Liver disease differential diagnosis

Cupruria In pronounced liver cell decay, there is not only a rise in the copper value in serum, but more particularly in the amount of copper excretion in the urine. Cupruria of < 50 pg/day rules out the presence of Wilson s disease (differential diagnosis e.g. kidney disease). The penicillamine test has proved successful after administration of 600 mg penicillamine, copper excretion increases to > 300 pg/6 hr (> 600 pg/24 hr). However, it should be noted that this test may show similar positive results in cholestatic liver diseases. 

HBD is a biochemical rather than electrophoretic assessment of the LD isoenzyme which is associated with heart. All five isoenzymes of LD exhibit some activity toward cx-hydroxy-butyrate as substrate, but heart LD shows the greatest activity. Serum HBD measurement is not as valuable as the electrophoretic determination of heart LD isoenzyme. High HBD activity has also been found in diseases of the liver. Rises associated with the hepatic effects of congestive heart failure can be disconcerting in the differential diagnosis of myocardial infarction. Wilkinson has used the serum HBD/LD ratio for the differentiation of myocardial disease from other disorders in which HBD activity is elevated, whereas Rosalki has not found the ratio to be helpful (39). 

Bile salt deficiency must also be directly studied. It may occur in the absence of obstruction or obvious liver disease (R7). The majority of patients with one form or another of the sprue syndrome will be found to have pancreatic enzymes and bile salts within the normal range. Pancreatic enzymes are absent or markedly deficient in patients with pancreatogenous malabsorption syndrome (B17, F13). It is surprising how frequently this necessary step in differential diagnosis is omitted. 

The presence of LP-X in the plasma of patients with liver disease has been considered as a sensitive indicator of biliary obstruction and, thus, useful in the differential diagnosis of diseases of the liver (S29, Wl). However, the recent demonstration (see Section 8.2) that particles resembling LP-X occur also in the plasma of patients with LCAT deficiency poses serious reservations regarding the specificity of the proposed test. 

Drug/Lab test interactions Asympiomai c reversible increases in AST and ALT aminotransferase levels have occurred in patients treated with LMWHs and heparin. Because aminotransferase determinations are important in the differential diagnosis of Ml, liver disease, and PE, interpret elevations that might be caused by LMWHs with caution. 

Roller s test (F. Roller, 1961) differentiates between a lack of coagulation factors due to hepatocellular damage or due to vitamin K deficiency. This test facilitates the differential diagnosis between hepatocellular and mechanical jaundice as well as between liver diseases and bile-duct diseases. The advantages are simple to perform, hardly any side-effects, low in costs. 

Differentiation of vascular-related liver diseases Detection of alterations regarding the bile ducts Differential diagnosis of mechanical jaundice Assessment of portal hypertension Extent of collateral vessels Unclarified diffuse alterations of the liver parenchyma... 

A number of liver diseases are accompanied by an enlargement of the liver. The liver can also be involved in extrahepatic or systemic pathological diseases, possibly with the simultaneous development of hepatomegaly. Differential diagnosis is extremely varied, necessitating a broad spectrum of investigations in individual cases. (1-3, 6-8, 10, 11) (s. tab. 11.1)... 

Numerous diseases can cause ascites. In terms of aetiology, liver diseases, malignant processes and chronic cardiac diseases rank right at the top. Yet inflammatory, renal, metabolic, vascular and endocrinological causes also have to be borne in mind when drawing up a differential diagnosis. The mechanisms at work in the formation of ascites are often still unresolved, as is the case, for example, in hypothyroidism, diseases of the ovaries or the POEMS syndrome (P.A. Bardwick et al., 1980). (100,168) (s. tab. 16.6)... 

In various diseases of the liver and biliary ducts, with or without jaundice, a wide range of secondary kidney diseases can occur. They differ greatly in their degree of severity and their prognosis and can cause considerable difficulties in the drawing up of a differential diagnosis. (53, 54) (s. tab. 17.6)... 

After exclusion of these differential diagnostic possibilities in liver diseases with renal symptoms, the likely diagnosis is hepatorenal syndrome. In the case of a severe and protracted course, this functional impairment of the kidneys can progress to true, acute renal failure, even with tubular necrosis. 

Lower gastrointestinal haemorrhage shows a frequency of 10-15% some 3-5% develop in the small bowel. Intestinal bleeding as a result of liver disease is rare. The initial problem consists in the fact that (7.) numerous and different causes of bleeding must be clarified by differential diagnosis and (2.) severe blood loss together with a concurrent liver disease is always particularly hazardous. 

The respective lesions in the area of the lobules and portal fields and at the hepatocytes, the mesenchyma and connective tissue differ in intensity from case to case (also depending on the respective stage of the disease) - yet the picture of acute hepatitis predominates. In each case of liver disease which remains unresolved in terms of differential diagnosis, thought must be given to the possibility of acute hepatitis with its wide range of aetiological causes, (s. fig. 22.6)... 

A severe cholestatic syndrome (H. Ballard et al., 1961) can be observed in patients suffering from alcoholic fatty liver, (s. fig. 28.16) The clinical picture may correspond to that of obstructive jaundice and cause great problems in differential diagnosis, particularly because such patients may not have been known before to be suffering from alcohol-induced liver disease. Extremely severe forms to the point of acute liver failure have been observed. 

Special questionnaires and laboratory tests have been developed for the early diagnosis or differential diagnosis of alcohol-induced liver disease, but also with respect to an assessment of therapeutic success and thus prognosis. 

Immunoglobulin A is often increased in alcohohcs. The IgA/IgG ratio can also be helpful in differential diagnosis. However, IgA is not elevated directly by alcohol, but by the underlying alcoholic liver disease. (140, 144)... 

Drugs always have to be considered in the differential diagnosis of any case of liver disease lacking unequivocal clarification. The diagnosis of a pharma-con-related liver disease depends on the reliable exclusion of other potential causes of the existing disease as well as on the so-called withdrawal trial. 

Drug-related hepatic damage can mimic almost any liver disease and must, therefore, always be included in the differential diagnosis, (s. tab. 29.6)... 

For every liver disease that cannot be clarified with certainty, each differential diagnosis should always include toxic substances in food, at work, in the house or garden and in those places where people pursue leisure activities. It is extremely difficult to identify the causal noxa. In the individual case, however, identification can be of considerable importance for general assessment purposes and possibly when an expertise is required. 

Differential diagnosis The following conditions should be excluded (7.) alcohol-induced liver disease, (2.) primary biliary cholangitis (86), (3.) porphyria cutanea tarda (108), and (4.) autoimmune hepatitis (89) or autoimmune cholangitis (132) associated with anti-HCV. 

Polyclonal increases in serum immunoglobulins are the normal response to infections. IgG response predominates in autoimmune responses IgA in skin, gut, respiratory, and renal infections and IgM in primary viral infections and bloodstream parasites, such as malaria. Chronic bacterial infections may cause an increase in serum levels of all immunoglobulins. In such cases, estimations of the individual immunoglobulins seldom provide more information than protein electrophoresis. They are of value, however, in the differential diagnosis of liver disease and of intrauterine infections. In primary biliary cirrhosis, the IgM level is greatly increased in chronic active hepatitis, IgG and sometimes IgM are increased and in portal cirrhosis, IgA and sometimes IgG are increased. In intrauterine infections, production of IgM by the fetus increases, and the IgM level in umbilical cord blood is increased. Estimations of IgE are used in the management of asthma and other allergic conditions, especially in children. 

The fasting venous plasma ammonia concentration is useful in the differential diagnosis of encephalopathy when it is unclear if encephalopathy is of an hepatic origin. It is especially helpful in diagnosing Reye s syndrome and the inherited disorders of urea metabolism. However, it is not a useful test to use in patients with laiown liver disease. 

Because the pattern and degree of elevation of enzyme activity vary with the type of liver disease, their measurement is extremely helpful in the recognition and differential diagnosis of liver damage. A number of factors govern the ability of Uver enzymes to assist in diagnosis including their (1) tissue specificity, (2) subcellular distribution, (3) relative activity of enzyme activity in liver and plasma, (4) patterns of release, and (5) clearance from plasma. 

Overall, I am of the opinion that serum immunoglobulins are very helpful in the differential diagnosis of liver diseases, provided diseases elsewhere can be excluded pattern 4 is over 95% reliable, and patterns 3, 5, 6 are about 90% reliable, allowing for their different clinical pictures. 

---