Page created on April 11, 2022. Last updated on April 23, 2022 at 16:12

Metabolic associated/non-alcoholic fatty liver disease does not have a topic, but is imo important. It’s kinda covered in pathology.

Alcoholic liver disease

Introduction and epidemiology

Alcoholic liver disease (ALD) is an umbrella term for liver conditions caused by significant and chronic alcohol abuse. It initially causes liver steatosis, which progresses to alcoholic hepatitis to cirrhosis unless alcohol consumption stops.

Almost all who abuse alcohol develop liver steatosis, which is reversible, but only a few progress to hepatitis and cirrhosis. Hepatitis C is often found in chronic alcoholics and leads to acceleration of alcoholic liver disease.

Excessive ethanol consumption causes more than 60 % of chronic liver diseases in the Western countries and is the 5^th leading cause of death. Alcoholic liver disease is a major cause of liver transplantation.

For pathomechanism, see the corresponding pathology 2 topic.

Etiology

Alcoholic liver disease is caused by significant alcohol consumption over long periods of time. The risk increases proportionally with the amount of alcohol consumed. There is no threshold above which ALD invariably develops, as this varies from person to person, but most people with ALD have been drinking ~10 units daily for decades.

According to the lecture (and they like to ask this), these are the “limits” for alcohol consumption:

• Females: 7 – 13 units/week = 10 – 20 g alcohol per day
• Males: 14 – 27 units/week = 20 – 30 g alcohol per day

When talking about alcohol consumption, it’s important to define how much a unit of alcohol is. In Europe in general, one unit is 10 g of alcohol, while it’s 14 g in the US. This corresponds to 250 ml beer, 100 ml of wine, or 30 ml of 40% hard liquor. In 100 ml of beer, there is 4 g of alcohol.

Some “fun facts” about alcohol drinking: women are more susceptible to alcohol-induced liver injury, and binge drinking may be as harmful as daily drinking.

Clinical features

The symptoms depend on the pathological stage:

• Alcoholic steatosis
  • Mostly asymptomatic
  • Nontender hepatomegaly
• Alcoholic steatohepatitis
  • Non-specific symptoms like nausea, loss of appetite, weight loss
  • Tender hepatomegaly
  • Jaundice
• Alcoholic cirrhosis
  • General symptoms of cirrhosis

Some cases of alcoholic liver disease are detected incidentally in the cirrhosis stage.

It’s important to keep in mind that alcohol abuse is dangerous to all organ systems, and symptoms of e.g. cardiomyopathy, neuropathy, and encephalopathy may be present.

Diagnosis and evaluation

For diagnosis of alcoholic liver disease, it’s important to establish the diagnosis of alcohol abuse, in which case heteroanamnesis may be required. The following laboratory alterations are typical:

• AST/ALT ratio > 2 (but both are elevated)
• Macrocytic anaemia
• Elevated GGTs

Serum ethanol levels can be measured, but this only elevated in case of intake in the last hours. Phosphatidylethanol, a phospholipid which is only formed after alcohol consumption, is a marker of longer-term alcohol intake. Carbohydrate-deficient transferrin (CDT) is another marker of long-term alcohol intake.

Ultrasound show characteristic findings depending on the stage. However, it cannot determine whether the cause of liver disease is alcoholic:

• Steatosis – hepatomegaly, increased liver echogenicity
• Steatohepatitis – larger hepatomegaly, periportal oedema
• Cirrhosis – nodular liver surface, atrophy, loss of structural homogeneity

CT and MRI, as well as special techniques like FibroScan, transient elastography (TE) and acoustic radiation force impulse (ARFI) may also be used.

It’s important to rule out other causes of liver disease, including viral and autoimmune.

Treatment

Abstinence is essential to reverse early stages of alcoholic liver disease and to prevent progression in later stages. Abstinence is difficult, and both non-pharmacological and pharmacological interventions should be utilised to achieve it.

In case of hepatitis, glucocorticoids may be helpful in severe cases to reduce mortality.

Other treatments which may be useful:

• Metadoxine – a drug which may increase alcohol elimination and may have a beneficial effect on ALD
• N-acetylcysteine
• Hepatoprotective antioxidants

Regular screening for cirrhosis, oesophageal varices, and hepatocellular carcinoma is indicated. If cirrhosis has developed, treatment aims at preventing complications like ascites, varices, and encephalopathy. See below.

Cirrhosis

Introduction and epidemiology

Cirrhosis is a chronic liver disease characterised by replacement of normal liver tissue by scar tissue. It’s an irreversible end-stage of hepatitis which cause significant morbidity and mortality. There is continuous loss of functional liver tissue, which is initially compensated and asymptomatic as the remaining liver can compensate. However, acute insults precipitate decreases in liver function, causing hepatic decompensation and development of dramatic and life-threatening complications. Cirrhosis is also an important risk factor for hepatocellular carcinoma.

Cirrhosis is a common condition worldwide.

For pathomechanism, see the corresponding pathology 2 topic.

Etiology

• Alcoholic liver disease
• Metabolic associated fatty liver disease
• Chronic viral hepatitis (C, B or D)
• Haemochromatosis
• Biliary obstruction (primary biliary cholangitis, primary sclerosing cholangitis)
• Autoimmune hepatitis
• Wilson’s disease
• Heart failure
• Alpha-1 antitrypsin deficiency

The most common causes in the Western world are alcoholic liver disease and metabolic associated fatty liver disease.

The following triggers may cause hepatic decompensation:

• Infection
• Alcohol use
• Hypovolaemia (bleeding or dehydration)

Classification

The liver function or cirrhosis severity can be classified according to the Child-Pugh or MELD scores. The latter is mostly used in the context of transplantation. The Child-Pugh score scores cirrhosis mortality based on:

• Bilirubin level
• Albumin level
• INR
• Ascites
• Encephalopathy

Clinical features

As long as there remains enough functional liver to compensate for the cell loss, the condition is known as compensated cirrhosis and is mostly asymptomatic. It may cause nonspecific symptoms like anorexia, weight loss, asterixis, malabsorption, muscle cramps, and fatigue.

Decompensation occurs when the liver function worsens due to an acute insult, or in end-stage cirrhosis where there is too little functional liver tissue left. This can cause a variety of symptoms and complications:

• Jaundice
• Pruritus
• Upper GI bleeding (from variceal bleeding)
• Ascites
• Hepatic encephalopathy
• Spontaneous bacterial peritonitis
• Hepatocellular carcinoma
• Hepatorenal syndrome
• Hepatopulmonary syndrome

Physical examination may reveal:

• Telangiectasia
• Caput medusae
• Hepatomegaly
• Splenomegaly
• Features of hyperoestrogenism (gynaecomastia, hypogonadism)

Complications not considered to equal decompensation:

• Portal vein thrombosis
• Cardiomyopathy
• Coagulopathy -> excessive bleeding

In end-stage cirrhosis there is collapse of liver functions, causing liver failure with severe and refractory decompensation symptoms.

Diagnosis and evaluation

Diagnosis of cirrhosis can usually be made based on clinical features, ultrasound, and special non-invasive investigations like FibroScan, transient elastography (TE) and acoustic radiation force impulse (ARFI). Ultrasound shows a shrunk liver with nodular surface and loss of homogeneity.

Typical laboratory findings of cirrhosis include:

• Elevated AST, ALT
• Elevated INR – due to decreased production of coagulation factors
• Hypoproteinaemia and hypoalbuminaemia
• Thrombocytopaenia
• Macrocytic anaemia

Determination of the etiology is based on patient history as well as laboratory examination:

• Viral hepatitis serology
• Alpha-1 antitrypsin – for deficiency
• Autoantibodies and hypergammaglobulinaemia – for autoimmune hepatitis
• Iron studies – for haemochromatosis
• Copper studies – for Wilson disease

Histology is the gold standard for the evaluation of cirrhosis, but it’s not usually required for the diagnosis.

Treatment

Treatment of cirrhosis involves preventing and treating complications. This also involves regular surveillance for worsening of the cirrhosis, and for development of hepatocellular carcinoma (by regular ultrasound (every 6 months) and monitoring of AFP).

To prevent triggers of decompensation, avoidance of hepatotoxic substances (including alcohol), as well as routine vaccinations, are important. Hepatic decompensation is usually self-limiting, but an episode of decompensation increases the risk for further episodes and complications later.

To avoid catabolic state, which could precipitate hepatic encephalopathy, it’s important to achieve sufficient energy and protein intake, ~80 – 100g protein and ~3000 Kcal/day, to avoid deficiency. Enteral nutrition should be added if patient cannot achieve this by regular foods.

Other important treatments for complications of cirrhosis include:

• Propranolol – decreases portal hypertension and the risk of variceal bleeding
• Ligation – to decrease the risk of variceal bleeding
• Transjugular intrahepatic portosystemic shunt (TIPS) – in case of persistent or recurrent upper GI bleeding due to portal hypertension, or ascites.
• Sodium restriction, fluid restriction, diuretics (MRA or loop) – in case of ascites
• Cephalosporins – for spontaneous bacterial peritonitis
• Lactulose ± rifaximin – for hepatic encephalopathy
• Fresh frozen plasma – for coagulopathy

Liver transplantation is the only curative treatment for cirrhosis. It’s indicated for all cases of cirrhosis where decompensation has developed. For more information, see surgery topic B52.