Cirrhosis

Cirrhosis is the result of chronic inflammation and is the end-stage of chronic liver diseases such as hepatitis B, hepatitis C, ALD, NAFLD.

Pathophysiology

Continuous insult and injury to the liver will cause hepatic fibrosis. This is due to activation of hepatic stellate cells which are a source of ECM build-up as they produce collagen. These stellate cells accumulate type I and type III collagen in the parenchyma of the liver as well as the space of Disse (the space between the hepatocyte and the sinusoid [which is the channel running through the portal tracts to the central vein]). This accumulation of collagen in the space of Disse is known as capillarisation of the sinusoids. With capillarisation, the sinusoids lose their fenestrations (holes) which prevents exchange between hepatocytes and plasma.

These stellate cells can then become contractile which increases portal resistance further.

These changes can alter vascular tone as well as the architecture of the liver → portal hypertension. With portal hypertension, we get diversion of the nutrient-rich blood away from the liver → encephalopathy. Portal hypertension also causes the development of ascites and gastric/oesophageal varices. Ascites is also due to impaired plasma protein synthesis and hypoalbuminaemia.

Loss of these nutrients can then cause malnutrition and sarcopenia. The sarcopenia can cause frailty which is a poor prognostic marker.

Fibrosis progresses to cirrhosis, after which it is not reversible. However, there is potentially some reversibility if there is no ongoing liver injury. At some point, the only option to treat cirrhosis is liver transplantation.

Cirrhosis can then lead to hepatocellular carcinoma due to the chronic inflammation as it creates a pro-oncogenic environment.

🔢 Classification

We can classify cirrhosis as compensated or decompensated:

1. Compensated cirrhosis - cirrhosis is present but liver synthetic function is preserved. No complications are present relating to portal hypertension, ascites, varices, encephalopathy and not even jaundice.
2. Decompensated cirrhosis - evidence of complications are present and there is reduced synthesis.

⚠️ Risk factors

• Alcohol abuse - risk of ALD.
• IV drug use - risk of hepatitis B and C.
• Unprotected sex - risk of hepatitis B and C.
• Obesity - increases risk of NAFLD.
• Country of origin - as hepatitis B and C are endemic to certain regions. This will be discussed in the CCC on viral hepatitis.

😷 Presentation

• Abdominal pain - RUQ pain and discomfort.
• Jaundice - more common in severe alcoholic hepatitis.
• Ascites and abdominal distension - common complication of cirrhosis.
• Weight loss/weight gain - weight loss and anorexia are common but weight gain may be due to ascites/oedema with portal hypertension.
• Fatigue
• Portal hypertension
• Pruritus - due to accumulation of bile salts in the skin layers with jaundice.
• Haematemesis and melaena - due to oesophageal or gastric varices, gastric irritation and coagulopathy.

🔍 Investigations

💯 Scoring

Child-Pugh-Turcotte score

Scores the severity of 5 features (bilirubin, albumin, INR, ascites, encephalopathy) from 1-3. Thus we can calculate a score out of 15 to assess the severity of the cirrhosis.

Model of End-stage Liver Disease (MELD) score

NICE recommends calculating a MELD score every 6 months in patients with compensated cirrhosis. It gives a percentage for estimated 3 month mortality and this can be used to stratify allocations for liver translplant.

🧰 Management

🥇 As cirrhosis is irreversible, there is not much one can do but prevent its progression through treatment of underlying chronic liver disease and preventing more damage.

🥇 We also need to monitor and treat complications which can be plentiful. They will be discussed below. As stated, a MELD score is repeated every 6 months, ultrasound and alpha-fetoprotein are repeated every 6 months too, and an endoscopy every 3 years if needed.

A high protein, low sodium diet is also necessary to help the ascites.

The only curative option is liver transplantation.

For patients not suitable, we can put in place a transjugular intrahepatic portosystemic shunt (TIPSS).

🚨 Complications

Malnutrition

Cirrhosis causes malnutrition and muscle wasting as muscle tissue becomes overused and as a result the protein supply in the rest of the body becomes deficient for muscle growth and maintenance. It also affects protein metabolism and glycogen stores → lack of fuel for muscle → muscle wasting and weight loss.

🧰 Management

• More regular meals (every 2-3 hours) with higher protein and higher calories especially if underweight.
• Reduce sodium to minimise fluid retention
• Alcohol cessation

Portal hypertension and varices

The portal vein is a large vein that brings nutrient-rich blood into the liver for processing. It forms from an anastomoses of the splenic vein and superior mesenteric vein. The portal vein then divides throughout the liver to form a part of the portal triad around the hepatic lobules. They then drain into the central vein in the sinusoids → left, middle and central hepatic veins → IVC.

However, in cirrhosis there is increased resistance due to build up of collagen fibres as well as alterations to vascular tone. This leads to portal hypertension. This results in back-pressure of blood. However, the portal vein is quite large and as a result does not get affected. The veins that do get affected are the more proximal anastomoses. These become swollen and filled with blood, these are called varices.

They commonly occur at 4 sites:

• Gastro-oesophageal junction - with gastric and oesophageal veins.
• Iliocaecal junction
• Rectum
• Anterior abdominal wall - para-umbilical veins.

Varices themselves are not an issue. However, as they have high blood flow going through them, they have a high risk of rupturing. Because of this high flow as well, the blood will not clot easily and patients will exsanguinate rapidly.

🧘‍♂️

Stable varices management:

• Propranolol - reduces portal hypertension as it is a non-selective B-blocker.
• Elastic band ligation of the varices. It should be performed at two-weekly intervals until all varices have been eradicated. It is considered superior to sclerosant therapy.
• Sclerosant injection - causes the veins to scar up and reroute the blood to other more competent veins. This is less effective than ligation.
• Transjugular inta-hepatic portosystemic shunt (TIPS) - an interventional radiology procedure where a wire is inserted from the jugular vein → vena cava → hepatic vein. They then make a connection from the hepatic vein (systemic system) and portal vein (portal system). This creates a portosystemic shunt that allows pressure in the portal system to be relieved,

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Major haemorrhage protocol: This is a good opportunity to outline the MHP that was discussed in the shock EHD. Of course a ruptured varice may lead to hypovolaemia very rapidly.

The protocol is as follows:

1. Recognition
2. Senior help
3. ABCDE
4. Take samples
5. Initiate major haemorrhage protocol
6. Haemorrhage control
7. Cell salvage
8. Resuscitate with major haemorrhage pack
1. Pack 1 - 4 RBCs, 4 FFP (fresh frozen plasma),
2. Pack 2 - 4 RBCs, 4 FFP, 2 pools platelets
3. Pack 3 - 4 RBCs, 4 FFP, 2 cryoprecipitate (pooled clotting factors), 1 pool platelets.
9. Repeat samples
10. Prevent
11. Treatment targets

Ascites

This is fluid collection on the peritoneal cavity. It occurs due to portal hypertension causing leakage of fluid out of the capillaries in the liver and into the peritoneal cavity. A reduction in the circulating volume causes reduced BP entering into the kidneys. This activates the RAAS to cause increased fluid retention. The ascitic fluid with cirrhosis is a transudative ascites (low-protein content).

🧰 Management

1. Low sodium diet
2. Spirinolactone - reduces aldosterone activity and decreases fluid retention as a result.
3. Paracentesis - an ascitic tap or ascitic drain.
4. Prophylactic antibiotics - to prevent spontaneous bacterial peritonitis in patients with a transudative ascites (<15g/litre of protein).
1. Ciprofloxacin or norfloxacin
5. TIPS or transplantation If refractory.

Hepatorenal syndrome

Portal hypertension leads to dilation of the portal vasculature. This takes blood away from the systemic circuit. Therefore the kidneys receive less blood and we get hypotension. This activates the RAAS → renal vasoconstriction to an already poorly perfused kidney. This can then cause AKI and renal failure. It can be fatal within 1 week and so an urgent liver transplant is needed, however, albumin can be given to increase oncotic pressure and prevent hypoperfusion.

Hepatic encephalopathy

Also known as portosystemic encephalopathy. It is believed that toxin build up is what affects the brain. In particular ammonia.

Ammonia is produced by intestinal bacteria as a byproduct of protein breakdown. Ammonia is usually broken down in the liver through the urea or ornithine cycle. In this cycle, ammonia is converted to urea which can be excreted via the kidneys.

This is unable to happen due to 2 reasons:

1. Hepatocyte functional impairment prevents the hepatocytes from converting the ammonia to urea.
2. Portosystemic collaterals allow the blood to bypass the liver and enter into the systemic system directly.

Interventional radiologists can also be used for angioplasty