Updated: 10/25/07 11:31 AM
HOME HEAL EDUCATE RESEARCH DIRECTORY OUTREACH


Authors: W. Volwiler, R.A. Willson, A.M. Larson, and J.D. Ostrow
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Q. Chronic Liver Diseases

  The clinical, biochemical, and morphological classification of chronic inflammatory diseases of the liver (continuing hepatitis) is presently undergoing extensive study, thus a clear simple organization is not yet available. The discussion in this section will focus upon the end stage of this spectrum -- cirrhosis of the liver.

1. Cirrhosis of the Liver



Cirrhosis = fibrosis + distortion of lobular architecture 		  Cirrhosis of the liver is defined pathologically as widely distributed, irregular hepatic fibrosis with distortion of the lobular architecture and vasculature, resulting from persistent inflammation and/or parenchymal cell necrosis, combined with nodular regeneration. Cirrhosis always has three basic features: a) destruction of liver cells; b) replacement of groups of lobules, entire lobules, or parts of lobules with fibrous tissue; and c) nodular regeneration of the residual hepatic parenchyma.

May be progressive or reversible   Cirrhosis is usually progressive; at a tempo which may be variable and intermittent. In the earlier stages, this is due to persistent or repeated damage to liver cells from the causative agent, but resorption of fibrous tissue and regeneration of hepatocytes may repair the damage and reverse the process if the offending agent is treated or removed.

By contrast, in late stages of cirrhosis, the secondary distortion of the hepatic circulation may lead to chronic ischemia, with increasing fibrosis, continued cell loss and eventually liver failure.



Etiology correlates with histology about two-thirds of the time 		  Although the morphological appearance of cirrhosis depends to a large measure upon the inciting agent or event, the various etiologic syndromes of cirrhosis correlate well with morphologic patterns in roughly only two-thirds of cases. In the remainder, the cause of the disorder matches the evolving fibrous-nodular design poorly or not at all, and strikingly different patterns of fibrosis and nodularity may sometimes be seen in different regions of the same liver. The three main morphologic types of cirrhosis are: a) coarse nodular cirrhosis (also known as macronodular or post-necrotic), b) fine nodular cirrhosis (also known as micronodular), and c) mixed cirrhosis.

2. Clinical Consequences of Cirrhosis

Clinical features of cirrhosis are due to effects of hepatocellular insufficiency and portal hypertension   Clinically, the features of cirrhosis and chronic end stage liver disease result mainly from hepatocellular insufficiency and portal hypertension.

  1. Diminished hepatocytic synthetic capacity leads to hypoalbuminemia, deficiency of clotting factors, and (usually) hypocholesterolemia (except with chronic cholestasis).


  2. Altered estrogen metabolism causes palmar erythema (red palms), spider angiomata, amenorrhea in females, complicated by alcohol-induced testicular atrophy and feminization in males. The excess of circulating estrogen results from increased aromatase activity in the hepatocytes, enhancing conversion of testosterone to estradiol.


  3. Impaired detoxification/excretory function, combined with shunting of blood around the liver, causes jaundice, encephalopathy, and excessive responses to administered drugs.


  4. Altered metabolism of vasoactive substances leads to splanchnic vasodilatation, activation of the renin-angiotensin-catecholamine system, sodium retention, ascites and edema, and functional renal failure (hepatorenal syndromes).


  5. Portal hypertension and the compensatory development of porto-systemic collateral circulation cause esophageal varices (often with GI hemorrhage), splenomegaly with pancytopenia, and ascites (hypoalbuminemia contributes).


  6. Bacterial overgrowth, with translocation of bacteria and toxins through the congested bowel wall into the portal system, leads to systemic infections and spontaneous bacterial peritonitis (infected ascites).
3. Prognosis in Chronic Liver Disease









Child-Turcotte-Pugh classifications of severity of cirrhosis 		  The prognosis of patients with cirrhosis is difficult to predict, but generally depends upon the number and severity of complications, best assessed by the Child-Turcotte-Pugh criteria ("Child's Classification"). Its validity has been well demonstrated and it gives a good indication of prognosis. This classification is composed of clinical and laboratory measures which are available to any physician (Table 7). The score for a "normal" person would be 5. Cirrhotic patients with scores of 5 or 6 (Child's A) have an excellent prognosis (a ten-year survival of 80%-90%). By contrast, those patients with scores greater than 10 (Child's C) have a very poor prognosis and often succumb within 6 to 12 months. Child's B cirrhotics (score 7-10) have an intermediate survival.

Major causes of death from cirrhosis   The most common causes of death from cirrhosis are hepatic failure, gastrointestinal hemorrhage, hepatocellular carcinoma, infections, and renal failure.



Table 7
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Child-Turcotte-Pugh (CTP)
Scoring System to Assess Severity of Liver Disease

  A major criticism of the CTP scoring system is that items such as encephalopathy and ascites are qualitative, too dependent on history and physical examination.

The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), that is used for adult liver transplant candidates. It gives each individual a “score” (number) based on how urgently he or she needs a liver transplant within the next three months. The number is calculated by a formula using three routine lab test results:
  1. bilirubin, which measures how effectively the liver excretes bile;
  2. INR (prothrombin time), which measures the liver’s ability to make blood clotting factors; and
  3. creatinine, which measures kidney function. (Impaired kidney function is often associated with severe liver disease.)
A patient’s score may go up or down over time depending on the status of his or her liver disease. Many patients will have their MELD score assessed a number of times while they are on the waiting list. This will help ensure that donated livers go to the patients in greatest need at that moment. Candidates under the age of 18 are placed in categories according to the Pediatric End-Stage Liver Disease (PELD) scoring system. PELD is similar to MELD but uses some different criteria to recognize the specific growth and development needs of children. PELD scores may also range higher or lower than the range of MELD scores. The measures used in the PELD score are as follows:
  1. bilirubin, which measures how effectively the liver excretes bile;
  2. INR (prothrombin time), which measures the liver’s ability to make blood clotting factors;
  3. albumin, which measures the liver’s ability to maintain nutrition;
  4. growth failure; and
  5. whether the child is less than one year old.
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