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