Cirrhosis of the liver

Cirrhosis of the liver

Description of Medical Condition

Cirrhosis refers to the pathological changes in the liver of extensive fibrosis and regenerative nodules and the clinical syndromes associated with this pathological state. Although often clinically silent, suspected only by altered biochemistry or liver imaging, it is characteristically associated with jaundice, fluid retention, wasting, coagulopathy, altered mental status, and fulminant gastrointestinal bleeding.

System(s) affected: Gastrointestinal, Endocrine/ Metabolic, Cardiovascular

Genetics: Minority of cases clearly inherited (hemachromatosis, hepatolenticular degeneration [Wilson disease] and alpha-antitrypsin deficiency in adults, many other very rare inherited diseases in the first few years of life). Glycogen storage disease is a common one.

Incidence/Prevalence in USA: 6th or 7th leading cause of death age 30 to 50, approximately 30,000 deaths/year

Predominant age: Etiology dependent, but peak in 40-50

Predominant sex: Male > Female

Medical Symptoms and Signs of Disease

1. Asymptomatic cirrhosis:

• May be skin changes including spider angioma, xanthomas, increased pigmentation, ecchymoses or bruising
• May be abdominal collateral circulation
• Hepatic firmness, hepatomegaly, splenomegaly

2. Diffuse liver failure

• Fatigue after minimal exertion
• Anorexia, loss of weight
• Weakness, malaise
• Heaviness or tenderness in right upper quadrant
• Absent or irregular menses
• Diminished sexual interest and impaired performance
• Jaundice, tea colored urine
• Leg edema and/or abdominal swelling
• Bruising, abnormal bleeding
• Hepatomegaly
• Episodic confusion, asterixis
• Hematemesis or melena
• Spider angioma
• Palmar erythema

3. Alcoholic etiology OCheilosis

• Parotid enlargement
• Night blindness

4. Biliary cirrhosis

• Xanthelasma
• Scratch marks

5. Nonalcoholic steatohepatitis

• Obesity — BMI >30

6. Age difference — under age 15 rarely see confusion and asterixis, extremely common after age 50. Jaundice infrequent under age 8, more common with increasing age.

What Causes Disease?

Chronic damage to the liver from toxins, viruses, cholestasis, or metabolic disorders. Scar tissue slowly replaces normal functioning liver tissue, progressively diminishing blood flow through the liver and preventing normal function.

Risk Factors

• Alcoholism and hepatitis C cause 60%
• Hepatitis B
• Progressive fatty liver
• Nonalcoholic steatohepatitis

Biliary cirrhosis

Hemachromatosis

Less frequent causes

• Wlson disease, alpha-1-antitrypsin deficiency
• Hepatotoxic drugs
• Chronic and recurrent heart failure
• Chronic biliary obstruction
• Sclerosing cholangitis
• Cystic fibrosis
• Polycystic or multiple telangiectasis diseases
• Veno-occlusive disease
• Granulomatous liver disease
• Idiopathic portal fibrosis
• Shared intravenous needles
• Multiple transfusions before 1994

Diagnosis of Disease

Differential Diagnosis

• Diffuse liver disease without cirrhosis vs with cirrhosis
• Cirrhosis vs metastatic or multifocal cancer in the liver
• Cirrhosis vs vascular congestion of the liver
• Temporary and reversible liver disease vs cirrhosis
• Hepatic encephalopathy
• Bleeding esophageal varices
• Ascites
• Jaundice
• Liver biochemical abnormalities

Laboratory

1. Changes of hepatic cell injury

• ALT, AST most commonly elevated
• Globulin increased if chronic
• Protein electrophoresis shows broad band elevation

2. Changes of cholestasis

• Alkaline phosphatase elevated
• GGTP elevated
• 5-nucleotidase, is liver specific alkaline phosphatase
• Bile acids elevated
• Cholesterol elevated (when condition chronic)

3. Changes of impaired amount of functioning liver

• Reduced albumin
• Prolonged INR for prothrombin time
• Elevated bilirubin

4. Changes suggesting portal hypertension and large spleen

• Diminished platelet count

5. Specific tests to determine etiology

• Hepatitis
• Hepatitis B surface antigen, hepatitis B DNA viral load
• Anti-hepatitis C antibody, hepatitis C RNA viral load
• Alcoholism — alcohol in serum in patient who claims to be abstinent
• Carbohydrate deficient transferrin
• Elevated GGTP (gamma glutamyl transpeptidase) with normal alkaline phosphatase and decreased K, Mg, Zn or phosphate
• Biliary cirrhosis — antimitochondrial antibody
• Chronic active hepatitis — anti-smooth muscle, or anti-nuclear antibody
• Hemachromatosis — iron saturation >50%, increased ferritin, gene
• Hepatolenticular degeneration (Wilson disease) ceruloplasmin, copper excretion
• Hepatocellular carcinoma — alpha fetoprotein

Drugs that may alter lab results: N/A

Disorders that may alter lab results: N/A

Pathological Findings

1. Fibrous scars, regenerative nodules a feature of all types of cirrhosis. Alcoholic cirrhosis has large nodules, necrotic cells surrounded by PMNs.

• Mallory bodies, usually increased fat. May have giant mitochondria.

2. Nonalcoholic steatohepatitis may have all of the features of alcoholic but usually more fat

3. Biliary cirrhosis. PMN infiltration in the wall of bile ducts, inflammation markedly increased in portal spaces. Progressive loss of bile ducts in portal spaces.

4. Hemachromatosis — marked increase in iron

5. Chronic active hepatitis — great increase in lymphocytes and cells damaged immediately adjacent to lymphocytes

6. Alpha-1 -antitrypsin deficiency- PAS positive bodies in hepatocytes

7. Hepatitis B and C. Periportal lymphocyte inflammation but damage in central vein region or throughout the lobule.

Special Tests

• Endoscopy: identifies esophageal varices or portal hypertensive gastropathy, other bleeding lesions, and to effect emergency treatment of the bleeding lesion if necessary
• Electroencephalography may be required to clarify etiology of confusion
• Diagnostic paracentesis to clarify etiology of ascites and possible complications
• Liver biopsy is the gold standard of diagnosis. Can be conducted safely in a percutaneous fashion if INR < 1. 5 and there is no bleeding tendency and modest or no ascites. Otherwise transjugular biopsy must be performed by an experienced radiologist, infrequently available.

Imaging

• Ultrasound sometimes required to verify ascites
• Doppler ultrasound used to indicate patency of hepatic and portal veins
• Ultrasound to identify status of biliary passages and presence of gall bladder stones, shows scars in liver. Usually done just before liver biopsy to determine optimal needle insertion site.
• If status of the extrahepatic biliary passages uncertain. CT scan or magnetic resonance exam. If stones likely or biopsy required ERCP is then performed.
• Abdomen CT scan may clarify scars of cirrhosis vs. metastatic disease or fatty liver
• MRI performed to clarify patency of blood vessels and collaterals as in Budd-Chiari syndrome, thrombosis of portal vein, varices or periumbilical collaterals. It also clearly identifies the extrahepatic biliary passages.
• Endoscopic ultrasound useful to identify dilated common duct or masses in the pancreas. Guided needle biopsy can determine histology.

Diagnostic Procedures

• History, examination, biochemistry and imaging provide diagnosis more than half the time
• Liver biopsy performed 80% of time to verify probable diagnosis or establish uncertain one and to clarify prognosis

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient care except for emergencies (major gastrointestinal bleeding, hepatic encephalopathy, systemic bacteria) infection, unexplained rapidly progressing hepatic decompensation, renal failure

General Measures

• Remove/treat the underlying cause when possible
• Patients must abstain from alcohol, drugs and supplements with no benefit
• Immunize for pneumococcal disease, hepatitis A and B. and influenza
• Review, alcohol, prescription medications, OTC medications and health food items
• Nutritious diet including 1-1.5 gm protein/kg body wt, from all food groups. Weight changes adjusted toward ideal body weight. Daily multivitamin recommended.
• Specific measures:

– Hemachromatosis — phlebotomy until iron stores depleted as judged by the ferritin and production of a mild iron deficiency anemia. Usually 25-150 units of blood must be removed.

– Fatty liver syndromes — weight reduction, control of abnormal lipids, tight control of diabetes

Surgical Measures

• Bleeding varices — endoscopic ligation; 4-6 treatments required (may also need propranolol). If bleeding occurs, consider TIPS (transjugular intrahepatic shunt). Rarely a surgically placed side to side portacaval shunt is performed (should be the basis for listing for transplantation).
• Ascites — may require paracentesis each 2 weeks, or more often, despite sodium restriction and diuretic therapy. TIPS may render the ascites easier to control.
• Transplantation — either cadaver liver (average wait time 18 months, 10% on waiting list die annually) or partial transplant from living donor (rapidly growing segment of liver transplants)
• Hepatocellular carcinoma. Cure with partial resection of liver in well compensated cirrhosis. Treat < 5cm nodules with direct ethanol injection, or infra-arterial chemoembolism.

Activity

Conditioning will overcome fatigue

Diet

Nutritious diet 1-1.5 gm protein unless liver encephalopathy. Low sodium useful in all patients, essential when there is ascites.

Patient Education

• Educate patient and family and/or care givers on possible complications and a course of action to be taken for each
• Avoid crowds particularly during flu season
• Should not use NSAIDs or gentamicin

Medications (Drugs, Medicines)

Drug(s) of Choice

• Hepatitis C — PEG-alpha-interferon weekly and ribavirin bid for 6 months (eliminates virus permanently in about 50% of patients). Patients
• Hepatitis B — lamivudine 100 mg daily for 1 to 2 years. Alternatively PEG-alpha interferon for one year.
• Biliary cirrhosis — ursodeoxycholic acid 10 mg/kg daily for patient’s life
• Wilson disease — penicillamine 1-3 gm/day as tolerated ortetrathiomolybdate from 100-400 mg/day. After one year zinc acetate alone 250 mg bid is used for maintenance.
• Autoimmune chronic active hepatitis — prednisone 5-20 mg/day as needed with azathioprine (Imuran) 0.5-1 mg/kg for at least 2 years, repeat with relapses
• Complications of cirrhosis

– Esophageal varices — propranolol long acting 40-160 mg/day sufficient to lower portal pressure by 20 mm of Hg or lower pulse rate by 25%. May add long acting nitrates, spironolactone or losartan if pressure is not lowered.

– Ascites — sodium restricted diet and spironolactone 100-400 mg/day with furosemide 40-160. Torsemide may substitute for furosemide.

• Encephalopathy — lactulose 15 mL of 50% solution 3 times daily, titrate up until 3 loose bowel movements daily. If fail to control, add oral neomycin 250 mg tid.
• Renal insufficiency — stop diuretics, nephrotoxic drugs, normalize serum electrolytes. Hospitalization with plasma expansion or temporary dialysis may be necessary.

Contraindications: Refer to manufacturer’s literature

Precautions: Refer to manufacturer’s literature

Significant possible interactions: Refer to manufacturer’s literature

Alternative Drugs

• Milkweed thistle taken according to the manufacturer’s recommendation improves symptoms and is without harm. It is widely used by patients for whom no specific treatment exists.
• Recombinant factor Vila rapidly corrects bleeding associated with hepatic coagulopathy

Patient Monitoring

• Yearly, if etiology of liver disease corrected and free of complications
• If varices recur, repeat endoscopy each 2-3 years to identify and treat
• Patients with cirrhosis develop hepatocellular carcinoma at the rate of 5% yearly. Those over 55. with hepatitis B or C, decreased INR (prothrombin), or decreased platelets are at highest risk. Many recommend obtaining a serum alpha-fetoprotein, a marker of hepatoma each 6-12 months and a yearly ultrasound. If a new mass appears it should be biopsied. If alpha fetoprotein has become elevated and the US is negative, then CT scan is appropriate. These should only be done if the patient is a candidate for definitive treatment with alcohol injection or surgery.
• Yearly vaccination for influenza. Review that Pneumovax, hepatitis A, B immunization are current.

Prevention / Avoidance

• Prophylactic antibiotics recommended for invasive procedures and when there is a gastrointestinal bleed
• Patients with esophageal varices requiring banding should be maintained on a proton pump inhibitor of gastric acid

Possible Complications

• Ascites
• Edema
• Hepatic encephalopathy
• Bleeding esophageal varices
• Hepatocellular carcinoma
• Susceptibility to bacterial infections
• Spontaneous bacterial peritonitis
• Renal failure
• Liver failure
• Coagulopathy
• Jaundice

Expected Course / Prognosis

• If the etiology is removed, variable course
• Life is shortened due to portal hypertension and its complications
• Course after diagnosis of cirrhosis 5-20 years of asymptomatic disease. Once complications start, death within 5 years without transplantation. If etiology cannot be removed, course is more rapid. Wth transplantation, approximately 15% die in first year, then about 5% a year.
• Transplantation: < 25% of cirrhotics have one due to organ shortage. Obtaining a portion of a living donors liver is the fastest growing group of liver transplantations.

Miscellaneous

Associated Conditions

N/A

Age-Related Factors

Pediatric:

• Jaundice and encephalopathy less frequent indicate more severe liver damage
• Many rare inborn errors of metabolism known, some treatable with diet, surgery

Geriatric: Jaundice and encephalopathy much more  common

Pregnancy

• Rare in cirrhosis but does not harm the disease
• Feasible after transplantation

International Classification of Diseases

571.2 Alcoholic cirrhosis of liver

571.5 Cirrhosis of liver without mention of alcohol

See Also

Ascites

Hepatitis A

Hepatitis B

Hepatitis C

Alcohol use disorders

Hemochromatosis

Esophageal varices

Hepatic encephalopathy

Hepatoma