8. [250]
refractory ascites) should consume more energy 9. [251]
5. Increased energy intake is not advised for individuals who are 10. [252]
overweight or obese who have cirrhosis 11. [253]
6. In obese patients with cirrhosis, lifestyle interventions aimed at 12. [224]
weight loss’s positive effects, which include reduced portal 13. [254]
hypertension 14. [255]
7. Patients with compensated cirrhosis who are not malnourished 15. [256]
need to consume 1.2 g/kg/d of protein
8. Patients with cirrhotic malnutrition and/or sarcopenia should
consume 1.5 g·kg−1 •ct1 of protein to replenish their bodies
Livers 2023, 3 207

Table 1. Cont.

Hepatic Dysfunction Required Dietary Modifications N. Reference

9 Patients with cirrhosis who are malnourished and have reduced

muscle mass should consume 30–35 kcal per kg and 1.5 g of
protein per kg daily
10 Protein catabolism is increased in cirrhotic patients with HE,
hence protein intake shouldn’t be restricted
11 Vegetable proteins or BCAAs (0.25 g·kg−1 •ctJ) should be given
orally in cirrhotic patients who are protein “intolerant” to help
them consume enough protein
12 To increase event-free survival or quality of life in patients with
advanced cirrhosis, long-term oral BCAA supplements 0.25
g•kg-Lcf l) should be administered
13 When prescribing a low-sodium diet, the moderate benefit in
the treatment of ascites should be weighed against the
increased risk of even less food consumption. After reducing
sodium intake, caution should be exercised to prevent
impairing the diet’s palatability
14 EN should be carried out on cirrhotic patients who cannot be
fed orally or who do not meet the nutritional aim by oral diet
15 In cirrhotic patients, PN should be utilised if oral and/or EN
are ineffective or impractical

1. Patients with liver cirrhosis who are scheduled for elective

surgery or who are on the transplant list should have their
nutritional condition promptly examined and assessed in order
to address malnutrition prior to surgery and consequently
enhance body protein status
2. Aim for a total daily protein intake of 1.2–1.5 g·kg−1 ·d−1 and a
total daily energy intake of 30–35 kcal•Jrg-l.J−1 (126–147
kcal•Jrg-l.J−1 ). These ranges cover suggested intakes based on
1. [257]
therapy objectives, such as nutritional status maintenance or
2. [258]
improvement
Liver Transplantation (LTx) and Surgery 3. [259]
3. Patients who are obese can get EN and/or PN with an
4. [260]
enhanced goal protein intake of 2.0–2.5 g·kg−1 IBW and a target 5. [261]
energy intake of 25 kcal·kg−1 IBWJ-1
4. The dietary management plan for NASH patients who are
overweight or obese and planned for elective surgery should be
followed
5. No suggestions can be offered for the conditioning of donors or
organs using certain feeding regimens, such as intravenous
glutamine or arginine, with the goal of reducing
ischemia/reperfusion damage

1. To lower the risk of infection after LTx, normal food and/or EN

should be introduced within the first 12 to 24 h following
1. [262]
Liver Transplantation (LTx): Preoperative surgery.
2. [263,
phase 2. Aim for an energy intake of 30–35 kcal•krr1•ct1 (126–141 kJ
264]
•krr1 •ct) and a protein intake of 1.2–1.5 g kg”1 •ct1 beyond the
immediate postoperative phase
Livers 2023, 3 208

Table 1. Cont.

Hepatic Dysfunction Required Dietary Modifications N. Reference

1. To lower the rate of infection after transplantation, enteral
formula should be given in conjunction with specific probiotics
2. Patients with HE who require EN can take formulations that are
BCAA-enriched
1. [265]
3. When oral nutrition or EN is neither possible nor practical, PN
Liver Transplantation (LTx): 2. [264]
should be preferred to no feeding in order to lower
postoperative phase 3. [266]
complication rates, the duration of mechanical ventilation, and
4. [267]
the length of hospital stay
4. When the cough and swallow reflexes are impaired, EN is
contraindicated, or it is not practical to employ EN, PN should
be administered in patients with unprotected airways and HE

4. Conclusions
Patients with chronic liver dysfunction (CLD) should have as their nutritional goals
the restoration of liver function, prevention of related comorbidities, and overcoming
malnutrition brought on by nutritional inadequacies. Patients with cirrhosis are more likely
to experience micronutrient deficiencies, patients with hepatocellular disease are more
likely to experience calorie and protein deficiencies, and patients with cholestasis liver
disease are more likely to experience calorie deficits and an increased risk of fat-soluble
vitamin deficits. Because the administration of dietary supplements has been shown
to be associated with a decreased risk of infection, in-hospital mortality, and improved
liver function, early detection of micronutrient and macronutrient deficiencies is crucial.
All chronic liver disorder (CLD) patients are screened to determine who is at risk for
complications that can be avoided.

Author Contributions: Conceptualization, A.N.A.-F. and N.A.B., investigation, K.M.A., A.-H.A.A.

and E.M.E.; resources, A.N.A.-F., N.A.B., K.M.A., A.-H.A.A. and E.M.E.; writing—original draft
preparation, A.N.A.-F. and E.M.E.; writing—review and editing, A.N.A.-F. and E.M.E.; visualization,
A.N.A.-F., N.A.B., K.M.A. and A.-H.A.A.; supervision, E.M.E. All authors have read and agreed to
the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

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