That Looks Like a Shrunken Raisin – Chronic … · Myxedema Pancreatic ... Coma Elevated serum...
Transcript of That Looks Like a Shrunken Raisin – Chronic … · Myxedema Pancreatic ... Coma Elevated serum...
That Looks Like a Shrunken Raisin –Chronic Complications of CirrhosisSHELDON C BERGER, DO, FACOI
Cirrhosis Definition
Defined histologically as a hepatic process characterized by fibrosis and conversion of the normal liver into structurally abnormal nodules
The progression of liver injury to cirrhosis may take weeks to years
Cirrhosis
Final common histologic pathway for multiple chronic liver diseases
Cirrhosis was first introduced by Laennec in 1826 Greek term scinrrhus and refers to orange or
tawny surface of the liver at autopsy
Cirrhosis
35,000 deaths each year in the United States from cirrhosis
2000 additional deaths from fulminant hepatic failure (FHF) – viral hepatitis, drugs, toxins
50-80% mortality with FHF
Fibrosis
Multiple liver processes or diseases may cause fibrosis – EtOH, viral hepatitis, fatty liver, NASH
Deposition of extracellular matrix, collagen and proteins
Potentially reversible in contrast to cirrhosis which is not reversible
Sign and Symptoms of CirrhosisYou know it when you see itGI bleeding – Upper vs Lower GIEsophageal and Gastric VaricesPortal hypertensive gastropathy
Portal hypertensionAscitesShrunken liverAbdominal painHepatic encephalopathyHepatorenal syndrome
Signs and Symptoms of Cirrhosis
Coagulopathy Fatigue Anorexia Weight loss Jaundice Spider angioma Palmar erythema Clubbing
Causes of Cirrhosis
Hepatitis C EtOH Hepatitis C with EtOH NAFLD/NASH Cryptogenic causes Hepatitis B Miscellaneous
Hepatitis C
CDC has recommended a 1-time blood test for hepatitis C for all baby boomers, 1945-1965
One-time HCV testing could identify over 800,000 people with the infection
Alcoholic Liver Disease
Alcoholic liver disease was the predominant source of cirrhosis in the United States
Nonalcoholic Fatty Liver Disease -NAFLD
Cofactors include – obesity, diabetes, hypertriglyceridemia
Steatosis common finding One third of Americans have nonalcoholic
steatohepatitis (NASH) One third of NASH patients will develop cirrhosis NAFLD and NASH will become the largest cause
of cirrhosis, bigger than EtOH and Hepatitis C
Miscellaneous Causes of chronic liver disease and Cirrhosis
Autoimmune hepatitis Primary biliary cholangitis (PBC) Secondary biliary cirrhosis – chronic bile duct
obstruction Primary sclerosing cholangitis (PSC) Hemochromatosis
Miscellaneous Causes of chronic liver disease and Cirrhosis
Alpha-1 antitrypsin deficiency Granulomatous disease – sarcoidosis Drug-induced liver disease Chronic right-sided heart failure – passive
congestion
Cirrhosis
There is often a poor correlation between histologic findings and clinical picture
Symptoms can range from asymptomatic with a reasonably normal life expectancy
Severe symptoms of coagulopathy, encephalopathy, variceal bleeding signal decompensation
Portal Hypertension
Caused by increased portal venous flow and increased resistance to portal flow
Increased splanchnic arterial flow and increased cardiac output driven by nitrous oxide
Portal Hypertension
Normal hepatic venous pressure gradient (HPVG) is 3-6 mm Hg
Variceal formation and then bleeding can occur with pressures greater than 12 mm Hg
Medical Treatment of Variceal and Nonvariceal Cirrhotic Bleeding
Nonselective beta blockers – not for acute bleeding, can be used for prophylaxis
Vasopressin with Nitroglycerin – not used any longer
Octreotide bolus and drip – decrease portal pressure by causing splanchnic vasoconstriction
Shunts
Peritoneovenous shunts – Denver and LeVeen Surgical shunts Transjugular intrahepatic portosystemic shunts
(TIPS)
Transjugular Intrahepatic Portosystemic Shunts (TIPS)
Refractory variceal bleeding Ascites treatment – can be effective in massive
ascites Can increase hepatic encephalopathy – up to
30% Mortality is increased in patients with MELD score
of 18 and total bilirubin > 3 Stent occlusion can occur, but is improved with
coated stents
Ascites
Accumulation of excessive fluid within the peritoneal cavity
Hepatic and nonhepatic causes Cirrhosis, neoplasm, CHF, TB Transudate - protein < 2.5 gr/dl – Cirrhosis and
CHF Exudate - protein > 2.5 gr/dl – neoplasm, TB
Ascites
Peritoneal and nonperitoneal causes of ascites may be a more useful classification
Serum-ascites albumin gradient (SAAG) Nonperitoneal diseases, like cirrhosis, produce
ascites with SAAG >1.1 gr/dl
Ascites – Medical Treatment
Sodium and fluid restrictions – Na+ < 2 gr/day and fluid < 2 l/day
Diuretics – spironolactone (50-300mg/d) blocks aldosterone receptor in distal tubule, and furosemide (40-240 mg/d) blocks sodium reuptake in loop of Henle
Albumin not supported by evidence-based medicine, but may increase the efficacy of diuretics
Paracentesis
Essential in determining the cause of ascites Performed for a new onset or worsening ascites Rule out infection – culture bottles are done at
the bedside Large-volume paracentesis for abdominal
discomfort, anorexia, dyspnea, reduce risk of umbilical hernia rupture
5-15 liters can be removed safely Colloid infusions (albumin) ?
Nonperitoneal Causes of Ascites
Cirrhosis Veno-occlusive disease Hepatic vein obstruction (Budd-Chiari) CHF Nephrotic syndrome Protein-losing enteropathy – Malnutrition Myxedema Pancreatic ascites Chylous ascites - trauma
Peritoneal Causes of Ascites
Malignant ascites – carcinomatosis Tuberculous peritonitis Granulomatous peritonitis – Candida,
Histoplasmosis, Cryptococcus, Entamoeba histolytica, Schistosoma mansoni, Sarcoridosis, SLE, foreign bodies
Ascites
Sodium retention occurs with cirrhosis Impaired free-water excretion and intravascular
volume overload Abdominal distention Bulging flanks Shifting dullness Ultrasound is the most diagnostic – 30 ml of
ascites
Spontaneous Bacterial Peritonitis (SBP)
Can occur in 15-26% of patients with cirrhosis Occurs most in low protein ascites Caused by translocation of GI tract bacteria across
the gut wall and by hematological spread E coli, Strep pneumoniae, Klebsiella and other gram-
negative bacteria Diagnosed by WBC > 250 Positive culture of the ascites Mortality of 20-30%
Hepatic Encephalopathy
Altered mental status Coma Elevated serum ammonia is the classic
laboratory abnormality Gamma-aminobutyric acid (GABA) EEG may be helpful, especially to rule out other
etiologies – seizure Head CT and MRI may be done to rule out
intracranial lesions
Hepatic Encephalopathy (HE)
Grade 0 – Subclinical, normal mental stateGrade 1 – Mild confusion, euphoria or depressionGrade 2 – Drowsiness, lethargy, personality
changesGrade 3 – Somnolent, but arousable, marked
confusion, amnesiaGrade 4- Coma with or without response to pain
Asterixis and fetor hepaticus can be associated with HE
Hepatic Encephalopathy Treatment
Look for other causes – intracranial lesions, infections, toxins, drugs, seizure
Increased encephalopathy with diuretics, GI bleeding, renal failure, infection, constipation, hypovolemia
Hepatic Encephalopathy Treatment
Lactulose is a nonabsorbable disaccharide sugar that stimulates the passage of ammonia into the gut lumen and holds it there
Initial dose of 30 ml once or twice a day Goal of 2-4 stools/day, usually loose Rifaximin (Xifaxan) – nonabsorbable antibiotic Antibiotics – Neomycin, metronidazole,
vancomycin, second line treatments Protein restrictions – rarely necessary
Hepatorenal Syndrome
Creatinine clearance rate of less than 40 ml/min Serum creatinine 1.5 mg/ml Urine volume < 500 ml/day Urine sodium <10 mEq/L Urine osmolality > plasma osmolality
Hematologic Complications of Cirrhosis
Anemia – results from folate deficiency, hemolysis and hypersplenism
Thrombocytopenia – secondary to hypersplenism and decreased levels of thrombopoietin
Coagulopathy – results from decreased production of coagulation factors
Neoplasms
Hepatocellular carcinoma (HCC) in 10-25% of cirrhotics, occurring 3%/yr in hepatitis B, EtOHand hepatitis C
Hepatomas can be treated with percutaneous treatments, radio and chemoembolization, radiofrequency ablation (RFA), ethanol injection or with surgery and liver transplantation
Cholangiocarcinoma
Cirrhosis Severity Assessment
Child-Turcotte-Pugh (CTP) system Originally for predicting operative mortality in
portocaval shunt surgery CTP > 10 is associated with 50% chance of death
within 1 year CTP is based on encephalopathy level, ascites
extent, bilirubin, Albumin, INR Child Class A=5-6 points, Child Class B=7-9 points,
Child Class C=10-15 points
Cirrhosis Severity AssessmentMELD Score
Model for End-Stage Liver Disease scoring system to assess the relative severity of liver disease and 3 month mortality
MELD Score of 6-40 MELD < 9 – 2.9% mortality MELD 10-19 – 7.7% mortality MELD 20-29 – 23.5% mortality MELD 30-39 – 60% mortality MELD > 40 – 81% mortality
Cirrhosis Prevention or Forestall the Development of Cirrhosis
Prednisone and azathioprine for autoimmune hepatitis
Direct acting agents for Hepatitis C Antiviral agents for Hepatitis B Phlebotomy for hemochromatosis Ursodeoxycholic acid for primary biliary
cholangitis Zinc, penicillamine and trientine for Wilson’s
disease
Cirrhosis Prevention or Forestall the Development of Cirrhosis
EtOH abstinence is the most important Shrink the fat in NAFLD/NASH
Control blood sugars and fats/triglyceridesWeight loss
Cirrhosis Follow Up Care
Screen cirrhotic patients for esophageal and gastric varices
Treat varices – beta blockers and banding Screen for hepatocellular cancer (HCC) – every
6-12 months with ultrasound, CT or MRI, with or without alpha fetal protein
Zinc replacement with zinc sulfate 220 mg BID –may improve dysgeusia and stimulate appetite
Cirrhosis Follow Up Care
Pruritus – Initially thought to be secondary to bile acids, endogenous opioids are more likely to be the culprit
Pruritus treatment – antihistamines, topical agents, cholestyramine, URSO, doxepin, rifampin
Naltrexone may be poorly tolerated Gabapentin may be unreliable Plasmapheresis
Cirrhosis Follow Up Care
No EtOH Osteoporosis – Calcium and Vitamin D Vaccinations for Hepatitis A and B in all chronic liver
disease patients Statins can be used safely in chronic liver disease Avoid high doses of acetaminophen Caution use of NSAID’s – risk of GI bleeding and
renal complications Encourage a good diet and exercise Not necessary to restrict protein
Liver Transplantation
Referral after first signs of hepatic decompensation