Chronic injury to hepatic parenchyma resulting in excessive fibrosis and conversion of liver architecture into structurally abnormal regenerative nodules.
Cirrhosis defined as fibrotic replacement of liver tissue can result from any chronic liver disease.
Most prevalent cases of cirrhosis are caused by alcohol use disorder, about 45% of all cirrhosis cases, hepatitis C 41%, and non-alcoholic fatty liver disease 26%, with many patients having overlapping causes.
Most newly diagnosed cirrhosis cases are due to non-alcoholic fatty liver disease, accounting for 61.8% of the incident cases and alcohol use disorder accounts now for 20%.
End result of many types of chronic liver disease.
Chronic inflammatory liver injury causes activation of hepatic myofibroblasts and macrophages that increase collagen accumulation in the extracellular matrix.
This process impairs the connection between hepatocytes and sinosoids where blood flows leading to formation of nodules of fibrosis, and impedes portal inflow resulting in portal venous hypertension.
Chronic liver injury result in increased vasoconstrictor signaling by endothelin-1 and decreased production of vasodilators, such as nitric oxide, further restricting sinusoidal flow.
Chronic liver injury causes loss of hepatocytes and reduces the liver’s capacity for metabolic activity, including protein synthesis, detoxification, nutrients storage, and bilirubin clearance.
Liver disease accounts for approximately 2 million deaths per year worldwide.
Fifth leading cause of death aged 45-54 years.
10% of patients admitted to the hospital die.
The mean age for cirrhosis is 59 to 62 years.
A total of 54 to 60% of cirrhosis cases occur among men.
Cirrhosis is increasingly common among younger patients.
Approximately 2/3 of patients with cirrhosis and extra hepatic organ failure have sepsis.
Hospitalization for patients with cirrhosis and sepsis are almost 3 times as expensive and twice as long as for patients who have sepsis without cirrhosis.
The in-house mortality rate for patients with cirrhosis and sepsis is upwards of 50%.
Infections increase the risk of death by a factor of four among patients with cirrhosis.
High mortality has been observed among patients with cirrhosis who have severe acute respiratory syndrome related to Covid-19 infection.
Infections in patients with cirrhosis, 48% are community acquired, 26% are associated with healthcare, and 26% are nosocomial.
Increase systemic inflammation in patients with cirrhosis contributes to kidney failure and death.
10th leading cause of death overall in the US, with the mortality rates of approximately 9.3 per 100,000 thousand persons.
Patients with cirrhosis may require endoscopic screening for esophageal varices, screening for hepatocellular carcinoma, therapy for hepatic encephalopathy, spontaneous peritoneal bacterial infection and consideration for liver transplant.
Approximately 5.5 million people in the U.S. have cirrhosis.
Liver biopsy is best diagnostic test for cirrhosis.
Consequences of cirrhosis include: esophageal and gastric varices, ascites, hepatic encephalopathy, hepatic insufficiency, hepatorenal syndrome and hepatocellular carcinoma.
And its complications are the 12th leading cause of death among adults, accounting for nearly as many fatalities associated diabetes.
Alcohol consumption and viral hepatitis are the most common factors in causing cirrhosis.
Can develop with as little as 2-4 drinks per day for a 10-year period.
Can develop in women with as little as 20 gm intake of alcohol per day for 5-10 years and in men 40 gm consumption per day for the same period of time.
Women have a significantly more rapid progression to cirrhosis from alcohol:20 years on average, as compared with the rate of progression to cirrhosis in men 35 years on average.
Can be caused by alpha1-antitrypsin deficiency, hemochromatosis, primary biliary cirrhosis, Wilson’s disease and primary sclerosing cholangitis.
10-year survival after the diagnosis of compensated cirrhosis is about 50%.
The 5-year survival after the diagnosis of decompensated cirrhosis is about 15%.
Prevalence of elevated serum aminotransferase levels is approximately 7.9% In the US, and approximately 10-17% of patients with unexplained aminotransferase elevations have previously unsuspected cirrhosis.
Clinical findings of cirrhosis include palmer erythema, spider nevi, gynecomastia, decreased body hair, and testicular atrophy resulting from decreased hepatic metabolism and clearance of androstenedione, allowing increased peripheral conversion to estrogen.
As the loss of functioning hepatic tissue progresses it leads to jaundice and hypoalbuminemia.
Chronic liver disease results in the priest production of coagulation factors I, II, V, VII, IX, and X.
In cirrhosis factors II, VII, V, X may be further reduced by vitamin K deficiency due to the presence of cholestasis.
Prothrombim time may be elevated because of factor VII is the 1st factor to be depleted in cirrhosis due to its short half-life.
Cirrhosis may be associated with thrombocytopenia due to hypersplenism or direct bone marrow subpression.
Up to 20% of cirrhotic patients have either umbilical or inguinal hernias due to elevated intra-abdominal pressure from ascites, muscle and fascial weakening from nutritional deficiencies.
White nails, called T2242y nails, with silver-white pallor of the proximal nail bed that may obscure the nail lunula may be present.
White nail changes may involve the entire nail with only now pink colored distal band remaining.
Spider nevi are arterial abnormalities with a central arteriole and numerous small radiating blood vessels that resemble a spider’s legs.
Spider nevi blanch when the central arteriole is pressed, and fills from the center outward.
The spider nevi usually found in the area drained by the superior vena cava.
The presence of 2-3 spider nevi is suggestive of the presence of cirrhosis.
Facial telangiectasia may be seen on the cheeks, nose, or head, and neck in cirrhosis.
Rate of transition from compensated to decompensated cirrhosis has remained unchanged for decades, at about 5-10% annually.
Ascites and hepatic encephalopathy occur at rates of 5% and 6%, respectively.
In patients with dilated abdominal veins the direction of the blood flow is away from the umbilicus, whereas in the female cable obstruction the direction of blood flow is either completely above the umbilicus downward or completely below the umbilicus upward.
In the presence of dilated abdominal veins, the blood flow is away from the umbilicus, in the presence of portal hypertension.
This is differentiated from the direction of blood flow with a inferior vena cava obstruction, in which collateral veins have blood flowing cranial towards the inferior Vena cava, while in superior vena cavil obstruction, the collateral veins flow caudal towards the inferior vena cava.
Almost 100% of patients with compensated disease from chronic viral hepatitis will live at least 2-5 years.
Palmer erythema is reddening Involving the thenar and Ihypothenar eminences that spares the center of the palm.
Median survival 4-7 years when splenomegaly, thrombocytopenia or clinically quiescent esophageal varices develop.
Estimated that 4-12% of patients develop esophageal varices annually.
About 90% of deaths due to cirrhosis in the U.S. can be avoided by preventing excessive alcohol intake and high-risk behaviors for viral transmission.
More than 95% of deaths result from toxic effects of prolonged alcohol.
Autopsy findings suggest the prevalence of cirrhosis in the U.S. is between 5-10% of the population.
Predisposes to development of primary hepatocellular carcinoma in as many as 3% of patients per year.
When liver decompensation occurs and if the patient is a suitable candidate, liver transplantation is the only treatment that extends life.
Patients hospitalized are almost three times more likely to die compared to patients without cirrhosis.
Relatively frequent cause of death in the U.S., 8.8 per 100,000 population per year.
Hepatitis C is the leading cause of cirrhosis in the U.S.
Patients with cirrhosis should be screened for hepatocellular carcinoma on a regular basis.
Patients who have had spontaneous bacterial peritonitis are at great risk for further infections and should receive prophylactic antibiotics.
Mortality rates range from 37-98% for cirrhotic patients who require admission to the ICU.
Mortality 3 times increased risk of in-hospital mortality compared with patients without cirrhosis.
Recommended that endoscopic screening be done to detect esophageal varices in patients with cirrhosis and no previous bleeding.
Patients have abnormalities in humoral and cell mediated immunity.
Patients with diffuse fibrosis frequently have hypocomplementemia with defective opsonization.
Reticuloendothelial system abnormalities lead to impaired ability of the liver to clear bacterial pathogens from the portal system.
There is a lack of evidence for an association between bleeding and laboratory tests of coagulation in liver disease.
The lack of bleeding in such patients despite diminished procoagulant synthesis, may be explained by a concomitant reduction in the production of anticoagulant proteins such as proteins S and C leading to equivalent thrombin generation with potential to activate pro and anti-coagulant pathways.
In early disease with moderate portal hypertension increased cardiac output compensates for modest reductions in systemic vascular resistance allowing arterial pressure and arterial blood volume to remain in the normal range.
In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target 30 g/L or more was not beneficial than current standard of care (ATTIRE trial Investigators).