The liver is the largest internal organ and consists of two main lobes separated by the hepatic vein. It’s found in the upper right corner of the abdomen and receives approximately 15ml blood/minute. The hepatic artery supplies 25% of the liver’s blood flow and provides most of the oxygen required. The portal vein drains most of the GI tract and supplies 75% of the liver blood supply. It transports recently absorbed material from the intestines to the liver.

The liver has many very important roles in:

homeostasis: liver plays a major role in protein, carbohydrate and lipid homeostasis

storage: stores glycogen, vitamins and iron. Iron is predominantly recycled in the body eg after blood cell breakdown.

blood cell production/breakdown: liver contains an extensive reticuloendothelial system

first pass metabolism: liver cells metabolise, detoxify and excrete both endogenous and exogenous compounds.

Drugs and toxins: metabolism and excretion

Liver disease is diagnosed by looking at multiple different factors. Personal medical history and family history of liver problems is looked at and drinking and eating habits are observed depending on if certain symptoms are present. Tests include liver function tests (LFTs), a complete blood count test, and CT scans, MRIs or ultrasounds to check for liver damage/tumours. A biopsy may also be taken.

Symptoms of liver disease include jaundice caused by high bilirubin levels and a change in bowel function eg fatty stools.

The liver has a very large functional reserve capacity and liver cancer patients with as much as 95% of their liver removed have been found to survive.

The liver doesn’t have any sensory receptors so direct liver pain isn’t felt but in the case of liver cancer the pressure of the tumour on surrounding organs may be felt.

Changes to lifestyle are typically enough to keep liver disease symptoms under control eg limiting alcohol, maintaining healthy weight, drinking more water or increasing dietary fibre and reducing fat, sugar and salt. Prescribing drugs to help with liver disease is usually done as a last resort.

Antiviral drugs are used to treat hepatitis. Steroids are used to reduce liver inflammation. Blood pressure medication and antibiotics may be provided. Symptom-specific medications may be provided eg to treat itchy skin from jaundice, or a person may take vitamins and supplements to boost liver health.

Blood pressure medication may be taken as hepatic portal hypertension causes liver damage. However, hepatic portal circulation is more linked to the venous system than the arteries so is treated differently to high blood pressure in general. Hepatic portal hypertension leads to varicose veins, haemorrhoids and oesophageal varices.

There are 5 hepatitis strains, A to E. Some variants are more dangerous and damaging than others, with hepatitis C being one of the most common. Hepatitis C can be acute or chronic and is often spread through contact with blood of an infected individual. Symptoms aren’t usually caused or seen in the early stages but it can lead to permanent liver damage.

Hepatitis B and C are major causes of chronic hepatitis. Use of the currently unlicensed interferon alfa against acute hep C may reduce risk of chronic infection. Interferons boost the immune response stimulating T cells and other immune cells to attack. Anti viral drugs ombitasvir with paritaprevir and ritonavir inhibits a wide range of both DNA and RNA viruses. Sofosbuvir inhibits hepatitis C virus NS5B protein.

Fatty liver disease may be alcoholic or non-alcoholic and is caused by fat build up in the liver. Alcoholic fatty liver disease is caused by heavy alcohol consumption and the factors causing non alcoholic FD are still not fully understood. Both can cause liver damage, leading to cirrhosis and liver failure if unmanaged. Cirrhosis is a degenerative disease of the liver resulting in scarring and liver failure.

Fatty liver disease causes irreversible damage (fibrosis) with implications for metabolism, bile production, cholesterol and haematological implications. Vitamin E, or pioglitazone, a diabetic drug, may be taken by adults with advanced liver fibrosis. Vitamin E is a potent antioxidant. Pioglitazone improves sensitivity of the hepatic tissue to insulin as it is a synthetic ligand for peroxisome proliferator-activated receptors (PPARs). They alter transcription of genes which influence carb and lipid metabolism.

Autoimmune hepatitis causes the immune system to attack the liver → inflammation.

Primary biliary cirrhosis results from damage to the bile ducts in the liver, causing bile build up. May lead to eventual cirrhosis and liver failure.

Primary sclerosing cholangitis is an inflammatory condition causing gradual bile duct damage so the ducts eventually block → liver bile build up. Can lead to cirrhosis/liver failure.

Autoimmune liver conditions are treated with corticosteroids and immunosuppressants such as prednisolone and azathioprine. Prednisolone increases neutrophil concentration and decreases T/B cells, monocytes, eosinophils and basophils. Also decreases cytokine release eg IL-2 and TNF-alpha. Azathioprine is an immunosuppressive agent which antagonises purine metabolism, inhibiting DNA, RNA and protein synthesis.

Liver cancers develop first in the liver. If cancer metastasises to the liver it’s known as secondary liver cancer. The most common liver cancer is hepatocellular carcinoma, which typically develops as several small cancer spots although it may also start as a single tumour. Liver disease complications may contribute to development of liver cancer.

Many monoclonal antibodies such as ipilimumab, tremelimumab, nivolumab, atezolizumab and avelumab have been studied for cancer treatment purposes. Liver cancer may also be treated using prednisolone or everolimus. Everolimus is an mTOR inhibitor. mTOR stands for mammalian target of rapamycin.

Cholestasis is an impairment of bile formation/flow. May present with fatigue, pruritus, dark urine, pale stools, jaundice and signs of fat soluble vitamin deficiencies. May be treated by colestyramine or sertraline. Colestyramine is a bile acid sequestrant and SSRIs are used to treat pruritus (itchy skin).