Cirrhosis: Clinical practice
Medicine and surgery
AssessmentsCirrhosis: Clinical practice
USMLE® Step 2 style questions USMLE
A 55-year-old man is brought to the emergency department due to confusion. He has not had fevers, vomiting, diarrhea, or epigastric pain. His last colonoscopy was 5 years ago and was notable for benign polyps, which were subsequently resected. Past medical history includes hypertension, hypercholesterolemia, gastroesophageal reflux disease and type 2 diabetes. He has been drinking a half-pint of vodka daily for 30 years. Temperature is 37.0°C (98.6°F), pulse is 80/min, respirations are 20/min, and blood pressure is 135/85 mmHg, BMI is 20 kg/m2. Physical examination reveals erythematous palms. Abdominal distension and shifting dullness is noted on abdominal examination. Neurologic examination is notable for flapping tremors and impaired recent and remote memory. Fecal occult blood test is positive. Which of the following is the mechanism of action of the most appropriate pharmacological agent in this patient?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS, Anca-Elena Stefan, MD
Cirrhosis is when chronic inflammation and liver damage causes the liver to become fibrotic and develop scar tissue.
At a cellular level, the hepatocytes become impaired and this leads to hepatic dysfunction and portal hypertension.
Cirrhosis is usually irreversible, so it’s usually called “end-stage” or “late-stage” liver damage, and often requires a liver transplant. However, in some cases, early treatment can slow down and even reverse the cirrhosis.
Compensated cirrhosis is when there are enough healthy cells to make up for the damaged ones, but minor complications like hemorrhoids can still occur.
Decompensated cirrhosis is when healthy cells can no longer keep up with the workload, causing major complications like hepatic encephalopathy, ascites, and esophageal and gastric variceal hemorrhage.
In compensated cirrhosis, although there aren’t any major complications, there may still be some symptoms such as loss of appetite, fatigue, and muscle cramps. There may also be easy bruising and excessive bleeding because there aren’t enough clotting factors produced by the liver.
Cirrhosis can also impair estrogen metabolism, causing amenorrhea and irregular menstrual bleeding in females, and low libido and gynecomastia in males.
On physical exam, there may be hepatomegaly - where the liver can feel firm and nodular, but when there’s a lot of scarring, the liver may be small so that it can’t be felt at all.
Another sign is spider angiomas- or spider nevi- which are swollen blood vessels just beneath the skin surface- on the truck, face and upper limbs.
Palmar erythema- which is redness of the hands- can sometimes be seen.
There can also be hypertrophic osteoarthropathy- which is when there’s nail clubbing and periostitis- which is inflammation around the small hand joints.
Sometimes, there are Dupuytren contracture, which is when one or more fingers are permanently flexed.
Portal hypertension can lead to splenomegaly, along with caput medusae- which are distended and engorged paraumbilical veins on the surface of the abdomen.
Finally, there may be minor complications such as hemorrhoids identified on a digital exam.
In terms of diagnosing cirrhosis, lab work includes a CBC- which most commonly shows thrombocytopenia- especially if there’s also splenomegaly, but can also show anemia and leukopenia.
Markers of liver injury are AST, ALT, alkaline phosphatase, and GGT and they’re usually elevated.
Total and conjugated bilirubin are usually normal in compensated cirrhosis.
Finally, markers of liver function like albumin can decrease as cirrhosis progresses, and PT, PTT, and INR- can increase as cirrhosis progresses.
In addition, Fibrosure or Fibrotest is done using alpha-2-macroglobulin, haptoglobin, total gamma globulin, apolipoprotein A1, GGT, and total bilirubin to generate a score that estimates liver fibrosis.
An abdominal ultrasound shows surface nodularity and increased echogenicity and sometimes there’s atrophy in the right lobe and hypertrophy of the left and caudate lobe.
If there’s portal hypertension, then the diameter of the portal vein is over 13 millimeters.
There’s also ultrasound-based elastography- which measures tissue elasticity. Normal liver elasticity ranges from 2.6 to 6.2 kilopascals and when it’s above 7 kilopascals, that means that there’s significant fibrosis and when it’s above 11 kilopascals, that means there’s cirrhosis.
A liver biopsy is the gold standard for diagnosing cirrhosis and also finding the cause, but it’s not always done, especially when other findings strongly suggest cirrhosis. If it’s done, a liver biopsy will often show bridging fibrosis and irregular nodules of regenerating hepatocytes.
Individuals with cirrhosis should avoid alcohol, medications that are hepatotoxic, such as acetaminophen and also herbal and dietary supplements, that can damage the liver like germander. Individuals should also be vaccinated for hepatitis A and B if they’re not already immune. Doses of certain medications, like tramadol which is an opioid pain medications, may need to be adjusted to prevent further harm to the liver.
Individuals with cirrhosis should be monitored every 3 to 6 months using a CBC, markers of liver injury and markers of liver dysfunction.
In addition, an ultrasound should be done and alpha fetoprotein levels can also be checked to monitor for possible tumors, since cirrhotic individuals are at increased risk for developing hepatocellular carcinoma.
Okay, now, with decompensated cirrhosis, there are major complications which may be triggered by things like acute infections, alcohol intoxication, constipation, or even bouts of dehydration. Treatment for these complications starts with resolving the triggering event - like treating the infection or abstaining from alcohol.
One major complication of decompensated cirrhosis is jaundice - which can happen because the liver is unable to conjugate bilirubin. Lab findings would show total bilirubin levels over 2 milligrams per deciliter.
Another complication is hepatic encephalopathy- and this happens because the liver is unable to effectively remove toxins- like ammonia- from the blood. These toxins can build up and get into the brain causing symptoms like insomnia or hypersomnia. As toxins accumulate, there can be mood changes, along with confusion and even coma in some cases.
On physical exam, there may be asterixis- a flapping tremor of the hand that appears when the wrist is extended- like a bird that’s flapping its wings.
Lab findings show high levels of ammonia, and it can be lowered using lactulose given orally or through an enema. Lactulose is a non-absorbable sugar that decreases absorption of ammonia in the intestines and prevents constipation.
If the individual doesn’t improve in 48 hours, then oral Rifaximin is given. That’s an antibiotic that kills ammonia-producing bacteria in the intestines and also has anti-inflammatory proprietes.
Individuals with recurrent hepatic encephalopathy can be given ongoing treatment with lactulose.
Now, although portal hypertension can seen in compensated cirrhosis - as things worsen, it can lead to major complications that are seen in decompensated cirrhosis.
Portal hypertension can cause peripheral edema as well as a build up of excess fluid in the peritoneal cavity - resulting in ascites.
Ascites can cause abdominal distention, as well as shifting dullness on percussion and a positive fluid wave test.
Additional lab work for ascites includes electrolytes in order to identify any imbalances, especially hyponatremia.
An abdominal ultrasound can confirm the diagnosis- usually the fluid in ascites appears anechoic.
Next, a paracentesis is done to collect ascitic fluid. The ascitic fluid is typically crystal clear, and bloody ascitic fluid suggests a tumor.
A cell count and differential is also done and with normal ascitic fluid there are below 250 neutrophils. In addition, total protein levels are below 3 grams per deciliter, saying that the fluid is a transudate- while an exudate has more than 3 grams per deciliter of protein.
Next, the ascitic fluid is tested for albumin to calculate the Serum-to-ascites albumin gradient- or SAAG. A SAAG above 1.1, means that portal hypertension is present.
Because salt helps retain water, treatment of moderate ascites includes sodium restriction to 2 grams per day.
In addition, a combination of diuretics like spironolactone- a potassium sparing diuretic- and furosemide- a loop diuretic- is commonly used to get rid of excess fluid. Individuals without peripheral edema typically lose about 0.5 kilograms daily, and individuals with peripheral edema lose about 1 kilogram daily. As the ascites resolves, the diuretics are tapered and then stopped.
If an individual develops hepatic encephalopathy or has severe hyponatremia- with sodium levels below 120 milliequivalents per liter, then diuretic treatment is stopped and serial paracentesis is done to reduce the ascites.
In severe hyponatremia, fluid intake is restricted to less than the urine volume.
Treatment of severe ascites is done using large volume paracentesis- where up to 5 liters of fluid is taken out of the abdomen at one time without causing hypovolemia. When more than 5 liters of fluid is taken out, albumin is given afterwards.
A major complication of ascites is spontaneous bacterial peritonitis- or SBP- which is an infection of the ascitic fluid. It can cause severe abdominal pain, fever, and an altered mental status.
A paracentesis of the ascitic fluid is done- and the fluid looks turbid or cloudy, the cell count is over 250 neutrophils per millimeter square and total protein is above 1 gram per deciliter, and the SAAG is above 1.1.
In addition, the glucose is usually above 50 milligrams per deciliter- which distinguishes SBP from a secondary bacterial peritonitis, where glucose is below 50 milligrams per deciliter and the LDH is below 225 international units per liter.
Cultures and cgram stains are also sent.
With SBP, there’s a single pathogen found and the common are Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae, whereas with secondary bacterial peritonitis, multiple pathogens are usually involved. Empiric antibiotics for SBP are IV Cefotaxime.
Another major complication of portal hypertension is variceal hemorrhage- specifically bleeding from dilated veins in the esophagus and stomach.
Esophageal and stomach variceal veins are usually seen on an upper endoscopy which is usually done within 12 hours of the bleeding. During that procedure variceal ligation or endoscopic sclerotherapy can be done to help stop the bleeding. In addition, IV octreotide, which is a somatostatin analogue, is used to help decrease portal blood flow.
If there’s massive bleeding or if endoscopic therapy fails to stop the bleeding, then balloon tamponade is done using a Blakemore tube. This applies direct pressure on the esophagus.
If endoscopic approaches fail, a transjugular intrahepatic portosystemic shunt or TIPS procedure can be done- which creates a path between the portal and systemic circulation in order to lower the portal pressure.