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==Overview==
==Overview==

Revision as of 17:58, 19 December 2017

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Cirrhosis Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Cirrhosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Tertiary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

Cirrhosis is a consequence of chronic liver disease characterized by the replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. Cirrhosis is most commonly caused by alcoholism and hepatitis C, but has many other possible causes.

Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis and is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis is generally irreversible once it occurs, and treatment generally focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a liver transplant.

Historical Perspective

The first description of the clinical picture and pathologic appearance of cirrhosis, was published in 1761. René Laennec coined the term "cirrhosis" in 1819. The word "cirrhosis" was derived from the Greek term kirrhos, meaning "tawny" (to describe the orange-yellow or tan color of the diseased liver). In 1930, the first theory explaining the pathogenesis of cirrhosis was advanced by Roessle and terms such as parenchymal degeneration, regeneration and scarring were mentioned.

Classification

Cirrhosis of the liver may be classified using two methods: classification based on etiology, and classification based on morphology. Currently, classifying cirrhosis based on morphology is not used, as it requires an invasive procedure to examine the gross appearance of the liver, and it provides little diagnostic value. Classifying cirrhosis according to etiology is a more acceptable form of classification, as it may be attained through non-invasive laboratory testing, and has a higher diagnostic value.

Pathophysiology

Cirrhosis occurs due to long term liver injury which causes an imbalance between matrix production and degradation. Early disruption of the normal hepatic matrix results in its replacement by scar tissue, which in turn has deleterious effects on cell function.

Causes

There are a wide range of causes for cirrhosis, including alcohol abuse, genetic diseases, cardiac causes, toxins, viruses, and malnutrition. The consequence to the liver is the same in all cases with the functional liver tissue being replaced by fibrous scar tissue and regenerative nodules.

Differentiating Cirrhosis from other Diseases

Cirrhosis may present in a similar way to some other diseases. History, physical examination, and diagnostic testing may help to differentiate cirrhosis from other diseases such as malignancy, constrictive pericarditis, Budd-Chiari syndrome, portal vein thrombosis and splenic vein thrombosis.

Epidemiology and Demographics

The most common cause of cirrhosis in the United States is chronic and heavy alcohol use, while the most common cause of cirrhosis worldwide and in Asian countries is the hepatitis virus. The gender that is most commonly affected by cirrhosis varies, depending on the underlying etiology. The incidence of cirrhosis increases with age; the median age of diagnosis of cirrhosis due to alcoholic liver disease is 52 years. The median age of diagnosis of cryptogenic/NAFLD/NASH cirrhosis is 60 years.

Risk Factors

Lifestyle and genetic risk factors play an important role in the development of cirrhosis in patients. Chronic alcohol use, chronic hepatitis B and C infection and genetic diseases such as cystic fibrosis are also significant risk factors for the development of cirrhosis.

Screening

Screening for HCC must be done in every cirrhotic patient. It is performed at a frequency of 6-12 months. Screening endoscopy for detection of esophageal varices must be performed at regular intervals in all patients.

Natural History, Prognosis and Complications

Cirrhosis is an irreversible process, the course of which is highly variable in patients. The natural history progresses in such a way that there is a lengthy stage of compensation, followed by the development of complications and sequelae as a result of the cirrhosis. The devastating complications include complete liver failure or the development of hepatocellular carcinoma. Other complications include portal hypertension, ascites, jaundice, itching, esophageal varices, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome and cardiomyopathy. Prognosis depends on the causes, existing complications and a variety of factors which make the prediction of life expectancy questionable. There are scores which classify disease severity and to determine suitability for liver transplantation in patients.

Diagnosis

Diagnostic Study of Choice

Liver biopsy is the gold standard test for the diagnosis of cirrhosis. The presence of bridging fibrous septa, parenchymal nodules bearing a mixture of replicating and sensecent hepatocytes and involvement of most or all of the liver are confirmatory of cirrhosis. Liver biopsy helps in confirmation of the diagnosis, determination of prognosis, underlying etiology, management of rejection subsequent to liver transplantation and evaluation of abnormal hepatic investigations. Sample of the liver may be obtained by Percutaneous, transjugular and laparoscopic radiographically- guided fine-needle approach. However, percutaneous liver biopsy is considered as the cornerstone of diagnosis.

History and Symptoms

Liver cirrhosis may present with non specific constitutional symptoms such as fever, anorexia, fatigue, nausea, vomiting, menstrual irregularities and testicular atrophy. Patients with decompensated cirrhosis may develop complications and present with jaundice, increase in abdominal girth due to ascites, pruritus, hematochezia, melena and confusion due to hepatic encephalopathy. Symptoms may also vary depending upon the underlying cause of cirrhosis. A detailed history of alcohol use, blood transfusions, history of viral hepatitis and family history of liver disease must be taken in all patients.

Physical Examination

Patients with cirrhosis usually present with signs of jaundice, palmar erythema, spider angiomata, gynaecomastia and alteration of mental status arising due to complications of cirrhosis. Abdominal examination may show signs of abdominal distension, caput medusae, splenomegaly and flank dullness on percussion. Other findings on examination include nail changes, presence of Clubbing, dupuytren's contracture(flexion deformities of the fingers) and Asterixis in cases with hepatic encephalopathy.

Laboratory Findings

A range of laboratory values may be obtained in the evaluation of cirrhosis, in order to determine disease severity and causation. Liver function tests, complete blood count, basic metabolic panel and coagulation factors are standard in the evaluation of cirrhosis. More specific testing for markers and serum enzymes may be performed when certain etiologies are suspected.

Imaging Findings

Although CT scans are not routinely used in evaluation and diagnosis of cirrhosis, it may show the presence of lobar atrophic and hypertrophic changes in the liver, ascites and varices. CT scans also visualize the presence of tumors, blocked bile ducts and help evaluate the size of the liver.

Electrocardiogram

In a few patients with cirrhosis, circulating toxins may cause the ECG to show prolongation of the QT interval. Low voltage complexes in the precordial leads may also be noticed in patients with fluid overload.

Chest X Ray

Chest x ray has a limited role in the diagnosis and management of cirrhosis, but can be helpful in identifying certain complications that can occur as a result of cirrhosis.

CT

Although CT scans are not routinely used in evaluation and diagnosis of cirrhosis, it may show the presence of lobar atrophic and hypertrophic changes in the liver, as well as ascites and varices in advanced disease. CT can also visualize the presence of tumors and blocked bile ducts, as well as evaluate the size of the liver.The use of magnetic resonance imaging (MRI) as a diagnostic test for cirrhosis is uncertain. MRI differentiates regenerating or dysplastic nodules and hepatocellular carcinoma. MRI is best used as a follow-up study to determine whether lesions have changed in appearance and size. MRI may accurately diagnose cirrhosis and determines disease severity. Decreased signal intensity on MRI may also reveal an iron overload and provides an estimate of the hepatic iron concentration. MR angiography is more sensitive than ultrasonography in diagnosing complications of cirrhosis such as portal vein thrombosis.

Echocardiography or Ultrasound

On ultrasonography, changes in the liver contour and increased nodularity may be evident. The echo texture may appear coarse along with an increase in echogenecity from focal fatty changes and irregular appearing areas. USG may also be used to screen for hepatocellular carcinoma, portal hypertension and Budd-Chiari syndrome.

Other Imaging Findings

Tc-99m labeled sulfur may be used in nuclear imaging to provide some indication of hepatic function in cirrhotic patients. In candidates for liver transplant, CTA is used to asses the drainage of the liver. All patients with cirrhosis must undergo a diagnostic endoscopy for the evaluation of varices. Gastric endoscopy is an option if gastric varices are suspected, and endoscopic ultrasound may also help in the visualization of varices. ERCP is performed if a biliary pathology such as primary sclerosing cholangitis is suspected as the underlying cause of cirrhosis.

Other Diagnostic Studies

The gold standard diagnostic test for cirrhosis is liver biopsy, although it is rarely necessary for diagnosis or treatment. NT-proBNP may be used to evaluate the complications of cirrhosis.

Treatment

Medical Therapy

The change that cirrhosis causes to the liver is irreversible, therefore treatment is mostly centered on ameliorating the complications of cirrhosis such as ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, esophageal varices and hepatorenal syndrome. Chronic constitutional symptoms such as pruritus, hypogonadism, osteoporosis and anorexia must be treated in patients. Maintenance of adequate nutrition (especially protein intake) is extremely important in cirrhosis patients. The underlying cause of cirrhosis needs to be managed and the treatment varies depending upon the cause of cirrhosis.

Surgery

Patients with decompensated liver cirrhosis are usually candidates for liver transplantation. Liver transplantation may be carried out based on MELD score and assessment of the patient’s quality of life, absence of contraindications and disease severity. In cases where transplantation is contraindicated, a patient may undergo the TIPS procedure. A transjugular intrahepatic portosystemic shunt, also TIPS, is an artificial channel in the liver from the portal vein to a hepatic vein, created via the jugular vein. The main purpose of the TIPS procedure is to decompress the portal vein which would in turn help to prevent rebleeding from varices, and also prevent ascites formation. TIPS is used to treat portal hypertension which is often due to cirrhosis.

Prevention

Primary prevention of cirrhosis includes avoidance of causative agents such as alcohol, high doses of certain supplements (vitamin A, copper and iron) and vaccination against hepatitis. Adequate caloric intake, physical activity, prevention of high risk behaviors, screening of blood products and vaccination for Hepatitis B play an important role in primary prevention. Secondary prevention in patients with cirrhosis is aimed at preventing further damage to the liver. Avoidance of alcohol and other hepatotoxins, treatment of underlying chronic liver disease and immunization against viral hepatitis for susceptible patients are key measures of secondary prevention of cirrhosis.

References

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