Cirrhosis



Cirrhosis Overview:

LOW ALBUMIN
Edema  work up edema
Ascites SAAG <1.1
  • Infection (Peritoneal TB)
  • Peritoneal Cancer
  • Pancreatic Ascites
  • Biliary Ascites
  • Nephrotic Syndrome
  • Lupus Serositis
  • Bowel Infarction or Obstruction
  • Post-Op Lymphatic leak
  • Hypothyroidism
>1.1 Portal
HTN
Varices (+) Bleed BAND then TIPS
(-) bleed Propanolol 40 mg PO bid or Nadolol 20-40 mg PO qd.
Hepato-Renal syndrome Octreotide 50 mcg x 1, then 50 mcg/hr IV drip x 3-5 d after endoscopic variceal band ligation.
SBP
(WBC > 500,
Neutrophils > 250)
Proph: Bactrim DS 1 tab PO qd or Norfloxacin 400 mg PO qd, or Cipro 750 mg po weekly.
Tx: Cefotaxime 2g IV Q8H x 5-7d
Alcoholic Hepatitis
R-sided CHF
Multi. Liver Mets.
Fulminant hepatic failure
Budd-chiari synd.
Veno-occlusive disease
Fatty liver of pregnancy
Portal vein thrombosis

 
Other Clinical Findings:
High PT (-) bleed monitor
(+) bleed Tx: FFP
Asterixis Flapping hand tremor
Spider Angiomata Decreased Estrogen Metabolism
 =
Increased Estrogen Levels
Gynecomastia
Testicular atrophy
Palmar Erythema
Low Body hair
Encephalopathy Lactulose 30-45 ml PO tid; titrate to 2-4 bowel movements daily
Add neomycin 1-3 g PO qid  OR  rifaximin 200 mg PO tid for refractory cases
Portal
HTN
Varices (+) Bleed BAND then TIPS
(-) bleed Propanolol 40 mg PO bid or Nadolol 20-40 mg PO qd.
Hepato-Renal syndrome Octreotide 50 mcg x 1, then 50 mcg/hr IV drip x 3-5 d after endoscopic variceal band ligation.

 

Etiology

  • Listed in order of prevalence:
    • Alcohol
    • Hepatitis C or B virus
    • Nonalcoholic steatohepatitis (from obesity or diabetes)
    • Hemochromatosis.
    • Primary biliary cirrhosis
    • Wilson disease
    • Alpha1-antitrypsin deficiency, and
    • Autoimmune hepatitis.

Diagnosis

  • Gold standard is percutaneous livery biopsy; presumptive diagnosis by abnormal labs, exam, & imaging (ultrasound or radionuclide liver/spleen scan)

Clinical Features

  • General: Muscle wasting, fetor hepaticus, anorexia, & testicular atrophy
  • Skin: Jaundice, spider angiomata, pruritis, and palmar erythema.
  • Thorax: Gynecomastia and pleural effusion (hepatic hydrothorax).
  • Extremities: Dupuytren contracture, white nails, and clubbing.
  • Abdomen: Ascites, caput medusae, and splenomegaly.
  • Neurologic: Confusion, decreased level of consciousness, and asterixis.

Workup

  • Labs: CBC, CMP, liver panel, PT, and Alpha-fetoprotein.
  • Labs to consider: Hepatitis B and C virus serologies, iron studies, Anti-mitochondrial Ab, Anti-nuclear Ab, and anti-smooth muscle ab, serum ceruloplasmin, and alpha-1-antitrypsin level.
  • A percutaneous liver biopsy is indicated if diagnosis is equivocal.
  • Imaging studies: abdominal ultrasound with doppler of portal vein blood flow.

Management of Complications

Management of Complications of Cirrhosis
(any complication indicates decompensated cirrhosis):

Ascites

General management of cirrhotic ascites:
  • Dietary restriction to 1-2 g sodium daily is essential for successful control
  • Consider fluid restriction < 1500 ml/d if serum Na < 125.
  • AVOID aspirin, NSAIDs, and COX-2 inhibitors; no role for bed rest
Management of moderate-volume cirrhotic ascites:
  • Spironolactone 50-200 mg PO q AM   
    OR
  • Amiloride 5-10 mg PO daily
Management of large-volume cirrhotic ascites:
  • Lasix : Spironolacton = 40 : 100
  • Begin Lasix 40 mg PO a AM and Spironolactone 100 mg PO q AM
  • Double dosage q 3-5 d until
    • Urine Na > Urine K and Weight loss 1 lb/day 
      OR
    • Maximal dose of Spironolactone 400mg PO q AM and Lasix 160 mf PO q AM.
  • Monitor for:
    • Encephalopathy.
    • Renal insufficiency.
    • Electrolytes imbalance.

Management of refractory ascites
(diuretic-resistant ascites):

  • Large-volume Paracentesis q 2-4 wk +/- infusion 8-10 g albumin for each liter of ascitic fluid if more than 5 liters of ascitic fluid removed.
  • Alternative is tranjugular intrahepatic portosystemic shunt (TIPS procedure)
    • Contraindications to TIPS:
      • Portosystemic Encephalopathy
      • CHF
      • Pulmonary hypertension,
      • Multiple hepatic cysts,
      • Active infection,
      • Biliary obstruction,
      • Hepatic or portal vein thrombosis,
      • Central hepatoma,
      • Severe thrombocytopenia
      • Coagulopathy.
  • Recommend referral of patient with ascites for liver transplant (60-70% 5-yr mortality)
 
 

Spontaneous Bacterial Peritonitis (SBP):

  • Clinical Features:
    • Abdominal pain,
    • Fever,
    • Encephalopathy,  OR
    • Asymptomatic (10%)
       
  • Diagnosis:
    • Ascitic fluid neutrophils > 250/mm or monomicrobial bactrial growth
       
  • Secondary bacterial peritonitis if:
    • Ascitic fluid WBC > 10,000
    • Glucose < 50
    • LDH > 250
    • Protein >1
    • Alk Phos > 240
    • CEA > 5    or
    • Polymicrobial gram stain or Culture grown
 
Treatment (SBP ):
  • Cefotaxime 2 g IV q8h or Ceftriaxone 2 g IV qd x 5-7 d if uncomplicated or 10-14 d if complicated SBP or positive blood cultures.
  • Albumin 1.5 g/kg IV on day 1, then 1 g/kg IV on day 3 had a 19% decrease in absolute mortality and decreases the risk of hepato-renal syndrome.
Prophylaxis (SBP):
  • Bactrim DS 1 tab PO qd, Norfloxacin 400 mg PO qd, or Cipro 750 mg po weekly.
  • Indicated for prior SBP, if ascitic fluid protein < 1 g/dl, or Tbili > 2.5 mg/dL.
  • Acute Variceal Bleed: Norfloxacin 400 mg PO bid or Ofloxacin 400 mg IV qd x 7 d improves survival and decreases risk of SBP or variceal rebleed.
 

Gastroesophageal Variceal Bleed:

  • Octreotide 50 mcg x 1, then 50 mcg/hr IV drip x 3-5 d after endoscopic variceal band ligation.
  • TIPS is a bridge to transplantation.
  • Prophylaxis with Propranolol 40 mg po BID or Nadolol 20-40 mg PO qd then titrate to decrease resting pulse 25% ( or resting pulse 55-65 bpm).
  • Prophylactic antibiotics x 7 d if acute bleed:
    • Norfloxacin 400 mg PO bid or Ofloxacin 400 mg IV qd, Decreases risk of death, SBP, or Variceal re-bleed.
 

Hepatic Encephalopathy:

  • Precipitants: GI bleed, medications, high protein intake, infection, or electrolyte disorder.
  • Treatments:
    • Lactulose 30-45 mL PO tid, titrate to 2-4 loose bowel movements daily.
    • Add Neomycin 1-3 g PO bid or Rifaximin 200 mg PO tid (or 550 mg PO bid) for refractory cases.
 

Hepatorenal Syndrome:

Diagnosis of exclusion; serum Cr > 1.5 mg/dL or CrCl < 40 mL/min and urinary indices mimic prerenal azotemia (UNa <10 mEq/L)
  • No sustained renal improvement after fluid challenge and stopping diuretics.
  • Therapy Options:
    • Midodrine 7.5 - 12.5 mg PO tid plus Octreotide 100-200 mcg SQ tid; or
    • Norepinephrine 0.5-3 mg/hr infusion
      • Duration of treatment: 5-15 days until serum Cr < 1.5 mg/dL.
    • Add albumin 1 g/kg IV on day 1, then 20-40 g IV qd.
 

Hepatopulmonary Syndrome:

  • Dyspnea and deoxygenation accompanying change from a recumbent to a standing position, and usually clubbing is present.
  • Diagnosis: Radioisotope perfusion lung scan.
  • Treatment: Liver Transplant.
 

Hepatic Hydrothorax:

Virtually always right-sided pleural effusion +/- ascites.
  • 1-2 g/day Sodium restriction and diuretics as per large-volume ascites (Spironolactone 100 mg PO q AM and Lasix 40 mg PO a AM).
  • TIPS for diuretic-resistant effusion.
  • Therapeutic thoracentesis is acceptable if necessary, but AVOID placement of a chest tube.
 

Tx of Decompensated Cirrhosis

  • Orthotopic Liver Transplant.

Evaluation of Ascites

  • Diagnostic Paracentesis for all new-onset ascites, decompensated liver disease, or for an acute upper GI bleed, and send peritoneal fluid for:
    • Protein, albumin, glucose, cell count, LDH, and culture (place fluid directly into aerobic/anaerobic blood culture bottle for optimal yeild).
    • If SAAG low, consider placing a PPD test and sending fluid for cytology.

Follow-Up

 Overall prognosis
 The overall median survival of patients with cirrhosis is approximately 10 years, but prognosis depends on the stage of the disease.

The 10-year survival rate in patients with compensated cirrhosis is approximately 90%, and the likelihood of transitioning to decompensated cirrhosis within 10 years is 50%. [39] The median survival time in patients with decompensated cirrhosis is approximately 2 years.

In clinical practice, the Child-Pugh-Turcotte and the Model for End-stage Liver Disease scores are the most commonly used scoring systems for the prediction of mortality related to liver disease.

Four clinical stages of cirrhosis have been identified and each is associated with a different prognosis.

Stage 1

  • Patients without gastroesophageal varices or ascites have a mortality of approximately 1% per year.

Stage 2

  • Patients with gastroesophageal varices (but no bleeding) and no ascites have a mortality of approximately 4% per year.

Stage 3

  • Patients with ascites with or without gastroesophageal varices (but no bleeding) have a mortality of approximately 20% per year.

Stage 4

  • Patients with GI bleeding due to portal hypertension with or without ascites have a 1-year mortality of 57%.
 Monitoring
Follow-up visits with PCP every 6 to 12 months .

Laboratory tests (LFTs, albumin, CBC, and prothrombin time), and imaging studies (annual abdominal ultrasound) to monitor signs and symptoms of advanced liver disease, to detect disease progression, and for the development of complications of portal HTN such as ascites, hepatic encephalopathy, jaundice, and variceal bleeding.

Hepatocellular carcinoma: Ultrasound and alpha-fetoprotein measurement every 6 months.

Upper GI endoscopy: for screening of gastroesophageal varices at the time of diagnosis and at 1- to 3-year intervals thereafter.
 

 Patient Instructions
 Patients with cirrhosis should be advised of the following in order to minimize any further insult to the liver:
- The importance of weight loss with an increased BMI, maintenance of adequate nutrition, and regular exercise.
- Avoidance of alcohol and other hepatotoxins such as  NSAIDs  and high doses of acetaminophen (>2 g/day).



Admit Orders: Cirrhotic ascites and edema

1. Admit to:

2. Diagnosis: Cirrhotic ascites and edema

3. Condition:

4. Vital Signs: Vitals q4-6 hours. Call physician if BP >160/90, <90/60; P >120, <50; T >38.5°C; urine output <25 cc/hr for 4h.

5. Activity: Bed rest with legs elevated.

6. Nursing: Inputs and outputs, daily weights, measure abdominal girth qd, guaiac stool.

7. Diet: 2500 calories, 100 gm protein; 500 mg sodium restriction; fluid restriction to 1-1.5 L/d (if hyponatremia, Na <130).

8. IV Fluids: Heparin lock with flush q shift.

9. Special Medications:

-Diurese to reduce weight by 0.5-1 kg/d (if edema) or 0.25 kg/d (if no edema).

-Spironolactone (Aldactone) 25-50 mg PO qid or 200 mg PO qAM, increase by 100 mg/d to max of 400 mg/d.
PLUS

-Furosemide (Lasix [refractory ascites]) 40-120 mg PO or IV qd-bid. Add KCL 20-40 mEq PO qAM if renal function is normal 
OR

-Torsemide (Demadex) 20-40 mg PO/IV qd-bid.

-Metolazone (Zaroxolyn) 5-10 mg PO qd (max 20 mg/d).

-Captopril (Capoten) 6.75 mg PO q8h; increase to max 50 mg PO q8h for refractory ascites caused by hyperaldosteronism.
 

-Famotidine (Pepcid) 20 mg IV/PO q12h.

-Vitamin K 10 mg SQ qd for 3 days.

-Folic acid 1 mg PO qd.

-Thiamine 100 mg PO qd.

-Multivitamin PO qd.


Paracentesis:
 
  Remove up to 5 L of ascites.
  If large volume paracentesis, give salt-poor albumin, 12.5 gm for each 2 liters of fluid removed (50 mL of 25% solution); infuse 25 mL before paracentesis and 25 mL 6h after.


10. Symptomatic Medications:

-Docusate (Colace) 100 mg PO qhs.

-Lactulose 30 mL PO bid-qid prn constipation.

-Acetaminophen (Tylenol) 325-650 mg PO q4-6h prn headache.


11. Extras:
 CXR, abdominal ultrasound, GI consult.

12. Labs: Ammonia, CBC, CMP, LFTs, albumin, INR/PTT. Hepatitis panel -- HBsAg, anti-HBs, hepatitis C virus antibody, alpha-1-antitrypsin.

Paracentesis Ascitic Fluid

Tube 1: Protein, albumin, specific gravity, glucose, bilirubin, amylase, lipase, triglyceride, LDH (3-5 mL, red top tube).

Tube 2: Cell count and differential (3-5 mL, purple top tube).

Tube 3: C&S, Gram stain, AFB, fungal (5-20 mL); inject 20 mL into bottle of blood culture.

Tube 4: Cytology (>20 mL).

Syringe: pH (2 mL).

 

Admit Orders: Hepatic encephalopathy

1. Admit to:

2. Diagnosis: Hepatic encephalopathy

3. Condition:

4. Vital Signs: q1-4h. Call physician if BP >160/90, <90/60; P >120, <50; R>25, <10; T >38.5°C.

5. Allergies: Avoid sedatives, NSAIDS, or hepatotoxic drugs.

6. Activity: Bed rest.

7. Nursing: Keep head-of-bed at 30 degrees; turn patient q2h, chart stools. Seizure precautions, egg crate mattress. Foley to closed drainage.

8. Diet: NPO for 8 hours, then low-protein nasogastric enteral feedings (Hepatic-Aid II) at 30 mL/hr. Increase rate by 25-50 mL/hr at 24 hr intervals as tolerated until final rate of 50-100 mL/hr as tolerated.

9. IV Fluids: D5W at TKO.

10.Special Medications:

- Sorbitol 70% solution, 30-60 gm PO now.

-Lactulose 30-45 mL PO q1h for 3 doses, then 15-45 mL PO bid-qid, titrate to produce 3 soft stools/d 
OR

-Lactulose enema 300 mL added to 700 mL of tap water; instill 200-250 mL per rectal tube bid-qid 
AND

-Neomycin 1 gm PO q6h (4-12 g/d) 
OR

-Metronidazole (Flagyl) 250 mg PO q6h.

-Ranitidine (Zantac) 50 mg IV q8h or 150 mg PO bid 
OR

-Famotidine (Pepcid) 20 mg IV/PO q12h.

-Flumazenil (Romazicon) 0.2 mg (2 mL) IV over 30 seconds q1min until a total dose of 3 mg; if a partial response occurs, continue 0.5 mg doses until a total of 5 mg. Flumazenil may help reverse hepatic encephalopathy, irrespective of benzodiazepine use.

-Multivitamin PO qAM or 1 ampule IV qAM.

-Folic acid 1 mg PO/IV qd.

-Thiamine 100 mg PO/IV qd.


11. Extras:
 CXR, ECG; GI and dietetics consults.

12. Labs: Ammonia, CBC, CMP, AST, ALT, GGT, INR/PTT, ABG, blood C&S x 2. UA

 

 

 

ITE 2013, Q81

81. A 63-year-old male with a history of alcoholism and compensated hepatic cirrhosis asks if there are pain medications he can use to treat his chronic low back pain and knee and hand osteoarthritis. He also has occasional headaches. He has not used alcohol for several years.
Which one of the following medications is CONTRAINDICATED in this patient?

A) Acetaminophen
B) Gabapentin (Neurontin)
C) Naproxen
D) Pregabalin (Lyrica)
E) Tramadol (Ultram)

ANSWER: C
  • Although patients with chronic mild liver disease may take NSAIDs, they should be avoided in all patients with cirrhosis, due to the risk of precipitating hepatorenal syndrome.
  • Pregabalin and gabapentin are not metabolized by the liver and can be quite helpful.
  • Acetaminophen, while toxic in high doses, can be used safely in dosages of 2–3 g/day.
  • Tramadol is also safe in patients with cirrhosis.


Reference: Hepatology 2004;39:1; NEJM 2004;350:1646; South Med J 2006;99:600; and Hepatology 2005;41:1.
Source: Tarascon Hospital Medicine