Abnormal liver function test results

24 Abnormal liver function test results



Case


A 45-year-old male was found to have abnormal liver function tests on routine investigations performed for an insurance examination. Serum alanine aminotransferase level was elevated at 105 IU/L. International Normalized Ratio (INR), albumin and bilirubin were normal. The patient also had a history of hypertension controlled on antihypertensive therapy and an elevated fasting serum triglyceride concentration. His father had type 2 diabetes, but there was no family history of liver disease. An abdominal ultrasound examination demonstrated changes consistent with fatty liver, but no other abnormality. Further investigations showed no evidence of autoimmune, viral or inherited liver disease. His ferritin was mildly elevated, but with normal transferrin saturation and no mutation of the haemochromatosis (HFE) gene. Physical examination revealed him to be overweight, but otherwise was unremarkable. The patient was advised to reduce his weight and exercise regularly. Under the guidance of a dietician a 5% weight loss was achieved with an improvement in alanine aminotransferase levels. Following that he failed to maintain the intervention, gained weight and discontinued medical review. Ten years later he again was found to have abnormal liver tests but also INR 1.6, albumin 28 gm/L and bilirubin 25 μg/L. He had become diabetic with symptomatic ischaemic heart disease. Abdominal ultrasound on this occasion showed a small irregular liver with splenomegaly, consistent with cirrhosis and an apparent mass in the liver. On a triple phase computed tomography (CT) scan of the liver, the 2-cm mass lesion was typical of a hepatocellular carcinoma and was managed surgically.



An Approach to the Patient with Liver Disease


The liver is a remarkable organ with substantial functional reserve and impressive regenerative capacity. The presence of abnormal liver function profiles, therefore, may not be apparent at the bedside. However, when abnormal liver function test results are found, their significance needs to be assessed in the light of clinical (bedside) findings. The pattern of liver function test abnormalities can be subdivided into either a hepatocellular or cholestatic disease category as discussed below. Organ imaging is an important complementary tool in the assessment of abnormal liver function profiles. The presence of normal liver function profiles makes hepatic disease unlikely, although there are many exceptions, including well-compensated cirrhosis, some cases of chronic hepatitis C, and those with certain space-occupying lesions of the liver.


Liver disease will present as one of a limited number of clinical syndromes. Each syndrome may be caused by a number of specific disease processes. A diagnosis is achieved by paying attention to historical features and physical findings (Box 24.1) and the results of laboratory and other investigations. Only then can specific treatment for the cause of the liver abnormality be planned. Therapy, in many instances, is directed to the management of the clinical problem in addition to treatment directed to the underlying condition.



In this chapter, liver function tests and their clinical relevance are discussed first because abnormalities are commonly detected in asymptomatic individuals. Next, the common clinical presentations of liver disease are covered. Finally, important liver diseases are described.



Liver Function Test Interpretation


In the initial assessment of a patient with abnormal liver function test results, a number of questions need to be considered:






Routine liver function tests usually include serum bilirubin, albumin, International Normalised Ratio (or prothrombin time), transaminases, alkaline phosphatase, gamma glutamyl transpeptidase and, in some laboratories, lactate dehydrogenase. Other tests should be ordered only for specific indications.



Bilirubin


Elevated serum bilirubin levels may occur in all forms of liver disease. However, it must be remembered that a jaundiced patient does not necessarily have significant hepatic disease. Serum levels of bilirubin reflect production, hepatic uptake, processing (conjugation) and secretion. The physiology of bilirubin and an approach to diagnosis and management of jaundice is described in Chapter 23.


The value of the ratio between conjugated and non-conjugated bilirubin in distinguishing the nature of a liver disorder is limited. Conjugated bilirubin levels are highest in cholestatic disease and in fulminant hepatic failure. Unconjugated hyperbilirubinaemia may reflect haemolysis, neonatal physiological jaundice or genetic defects in bilirubin transport and conjugation (Gilbert’s and Crigler-Najjar syndromes). Haemolysis rarely produces total bilirubin levels greater than 50–90 μmol/L.


In acute liver disease, the bilirubin level is of little prognostic significance. On the other hand, rising serum bilirubin levels reflect the approach of end-stage disease in many chronic liver diseases. For example, in primary biliary cirrhosis this signals the need to consider liver transplantation. In secondary malignancy it is often a signal of a preterminal event.


In the presence of chronic liver disease, when hepatic reserve is limited, relatively small increases in bilirubin production (as with haemolysis) can produce a disproportionate increase in serum bilirubin. When there is cholestasis, renal failure will reduce the clearance of conjugated bilirubin sufficiently to increase serum levels. Furthermore, conjugated bilirubin binds irreversibly to albumin such that bound bilirubin will not be cleared until the albumin it is bound to is catabolised.



Tests reflecting hepatic function




Prothrombin time or INR


As with albumin, the vitamin K-dependent clotting factors are synthesised by the liver. The plasma concentrations of prothrombin and factors VII, IX and X often fall in the presence of significant liver disease. The prothrombin time assesses the activity of these coagulation factors. The INR is the ratio between the clotting time (in seconds) using the patient’s plasma divided by that for a control sample using standardised reagents (normal range: 0.8–1.2).


Because of the relatively short half-life of some of these proteins, abnormalities can develop quickly following the onset of hepatic decompensation. In certain circumstances, this may occur within hours (e.g. fatty liver of pregnancy).


Cholestasis can result in vitamin K malabsorption and, in so doing, lead to a raised INR. In that situation, parenteral vitamin K promptly reverses the abnormality. On the other hand, a raised INR that is unresponsive to vitamin K often suggests significant hepatocellular dysfunction.


In a patient with liver disease who is bleeding, the abnormal clotting may represent direct losses and consumption of clotting factors. Stored blood has no effective clotting factors, and contains anticoagulant. After a large transfusion, the clotting factors must therefore also be replaced by giving fresh frozen plasma.


It should be noted that the INR does not necessarily reflect the severity of chronic liver disease. It may be normal or near normal in the presence of advanced cirrhosis. In fulminant hepatic failure, serial INR measurements are of prognostic value with recovery being more likely if the INR decreases. Prognosis is poor when the INR is greater than 3. In vitro tests of clotting factors, such as the INR, will not necessarily reflect the coagulation status of the patient with liver disease.



Tests of Liver Injury






Alkaline phosphatase


Alkaline phosphatase (ALP) is an enzyme localised to the biliary membrane of hepatocytes. An elevation of the serum ALP level is a marker of biliary disease or a hepatic infiltrative disorder.


Although cholestasis may be present with a normal ALP level, in three-quarters of patients with cholestasis, serum ALP levels will be three or more times greater than the upper limit of normal. Mild elevations of hepatic ALP levels are often seen in hepatocellular injury. Serum ALP levels may also be elevated, at times in isolation, in other disorders affecting the liver, including congestive cardiac failure and lymphoma. A mild elevation is often seen in patients with a non-hepatic illness; this returns to normal over a period of weeks to months, after the underlying condition is treated.


ALP is also found in bone, intestine, kidney and placenta. Consequently, damage to these organs will elevate the serum ALP level. Furthermore, during pregnancy and periods of rapid growth (neonatal and adolescent periods), serum levels of this enzyme are higher. When the serum ALP level is elevated in the absence of other abnormalities in the liver function tests, a non-hepatic cause, such as Paget’s disease, tumours involving bone, acromegaly and fractures, should be considered. Milder rises in ALP may occur following infarction involving the heart, lung, gastrointestinal tract or kidneys.


5′-nucleotidase, a membrane-associated enzyme, is elevated in the plasma primarily in cholestatic liver disease. Although present in pancreas, brain, intestine and heart, this enzyme is more specific for liver disorders than is alkaline phosphatase.






Other tests useful in hepatic assessment


A marked elevation (over 1000 U/L) of alpha-fetoprotein is most often due to hepatocellular carcinoma. This test has been used for screening an individual with chronic hepatitis B for the development of hepatocellular carcinoma, having a sensitivity of 70%. It is of limited value, however, because the sensitivity falls to 30% in non-hepatitis B hepatocellular carcinoma. Milder elevations occur in both acute and chronic liver disease of many causes (Ch 25).


Autoantibodies are helpful in diagnosing certain forms of liver disease (Table 24.1). Serum concentration of caeruloplasmin and iron studies are important tools in the diagnosis of Wilson’s disease and haemochromatosis, respectively (Table 24.2), but are also altered by liver injury unrelated to either of these conditions. Tests for viral hepatitis are also important (Table 24.3).


Table 24.1 Tests for autoimmune liver disease



























Test Condition Comment
Antinuclear antibody (ANA) Autoimmune chronic hepatitis Diagnosis requires liver biopsy
Smooth muscle antibody (SMA) (anti-actin) Autoimmune chronic hepatitis Diagnosis requires liver biopsy
Anti-liver kidney microsomal antibody (anti-LKM1) Autoimmune chronic hepatitis Diagnosis requires liver biopsy
Antimitochondrial antibody (AMA) Primary biliary cirrhosis(95%) Diagnosis requires liver biopsy
Antineutrophil cytoplasmic antibody (pANCA) Primary sclerosing cholangitis Diagnosis requires magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography

Table 24.2 Tests for metabolic disorders affecting the liver



































Test Condition Comment
Iron studies Haemochromatosis See text
Copper and caeruloplasmin Wilson’s disease See text
Alpha-1 antitrypsin level and phenotype Alpha-1 antitrypsin deficiency Heterozygotes may have abnormal liver function tests without significant liver disease
Thyroid function tests Hypothyroidism Fatty liver
Blood glucose level Diabetes mellitus Fatty liver, haemochromatosis
Insulin/C-peptide Insulin resistance Fatty liver, metabolic syndrome
Cholesterol and triglycerides Primary and secondary hyperlipidaemia Fatty liver, alcoholic liver disease

Table 24.3 Tests for viral hepatitis











































































































Test Meaning of a positive result Comment
1. Tests for hepatitis A virus (HAV)    
Anti-HAV IgM Recent acquisition of HAV Acute hepatic illness likely to be HAV
Anti-HAV IgG Past infection/vaccination Immunity
2. Tests for hepatitis B virus (HBV)    
HBsAg (surface ag) Present/chronic infection Structural component of virus
Anti-HBsAg (surface ab) Past infection/vaccination Immunity
Anti-HBc IgM (core ab) Recent acquisition of HBV The test for acute HBV infection
HBeAg (e ag) Marker of viral replication High risk of infectivity
Anti-HBeAg (e ab) Suggests no viral replication Unlikely to be infectious
HBV DNA Presence of complete virus High risk of infectivity
3. Tests for hepatitis C virus (HCV)    
Anti-HCV Exposure to HCV Interpret in conjunction with other clinical and laboratory data
HCV RNA by PCR Presence of virus
HCV genotyping Treatment planning and response
4. Tests for hepatitis D virus (HDV)    
Anti-HDV IgG/IgM Exposure to HDV Acute or chronic HDV
Delta antigen HDV present Acute or chronic HDV
5. Tests for hepatitis E virus (HEV)    
Anti-HEV IgM Recent acquisition of HEV Acute hepatitic illness likely to be HEV
6. Tests for other organisms    
Cytomegalovirus (CMV) IgM Recent acquisition of CMV Acute hepatitic illness likely to be CMV
Epstein-Barr virus (EBV) IgM Recent acquisition of EBV Acute hepatitic illness likely to be EBV
Anti-HIV HIV-AIDS Opportunistic hepatobiliary infections
Toxoplasmosis serology Consider toxoplasmosis
Q fever serology Consider Q fever

ag = antigen; ab = antibody; PCR = polymerase chain reaction.



Liver biopsy


Histological and, on occasion, chemical analysis and microbiological examination of the liver are essential in the diagnosis of many hepatic disorders. The usual technique for obtaining a liver biopsy involves a percutaneous approach through a lower intercostal space in the right midaxillary line. Ultrasound scanning or CT can be used to optimise the needle entry point or target specific abnormalities. Haemorrhage from the biopsy wound to the liver or injury to adjacent organs are the major risks. These may be significant in approximately 1% of biopsies. The risk of haemorrhage is minimised by ensuring a platelet count greater than 80 × 109/L (80,000/mm3) and an INR less than 1.2. When coagulopathy or gross ascites prevents a percutaneous biopsy, a transjugular approach can be used.


The decision to proceed to liver biopsy is reached when the potential information gained outweighs the risks of the procedure. In particular, obtaining information about the patient’s prognosis or diagnostic information that might alter therapy is the important consideration. Although it is not always appropriate to perform a liver biopsy to only achieve a diagnosis, it is not unusual for the clinical diagnosis to be altered by the information gained at biopsy. The clinical course of the illness should also be considered. The patient with improving liver function test profiles and resolving symptoms is probably best observed rather than biopsied early. It should be noted, however, that, in certain conditions such as chronic hepatitis C and haemochromatosis and in some alcoholic patients, hepatic fibrosis can progress to cirrhosis with little clinical or laboratory evidence of aggressive liver disease.


The significance of liver biopsy features is considered in relation to specific disorders later in this chapter. The extent, nature and activity of inflammatory and fibrotic processes are of particular concern. The presence of fibro-inflammatory changes is more likely to be related to a progression to cirrhosis. The absence of such changes carries a better prognosis. Sampling error can be a problem as the tissue sample represents only a tiny proportion of the liver mass and the disease process may not be uniform across the organ. Cirrhosis can be missed in 10–20% of cases, depending on the size and number of samples taken.



The Well Patient with Abnormal Liver Function Profile


Many patients now present to their practitioner apparently in good health but with an abnormal set of liver function test results, often found at routine insurance medical examination. These patients raise a whole range of diagnostic possibilities and, in evaluating them, a full history and examination is required. The most common causes of abnormal liver function test results in otherwise well individuals are non-alcoholic fatty disease (which may or may not be associated with significant inflammation) and alcohol-related liver damage. Another common cause will be the ingestion of medications. However, the presence of other serious, progressive and eventually potentially life-threatening conditions needs to be considered.



History


All patients with abnormal liver function test results need to be questioned about their family history of liver disease, and their ingestion currently or in the past of alcohol and medications.


A history of diabetes mellitus, thyroid disease and high lipid levels should be sought; these together with obesity are associated with hepatic steatosis. The features of the metabolic syndrome with rising body weight and reduced physical activity are common in those with non-alcoholic fatty liver disease, especially when there is a family history of type 2 diabetes.


A history of overseas travel and exposure to blood products from transfusions or injection of drugs, legally or illegally, needs to be sought (e.g. hepatitis B or C). A history of known exposure to patients with infectious liver diseases should be asked about. A sexual history must be obtained because exposure to some viruses is much more common in individuals with multiple sexual partners (e.g. hepatitis B and HIV).


When there is a family history of liver disease, social background requires close review. ‘Learned’ excessive alcohol consumption can lead to liver disease without the patient being aware that their intake is potentially dangerous. The amount of alcohol the ‘social drinker’ consumes varies according to his or her background.


There is a possibility of genetic predisposition to alcoholic liver disease.


Migration from areas of high prevalence of hepatitis B or C (e.g. Southeast Asia) should be noted. These viruses, acquired at birth or in early childhood, may not generate symptoms for many years.


Haemochromatosis is preferably diagnosed prior to the onset of symptoms; abnormalities of liver function tests and abnormal iron study findings are clues. However, a history of joint pains, diabetes mellitus, cardiac disease or impotence in the patient or the existence of an affected relative suggests the possibility of haemochromatosis.


Wilson’s disease is likely to be asymptomatic only in younger children. At older ages, features of cirrhosis or neurological abnormalities are likely. Alpha-1 antitrypsin deficiency, homozygote or heterozygote, may present with the incidental finding of abnormal liver function profiles in an otherwise well patient.


In the otherwise well patient, a history of abdominal pain (e.g. biliary pain: Ch 4), loss of appetite or weight (Ch 17), or a change in the colour of stools or urine (Ch 23) needs to be sought but is almost invariably absent.




Investigation


The approach to investigations is guided by the history, examination and liver function test pattern. Further testing is based on the provisional diagnosis and likely prognosis. When no hints as to the diagnosis have been found, a systematic investigation for potentially dangerous causes of liver disease needs to be considered. This would normally be done after a period of observation with serial liver function tests to determine whether there is a spontaneous recovery, a stable abnormality or deterioration.


Liver imaging is of value (Ch 23). Abdominal ultrasound scans can provide information about the size and shape of the liver and spleen. Often any mass lesions present can also be identified. Ultrasonography will often detect fatty liver. Abdominal CT will provide information on the presence or absence of space-occupying lesions while, in addition, providing insight into liver density, which may be increased in haemochromatosis. Magnetic resonance imaging will usually add little to the information provided by a CT scan but can be of value in certain circumstances, such as in the assessment of mass lesions and of the biliary tract.


Tests for evidence of viral hepatitis (Table 24.3), autoimmune liver disease (Table 24.1) and other causes of chronic liver disease (iron or copper overload, and other inherited liver diseases) (Table 24.2) should be done if hepatocellular disease is possible. If the diagnosis remains unclear and the prognosis of concern, a liver biopsy is required.


Chronic hepatitis is an ongoing inflammatory process. The causes are listed in Table 24.4. If fibrosis follows as part of the healing process consequent to this inflammation, progression to cirrhosis and eventual liver failure is possible. For this reason, potentially controllable chronic hepatitis needs to be identified and treated before irreversible injury has occurred.


Table 24.4 Important causes of chronic hepatitis and cirrhosis









Chronic hepatitis Cirrhosis


















In each of the conditions generating chronic hepatitis there is an ongoing inflammatory attack directed toward the hepatocyte. This can be the result of direct hepatocyte injury, as is the case in hepatitis C infection (the most common cause of chronic hepatitis in Australia) and Wilson’s disease, which is rare. On the other hand, liver cell injury may be immune-mediated, as occurs with hepatitis B infection, autoimmune chronic hepatitis and certain drug reactions.


Evidence of continuing hepatic inflammation based on a persistent elevation of serum transaminases (6 months or more) is usually required to entertain the diagnosis of a chronic hepatitis. However, it can take many months for serum transaminases to return to normal levels following some acute hepatic illnesses. Once the presence of chronic hepatitis is considered likely, establish the aetiology of the illness, the extent of liver damage and the activity of the inflammatory process. These latter two features can be assessed only by the histological examination of a liver biopsy.



The Sick Patient with Jaundice: Acute Liver Disease



Acute hepatitis



History


Acute hepatitis of any cause can present with similar clinical features. Typically there is nausea with or without vomiting, right upper quadrant pain, weakness, fever, fatigue, itching and jaundice. An acute icteric illness may follow infection with one of the hepatitis viruses (see below). A similar clinical picture may be seen in Epstein-Barr virus and cytomegalovirus infections, in toxoplasmosis and occasionally in other viral infections. Viral exposure is suggested by parenteral risk factors such as intravenous drug use, tattooing, intimate contacts with hepatitis-infected patients, blood transfusion, travel to endemic areas and during local epidemics. Acute autoimmune disease is suggested by the presence of other autoimmune disorders (e.g. thyroid disease). A careful and complete drug history is vital. Both recently commenced drugs and those taken for prolonged periods should be considered. In patients showing evidence of depressive behaviour, drug overdose must be considered. If paracetamol (acetaminophen) has been used, then a careful ethanol consumption history is vital (see the next page). Normally safe, therapeutic doses of paracetamol may produce significant liver injury in those chronically consuming excessive amounts of ethanol. It should also be noted that inadvertent paracetamol overdose may occur due the patient’s lack of knowledge of safe dosage or the use of multiple different preparations containing the drug. Excessive ethanol consumption, especially recent bingeing, could indicate acute alcoholic hepatitis. Gallstone disease can occasionally present as an acute hepatitic illness that can be difficult to differentiate clinically. A family history of liver disease should be noted. Wilson’s disease may present as an acute illness, usually in childhood.


Acute hepatitis may occur in a previously well person or in the presence of underlying chronic liver disease. In the latter case, the result can be devastating when preexisting liver disease results in little functional hepatic reserve. In pregnancy, acute viral hepatitis is the most common cause of this syndrome, but consideration should be given to pregnancy-related liver disease (see ‘Liver disease in pregnancy’ later in this chapter).






Acute Liver Failure




History


The historical features of acute hepatitis should be enquired about. However, details will need to be obtained from others when the patient has established encephalopathy. Acute infection with the hepatotropic viruses A, B, D or E (and very rarely C) can cause fulminant hepatic failure. In late pregnancy, acute fatty liver should be considered. Ask about drugs, which may cause direct toxic effects (e.g. following overdose of paracetamol) or cause idiosyncratic reactions (e.g. halothane and sulfonamides).


Following an acute overdose of 140 mg/kg or more of paracetamol, the glucuronide and sulfate pathways in the liver become saturated and hepatic glutathione becomes depleted, leading to reactive metabolites covalently binding to liver cells causing lysis. Hepatotoxicity manifests 24–48 hours after ingestion. The early identification of paracetamol overdose is crucial. Serum levels should be measured 4 and 24 hours after suspected ingestion; the administration of N-acetylcysteine will prevent progression to hepatic failure. It gives maximal benefit if instituted within 8–10 hours of ingestion (but is indicated after that time as well). ALT levels are typically very high while the bilirubin is relatively low. An intake of a normally subtoxic dose of paracetamol in the presence of chronic alcohol abuse may lead to acute hepatic failure. In the USA approximately 50% of paracetamol overdose is non-intentional with the drug taken over days. In these cases the serum drug levels are lower. Toxicity normograms are of no value in this circumstance.


Fluorinated hydrocarbon solvents (in glue sniffing) and mushroom poisoning have also been linked to acute hepatic failure. Wilson’s disease may rarely present in acute liver failure, and death usually follows without liver transplantation.


In fulminant hepatic failure there is a sudden loss of functional hepatocyte mass, often associated with portal hypertension. The associated complications of encephalopathy, coagulopathy, renal failure and sepsis evolve. Multi-organ failure often occurs, with the patient’s death from cerebral oedema or infection.



Assessment and management


Examination is directed towards assessing the possible aetiology and evolving complications of hepatic failure (outlined below). Serial liver function tests can be useful, but a falling ALT level may reflect either recovery or progression to massive hepatic necrosis. A temperature above 38°C or below 36°C, a pulse rate above 90 beats per minute and/or a white cell count above 12,000 or below 4,000 are associated with a greater mortality. The prognosis, and therefore need for liver transplantation, of a patient in acute liver failure can be assessed using the Kings College Criteria (Table 24.5).


Table 24.5 Kings College Criteria for listing of a patient in acute liver failure (ALF) for liver transplantation












Type Criteria
Paracetamol-induced ALF Arterial pH < 7.30 after fluid resuscitation or all of:


Non-paracetamol-induced ALF INR > 6.5 or any three of:





INR = International Normalized Ratio.


From O’Grady JG, Alexander GJM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97:439–445.


The patient with fulminant hepatic failure needs to be admitted directly to a unit capable of offering liver transplantation. Admission to intensive care is required with careful management of cerebral oedema, gastrointestinal bleeding, infection and renal failure.



Hepatic encephalopathy and cerebral oedema


This may develop rapidly and may even precede the onset of jaundice. Raised ammonia levels associated with liver failure cause brain swelling, inflammation, increased cerebral blood flow and a breakdown of the blood–brain barrier. Deeper grades (described later in this chapter) of encephalopathy are associated with a worse prognosis. Unlike the encephalopathy of chronic liver disease, there is often early agitation and delusional ideation. Cerebral oedema is more likely to occur when encephalopathy develops rapidly after the onset of jaundice. However, survival is worse in those in whom encephalopathy evolves slowly. Cerebral oedema, present in up to 80% of those in grade IV encephalopathy, is a significant cause of death. Clinically, this is reflected by systemic hypertension, bradycardia with progressive rigidity and decerebrate posturing. Direct pressure monitoring with a subdural or epidural transducer is the only reliable means of assessing cerebral pressure. Prognosis is particularly poor and liver transplantation inappropriate when the cerebral perfusion pressure is less than 50 mmHg, and is refractory to mannitol therapy. Grade III and IV encephalopathies (see below) are associated with a worse prognosis.


Management aims to reduce systemic vasodilatation and cerebral perfusion pressure, maintaining a low mean arterial pressure and central venous pressure. Mannitol, sodium, hypothermia (when there is hyperacute high grade encephalopathy and requiring vasopressors) and dialysis (in those developing renal impairment) have been used in the treatment of cerebral oedema.







Patients Presenting with Cirrhosis and its Complications


Cirrhosis represents the non-specific end-stage of hepatic disease that has disrupted the structural organisation of the liver. The presence of cirrhosis is established on a liver biopsy. Fibrosis or scarring surrounding regenerative nodules of hepatocytes is its hallmark. Although cirrhosis is a histological diagnosis, its presence is clinically suspected by finding signs of chronic liver disease and portal hypertension (Box 24.1) or on high quality imaging. Symptomatic liver disease and eventually liver failure occur as the result of impaired hepatocellular function within the distorted architecture of the regenerative nodules and, with progression, eventual loss of an effective liver cell mass. Distortion of the hepatic circulation contributes to portal hypertension and inefficient/ineffective perfusion of parenchymal cells. Portal systemic shunts may develop, allowing blood from the gastrointestinal tract to flow directly to the systemic circulation.


Cirrhosis should be considered as either compensated, with no signs of complications and a relatively good prognosis, or decompensated (Ch 25). Those with compensated cirrhosis are likely to be asymptomatic and the diagnosis may be made incidentally during the investigation of an unrelated condition. In this situation, counselling regarding diet, ethanol consumption and the identification and management of any underlying treatable condition are warranted (see ‘The well patient with abnormal liver function profile’ above). Recent data have indicated that the removal or cure of the underlying disease process can be followed by a reduction in hepatic fibrosis (e.g. after the cure of hepatitis C).


The serum levels of liver enzymes (ALT, AST and ALP) can be mildly abnormal or even normal in compensated cirrhosis. However, because of reduced hepatic synthetic function or poor nutrition, the serum albumin concentration is often reduced, and the INR may be increased. There may be thrombocytopenia related to splenomegaly from portal hypertension. Anaemia can be multifactorial but is often related to gastrointestinal blood loss, poor nutrition (e.g. in alcoholics), chronic disease and hypersplenism.


The Child-Pugh score (Table 24.6) provides a useful means of assessing the severity of cirrhosis and the prognosis. A Child-Pugh ‘A’ classification applies to a score of less than 7; ‘B’, a score between 7 and 9; and ‘C’, greater than 9. The 1-year survival of these classification groups is 100%, 80% and 45%, respectively. A higher score also indicates those more likely to succumb to complications during hepatic and no hepatic surgical procedures.



The MELD (Model for End Stage Liver Disease) score is a validated means of assessing the prognosis and survival of a patient with chronic liver disease that incorporates bilirubin, INR and creatinine values. This score can be used to prioritise the allocation of organs within a liver transplantation program (see Ch 25).

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May 30, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on Abnormal liver function test results

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