Best Dx/Best Rx: Cirrhosis of the Liver

From: Subject: Best Dx/Best Rx: Cirrhosis of the Liver Date: Wed, 3 Jun 2009 21:38:53 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_01F2_01C9E493.B0C696E0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_01F2_01C9E493.B0C696E0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0409.htm Best Dx/Best Rx: Cirrhosis of the Liver

Cirrhosis = of the=20 Liver

Ram=F3n Bataller, M.D.
Pere Gin=E8s,=20 M.D.
Institut de Malalties Digestives i Metab=F2liques, Hospital = Clinic,=20 Barcelona, Spain

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features=20

A diffuse disorganization of normal hepatic = structure by=20 extensive fibrosis associated with regenerative nodules=20
High morbidity and mortality=20
Advanced disease is usually = irreversible=20
Insidious onset of symptoms=20
Generalized weakness, anorexia, malaise, = weight=20 loss=20
Loss of skeletal muscle mass=20
Symptoms may be absent or minor in = "compensated"=20 cirrhosis=20
Symptoms of hepatocellular dysfunction and = portal=20 hypertension=20
- Progressive jaundice, skin = hyperpigmentation,=20 pruritus, xanthelasmas=20
- Bleeding from gastroesophageal = varices=20
- Ascites=20
- Neuropsychiatric symptoms=20
- Coagulopathy, mucosal bleeding in advanced=20 disease=20
- Malnutrition
- Fat-soluble vitamin deficiency=20
- Nervous system, heart, and pancreatic = symptoms in=20 alcohol-related liver disease
Complications=20
- Ascites=20
- Gastrointestinal bleeding=20
- Hepatorenal syndrome=20
- Spontaneous bacterial peritonitis=20
- Hepatopulmonary syndrome=20
- Hepatic encephalopathy=20
- Hepatocellular carcinoma =

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Differential=20 Diagnosis=20

Hepatic encephalopathy=20
- Intracranial lesions=20
- Central nervous system infections=20
- Other metabolic causes of = encephalopathy=20
- Toxic encephalopathy from alcohol or = drugs=20
- Postseizure encephalopathy=20
- Psychiatric disorders =

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Best=20 Tests
Physical = Examination

Liver is enlarged in initial phases, decreased = in size=20 in advanced disease=20
Splenomegaly=20
Ascites and/or peripheral edema=20
Altered mental status, decreased = consciousness,=20 asterixis in patients with hepatic encephalopathy
Muscle wasting, palmar erythema, vascular = spiders,=20 gynecomastia, axillary hair loss, testicular atrophy, fetor = hepaticus=20
Dupuytren contractures, parotid gland = enlargement,=20 peripheral neuropathy in alcoholic patients

Laboratory Tests

Serum aspartate aminotransferase (AST): = frequently=20 elevated, but levels > 300 U/L uncommon=20
Serum alanine aminotransferase (ALT): may be = relatively=20 low (AST/ALT > 2)=20
Prothrombin time: frequently prolonged=20
Serum albumin levels: decreased=20
Total serum globulin concentration: increased = in=20 advanced cirrhosis
Alkaline phosphatase: moderately increased; = markedly=20 increased in patients with biliary disease=20
Blood count=20
- Leukopenia and thrombocytopenia may be = present=20
- Normocytic anemia; may be microcytic, = hypochromic,=20 macrocytic, or hemolytic
Serum cholesterol and triglyceride levels: may = be=20 increased in biliary obstruction; low in advanced cirrhosis=20
Blood glucose: glucose intolerance and = diabetes mellitus=20 may be present=20
Serum sodium; hyponatremia is common=20
Respiratory alkalosis may be present with low = serum=20 bicarbonate and high serum chloride=20
Serum magnesium and phosphate levels: = hypomagnesemia and=20 hypophosphatemia
Creatinine and urea blood levels: elevated in = renal=20 failure in patients with ascites
Viral serologies to identify causative = agent=20
α-Fetoprotein serum levels: at diagnosis = and every 6 mo=20 to detect early hepatocellular carcinoma (HCC); mild elevations are = common in=20 cirrhosis

Imaging

Real-time ultrasound=20
- Demonstrates morphologic characteristics of=20 cirrhosis=20
  - Irregular/nodular liver edges=20
  - Altered liver structure=20
  - Signs of portal hypertension, such as=20 portocollateral veins
- Detects hepatic steatosis, ascites, = splenomegaly, and=20 portal vein thrombosis=20
- Rules out extrahepatic causes of = jaundice=20
- Detects early HCC
Color flow Doppler ultrasound=20
- Shows portal hemodynamics=20
- Detects hepatic tumors and tumor = vascularization=20
Dynamic studies using CT and MRI: useful in = assessing=20 cirrhosis and diagnosing hepatic tumors; expensive=20
Endoscopy: to assess presence and size of = esophageal=20 varices

Liver Biopsy

Not always necessary if clinical picture, = labs, imaging=20 suggest cirrhosis=20
Unequivocally establishes diagnosis=20
Helps determine cause and extent of liver = damage=20
Percutaneous biopsy for most patients; = transjugular=20 biopsy for those with severe coagulopathy (INR > 1.5 and/or = platelet count=20 < 50,000/mm=B3)=20
Use with caution in patients with ascites or = severe=20 obesity=20
Subject to sampling error, especially in = macronodular=20 cirrhosis=20
Histologic findings=20
- Extensive fibrosis and regenerative = nodules=20
- Periportal lymphocyte infiltration suggests=20 HCV-induced cirrhosis=20
- Mallory bodies, polymorphonuclear leukocyte=20 infiltration, and steatosis indicate alcohol-induced cirrhosis = and/or=20 nonalcoholic steatohepatitis (NASH)=20
- Biliary involvement indicates primary = biliary=20 cirrhosis (PBS)=20
- Massive iron deposition indicates=20 hemochromatosis

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Best=20 Therapy

Adequate caloric and protein intake=20

Mild exercise, including walking and = swimming=20

Surgery and general anesthesia carry increased = risks=20

Zinc sulfate (50=96200 mg/day) for zinc = deficiency

Topical testosterone for male patients with = hypogonadism=20

Calcium and vitamin D for patients at high = risk for=20 osteoporosis=20

Aminobisphosphonates for decreased bone = mineralization=20

Vaccination against hepatitis A, hepatitis B,=20 pneumococci, and influenza=20

Avoid hepatotoxic medications (acetaminophen = considered=20 safe at dosages < 3 g/day)=20

Avoid nonsteroidal anti-inflammatory drugs = (NSAIDs) and=20 nephrotoxic antibiotics (e.g., aminoglycosides) in patients with=20 ascites=20

Pegylated interferon plus ribavirin=20

Consider for patients with compensated = cirrhosis due=20 to hepatitis C virus (HCV) infection=20
For patients with decompensated cirrhosis = awaiting=20 orthotopic liver transplantation (OLT), initiate several months = before OLT=20 to prevent graft reinfection=20
Response lower than in noncirrhotic = patients=20
May worsen existing anemia and/or=20 thrombocytopenia=20
Pegylated interferon

Dose:=20

Alpha 2a, 180 =B5g/wk S.C.; cost/mo: = $1,700=20
Alpha 2b: 1.5 =B5g/kg/wk S.C.; cost/mo:=20 $2,700

Ribavirin=20

Dose: 800=961,200 mg/day p.o.; cost/mo:=20 $1,100-$1,600

Orthotopic liver transplantation=20

1-year survival rate, 85%; 5-year = survival rate,=20 > 70%=20
Indications=20

Hepatocellular liver disease=20

Serum bilirubin > 3 mg/dl=20
Serum albumin < 2.5 g/dl=20
Prothrombin time >5 sec above=20 control

Cholestatic liver disease=20

Serum bilirubin > 5 mg/dl=20
Intractable pruritus=20
Progressive bone disease=20
Recurrent bacterial = cholangitis=20

Both hepatocellular and cholestatic = liver=20 disease=20

Recurrent or severe hepatic=20 encephalopathy=20
Refractory ascites=20
Spontaneous bacterial = peritonitis=20
Recurrent portal hypertensive = bleeding=20
Progressive malnutrition=20
Hepatorenal syndrome =

Hepatocellular carcinoma (< 3 = nodules; no=20 nodule > 5 cm; no portal invasion)

Contraindications=20

Severe cardiovascular or pulmonary disease=20
Active drug or alcohol abuse=20
Malignancy outside the liver=20
Sepsis=20
Psychosocial problems jeopardizing posttransplant = care=20

Pruritus

Cholestyramine, 4 g/day; cost/mo: $40=20
Ursodeoxycholic acid, 10 mg/kg/day; cost/mo: = $140=20
Naltrexone, 50 mg/day; cost/mo: $100=20
Rifampicin, 10 mg/kg/day; cost/mo: $100 =
Ondansetron, 8 mg q. 12 hr; cost/mo: = $2,200=20

HBV-Related = Cirrhosis

Lamivudine: may improve or stabilize liver = disease in=20 some patients; resistance can develop with prolonged treatment=20
- Dose: 100 mg/day=20
- Cost/mo: $230
Adefovir: active against wild-type and=20 lamivudine-resistant HBV=20
- Dose: 10 mg/day=20
- Cost/mo: $610
Entecavir: active against wild-type and=20 lamivudine-resistant HBV=20
- Dose: 0.5=961.0 mg/day=20
- Cost/mo: $660-$1,310 =

Alcohol-Induced = Cirrhosis

Abstinence from alcohol=20
Nutritional support=20
Colchicine of questionable benefit =

Superimposed Alcoholic=20 Hepatitis

Glucocorticoid: alternative therapy; improves = short-term=20 survival in high-risk subgroup=20
- Methylprednisolone, 32=9640 mg/day for 4 wk, = then=20 tapered for 1=962 wk; cost/mo: $200
Pentoxifylline: alternative therapy; improves = short-term=20 survival=20
- Dose: 400 mg q. 8 hr=20
- Cost/mo: $20

Primary Biliary Cirrhosis

Ursodeoxycholic acid: relieves pruritus and = improves=20 biochemical blood test results, may delay need for liver=20 transplantation=20
- Dose: 13=9615 mg/kg/day=20
- Cost/mo: $230

Cirrhosis Due to Autoimmune = Hepatitis=20

Use immunosuppressant therapy with caution = because it=20 may favor infections

Cirrhosis Due=20 to Genetic Metabolic Diseases=20

Hemochromatosis=20
- Phlebotomy
Wilson Disease=20
- Copper chelators (e.g., D-penicillamine, trientine)=20
- Zinc

The = authors have no=20 commercial relationships with manufacturers of products or providers of = services=20 discussed in this module.

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Best=20 References

Blei AT: Lancet 365:1383, 2005 [PMID = 15836876]

Bosch J, et al: Semin Hematol 41:8, 2004 [PMID=20 14872414]

Cardenas A, et al: J Hepatol 42(suppl):S124, 2005 = [PMID=20 15777567]

Gines P, et al: N Engl J Med 350:1646, 2004 [PMID = 15084697]

Wright TL: Hepatology 36:S185, 2002 [PMID=20 12407593]

August=20 2006