ACTA2 is associated with TGF β pathway that enhances contractile properties of HSCs leading to fibrosis. Furthermore, it secretes TIMP1 and TIMP2, naturally occurring inhibitors of matrix metalloproteinases, which prevents them from breaking down the fibrotic material in the extracellular matrix.As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, and enlarged, resulting in its retention of platelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis. Diagnosis
The diagnosis of cirrhosis in an individual is based on multiple factors. Cirrhosis may be suspected from laboratory findings, physical exam, and patient history. Imaging is generally obtained to evaluate the liver. A liver biopsy will confirm the diagnosis; however, is generally not required. Imaging
Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and shrunken liver in advanced disease. On ultrasound, there is increased echogenicity with irregular appearing areas. Other suggestive findings are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. An enlarged spleen, which normally measures less than 11–12 cm in adults, may suggest underlying portal hypertension. Ultrasound may also screen for hepatocellular carcinoma and portal hypertension. This is done by assessing flow in the hepatic vein. An increased portal vein pulsatility may be seen. However, this may be a sign of elevated right atrial pressure. Portal vein pulsatility are usually measured by an pulsatility indices (PI).
In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. Mixed cirrhosis consists of nodules of different sizes. Grading
The severity of cirrhosis is commonly classified with the Child–Pugh score (also known as the Child–Pugh–Turcotte score). This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others. It was first established to determine who would benefit from elective surgery for portal decompression. This scoring system uses multiple lab values including bilirubin, albumin, and INR. The presence of ascites and severity of encephalopathy is also included in the scoring. Patients are classified into class A, B, or C. Class A has a favorable prognosis while class C is at high risk of death. The Child-Pugh score is a validated predictor of mortality after a major surgery. For example, Child class A patients have a 10% mortality rate and Child class B patients have a 30% mortality rate while Child class C patients have a 70 to 80% mortality rate after abdominal surgery. Elective surgery is usually reserved for those in Child class A patients. There is an increased risk for child class B individuals and they may require medical optimization. Overall, it is not recommended for Child class C patients to undergo elective surgery.In the past, the Child-Pugh classification was used to determine patients who were candidates for a liver transplant. Child-Pugh class B is usually an indication for evaluation for transplant. However, there were many issues when applying this score to liver transplant eligibility.