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Taking note of and recording a patients presenting symptoms as well as medical history in any medical branch is a crucial and fundamental step for a successful, accurate and precise diagnosis for any medical problems (Worman, 2006).
The same is therefore true with the patient in this case study. The patient was of young age and was presented with jaundice. Other recent symptoms prior to admission included being lethargic for a number of days, suffering from pruritus as well as having abdominal pain.
A medical history of the patient confirmed excessive amounts of alcohol consumption (10-15 units) and drug use (ecstasy/MDMA). There was no history of recent foreign travel, the patient was not homosexual and did not have any contact with anyone who had hepatitis.
Jaundice is characterized by yellowing of the skin and sclera and was apparent in the patient. This is caused by an increase in serum bilirubin concentrations above 40µmol/L and is a sound indication, although not restricted to, liver disease (Worman, 2006; Gaw et al, 2001).
The patient was of young age (23 years), and this eliminated the possibilities of catching certain diseases which do not occur in young patients but instead occur more commonly among older people and vice versa. One such disease which is more prominent in young people is Wilsons disease (Giannini, 2005).
Since the patient was jaundiced and also had symptoms of being lethargic which is characterized by being lazy and sluggish, suffering from pruritus which is generalized itching caused by the accumulation of toxins and bile acids due to liver disorders and abdominal pain which can be caused by fluid retention (in cirrhosis) all seem to suggest and hint towards liver injury (Worman, 2006)(Hazin, 2009; Gaw et al, 2001).
Alcohol and drug use, both of which were consumed by the patient, is a vital piece of information as it can help in the diagnosis and subsequently the prognosis. Both alcohol and ecstasy escalate the risk of organ damage (Vijay, 2009). The liver being the organ more susceptible due to its role in detoxification of the harmful substances. The damage caused by these substances in endless and could result in fatal consequences if not taken into consideration, as the amount ingested and the time of ingestion could help in diagnosis (Worman, 2006).
The patient had no history of recent foreign travel, this is particularly important as some diseases are more prevalent in some parts of the world more than others, or may have diseases which are only found in certain localities within a region. Examples include the contraction of hepatitis viruses. Hepatitis B infections for example are more prevalent in Asia and Africa (Worman, 2006). Since the patient had not been on recent foreign travel, diseases which are not found in the native country can be set aside and those diseases present in the local region be considered. This therefore aids and increases the chances of a fast and accurate diagnosis (Worman, 2006).
The patient confirmed not to be a homosexual. The sexual character therefore of the patient also enhances the chance of a quick diagnosis. This is because certain diseases are most likely to be spread by sexual activity, some such being hepatitis virus B as well as other hepatitis infections; possibly due to orofecal transmission (Worman, 2006; Giannini, 2005). Therefore knowing the patient sexual character is crucial and avoids irrelevant diagnosis.
Contact of the patient with anybody infected by hepatitis was denied and therefore spread of certain hepatitis viruses such as hepatitis B and C which are mainly spread by blood and sexual contact can be put aside and other more relevant causes examined (Worman, 2006).
Liver function tests or LFT's as they are commonly known is a clear misnomer as they don't reflect liver function but rather the integrity of the hepatocytes and/or cholestasis(Gaw et al, 2001; Marshall, 2000; Giannini, 2005). LFT's provides crucial information which leads to the successful diagnosis of the type of liver disease existing, the likely extent of the damage caused and is vital in prognosis (Gaw et al, 2001; Giannini, 2005).
Biochemical LFT's are inexpensive, non-invasive, abundantly available and of high value to physicians (Marshall, 2000). LFT's provide results for serum bilirubin concentrations, aminotransferases, alkaline phosphatase activity, serological tests for viral antigens and antibodies, copper and caeruloplasmin concentrations as well as nuclear and smooth muscle antibodies (Gaw et al, 2001).
Cholestasis, acute hepatocellular damage and chronic liver disease are the major types of liver related illnesses which the LFT's help to differentiate between (Gaw et al, 2001). Serum bilirubin and alkaline phosphatase concentrations and activities respectively can indicate cholestasis while serum aminotransferase activities give a good idea on the general integrity of the liver cells (Gaw et al, 2001).
The patient had 6 different types of biochemical liver function tests performed; Serum bilirubin concentration, AST activities, ALP activities, serological tests for hepatitis A,B and C viruses, copper and caeruloplasmic concentrations with a final measure of the nuclear and smooth muscle antibodies.
Serum bilirubin concentration is a measure of the amount of bilirubin present in the plasma.
Bilirubin is acquired and derived from the haem moiety, which also includes an iron-containing protoporphyrin which is mostly seen in haemoglobin (Gaw et al, 2001). It is insoluble and is therefore almost completely bound to albumin. It is later taken up by the liver cells where more soluble conjugated mono- and di-glucuronoids are formed by UDP-glucronyltransferase (Gaw et al, 2001; Giannini, 2005). The newly formed conjugated bilirubin is then excreted into the bile along the bile duct into the small intestines where it forms stercobilinogen due to bacterial action and excreted into the faeces. Small quantities are present in the urine and are known as urobilinogens (Gaw et al, 2001; Marshall, 2000).
Therefore an increase in bilirubin concentrations could be caused due to; Haemolysis, damage to hepatocytes inhibiting the conjugating mechanism usually caused by drugs and toxins and finally cholestasis which is a full or partial blockage or the biliary system (can be extra- and intra-hepatic) (Gaw et al, 2001; Marshall, 2000).
If levels of bilirubin increase to dangerously high levels, irreversible brain damage could result (Gaw et al, 2001).
Measurements of aspartate aminotransferase activity (AST) is a very good test of acute hepatocellular damage, although it is very sensitive, it is not very specific for the likely cause of the damage which could include hepatitis, toxic injury as well as drug overdose and severe hypoxia (Gaw et al, 2001). AST is found in many tissues namely heart, kidneys and red blood cells. A more specific region where it is found in high concentrations is in zone 3 of the hepatic acinus, therefore an increase in AST is mostly likely due to the zone 3 region most probably due to a toxic insult.
AST levels could increase greater than 10-20 times its upper reference level which can be due to acute hepatitis caused by toxins as well as liver necrosis most likely due to alcohol.
AST activity therefore is a clear indication of acute or chronic liver injury (Giannini, 2005).
Alkaline phosphatase or ALP is an enzyme with transporting functionality of metabolites across cell membranes (Giannini, 2005). ALP activity can be associated with cholestasis, which may be either intra- or extra-hepatic as well as cirrhosis. ALP is also found in the kidneys, small intestines and bone in significant quantities therefore can also be associated with bone disease (Gaw et al, 2001; Giannini, 2005).
Serological tests for hepatitis A, B and C viruses were also carried out. It is reported that jaundice occurs in approximately 70% of patients with acute hepatitis A, between 30 and 50% with hepatitis B and 20-30% of cases with hepatitis C (Giannini, 2005). These statistics show that the results and importance of carrying out serological tests for hepatitis A, B and C can greatly decrease the time it takes to reach a successful diagnosis. The results of these test is either noted as positive or negative indicating whether the patient in infected with the virus or not respectively.
Copper and caeruloplasmin concentration give an indication whether the patient is suffering from Wilsons disease which is an inherited disorder of copper metabolism and can be fatal if not treated.
Biochemical testing for copper and caeruloplasmin is therefore vital. Decreased caeruloplasmin and copper in the serum (less than 10µmol/L) is an indicator of Wilsons disease (Gaw et al, 2001; Marshall, 2000)
A final test for the patient was for nuclear and smooth muscle antibodies. An increase in the number of antinuclear and antismooth muscle antibodies could indicate autoimmune hepatitis. The chances of being diagnosed for autoimmune hepatitis is further increased in patients with jaundice which is present in our patient. The tests for these antibodies are therefore very important in diagnosis (Marshall, 2000; Giannini, 2005).
The tests above are carried out by various different biochemical assays. Hepatic tests can be carried in labs by using automated blood chemistry panels, biochemical test kits or even manual methods of analysis (Gaw et al, 2001; Giannini, 2005). The blood specimen acquired from the patient for biochemical analysis such as LFT's is normally venous blood, plasma or serum (Gaw et al, 2001).
The results of the liver function tests for the patient carried out on samples obtained at admission are shown below in TABLE 1 along with the results obtained for serum bilirubin and aspartate aminotransferase after 10 days of admission. The normal reference intervals are provided where appropriate.
Table 1: The results of liver function tests along with the normal reference intervals. The results for serum bilirubin and aspartate aminotransferase are shown at the time of admission and 10 days after admission. Reference intervals obtained from (Gaw et al, 2001)
Values for the liver function tests exceeding the upper reference interval are normally termed as abnormal results (Giannini, 2005).
The serum bilirubin values in the patient at admission were greater than 5 times the upper reference interval. This explains why the patient was icterus. These high levels of serum bilirubin could have been cause due to 3 main reasons:
Haemolysis causing hyperbilirubinaemia. This great increase in bilirubin production could have overwhelmed the livers capacity to remove and conjugate the bilirubin therefore allowing it to accumulate in the serum (Gaw et al, 2001; Marshall, 2000).
Failure of the hepatocytes to conjugate the bilirubin. This could be a likely outcome since drugs such as MDMA (Ecstasy) which was used by the patient are known to cause acute hepatic failure as well as asymptomatic liver injury by a mechanism still not fully understood but hypothesis include impaired metabolism and hypoxia in the liver (BrnÄiÄ‡ et al, 2006). Drugs can also directly affect the fragile biochemistry of the hepatocytes leading to drug-induced hepatitis (Kaplowitz, 2004). Obstruction of the biliary system is another cause of an increased bilirubin concentration. Extra-hepatic and intra-hepatic biliary obstruction can take place and can be caused by gallstones, cirrhosis, liver cancer and even infection (Gaw et al, 2001).
Aspartate aminotransferase values in the patient at admission were greater than 15 times the upper reference interval. This illustrates acute hepatocyte damage with unknown aetiology. Causes may include toxic injury due to drug overdose or even hypoxia (Gaw et al, 2001; Marshall, 2000; Giannini, 2005). Aspartate aminotransferase levels greater than 10 times the upper reference interval could indicate acute hepatitis mainly due to toxins as well as liver necrosis due to alcohol consumption (Marshall, 2000).
Alkaline phosphatase levels were within the reference intervals therefore obstructions in the biliary system (cholestasis) is unlikely because cells present in the bile canaliculi increase alkaline phosphatase production, at least 2 times the upper reference interval in response to cholestasis (Gaw et al, 2001; Marshall, 2000).
Serological tests for hepatitis A, B and C were negative therefore chronic hepatitis or cirrhosis may be unlikely, but could be a possibility due to the patient drinking excessive amounts of alcohol (10-15 units within 2 days) (Gaw et al, 2001; Marshall, 2000).
Copper and caeroplasmin levels were normal and therefore Wilsons disease can be discarded (Gaw et al, 2001). Since the patient was a young adult, cirrhosis due to Wilsons disease is also unlikely (Marshall, 2000).
Nuclear and smooth muscle antibodies were negative and therefore autoimmune hepatitis is also unlikely (Marshall, 2000)
The patient 4 weeks previously claimed to have taken MDMA (ecstasy) as well as excessive alcohol. The liver is the main site where detoxification of toxins such as drugs and alcohol takes place. Aspartate aminotransferase is present in very high amount in the hepatic acinus more specifically in zone 3. Therefore damage to zone 3 by toxins such as MDMA and alcohol cause a great elevation in aspartate aminotransferase levels (Giannini, 2005). This was seen in this patient, where aspartate aminotransferase levels increase from 747 U/L to 1521 U/L in 10 days, (31 times the upper reference interval) therefore increasing the chances of hepatitis (Giannini, 2005). The extent of the damage to zone 3 includes spotty necrosis as well as increased amounts of hepatic necrosis (Davies, 1997).
Drugs such as MDMA (ecstasy) directly as well as indirectly effect hepatocyte organelles including mitochondria, endoplasmic reticulum and the nucleus by either promoting or inhibiting signalling kinases and transcription factors leading to cellular stress and ultimately cell death by apoptosis or necrosis leading to liver injury (Kaplowitz, 2004). Damage to the endoplasmic reticulum of the hepatocytes interferes with the conjugation of bilirubin or even uptake of unconjugated bilirubin thereby increasing serum bilirubin concentrations leading to jaundice, as was seen in this patient (Marshall, 2000).
Alcohol or ethanol is metabolized by alcohol dehydrogenase2 (ADH2) as well as cytochrome p4502E1 into acetaldehyde (ACH). Acetaldehyde (ACH) is then metabolized to acetate by aldehyde dehydrogenase (ALDH). The mitochondrial enzyme aldehyde dehydrogenase2 is thought to be the major enzyme responsible for producing acetate from acetaldehyde and is present in the liver (Vijay et al, 2009). An experiment carried out by Vijay et al (2009) showed that MDMA (ecstasy) causes oxidative modification and inactivation of numerous mitochondrial proteins such as aldehyde dehydrogenase2 in the liver. This causes acetaldehyde levels to increase causing symptoms of headache and nausea (Vijay et al, 2009). The patient present in the case study also had used alcohol as well as MDMA (ecstasy) causing increased organ damage and may also account for him appearing lethargic with abdominal pains.
From the above results, symptoms and medical history the patient's most likely diagnosis is that of drug induced hepatitis. The diagnosis is further confirmed by Dykhuizen et al (1995) where he presented 3 case reports of patients diagnosed with drug induced hepatitis or ecstasy induced hepatitis. Case report 2 presented a patient of similar age, sex, symptoms, who had drunk approximately 10-15 units of alcohol in the last 2 days and who had 4 weeks previously taken ecstasy, which is exactly the same as in this patient. The liver function tests were also very similar.
Treatment of the patient with drug induced hepatitis should start firstly with the cessation of alcohol as well as any other drugs (MDMA) (Kaplowitz, 2004). The patient should then be treated with prednisolone 40mg daily which should follow a decrease in serum bilirubin and aspartate aminotransferase levels as suggested by Dykhuizen et al (1995).
Other tests which may help in assessing the extent of liver damage may include imaging techniques (CT scans, MRI) and liver biopsy or prothrombin time as an indicator of hepatocellular damage.
Drug induced hepatitis can instantaneously progress to fulminating liver failure or chronic hepatitis (BrnÄiÄ‡, 2006). Recovery can take approximately 3 weeks to 3 months and is made possible due to the fact that the liver can handle large amounts of insults and has a very high capacity for regeneration (Dykhuizen et al, 1995; Marshall, 2000).
Liver transplantation could be an option if the situation worsens. Death could be possible although it is rare (Dykhuizen et al, 1995).