Alcoholic Liver Disease

Fig. 13.1
Mechanisms for ALD: “2nd Hit”

Oxidative Stress and Lipid Peroxidation

Oxidative stress is an imbalance between pro-oxidants and antioxidants (Reviewed-[5]). Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are products of normal metabolism and can be beneficial to the host (e.g., by contributing to bacterial killing) [5]. Overproduction of ROS and/or RNS or inadequate antioxidant defenses (e.g., low levels of vitamins, selenium, mitochondrial glutathione), or both, can lead to liver injury. The stimulus for oxidative stress in the liver comes from multiple sources. In hepatocytes, CYP2E1 activity increases after alcohol consumption—in part because of stabilization of messenger RNA (mRNA). Similarly, CYP2E1 activity is increased in NAFLD. The CYP2E1 system leaks electrons to initiate oxidative stress [5]. CYP2E1 is localized in the hepatic lobule in areas of alcohol-induced liver injury. Moreover, overexpression of CYP2E1 in mice and in HepG2 cells (a human hepatoma cell line) in vitro leads to enhanced alcohol hepatotoxicity. Nonparenchymal cells and infiltrating inflammatory cells (e.g., polymorphonuclear neutrophils) are another major source of pro-oxidants that are used for normal cellular processes, such as killing invading organisms. Infiltrating neutrophils use enzyme systems such as myeloperoxidase to generate hypochlorous acid (HClO–, a halide species that causes oxidative stress) and RNS.

Nutritional Abnormalities

Moderate/severe alcoholic hepatitis (AH) is regularly associated with malnutrition. In large VA Cooperative Studies, virtually every patient with AH had some degree of malnutrition [6]. Almost 50 % of severe AH patients’ energy intake came from alcohol. Although calorie intake was frequently adequate, intake of protein and critical micronutrients was often deficient. In these VA cooperative studies, the severity of liver disease correlated with malnutrition. Patients were given a balanced 2500-kcal hospital diet. Voluntary oral food intake correlated in a stepwise fashion with 6-month mortality data. Thus, patients who voluntarily consumed more than 3000 kcal/day had virtually no mortality, whereas those consuming less than 1000 kcal/day had greater than 80 % 6-month mortality.

A classic example of micronutrient deficiency in ALD is zinc deficiency [7, 8]. Alcoholics regularly have decreased dietary intake of zinc, as well as poor absorption and increased excretion. Moreover, oxidative stress causes zinc to be released from critical zinc-finger proteins. These cumulative effects negatively impact critical zinc-finger functions. This can lead to liver injury, altered fat metabolism, impaired liver regeneration, etc., as well as produce classic clinical manifestations of zinc deficiency in humans such as night blindness or skin lesions.

The type of dietary fat consumed also appears to play an important role in the pathogenesis of ALD. Several studies have shown that dietary saturated fat protects against alcohol-induced liver disease in rodents, whereas dietary unsaturated fat, enriched in linoleic acid (LA), promotes alcohol-induced liver damage [9]. The mechanism(s) by which the combination of LA and alcohol promotes liver injury are not fully understood. LA is the most abundant polyunsaturated fatty acid in human diets and in human plasma and membrane lipids. Dietary intake of LA has more than tripled over the past century. LA can be enzymatically converted to bioactive oxidation products, OXLAMs, primarily via the actions of 12/15-lipoxygenase (12/15-LO), or non-enzymatically via free radical-mediated oxidation response to oxidative stress. OXLAMs (either alone or in conjunction with ethanol) can induce increased gut permeability and hepatic mitochondrial dysfunction in experimental ALD. Obesity can also accelerate ALD. As noted above, high fat diets rich in linoleic acid worsen ALD. We also have preliminary research showing that high fructose (sugared pop) diets worsen experimental ALD.

Intestinal Barrier Dysfunction/Microbiota

Alcohol, and specifically its metabolite acetaldehyde, disrupts tight junction proteins and increases gut permeability both in vitro and in vivo; and increased endotoxin levels are regularly observed in rodent models and in humans with ALD. Endotoxin stimulates the production of TNF and other proinflammatory cytokines through Toll-like receptor (TLR4) signaling, which plays a critical role in the development and progression of ALD (Fig. 13.2). Other bacteria-derived toxins, such as peptidoglycan and flagellin, may also impact TLR signaling and proinflammatory cytokine production [10]. Indeed, injected peptidoglycan increases liver injury/inflammation in alcohol-fed compared to control-fed mice, and ethanol feeding increases peptidoglycan levels [10, 11]. Moreover, chronic alcohol feeding increases hepatic TLRs and thus sensitizes hepatocytes to inflammation/injury induced by translocation of gut derived bacteria/toxins. Endotoxin not only plays a role in the fatty liver and liver injury of experimental ALD, but it also appears to play a role in hepatic fibrosis. In vitro assays as well as in vivo mixed chimerism studies show that endotoxin primes stellate cells for Transforming Growth Factor-β (TGF)-stimulated collagen production (reviewed-[12]). Thus, LPS also plays a role in fibrosis induction and progression.


Fig. 13.2
Altered gut: liver axis in ALD

Alterations in the gut microbiome likely play a major role in the development/progression of gut barrier dysfunction, endotoxemia, and liver injury/fibrosis in ALD [13]. We showed that ethanol consumption caused a time-dependent decline in the abundance of both Bacteriodetes and Firmicutes, which was accompanied by a proportional increase in Actinobacteria and Proteobacteria [14]. The stability of the normal intestinal microbiome is influenced by several factors in the luminal environment including gastric acidity, gut motility, bile salts, immunological defense factors, colonic pH and competition between microorganisms for nutrients and intestinal binding sites. An altered luminal environment may lead to modifications in the microbial composition by supporting the growth of specific genera. Thus, a major increase of Alcaligenes (an alkaline tolerant genus) correlated with an increase in fecal pH and a decrease in fecal short-chain fatty acids (SCFA). Further, some SCFAs (e.g., butyrate) have important signaling functions and epigenetic consequences, and are a critical energy source for the intestine [15]. These alterations in gut bacteria and their metabolites represent not only major mechanisms for ALD but also therapeutic targets for intervention with agents such as probiotics and prebiotics.

Other Mechanisms

There are multiple other mechanisms that are likely important in ALD. ER stress, or the unfolded protein response (UPR) pathway, is activated by conditions of protein overload or increased unfolded proteins. Once triggered, this signaling pathway results in adaptation and recovery of homeostasis; however, severe or prolonged ER stress can ultimately result in cell death. Alcohol-induced ER stress is seen in experimental alcohol-feeding models in mice, micropigs, rats, and zebrafish [1619]. ER stress has been also been reported in human patients with ALD [20, 21].

Fibrin/Extracellular Matrix plays a critical role in the progression of ALD. Fibrosis results from an imbalance between production and resorption of extracellular matrix (ECM) caused by a complex interplay between activation/transdifferentiation of hepatic stellate cells (HSCs), profibrogenic growth factors and cytokines, and alterations in the fibrin coagulation system. Hepatic injury in experimental models of liver disease often involves dysregulation of the fibrin cascade, resulting in the formation of fibrin clots that can cause hepatocellular death and induce inflammatory signaling in the liver. Inhibition of fibrinolysis by plasminogen activator inhibitor-1 (PAI-1) can cause fibrin-ECM to accumulate, even in the absence of enhanced fibrin deposition by the thrombin cascade. An imbalance in coagulation factors as well as elevated PAI-1 levels and hypofibrinolysis are common in patients with ALD [22].

Both genetic and epigenetic factors are important for disease pathogenesis and progression in ALD. The genetic variations are often associated with conformational changes in protein structures and functions due to single nucleotide polymorphisms (SNPs), whereas epigenetic changes are phenotypic changes due to altered gene expression without affecting the underlying DNA sequence. In ALD, polymorphisms of alcohol metabolizing enzymes such as ADH and CYP2E1, as well as antioxidant enzymes and cytokine coding genes, have shown strong correlation with the progression of ALD [23]. Important epigenetic modifications in ALD include microRNAs, DNA methylation, and histone modifications.

Clinical Features of Alcoholic Liver Disease


Most patients with alcoholic steatosis are asymptomatic, although some may have nonspecific symptoms such as abdominal fullness or fatigue. Patients with alcoholic hepatitis frequently have abdominal fullness (up to 80–90 % of cases), jaundice (37–60 %), fever (23–56 %), abdominal distention (35–57 %), gastrointestinal bleeding (10–23 %), changes in consciousness (18–45 %), and abdominal pain [24, 25].

Patients with compensated cirrhosis are frequently asymptomatic, but they may have anorexia, nausea, weight loss, fatigue, weakness , abnormal menstruation, loss of libido, muscular cramps, and/or difficulty concentrating on mental tasks. Patients with decompensated cirrhosis are often jaundiced, have evidence of muscle wasting, feel weak, and develop fluid retention with edema and abdominal distention. In addition, many complain of itching and others present with hematemesis or melena. Easy bruising, altered sleep pattern, and confusion are also frequent complaints.

When obtaining the history, it is important to assess the duration and amount of alcohol consumption. The most commonly employed validation tool to detect hazardous alcohol consumption is the Alcohol Use Disorders Identification Test (AUDIT) . A score of 8 or more (7 or more for adults over age 65) indicates alcohol use disorder or alcohol dependence (sensitivity >90 % and specificity >80 %). A shorter screening can be done with the 3-question AUDIT-C tool that gives 0–4 points for the answer to each question and is considered positive for males with a score of ≥4 points and for females with a score of ≥3 points [26], with moderate risk being 3–5 points, high risk 6–7 points and severe risk 8–12 points.

The National Institute on Alcohol Abuse and Alcoholism has a single-question test: “How many times in the past year have you had 5 or more drinks for males, or 4 or more drinks for females, in a day?” An answer of one or more times constitutes a positive test. This question has a sensitivity of 82 % and specificity of 79 % for unhealthy alcohol use [27]. A less powerful tool is the CAGE questionnaire (the name is an acronym of its four questions) in which two or more positive answers indicate hazardous alcohol use [28].

Depending on individual susceptibility, alcohol-induced organ injury requires alcohol consumption of ≥20 g/day for females or ≥40 g/day for males; however, larger amounts than this threshold are usually needed. More than 60 % of individuals who drink more than 60 g of alcohol a day will develop fatty liver [29, 30]. A “standard” alcohol drink has 14 g of alcohol and is equivalent to 12 oz. of beer, 5 oz. of wine, 8–9 oz. of malt liquor, or 1.5 oz. of distilled spirits (whiskey, bourbon, etc.). The value of the alcohol intake history depends on the recall ability and the truthfulness of the patient. The NIAAA has highly valuable alcohol abuse information on its website entitled, “Rethinking Drinking” [http://​rethinkingdrinki​ng.​niaaa.​nih.​gov/​].

Physical Exam

On physical exam, signs of fatty liver can range from mild hepatomegaly, with blunting of the normally sharp liver edge, to massive hepatomegaly. In patients with alcoholic hepatitis, hepatomegaly (80–90 % of cases), jaundice (40–60 %), and fever (23–56 %) are very common. If the injury is severe, the patients will have ascites, hepatic encephalopathy, splenomegaly, evidence of muscle wasting, and sometimes gastrointestinal hemorrhage with portal hypertensive gastropathy or gastro-esophageal varices [24, 25].

Patients with compensated cirrhosis often have hepatomegaly with hard liver consistency and a nodular surface. They may also have splenomegaly and, less often, right upper quadrant pain. Less common findings include gynecomastia and testicular atrophy [31], amenorrhea, parotid enlargement [32], cutaneous spider angioma [33], Dupuytren’s contractures [34], digital clubbing [35] (found especially in patients with hypoxemia related to hepatopulmonary syndrome), palmar erythema, and nail changes.

Patients with decompensated cirrhosis may also have mental changes of hepatic encephalopathy with variable degrees of confusion with or without asterixis, jaundice, ascites, and peripheral edema. Some patients will have evidence of gastrointestinal bleeding or other organ damage, including alcoholic gastritis or pancreatitis, alcoholic neuropathy or, less commonly, alcoholic cardiomyopathy. Signs of alcohol withdrawal are common in patients with alcoholic hepatitis who have recently discontinued alcohol.


Patients with ALD should have a complete blood count, international normalization ratio (INR), comprehensive metabolic panel, and GGT. Because there is the risk of overlapping viral hepatitis, serologies for current infection or past exposure to hepatitis A, B, and C are advised. Patients who are not immune should be vaccinated against hepatitis A and B. If the ALT is elevated, a full workup for other causes of liver disease and cirrhosis is also advisable because other immune or metabolic causes may be uncovered (Table 13.1).

Table 13.1
Liver Disease Differential and Appropriate Blood Tests


Blood test



A1 antitrypsin deficiency

A1 genotype and levels

Wilson’s disease


Autoimmune Hepatitis


Primary biliary cirrhosis


Hepatitis A

Hepatitis A antibody

Hepatitis B

Hepatitis B surface antigen and core antibody

Hepatitis C

Hepatitis C antibody

Consumption of alcohol in excess of 50 g/day causes elevation of AST (sensitivity 50 %, specificity 82 %) and ALT (sensitivity 35 %, specificity 86 %) [36]. The elevation of AST is typically higher than that of ALT, and 79 % of patients with alcoholic hepatitis have an AST:ALT ratio > 2. Patients with alcoholic hepatitis with ALT > AST frequently have overlapping causes for liver disease, including superimposed viral hepatitis or drug injury (most often acetaminophen). Elevated γ-glutamyl transpeptidase (GGT) is more sensitive for alcohol abuse (56–73 %), but less specific (53–70 %) than carbohydrate deficient transferrin (CDT) or MCV [37]. Using a combination of these tests may be warranted. Elevated bilirubin, in the absence of biliary obstruction, is a marker of the severity of the alcoholic liver injury and is very important as a component of the Maddrey Discriminant Function, MELD score, Glasgow Alcoholic Hepatitis Score, the Lille model and the Child-Turcotte-Pugh Calculator index (discussed subsequently).

Liver Biopsy

In the presence of a history of alcohol abuse associated with typical liver enzyme elevations, diagnosis is very reliable with sensitivity of 91 % and specificity of 97 % [38], and liver biopsy is often not performed. Patients with atypical presentation or those who have markers of other types of liver disease (autoimmune hepatitis, hemochromatosis, viral hepatitis, etc.) are good candidates for liver biopsy. Liver biopsy helps to clarify the diagnosis and will give the stage of disease, which is useful in deciding if surveillance for hepatocellular carcinoma is needed. Patients with cirrhosis require imaging every 6 months.

Natural History and Prognosis

Chronic alcohol consumption can lead to a spectrum of liver injuries which can occur sequentially, separately, or simultaneously in the same patient [39]. Alcoholic steatosis is the initial and most common manifestation of alcoholic liver disease. It is characterized histologically by both microvesicular and macrovesicular fat accumulation within the hepatocytes, with minimal inflammatory response or hepatic fibrosis [40]. Patients with steatosis are usually asymptomatic. They typically have normal to very mild elevations of their liver enzymes, such as GGT, ALT, and AST. Serum bilirubin and markers of hepatic function (international normalized ratio (INR), albumin levels) also tend to be normal. Alcoholic steatosis is reversible with abstinence [41].

Early studies by Dr. Charles Lieber using volunteers demonstrated the relative ease with which alcohol consumption causes fatty liver [42, 43]. Indeed, volunteers who drank heavily (46 % of calories as alcohol) for 1–2 weeks exhibited fatty liver on biopsy.

A subset of people who continue to drink heavily will develop AH. Why only a subset of people develop more advanced and ominous disease is unclear, but probably relates at least in part to risk factors. These risk factors can be modifiable or nonmodifiable (Table 13.2). The most important modifiable risk factor is continued drinking. Nonmodifiable risk factors include sex (females are at higher risk) and genetics (certain polymorphisms, as discussed previously in the Mechanisms section). Alcoholic Hepatitis is a necro-inflammatory process characterized by predominant neutrophilic infiltration, ballooning degeneration of hepatocytes, and hepatocyte necrosis [44]. Acutely, the development of alcoholic hepatitis is associated with a significant increase in mortality and the potential to develop portal hypertension and its complications, even without developing major fibrosis [45]. In the long term, for those who survive, this disease process is associated with an accelerated course of fibrosis progressing to cirrhosis in 40 % of cases [46]. These distinctions in the natural progression of alcoholic liver disease also have therapeutic implications, explaining why a subset of alcoholics with inflammatory features are candidates for treatment with anti-inflammatory agents (i.e., corticosteroids and pentoxifyline) in an attempt to reduce proximal mortality, whereas patients without major inflammatory features may be better candidates for treatment geared toward reducing long-term hepatic injury/cell death, hepatic dysfunction, or possibly enhancing liver regeneration.

Table 13.2
Risk factors

• Continued drinking

• Age, sex

• Race

• Diet/nutrition

• Genetics/epigenetics/family history

• Smoking

• Obesity

• Occupational/Environmental exposure

• Medications/drugs of abuse

• Other liver diseases

Due to the important acute prognostic implications of alcoholic hepatitis and possible subsequent cirrhosis , multiple scoring systems have been developed to assess the severity of liver disease in terms of patient survival in order to assign patients to proven treatment modalities. The Child-Turcotte-Pugh (CTP) , the oldest scoring system, incorporates the serum bilirubin level, albumin level, PT, and the severity of ascites and hepatic encephalopathy in assigning a numerical score that is used to categorize patients (class A = scores 1–6, class B = scores 7–9, class C = scores 10–15), with a higher score denoting more severe disease [47]. It is the most widely used scoring system to evaluate severity of cirrhosis . Since 2002, the United Network for Organ Sharing (UNOS) has utilized the MELD score to grade the severity of liver disease in patients awaiting liver transplant. This represents a more objective analysis, utilizing only the serum bilirubin, creatinine, and INR [48]. This scoring system has been validated in multiple studies to accurately predict the 3 month mortality of patients with liver disease, especially those patients awaiting liver transplantation [49].

The CTP and MELD score are proven modalities to assess the gravity of liver disease due to a variety of causes. However, due to the particularly inflammatory nature and high degree of early mortality associated with acute alcoholic hepatitis , varying scoring systems have been, and continue to be, specifically developed and used in the assessment of this form of liver disease. Since its development in the in the late 1970s, the Discriminant Function (DF) of Maddrey, which incorporates the serum bilirubin and PT, has been widely used to predict short-term mortality in patients with alcoholic hepatitis and to select in an evidence-based manner, those who are likely to benefit from treatment with corticosteroids [50]. Patients are classified into those who have nonsevere alcoholic hepatitis (DF < 32) and those who have severe alcoholic hepatitis (DF > 32). As the proximal early mortality is 10 % versus 30–60 % in the groups with and without treatment, respectively [51], the latter group is usually treated with corticosteroid therapy unless contraindicated [52]. A useful link to calculate 90-day mortality in acute alcoholic hepatitis, based in the MELD score, can be found at http://​www.​mayoclinic.​org/​medical-professionals/​model-end-stage-liver-disease/​meld-score-90-day-mortality-rate-alcoholic-hepatitis. Other specific scoring systems include the Glasgow alcoholic hepatitis score (GAHS) which is a composite of scores related to patient age, leukocyte count, serum urea levels, serum bilirubin level, and PT ratio [53], with a score ≥9 signifying poor prognosis. In this study, patients with both, a DF > 32 and a GAHS > 9, had 28 day survival, if corticosteroid-treated versus corticosteroid-untreated, of 78 % vs. 52 %, and an 84-day survival of 59 % versus 38 %, respectively. If the GAHS was less than 9, there was no difference in outcome between the corticosteroid treated or untreated groups. A more recent scoring system, the ABIC score [(age × 0.1) + (serum bilirubin × 0.08) + (serum creatinine × 0.3) + (INR × 0.8)], has shown promising results in the prediction of 3 month mortality in patients with alcoholic hepatitis [54]. This model stratifies the severity of alcoholic hepatitis as low (score < 6.71), intermediate (score: 6.71–8.99), and high (score ≥ 9.0). Theses scores correspond to a 90 day survival of 100 %, 70 %, and 25 % respectively, and 1-year survival of 97 %, 64 % and 33 % respectively.

The Lille score is unique in that it is not only clinically useful in assessing the severity of patients presenting with alcoholic hepatitis , but it is also used to assess the response of patients with more severe forms of alcoholic hepatitis being treated with systemic corticosteroids. The score includes six variables: age, albumin level, bilirubin level at day 0, bilirubin level at day 7, PT, and the presence of renal insufficiency [55]. A score of <0.45 predicts a 6 month survival of 85 ± 2.5 % while a score >0.45 predicts a 6 month survival of only 25 ± 3.8 % (sensitivity and specificity at 81 % and 76 %, respectively) [56]. Patients with a score of ≥0.45 on day 7 while on therapy with corticosteroids (null responders), which represent close to 40 % of the corticosteroid treated patients, are recommended to be switched over to alternative forms of treatment because they will not benefit from the continuation of corticosteroid therapy.


Interventions for ALD patients reside on a continuum (Fig. 13.3). All patients should control the modifiable risk factors of alcohol use, obesity, and smoking. Most with advanced disease will benefit from treating malnutrition. Some may need pharmacotherapy. Only a few will be transplant candidates, and they are patients with severely decompensated ALD who have stopped drinking.


Fig. 13.3
ALD interventions

Lifestyle Modification

When managing a patient with ALD, steps should be taken to achieve alcohol cessation. Many studies have shown that patients who quit drinking have improved survival; moreover, even cutting back on alcohol consumption can lead to some improvement in liver disease [57]. Brief-interventions, during which a patient has regular conversations with a nurse or physician focusing on feedback, responsibility, advice, empathy, and optimism, have been shown to reduce drinking [58]. Patients should be encouraged to consider behavioral programs such as Alcoholics Anonymous. For patients who continue to crave alcohol despite brief-interventions and attending behavioral programs such as Alcoholics Anonymous, pharmacologic adjuncts can be offered. Baclofen is the only drug for alcohol dependence currently under investigation that has good safety data in patients with cirrhosis , making it a reasonable first-line choice in this patient population [59]. However, data are limited in ALD and more research is required.

Cigarette smoking [60] and obesity [61] are both independent risk factors for fibrosis in ALD and must also be addressed. While a patient may fit the definition of obesity (BMI > 30), he/she may still have concurrent nutritional deficiencies in macronutrients (e.g., protein) or in micronutrients (e.g., zinc), and nutrition must be evaluated.

Nutrition Therapy

Many patients with advanced ALD are malnourished, and liver disease severity correlates with the degree of malnutrition. While visceral proteins (albumin, prealbumin, and retinol binding protein) are the most common laboratory tests used to assess a patient’s nutritional status, these results can be confounded by the underlying liver disease or superimposed infections. Evaluating clinical findings such as muscle wasting, edema, loss of subcutaneous fat, and glossitis/cheilosis are helpful in subjectively identifying protein energy malnutrition (PEM). Nutritional assessments of alcoholic patients can reveal adequate calorie intake. Indeed, in some studies, almost 50 % of patients’ energy intake was from alcohol alone, leading to deficient protein and micronutrient intake [62]. ACG and AASLD guidelines recommend 1.2–1.5 g/kg of protein and 35–45 kcal/kg of body weight in patients with ALD [63]. For a 175 lb patient, that translates to about 96–120 g of protein a day and 2800–3600 cal a day. Adherence to sodium restriction is vital in patients starting to retain fluid (peripheral edema, ascites), which is usually seen in more advanced disease.

Patients with stable cirrhosis have nutritional deficiencies almost as severe as those found in patients with alcoholic hepatitis [64]. The frequency of malnutrition increases with the severity of disease. For example, the risk of profound malnutrition increases from 45 % in patients with Child’s class A to 95 % in those with Child’s C cirrhosis [64, 65]. Patients with cirrhosis who require hospitalization have a substantially higher prevalence of malnutrition compared with general medical inpatients and have significantly longer hospital stays and a twofold higher risk of in-hospital mortality [66]. Even in patients with stable, compensated cirrhosis, malnutrition is associated with higher mortality and complication rates within a year [65, 67].

Hepatic glycogen stores are depleted in patients with cirrhosis. As a result, these patients go into an early starvation mode after only 12 h of fasting compared to 48 h in normal individuals. Thus, even short periods of inadequate nutrition can result in peripheral muscle proteolysis, which contributes to protein malnutrition. Patients with decompensated cirrhosis may also be hypermetabolic. Not surprisingly, the protein intake recommended for patients with cirrhosis is higher than for healthy adults [67, 68]. The positive impact of judicious nutritional supplements in patients with cirrhosis is illustrated by a recent randomized trial showing that a nighttime snack of 700 kcal each evening resulted in an accrual of 2 kg of lean tissue over 12 months [69]. We stress the importance of taking a snack at about 9 pm to all our advanced cirrhotics (Table 13.3).

Table 13.3
Nutritional recommendations for ALD patients

• Evaluate for clinical signs of malnutrition in all ALD patients

• Daily Caloric Intake: 35–40 kcal/kg

• Daily Protein Intake: 1.2–1.5 g/kg

• Evening Snack of 700 cal and 26 g of protein for advanced disease

• Avoid n-6 unsaturated fats (linoleic acid)

• Multivitamin in most patients

  – Zinc sulfate 220 mg

  – Magnesium oxide 400 mg

The increased nutritional requirements and the vulnerability to early starvation in cirrhotic patients underscore the importance of avoiding protein restriction in patients with encephalopathy. Prolonged protein restriction has no beneficial effect on encephalopathy and can be nutritionally catastrophic [64, 67, 70]. If, despite appropriate medical therapy, standard enteral formulas lead to encephalopathy, a branched chain amino acid-enriched formula can be given as a supplement to meet nitrogen needs [64, 68].

Patients with alcoholic liver disease also may have a plethora of vitamin and mineral deficiencies [64, 65]. In addition to the commonly recognized deficiencies in folate and B vitamins, deficiencies in fat soluble vitamins (A, D, and E) and minerals (magnesium, selenium, and zinc) are common causes of symptoms and physical findings in these patients [65]. Zinc deficiency, for example, may be an important component of the skin lesions, night blindness, mental irritability, confusion and hepatic encephalopathy, anorexia, altered taste and smell, hypogonadism, and altered wound healing so commonly seen in patients with alcoholic liver disease [8]. Assessment and judicious corrections of each of these deficiencies is an important aspect of the care of these patients. We advise that most patients take a multivitamin and we frequently supplement with zinc sulfate 220 mg daily, as well as magnesium oxide 400 mg daily.

Drug Therapy for Severe Alcoholic Hepatitis

A host of drugs have been tried in clinical trials to treat AH or, in some cases, alcoholic cirrhosis, and most have been ineffective (Reviewed-[1, 7177]). Antioxidants of a variety of types including vitamin E and antioxidant cocktails have not proven to be effective in AH [73, 75, 77]. Lecithin was used in a large VA Cooperative Study to combat alcoholic fibrosis without statistically significant benefit [72]. Most recently, specific anti-TNF drugs have been ineffective in AH. Other drugs used in large trials are listed in Table 13.4 [71].
Nov 20, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Alcoholic Liver Disease

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