ALD

Alcoholic Liver Disease

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What is ALD?

Alcoholic liver disease (ALD) is an umbrella term used to refer a spectrum of liver injuries caused by the overconsumption of alcohol, leading to inflammation, and scarring of the liver tissue as a result of progressive destruction and regeneration of liver parenchyma. The spectrum of alcoholic liver disease includes alcoholic fatty liver disease, alcoholic hepatitis, and cirrhosis. It is an increasingly common condition, accounting for over a third of liver disease related deaths in the UK and rising. In the early phases of disease, it is often asymptomatic, however without early action and cessation of alcohol consumption, it can progress and become fatal.

Pathophysiology

Alcohol primarily metabolised in the liver, which is why alcohol overconsumption can lead to such devastating effects on the hepatic system.

• Alcohol dehydrogenase (ADH) is the primary system which converts alcohol to acetaldehyde, and this cannot be upregulated once it reaches its limit.

• Cytochrome P450 2E1 (CYP2E1) also converts alcohol to acetaldehyde, and this enzyme tends to be upregulated in heavy alcohol consumers.
• Acetaldehyde is a highly reactive toxic metabolite which contributes to progressive liver damage as alcohol consumption increases.

Alcoholic fatty liver disease-- Triglycerides accumulate amongst liver tissue as a result from processes which are enhanced in alcohol over-consumption. This process can be enhanced if a person is also overweight/obese, leading to compounding non-alcoholic related fatty deposition in the liver. At this stage of ALD, it is potentially reversible if managed effectively. Alcoholic hepatitis-- this is a stage where there is combined liver steatosis (harmless build-up of fat) and inflammation, with focal regions of liver necrosis. Alcoholic cirrhosis-- progressive process of hepatic tissue inflammation, degeneration and regeneration leads to excessive fibrogenesis and scarring of the liver. This reduces the functional capacity of the liver, as well as distorting the normal architecture, leading to micronodules in the liver

Alcoholic hepatitis

30%

present in patients who overconsume alcohol

clinical features

70%

Hepatomegaly present in ALD patients

31%

reported prevalence of spider angiomas in patients with liver cirrhosis

30%

Dupuytren's contracture present in ALD

>50%

As inflammation and scarring occurs, alcoholic cirrhosis progresses and can lead to portal hypertension. this can result in Ascites (within 10 years of the diagnosis of cirrhosis, >50% of patients will develop this))

Other features

Early on, patients tend to present with non-specific signs and symptoms

• Fatigue • Malaise • Abdominal pain • Anorexia • Weakness • Nausea and/or vomiting

As patient deteriorates signs and symptoms progress. They can differ depending on severity

• Alcoholic hepatitis• Jaundice (common) • RIQ pain (common) • Hepatomegaly • Palmar erythema • Peripheral oedema • Clubbing • Dupuytren's contracture • Pruritis • Xanthomas • Spider naevi

As the liver metabolises estrogen, with progressive liver damage estrogen levels rise which can lead to a variety of estrogenic effects including:

• Gynaecomastia and testicular atrophy (in males)
• Loss of body hair
• Amenorrhoea (in females)
• Loss of libido

Inflammation and scarring occurs, alcoholic cirrhosis progresses, leading to portal hypertension resulting in its own variety of features

• Ascites
• Dilated veins (e.g. caput medusae)
• Variceal bleeding and haemorrhage
• Splenomegaly

Investigations

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

ALT----Raised in hepatocellular pattern of liver injury, including ALD, Occasionally also raised in skeletal muscle injuryAST----Raised in hepatocellular pattern of liver injury, including ALD, May also be raised in acute cardiac or skeletal muscle injury

The ratio of AST:ALT is of benefit in acute alcoholic hepatitis.

AST: typically 100-200IU/L ALT: May be normal or only mildly raised, even in severe cases. Ratio of AST:ALT is normally >2, a ratio of >3 is strongly suggestive of acute alcoholic hepatitis

Serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)

GGT----Raised in association with chronic heavy alcohol consumption (>70% of individuals), Not specific to ALD ALP----Raised in cholestatic pattern of liver injury May be normal, or if raised, may indicate cholestasis related to ALD

Serum Bilirubin

May be elevated in liver disease, whether caused by ALD or otherwise. Liver disease (many types, including ALD) will have elevated conjugated bilirubin

Serum Albumin

Reduced serum albumin Liver synthesises albumin, therefore low levels indicates diminished synthetic function

Serum Prothrombin time, INR

Elevated prothrombin time/INR Indicates diminished synthetic function of liver

Liver Ultrasound

May be used to differentiate abnormal LFTs caused by other pathologies If known ALD and cirrhosis, is useful to screen for hepatocellular carcinoma development

Liver Biopsy

Not usually necessary for ALD due to invasiveness of procedure If performed, may be percutaneous or transjugular Histological findings vary depending on stage of ALD

Management

Ideally, the aim of treatment in ALD is to prevent and/or slow the progression of liver damage, which can be fatal. GENERAL MEASURES Alcohol abstinence---- Likely the most important part of management is the complete cessation of alcohol consumption. This not only slows the progression of disease, but improves the long-term survival for patients, even in the late stages of disease where there is existing cirrhosis with de-compensationWeight loss---- This is particularly important in overweight or obese patients, where a component of liver disease may be caused by non-alcoholic fatty liver Vaccinations---- In the absence of past or current infection, hepatitis A and B immunisations should be provided to reduce likelihood of infection and compounding liver damage Nutrition---- A high protein dit should be instituted, particularly in those with alcoholic hepatitis (1-1.5g of protein/kg for adequate recovery) Consider feeding tube for enteral feeding if anorexia or altered mental status

Treatments

ALCOHOL WITHRAWAL

ACUTE ALCOHOLIC HEPATITIS

The standard for treating acute alcohol withdrawal is benzodiazepines (e.g. diazepam)

• Quick-acting benzodiazepine (e.g. lorazepam) for alcohol withdrawal seizures
• Oral lorazepam is the first-line treatment for delirium tremens in alcohol withdrawal

END-STAGE ALD

• glucocorticoids (e.g. prednisolone) are considered the standard of care for acute alcoholic hepatitis and are often used
• May improve short-term survival, but are unlikely to show a long-term benefit
• Pentoxifylline can be used as an alternative to glucocorticoids if they are contraindicated (e.g. hepatitis B viral infection, tuberculosis, other serious infection)

• In patients with end-stage ALD (cirrhosis with decompensation), liver transplantation can be considered
• Usually must be alcohol free for >6 months