Chronic Liver Disease and Cirrhosis

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page sections introduction the case of Thomas R causes and risk factors pathophysiology signs and symptoms investigations differential diagnosis treatments consequences and course resources and references topic development

Chronic Liver Disease and Cirrhosis

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Introduction
Chronic liver disease is very common aorund the world and has many causes, including inflammatory, toxic, metabolic, and congestive liver problems. Cirrhosis is often the irreversible end result of chronic liver disease. Cirrhosis may be asymptomatic, with incidental diagnosis following laboratory testing. In other patients, signs and symptoms that can bring it to attention include ascites, jaundice, and gastrointestinal bleeding.

The Case of Thomas R.

Thomas is a 68 year old man who recently retired as a truck driver. You know some of his lifestyle choices have been potentially dangerous, with unsafe sex, as well as alcohol and drug use. He comes to you because he has recently noticed his skin turning yellow, though he feels fine otherwise. Physical exam reveals, amongst other findings, a hard, nodular liver. You are of course concerned about the possibility of liver disease. What further questions do you ask him? What might you find on physical exam? How do you proceed with diagnosis? What is Mr R's prognosis? return to top

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Chronic Liver Disease and Cirrhosis

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Causes and Risk Factors

Chronic liver disease (occurring over 6 months) can be caused by many things, and it can be difficult to find the cause. Chronic hepatitis follows acute hepatitis B in 5-10% of the time, and acute on chronic cases can occur. Chronic hepatitis C occurs in up to 75% of people with infection. Autoimmune liver disease most often occurs in young women and is characterized by many plasma cells, hypergammaglobulinemia, as well as anti-nuclear or anti-smooth muscle antibodies. Nonalcoholic fatty liver disease most commonly occurs in people who are overweight, and have diabetes and hyperlipidemia.

drugs alcohol toxins vitamin A methotrexate

infections hepatitis B hepatitis C schistosomiasis

fatty liver disease obesity T2DM hyperlipidemia total parental nutrition

other conditions congestive heart failure hemochromatosis Wilson's disease autoimmune diseases sarcoidosis Bud-Chiari syndrome a1-AT deficiency idiopathic

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Pathophysiology
Acute injury can lead to chronic inflammation and hepatocyte death, associated with lymphocyte infiltration and the development of fibrosis. Normal hepatocyte function is disturbed by resulting inadequacy of blood flow and ongoing inflammatory, toxic, and metabolic damage. Decreased cell numbers lead to reduced metabolic action on bilirubin and loss of synthetic function of proteins such as clotting factors and albumin. Decreased production of transaminases can result in normal or low values.

Disruption of normal architecture through fibrosis distorts the vasculature. Pressure increases and subsequent portal system hypertension leads to blood backup into veins in the esophagus, abdominal wall, and elsewhere. Spleen enlargement leads to platelet sequestration and thrombocytopenia.

Cirrhosis is characterized by deposition of interconnective bands of fibrous tissue which surround nodules of regenerating hepatocytes. The grade of injury is determined by the numbers and location of inflammatory cells, while the stage of disease depends on degree, location, and distortion caused by fibrosis. Small nodules <3mm are typical of alcoholic cirrhosis, while larger nodules follow chronic active hepatitis.

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Hepatic encephalopathy is believed to result from substances produced by gut bacteria that are toxic to the brain. These include ammonia, mercaptans, phenols, and short-chain fatty acids. Normally these are metabolized by the liver following transport from the gut via the portal system, after which they are excreted. However, with advanced liver disease, both portal transport to the liver and hepatocyte metabolism may be compromised, resulting in entry into the circulation by these substances. return to top

Signs and Symptoms

Liver damage is most often silent until 75% of the liver function is lost. Cirrhosis too can be asymptomatic initially.

Decompensation results in ascites, jaundice, and encephalopathy.

Cirrhosis: fibrosis encircled with regenerative nodules. Stages I-IV can be diagnosed histologically Fatty liver disease can cause macrocytosis.

history

physical exam

History
anorexia nausea abdominal discomfort itchiness Autoimmune hepatitis can lead to amenorrhea, rashes, acne, vasculitis, thyroiditis, and Sjogren's syndrome.

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Investigations
lab investigations diagnostic imaging biopsy

Lab Investigations

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Serum transaminases (ALT, AST) are typcially elevated over 10x, while serum alkaline phosphatase is less than 3x normal. However, if liver disease is significant, these markers may be normal. Decreased synthetic function can lead to prolonged prothrombin time (INR), hypoalbuminemia, and unconjugated hyperbilirubinemia. Thrombocytopenia and leucopenia can follow portal hypertension and splenic sequestration. New-onset ascites may be evaluated by paracentesis, with cell count, protein count, albumin, and C&S. Paracentesis should also be performed in cases of encephalopathy. Hepatocellular carcinoma screening using alpha-fetoprotein may be considered.

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Differential Diagnosis
The differential for encephalopathy includes: constipation medications, including benzodiazepines, and nonadherence to prescribed medications infection, including spontaneous bacterial peritonitis electrolyte abnormalities gastrointestinal bleeding return to top

Treatments
Management guidelines suggest that the best care is provided by a team approach of primary care provider and specialist(s). Abstinence from alcohol is critical, especially if transplant is being considered. Immunizations against hepatitis A and B should be offered as appropriate. Ascites may be treated with salt restriction and dieuretics, including combination furosemide and spironolactone. Spontaneous bacterial peritonitis should receive prompt antibiotics with cefotaxime or ciprofloxacin. Prophylaxis should be considered after resolution. Encephalopathy should be treated first at the level of reversible causes. If this does not change the patient's status, dissarcharides such as lactulose may be used. These are believed to cause absorption of nitrogen by gut bacteria, reducing ammonia production. Antibiotics that remain in the gut such as rifaximin may also be used to reduce the gut load of bacteria. Patients with encephalopathy should not drive. Esophageal varices may be treated if identified via screening through beta blockade or endoscopic ligation. Frank bleeding should be treated with fluid recuscitation, somatostatin analogue, and endoscopy for ligation when stable. Surgical repair

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using the transjugular intrahepatic portsystemic shunt (TIPS) may be explored as a last resort. return to top

Consequences and Course

Compensated cirrhosis can lead to uncompensated cirrhosis, hepatocellular carcinoma, or death. Fulminant liver failure is a serious result of acute liver damage. Complications of cirrhosis include portal hypertension, hepatocellular dysfunction, and hepatocellular carcinoma. return to top

Resources and References

Canadian Liver Foundation American Liver Foundation Medline Plus resources on liver diseases return to top

Topic Development
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