Cirrhosis and Portal hypertension
Cirrhosis:
Definition: progressive fibrosis and nodular regeneration of hepatic architecture resulting from hepatocellular injury. Generally irreversible in the advanced stages
Etiology:
Alcohol, Viral hepatitis (HBV, HCV), Autoimmune hepatitis, Metabolic diseases (Hemochromatosis, Wilson’s disease), Biliary Tract Disease such as primary biliary cirrhosis, Vascular disease (Budd-Chiari syndrome, chronic heart failure cirrhosis), Nonalcoholic fatty liver disease
Clinical Presentation:
· Stigmata of chronic liver disease
-Spider angiomata (vascular lesions found on trunk, face, upper extremities), Palmar erythema, Clubbing, Dupuytren's contracture (thickening and shortening of the palmar fascia, which causes flexion deformities of the fingers), Gynecomastia, testicular atrophy, shrunken palpable firm nodular liver, Muehrcke's nails (horizontal white nail lines), Splenomegaly, Ascites, Caput medusae, Jaundice/dark coca-cola urine, Fetor hepaticus (sweet smelling breath), Asterixis, Encephalopathy, Hemorrhoids
· Laboratory findings
-Variably elevated AST/ALT/alk phos, Progressive increase in bilirubin, Synthetic malfunction of the liver: low albumin/ prolonged PT/ low cholesterol/ hypoglycemia (late)/ increased PT, Anemia (multi-factorial), Thrombocytopenia (splenic sequestration), Leukopenia, neutropenia (splenic sequestration)
· Diagnosis
-Abdominal ultrasound (cirrhosis, HCC, ascites, assess patency of portal, splenic, hepatic veins with Doppler), Hepatitis serologies (HBsAg, anti-Hbsurface antigen, anti HCV), iron studies, echo if signs of right sided heart failure
-+/- liver biopsy if diagnosis unclear to r/o treatable cause
· Complications:
o Hepatorenal syndrome: type 1 is rapidly progressive and type 2 slower onset. Defined with increased creatinine (progressive azotemia), bland urine sediment with mild proteinuria, no response to volume challenge. Etiology: GI bleed, overdiuresis, infection, paracentesis, drugs (aminoglycoside antibiotics, NSAIDs)
§ Treatment: first give 1 liter of fluid to see if urine output increases, otherwise treat with octreotide/midodrine, hold diurectics
o Portal Hypertenion and ascites: see below for detail
o Hepatic encephalopathy: failure of liver to detoxify harmful, noxious agents (NH3 and others). Etiology: GI bleed, excess dietary protein, constipation, infection (especially SBP), renal failure, HCC, hypotension, dehydration, sedatives, med non-compliance.
§ Initially euphoria, confusion, slurred speech, disordered sleep (stage 1) àlethargy, confusion worsens, asterxsis (stage 2) à marked confusion, sleepy but arousable (stage 3) à coma (stage 4)
§ Treatment – exclude OTHER causes of encephalopathy. Treat underlying precipitant of hepatic encephalopathy if possible. Protein restriction, lactulose (30 cc every hour for goal 3-4 bowel movements daily.
Portal Hypertension
Definition:
Portal hypertension frequently complicates cirrhosis and is present with GI bleeding, ascites, and splenomegaly.
It is established by determining the pressure difference between the hepatic vein and the portal vein. A pressure gradient of greater than 10 mmHg is seen in portal hypertension, and complications can occur when the pressure gradient is greater than 12 mmHg.
Etiology:Most common etiology in Tanzania for portal HTN is schistosomiasis: other causes include cirrhosis, cystic fibrosis, splenic and portal vein thrombosis, sarcoidosis
***Schistosomiasis***
Definition: a common, chronically debilitating disease worldwide. Caused in humans by infection with the mammalian blood flukes or trematodes, Schistosoma.
Transmission: occurs when humans are exposed to water infested with the intermediate snail host while swimming, washing, or collecting water. Schistosome cercariae released from the snails penetrate human skin and enter blood vessels, passing via the lungs to the liver where they mature into adults. The adults mate and produce eggs and these eggs can embolize to various other organs
Pathophysiology in liver disease: NON cirrhotic, peri-portal fibrosis of the liver [no nodular regenerative activity] caused by inflammatory response to schistosomal eggs,. PRE-sinusoidal portal hypertension
Clinical features of hepatic disease: often occurs in the left lobe. Most common feature is portal hypertension, severe hepatosplenomegaly, ascites, esophageal or gastric varices. Liver enzymes usually normal with few stigmata of cirrhosis
Diagnosis: history of exposure, eggs in urine or feces
Treatment: high rate of reinfection so total cure is difficult, also sometimes full treatment does not produce full cure. Praziquantel effective against all schistosome species, cure rate is 70%
Complications or signs/symptoms of portal hypertension:
Esophageal varices:
-Pathophysiology: Develop as a consequence of portal hypertension (increased resistance to blood flow in the portal venous system). Occurs from development of portal-systemic collateral channels (retrograde flow from the high-pressure portal venous system to lower-pressure systemic circulation; this happens especially in esophagus and causes significant upper GI bleed
-Signs/symptoms: upper GI bleed, high mortalitiy
-Treatment: IV access, packed red blood cells, too much IV fluid can increase portal pressure and result in recurrent GI bleed, endoscopy with banding if available
-Prevention of upper GI bleed in patients with portal HTN is non-selective beta blockers (titrate to goal heart rate less than 25% of baseline). Want to decrease portal pressures to < 12 mmHg
Other sources of GI bleeding: hemorrhoids, rectal varices
Ascites:
-Definition: abnormal accumulation of fluid within the peritoneal cavity. It is a common manifestation in decompensation of cirrhosis also
-Pathophysiology: one theory is that portal hypertenion leads to leakage of fluid into peritoneum, thus leads to a decrease in plasma volume and this leads to sodium retention. Another theory is that portal hypertension leads to systemic vasodilatation due to release of nitrous oxide, this leads to decreased effective arterial volume and renal sodium retention
-Signs/Symptoms: abdominal distention, abdominal discomfort
-Evaluation: physical exam findings of shifting dullness. Abdominal ultrasound will detect fluid if > 100 cc. Paracentesis
-Paracentesis: diagnostic is indicated in all patients with new ascites, signs of infection (abdominal pain, fever, leukocytosis, acidosis), coagulopathy is not a contraindication
-SAAG (serum-ascites albumin gradient): if ratio is > 1.1-> portal HTN as etiology of ascites (cirrhosis, schistosomiasis, heart failure, budd chiari) .
if ratio is < 1.1 -> peritonitis (TB), peritoneal cancer, pancreatitis
-Treatment:
-decrease sodium intake (less than 2 grams a day)
-diuretics: spironolactone and lasix (can increase slowly until goal diuresis of 1 liter a day is obtained)
-therapeutic paracentesis (large volume): if diuretics are not working, moniter blood pressure during procedure since removing a lot of fluid can result in hypotension
-Complications: spontaneous bacterial peritonitis, > 250 neutrophils on diagnostic tap or positive gram stain, needs IV antibiotics
Cirrhosis and Portal Hypertension Clinical Cases
Case 1
50 yo male with history of schistosomiasis, HTN is admitted to the hospital with abdominal distention and fatigue. He tells you that for the past few months, he noticed that his abdomen is getting bigger. No fevers, chest pain or shortness of breath. Mild nausea but no vomitting. He has not noticed any peripheral edema. His blood press on admission 140/79 and HR is 90. He is afebrile.
1. What physical exam findings to you expect to find?
a. severe hepatosplenomegaly, ascites, esophageal or gastric varices. Liver enzymes usually normal with few stigmata of cirrhosis
2. What is the most likely etiology of his abdominal distention?
a. Ascites
3. What imaging study do you want to order to confirm your diagnosis?
a. US abd.
You order routine blood work and an abdominal ultrasound. His blood work is still pending but his abdominal ultrasound is completed. The ultrasound shows ascites and portal hypertension, normal looking liver.
1. What procedure should you perform in this patient?
a. Paracentesis
2. What laboratory values to you want from the fluid and serum? Why?
a. SAAG (serum-ascites albumin gradient): if ratio is > 1.1-> portal HTN as etiology of ascites (cirrhosis, schistosomiasis, heart failure, budd chiari)
b. if ratio is < 1.1 -> peritonitis (TB), peritoneal cancer, pancreatitis
3. What is the cause for his portal hypertension?
a. Peri-portal fibrosis 2/2 inflammatory response to eggs
4. What is this patient at significant risk for?
a. Variceal bleed, also re-infection
Case 2
45 yo female with no past medical history presents with upper GI bleed. She tells you that she vomitted up bright red blood while she at home. This only happened once. She denies naseau/vomiting. She denies lightheaded/dizziness. She does not take any medications. The patient does report going to Lake Victoria everyday.
1. What is the most likely underlying cause of her upper GI bleed?
a. Variceal bleed 2/2 peri-portal htn from schistosomiasis.
2. What imaging study do you want to order to confirm? And what are you specifically looking for in the study?
a. EGD if available to look for engorged or bleeding vessels.
b. US to evaluate liver.
3. Can this patient have cirrhosis?
a. Would be unusual, given lack of of medical history, but not impossible.
