Liver disease assessment

Prothrombin time PT is performed by adding thromboplastin (tissue) factor and calcium to citrate-anticoagulated plasma, recalcifying the plasma, and measuring the clotting time. The major utility of PT is to measure the activity of the vitamin K-dependent factors II, VII, and X. The PT is used in evaluation of liver disease, to monitor warfarin anticoagulant effect, and to assess vitamin K deficiency. 

A complete history and physical examination should assess (1) presence or absence of cardiovascular risk factors or definite cardiovascular disease in the individual (2) family history of premature cardiovascular disease or lipid disorders (3) presence or absence of secondary causes of hyperlipidemia, including concurrent medications and (4) presence or absence of xanthomas, abdominal pain, or history of pancreatitis, renal or liver disease, peripheral vascular disease, abdominal aortic aneurysm, or cerebral vascular disease (carotid bruits, stroke, or transient ischemic attack). 

Routine liver assessment tests include alkaline phosphatase, bilirubin, aspartate transaminase, alanine transaminase, and y-glutamyl transpeptidase (GGT). Additional markers of hepatic synthetic activity include albumin and prothrombin time. The substances are typically elevated in chronic inflammatory liver diseases such as hepatitis C, but may be normal in others with resolved infectious processes. 

Testa, R., Caglieris, S., Risso, D., Arzani, L., Campo, N., Alvarez, S., Giannini, E., Lantieri, P.B., and Celle, G., Monoethylglycinexylidide formation measurement as a hepatic function test to assess severity of chronic liver disease. Am.. Gastroenterol, 92, 2268-2273, 1997. 

The greatest concern is that pemoline on rare occasions causes a chemical hepatitis (liver malfunction). For this reason, patients with known liver disease should never take pemoline. Patients should have a baseline laboratory assessment of liver... 

Rare cases of hepatic failure, some leading to death or liver transplant, have occurred with the use of terbinafine for the treatment of onychomycosis in individuals with and without pre-existing liver disease. In the majority of liver cases reported in association with terbinafine use, the patients had serious underlying systemic conditions and an uncertain causal relationship with terbinafine. Terbinafine is not recommended for patients with chronic or active liver disease. Before prescribing terbinafine, assess pre-existing liver disease. Hepatotoxicity may occur in patients with and without preexisting liver disease. Pretreatment serum transaminase (ALT and AST) tests are advised for all patients before taking terbinafine. 

Hepatocyte transplantation is being explored as an alternative to whole-organ transplantation. In addition, gene transfer therapy is being developed for familial hypercholesterolemia. A non-invasive method to serially assess the metabolic status and proliferation of hepa-tocytes transferred as treatment for end-stage liver disease or genetic... 

Apart from the usual questions (for example, is paracetamol an appropriate analgesic for the type of pain ), we do not know enough about the breadth and severity of the liver disease. This is key information when deciding whether a particular drug can be used, and therefore it is very difficult to generalise and answer a non-patient-specific enquiry. Further information on the assessment of liver function and how this relates to drug handling can be found in Chapter 4. 

Obtain as much information as possible about your patient s liver function, and use this to assess the type, extent and severity of liver disease or dysfunction. You may find the aide memoire in the Appendix helpful to remind you of the relevant data. 

If the BNF and SPC do contraindicate or caution against the use of the drug in liver disease, then fnrther investigation and research is generally needed. This is becanse the recommendation may be based on a lack of or inconclusive data, rather than adverse data. In these situations, application of knowledge from first principles is often appropriate, and a risk-benefit assessment for yonr specific patient should be considered. Use of drugs outside their product licence may be considered appropriate in some situations. 

As with most medications, no robust assessment of the use of paracetamol in liver disease has been performed, although small studies of paracetamol metabolism in various forms of liver disease have been undertaken. Although limited, the results of some of these studies are summarised below. 

There are few, if any, noteworthy studies of NSAID use in liver disease. This is because they are rarely used in liver disease because of their adverse effect profile. Most studies conducted used a single dose only, thus neglecting to assess the effects of multiple doses that are used in real-life scenarios. 

Many centres prefer to avoid using NSAIDs in any patient with liver disease because of their side-effect profile. However, if the liver disorder is purely cholestatic in origin and the disease has not progressed to cirrhosis and portal hypertension, NSAIDs may be an option. Any risk-benefit assessment should consider the potential risk of hepatotox-icity, albeit rare. There are no specific contraindications in this patient because they are not cirrhotic, do not have deranged clotting, and are unlikely to be at increased risk of deteriorating renal function. If deemed necessary an NSAID could be used cautiously. 

In 2006 the National Lipid Association s Statin Safety Assessment Task Force concluded that chronic liver disease and compensated liver disease are not contraindications to the use of statins, but that they are contraindicated in decompensated disease or liver failure [2, 3] see Hepatic Adverse Effects. 

It is less likely in other forms of liver disease, such as acute hepatitis and cirrhosis. Cirrhosis may actually protect against atherosclerosis [5, 8, 9]. The reasons for this are not clear. Secondary hypercholesterolaemia frequently occurs in cholestatic conditions, but usually does not require treatment [10]. Other risk factors for hyperlipidaemia and cardiovascular disease should be assessed, as their presence may independently indicate a need for medical intervention [9]. In PBC, patients with severe, chronic disease do not appear to have an increased cardiovascular risk as a result of their hypercholesterolaemia this may be due to the presence of cirrhosis. In contrast, in less severe PBC... 

A 2006 review by the National Lipid Association s Statin Safety Assessment Task Force concluded that hepatic function does not appear to be compromised by statin use and that there was no apparent link between elevations in LFTs and the development of liver toxicity. They noted that TFT monitoring may itself be of little value in the absence of other symptoms of liver toxicity, but should be performed for medicolegal reasons, as it is recommended in the product SPCs. The expert group concluded that the use of statins is not contraindicated in chronic and compensated liver disease, but that it is contraindicated in decompensated disease or liver failure [2, 3]. 

Before starting HRT patients should be assessed individually considering their risk of osteoporosis, the current status of their liver disease, and any other coexisting medical risks. They should also be assessed for any history, including family history, of jaundice. The risks and potential benefits of treatment should be carefully explained. 

The risks and benefits of HRT should be assessed for each patient by taking into consideration individual risk factors and the severity of their liver disease. These should be discussed with the patient before the initiation of therapy. Liver function tests should be monitored before treatment is begun, and then during treatment as appropriate. The optimum duration of therapy has yet to be defined in liver patients. The minimum effective dose should be used for the shortest period. The decision to continue treatment must be made on an individual basis, in view of the risks associated with use of HRT. 

Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise and anorexia. Measure amylase and lipase if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider reducing dose. Methadone may cause Q-T prolongation the CSM has recommended that patients with heart and liver disease on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG, which may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily, and thus t plasma concentrations necessitates close monitoring of cardiac and respiratory function 2. Recommended that a small test dose (one-quarter of the usual dose) be administered initially to assess response... 

In the diagnosis and assessment of liver disease, the clinical, laboratory and ultrasound findings must always be interpreted integratively and simultaneously, together with the histology and any additional imaging procedures (insofar as these are indicated). 

In a variety of liver diseases, it often happens that only certain partial functions or cellular structures are impaired this impairment can differ widely in intensity and extent in the individual patient. Therefore, when applying only a few biochemical tests, pathological changes may well be overlooked. For the detection of hepatocellular damage or disorders of hepatic functions, a variety of examination methods will have to be employed in order to provide a comprehensive assessment derived from the various single findings. 

An elevation of ChE activity can be detected in fatty liver, obesity, diabetes mellitus, exudative enteropathy, nephrotic syndrome, hyperthyroidism, Meulengracht s icterus, chronic obstructive jaundice, etc. Specificity in liver diseases is 61%, and sensitivity is 49%. In cirrhosis, however, sensitivity is 88% normal ChE therefore widely excludes cirrhosis. In connection with other hepatobiliary enzymes, ChE can be useful in the diagnosis and assessment of the course of liver disease. There is a very good correlation of ChE activity with coagulation factors in liver diseases however, the correlation is less significant with albumin synthesis. 

Clinical and enzymatic data of 520 of our patients suffering from various liver diseases were evaluated to assess the diagnostic accuracy of each method, (s. tab. 4.2) In the detection of hepatopathy , application of 3-7 hepatobiliary enzymes yielded a sensitivity of 95-97%. (13) (s. tab. 5.11)... 

Coagulation factors are proteins with varying but usually short half-lives, (s. tab. 5.12) Their determination allows the assessment of hepatic function. However, the respective half-life has to be considered. Disorders of coagulation factors are therefore important functional parameters in hepatic diseases - both in severe acute and in chronic cases. In liver diseases, there may be a lack of coagulation factors, which is predominantly and primarily caused by a disorder of the hepatocyte synthesis capacity. This lack can also be due to other causes (1.) accelerated catabolism, (2.) altered biosynthesis of inhibitors, (3.) production of abnormal factors, and (4.) increased demand due to intravasal coagulation. 

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