CIRRHOSIS OF LIVER
October 24, 2017
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October 24, 2017
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CIRRHOSIS OF LIVER

CIRRHOSIS OF LIVER

The liver is in the upper right part of the tummy(abdomen). It has many functions which include:

1.Storing fuel for the body (glycogen) which is made from sugars. When required, glycogen is broken down into glucose which is released into the bloodstream.

2.Helping to process fats and proteins from digested food.

3. Helping to remove or process alcohol, poisons and toxins from the body.

4.Making bile which passes from the liver to the gut and helps to digest fats

5.Making proteins that are essential for blood to clot (clotting factors)

6.Processing many medicines that one may take.

Understanding cirrhosis

Cirrhosis is a diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. Cirrhosis represents the final histological pathway for a wide variety of liver diseases. The progression to cirrhosis is very variable and may occur over weeks or many years. Around 80-90% of the liver parenchyma needs to be destroyed before there are clinical signs of liver failure. However, there is often a poor correlation between the histological findings and the clinical picture.

The fibrosis causes distortion of the hepatic vasculature and can lead to an increased intrahepatic resistance and portal hypertension. Portal hypertension can lead to oesophageal varices as well as hypoperfusion of the kidneys, water and salt retention and increased cardiac output. Damage to liver cells (hepatocytes) causes impaired liver function and the liver becomes less able to synthesise important substances such as clotting factors and is also less able to detoxify other substances.

Antecedents of cirrhosis

A number of chronic liver diseases can lead to cirrhosis. The cirrhotic process can take from weeks to many years to develop, depending on the underlying cause and other factors, including patient response to the disease process. For example, chronic hepatitis C infection can take up to 40 years to progress to cirrhosis in some people.

Common causes of cirrhosis include:

Alcohol abuse.

Hepatitis B infection

Hepatitis C infection (up to 20% can develop cirrhosis).

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) – up to 10% of patients with NASH can develop cirrhosis.

Less common causes include:

  1. Primary biliary cirrhosis.
  2. Haemochromatosis.
  3. Biliary obstruction (may be due to biliary atresia/neonatal hepatitis, congenital biliary cysts or cystic fibrosis).
  4. Autoimmune hepatitis.
  5. Congestive heart failure or tricuspid regurgitation (although this is rarely seen now due to improved management).
  6. Inherited metabolic disorders – eg, tyrosinaemia, Wilson’s disease, porphyria, alpha-1-antitrypsin deficiency, glycogen storage diseases.
  7. Sarcoidosis or other granulomatous disease.
  8. Primary sclerosing cholangitis.
  9. Venous outflow obstruction in Budd-Chiari syndrome or veno-occlusive disease.
  10. Infections including congenital and tertiary syphilis and schistosomiasis.
  11. Drugs and toxins including methotrexate, amiodarone and isoniazid.

Prevalence

  • The number of people living with both alcoholic cirrhosis and non-alcohol-related cirrhosis seems to be rising.
  • It is difficult to estimate the exact prevalence of cirrhosis, as previously undiagnosed cirrhosis is often found at post-mortem.
  • There is concern that there are growing levels of dangerous alcohol consumption which may lead to increased numbers of people with cirrhosis.

Causes of cirrhosis

Hepatitis B is the most common cause in parts of Asia and in sub-Saharan Africa. There may also be a genetic predisposition to cirrhosis which may explain the variable rates of its development in people with similar risk factors (such as alcohol abuse or hepatitis C infection).

Alcoholic liver disease and hepatitis C are the most common causes in developed countries.

Continued alcohol consumption increases the rate of progression of cirrhosis from any cause.

Risk factors for the development of cirrhosis in those with chronic hepatitis C infection:

  1. Age>50 years
  2. Being male.
  3. Regular (moderate) alcohol consumption.

Risk factors for the development of cirrhosis in those with NASH:

  1. Hypertension.
  2. Hyperlipidaeia
  3. Insulin resistance or type 2 diabetes.
  4. Obesity.
  5. Older age.

Symptoms

Cirrhosis is often asymptomatic until there are obvious complications of liver disease. Up to 40% of people with cirrhosis may be asymptomatic. Blood testing for other reasons may reveal abnormal liver function and prompt further investigation which shows cirrhosis.

The history should include a thorough enquiry for possible underlying causes of cirrhosis, including a full drug and alcohol history (including over-the-counter drugs, complementary medicines and recreational drugs), risk factors for hepatitis infection, and family history of autoimmune or liver diseases.

Manifestations

Cirrhosis may present with vague symptoms such as fatigue, malaise, anorexia, nausea and weight loss. In advanced, decompensated liver disease, presentation may include:

  1. Easy bruising.
  2. Bleeding oesophageal varices.
  3. Oedema.
  4. Ascites.
  5. Spontaneous bacterial peritonitis.
  6. Poor concentration and memory.

Physical signs

Physical signs are variable and depend upon the extent of disease.

Cutaneous features of cirrhosis include:

  1. Skin telangiectasias (called ‘paper money skin’).
  2. Palmar erythema.
  3. Jaundice.
  4. Scratch marks secondary to pruritus.
  5. Spider angiomata/naevi (mainly found on the trunk and face).
  6. contracture.
  7. Petechiae or purpura.
  8. Hair loss.
  9. Finger clubbing.
  10. White nails (horizontal white bands or a proximal white nail plate; sign of hypoalbuminaemia).
  11. Dupuytren’s
  12. Bruising.

Some more signs :

Oedema.

Kayser-Fleischer ring (a brown-green ring of copper deposit around the cornea, pathognomonic for Wilson’s disease).

Hepatomegaly and a nodular liver.

Gynaecomastia and male hair loss pattern.

Hypogonadism/testicular atrophy/amenorrhoea (due to the direct toxic effect of alcohol in alcoholic cirrhosis or iron in haemochromatosis).

Signs of portal hypertension include:

Ascites (can be detected clinically when ≥1.5 litres of fluid is present).

Caput medusae (veins seen radiating from the umbilicus).

Enlarged spleen.

Signs of hepatic encephalopathy:

Asterixis (‘flapping tremor’); suggests hepatic encephalopathy. To detect asterixis, take the patient’s hand and gently hyperextend the wrist and joints of the hand, pushing gently on the tips of the four fingers. Ignore the thumb. Hold that position for several seconds and you will feel a slow, clonic flexion-relaxation movement against your hand if asterixis is present.

Tests

These will depend to a considerable extent upon clinical suspicion of the aetiology.

Blood investigations-

LFTs: should include aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, gamma-glutamyltransferase (gamma-GT); AST and ALT are raised due to hepatocyte damage; gamma-GT is high in active alcoholics.

Albumin: there is hypoalbuminaemia in advanced cirrhosis.

FBC: occult bleeding may produce anaemia; hypersplenism may cause thrombocytopenia; macrocytosis can suggest alcohol abuse.

Renal function tests and electrolytes: hyponatraemia may be present (due to increased activity of antidiuretic hormone).Poor renal function may represent hepatorenal syndrome.

Red cell folate: alcohol abuse is often associated with a diet inadequate in folate.

Coagulation screen: abnormalities of coagulation are a sensitive test of liver function; prothrombin time is reduced in advanced cirrhosis.

Ferritin: low ferritin may indicate iron deficiency from diet or blood loss; ferritin is raised in haemochromatosis.

Viral antibody screen: to look for evidence of hepatitis B or C infection.

Fasting glucose/insulin/triglycerides and uric acid levels: these should be measured if NASH is suspected.

Autoantibody screen: anti-mitochondrial antibodies are a very strong indicator of primary biliary cirrhosis.

Alpha-1-antitrypsin level: to assess for alpha-1-antitrypsin deficiency. Ceruloplasmin and urinary copper: to look for Wilson’s disease.

Fasting transferrin saturation and HFE (haemochromatosis C282Y) mutation: along with a raised ferritin, these tests can screen for haemochromatosis.

Radiology tests

Ultrasound scan of liver and possibly CT or MRI scan: their main use is to detect complications of cirrhosis, such as splenomegaly, ascites or hepatocellular carcinoma.

CXR: this may show an elevated diaphragm and even pleural effusion (due to the passage of ascitic fluid across the diaphragm).

Liver biopsy

Histology is usually needed for the definitive diagnosis of cirrhosis and liver biopsy is the gold standard. It may also give a clue to the underlying cause.

If there are clear signs of cirrhosis, such as ascites, Coagulopathy and a shrunken nodular-appearing liver, confirmation of diagnosis by biopsy may not be necessary.

Cirrhosis grading/classification

The Child-Pugh-Turcotte (CPT) classification system is a widely used and validated way to estimate prognosis in those with cirrhosis.

Child-Pugh (Child-Pugh-Turcotte) Classification

Criterion Score 1 point Score 2 points Score 3 points
Serum albumin (g/L) >35 28-35 <28
Serum bilirubin (total) <34 μmol/L (<2 mg/dL) 34-50 μmol/L (2-3 mg/dL) >50 μmol/L (>3 mg/dL)
International Normalized Ratio (INR) <1.7 1.7-2.2 >2.2
Ascites Absent Controlled medically Poorly controlled
Encephalopathy Absent Controlled medically Poorly controlled

A score of 5-6 is class A (life expectancy 15-20 years); a score of 7-9 is class B (life expectancy 4-14 years); a score of 10-15 is class C (life expectancy 1-3 years). This aligns with a perioperative mortality (for abdominal surgery) of 10%, 30%, and 80% respectively.

Treatment of Cirrhosis

The aim of treatment is to delay progression of cirrhosis and to prevent and/or treat any complications of cirrhosis.

Pruritus (itching) is a common complaint in cholestatic and non-cholestatic liver diseases. Mild itching complaints may respond to treatment with antihistamines and topical ammonium lactate. Colestyramine is the mainstay of therapy for the pruritus of liver disease.

Zinc deficiency is often seen in patients with cirrhosis and treatment with zinc supplements may be helpful.

Specific treatment for the underlying cause

Ensure adequate nutrition, including calorie and protein intake.

Prophylactic antibiotic use in patients with cirrhosis and upper gastrointestinal bleeding significantly reduces bacterial infections and seems to reduce all-cause mortality, bacterial infection mortality, rebleeding events and length of hospitalisation.

Alcohol: the most important measure for someone with alcoholic cirrhosis is for them to stop drinking. Continued alcohol intake can also increase the rate of progression of cirrhosis from any cause.

Rifampicin has helped some patients unresponsive to colestyramine. Severe pruritus may require treatment with ultraviolet light or plasmapheresis.

Patients with cirrhosis may develop osteoporosis and those at risk of osteoporosis should be given preventative treatment.

Regular exercise should be encouraged and is important to prevent muscle wasting.

Patients with chronic liver disease should receive vaccination to protect them against hepatitis A, influenza and pneumococci.

Drug prescribing: care is essential to avoid any drug that may not be properly metabolised in the presence of liver failure, have an adverse effect on the degree of liver failure or be a cause of drug induced liver disease.

Liver transplantation is the ultimate treatment for cirrhosis and end-stage liver disease.

Follow up

Monitoring of oesophageal varices.

Monitoring for hepatocellular carcinoma.

Complications of cirrhosis

If complications develop, the patient should be transferred to a specialised liver unit where there is the expertise to manage the complications and where the patient can also be assessed as to their suitability for liver transplantation.

Ascites

This is a common feature of cirrhosis.

It is an accumulation of excessive fluid within the peritoneal cavity due to the increased plasma volume ‘spilling over’ into the abdominal cavity.

Hepatocellular carcinoma

Cirrhosis is a major risk factor for hepatocellular carcinoma. The risk varies according to the cause of cirrhosis.

It is most often associated with cirrhosis caused by hepatitis C infection, followed by cirrhosis caused by hereditary haemochromatosis.

Worldwide, hepatocellular carcinoma as a result of cirrhosis secondary to hepatitis B infection causes a large number of deaths.

The risk of hepatocellular carcinoma is lower in those with alcoholic cirrhosis (8% five-year occurrence) or primary biliary cirrhosis (4% five-yearoccurrence).

Patients with cirrhosis should be screened for hepatocellular carcinoma.

Anaemia, thrombocytopenia and coagulopathy

Anaemia may result from folate defeciency, haemolysis or hypersplenism.

Thrombocytopaenia is usually secondary to hypersplenism and decreased levels of thrombopoietin. Coagulopathy results from decreased hepatic production of coagulation factors. If present, Cholestasis causes decreased vitamin K absorption, leading to reduced hepatic production of factors II, VII, IX and X.

Patients with cirrhosis also may develop fibrinolysis and Dissimated Intravascular Coagulation (DIC)

Oesophageal varices

These can occur as a result of portal hypertension.

Spontaneous bacterial peritonitis

Ascites may be associated with spontaneous bacterial peritonitis.

It is thought to be caused by the spread of bacteria across the gut wall and/or haematogenous bacterial spread. Escherichia coli is among the most common organisms implicated.

This may be prevented by adequately treating ascites and treating those with high neutrophil counts in their ascitic fluid (>250 neutrophils/ml) with empirical intravenous antibiotics and albumin. Patients who survive an episode of spontaneous bacterial peritonitis should receive long-term prophylaxis with oral antibiotics such as norfloxacin, levofloxacin or trimethoprim.

Other less common complications can include:

Hepatopulmonary syndrome – there is pulmonary arteriolar vasodilation, shunting and hypoxaemia. Transplantation may reverse this.

Surgery and general anaesthesia have increased risks in the patient with cirrhosis

Cirrhotic cardiomyopathy – there is cardiac hypertrophy and a blunted stress response of the heart. May cause significant problems perioperatively and mean that liver transplantation may be too dangerous.

Portopulmonary hypertension – an irreversible condition that can occur in those with refractory ascites.

Outlook

This depends on the underlying cause and on the success of the treatment of the underlying cause.

Patients with fulminant hepatic failure have a 50-80% mortality rate unless they receive a liver transplant.

If someone with alcoholic cirrhosis continues to drink alcohol, the rate of decompensation can be rapid.

Prevention of Cirrhosis

Sensible drinking is essential for everyone and patients should be advised about the recommended limits.

There is no vaccine against hepatitis C but some treatments may delay progression and alcohol must be avoided.

Worldwide, the most important factor in prevention of cirrhosis is Hepatitis B vaccination for all.

Beware of hepatotoxic medications, including herbal remedies.

Weight reduction and exercise can improve liver function in patients with NASH.

CONCLUSION:

Liver Cirrhosis is grave condition where normal liver tissue is replaced by scar tissue (fibrosis) is termed as Cirrhosis. Its progression is slow and often does not cause symptoms in its early stages. However, liver gradually becomes more and more malfuncyional and serious problems can develop. Two most common causes of cirrhosis are heavy alcohol drinking and hepatitis C infection. Treatments may vary, depending on the cause. A liver transplant may be the only option in a severe condition.