Liver disease diagnosis

Pinzani M, Rombouts K, Colagrande S (2005). Fibrosis in chronic liver diseases diagnosis and management. JHepatol42 Suppl S22-36. 

A specific enzymatic-fluorimetr g method based upon the use of 7o( -HSD has also been described. The sensitivity of this method is poor, but it allows quantitative measurements of the primary SBA alone (7 o(-hydroxy bile acids), which may l e ore useful than total SBA detection in liver disease diagnosis ... 

Diagnosis of liver diseases by laboratory results and discriminant analysis. Identification of best combinations of laboratory tests. Scand. J. Clin. Lab. Invest. 

Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

Liver biopsy plays a central role in the diagnosis and staging of liver disease. 

Medical indications Chronic pulmonary disease (excluding asthma) chronic cardiovascular diseases, diabetes mellitus chronic liver diseases, including liver disease as a result of alcohol abuse (e.g., cirrhosis) chronic alcoholism, chronic renal failure or nephrotic syndrome functional or anatomic asplenia (e.g, sickle cell disease or splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery]) immunosuppressive conditions and cochlear implants and cerebrospinal fluid leaks. Vaccinate as close to HIV diagnosis as possible. 

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 ability of the liver to act as a depot for vitamin Bi2 (B28, G13) enables us to use this vitamin as an index of proper hepatic function. Hepatic disorders lead to an increased Bi2-binding in the serum (J5, R3), suggesting that the blood assumes a greater role in the conservation of B12. We have reported that patients with liver disease excreted invariably less than 10 fig of Bi2> 8 hours after a 50-[ig intramuscular load dose of the vitamin. In contrast, normal subjects excreted 24-40 pg, i.e., 50-80% of the vitamin in the same test (B14). These results were correlated with various chemical determinations indicative of hepatic disorders (Bl). In Table 16 the clinical diagnosis and the various liver-... 

Van der Sluijs P, Meijer DKF, In Liver Diseases. Targeted Diagnosis and Therapy Using Specific Receptors and Ligands (Eds Wu GY, Wu CH), pp. 235-264. Marcel Dekker, Inc., New York, 1991. 

Vulnerability of the liver to injury necessitates routine evaluation of hepatic function in patients and asymptomatic individuals to avert or control adverse clinical conditions. Thus, a plethora of methods has been developed for the diagnosis of liver diseases and dysfunctions. One such method uses physical palpation to determine alterations or changes in the orientation of the liver, which provides valuable information about the organ status but the quality of information is subjective and imprecise [3]. Another common method for the diagnosis of more serious hepatic injuries involves liver biopsies coupled with biochemical tests to determine the extent of liver injury and prognosis [4-7]. However, in acute and some chronic hepatic disorders, dynamic and continuous hepatic function monitoring would be advantageous. 

Transaminases are also found in other tissues, from which they leak from the cells into the blood when injury occurs. Measurement of serum enzyme activity (serum enzyme diagnosis see also p. 98) is an important method of recognizing and monitoring the course of such injuries. Transaminase activity in the blood is for instance important for diagnosing liver disease (e.g., hepatitis) and myocardial disease (cardiac infarction). 

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. 

Diagnosis is established by a combination of clinical examination (variceal bleeding is unlikely in the absence of stigmata of liver disease) and endoscopy. Bleeding ulcers may then be recognised as actively bleeding, or though the presence of a black base to the ulcer with, occasionally a visible vessel. 

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

Renal disease is detected through urinanaly-sis done yearly on PIZZ individuals with liver disease. Detection of proteinuria would lead to examination of a quantitative 24-hour urine for protein. If confirmation of the diagnosis is essential, then renal biopsy would be necessary. 

Causes of cirrhosis can usually be identified by the patient s history combined with serological and histological investigation. Alcoholic liver disease and hepatitis C and B are the most common causes of cirrhosis. The association of excessive alcohol consumption with liver disease has been recognised for centuries. After the identification of the hepatitis C vims and of non-alcoholic steatohepatitis in obese patients with diabetes, the diagnosis of cirrhosis without an apparent cause (cryptogenic cirrhosis) is rarely made. Genetic causes of cirrhosis include haemochromatosis and Wilson s disease. 

A biopsy is often required to make a diagnosis of most types of liver disease. A specimen of liver can be used to identify fibrosis, cirrhosis, cholestasis and hepatitis, both acute and chronic, and tumours. Biochemical measurements can also be taken from a biopsy specimen to determine iron and copper content, virology, microbiology and haematology (e.g. increased numbers of eosinophils in a drug-induced cause). The biopsy can give an indication of the extent of the liver damage. See Chapter 3 for slides of liver biopsies. 

In order to demonstrate the drug-handling issues that are relevant in different types of liver disease, five patients are discussed. Each patient has a specific diagnosis, which serves as an example of a specific type of liver dysfunction. Even if your patient does not have the same diagnosis as one of these examples, their pattern of liver dysfunction, and hence their drug handling, is likely to be similar to one of the five. Full details of each case can be found in Appendix 1. 

Diagnosis (type/cause) (if known) Thioguanine-induced liver disease... 

Liver biopsy is of only limited use in diagnosis, although certain features, e.g. eosinophil infiltration, may provide a pointer to drug-induced liver disease. 

The target of a detailed diagnosis is generally achieved using various and mutually complementary examination techniques. Diagnostic methods in liver disease are founded on four diagnostic pillars, which are applied stepwise and nearly always provide the basis for an exact and detailed diagnosis. Complex or invasive techniques are only used when they are clearly indicated. (19) (s. fig. 4.2)... 

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