AMOEBIC LIVER ABSCESS - PAST, PRESENT AND FUTURE

Twenty years back (1977), I wrote the script of my monograph "Amoebic Liver Abscess" (ALA). Today when I look back, I have an impression that no significant contribution to this subject has taken place over these years. In all other diseases advances in diagnosis and management have been phenomenal.
What are the reasons? Is this impression false or real? It is a fact, that "Metronidazole" has changed the picture of this illness in such a way that there are hardly any patients of complicated ALA any more. Pericardial amoebiasis, pleuropulmonary amoebiasis and rupture of the abscess presenting as acute abdomen have become rare. Also early diagnosis with the help of sonography (and sometimes serological tests) leads to initiate treatment early. However, I sincerely feel that some problems in ALA still need to be sorted out.
When I wrote in my monograph, that the entity of "Amotbic Hepatitis" does not exist (when in fact in the past this was a very common diagnosis made in practice and is still being "carried forward" in many text books), I had come to this conclusion based on the early liver imaging which was then available to me - mostly isotope liver scans (done by very slow scanners and poor isotopes), and on laparoscopic and post mortem appearances! Today with most advanced imaging available, not many people have taken interest to do research on patients diagnosed as having "Amoebic Hepatitis", to see what pathology they really have in the liver. Why were they diagnosed as "hepatitis?" Few years back I showed that most of these cases, had multiple small liver abscesses.[3,13,16,20] But still more studies are required. We have heard in the past in the conferences of the Association of Physicians of India, doctors reading papers on analysis of as many as six hundred patients of amoebic hepatitis!
What is the relationship of colonic amoebiasis with ALA? Arun Chitle the senior most histopathologist of India, has seen E-Histolytica only in ten patients out of "13000" colonic biopsies which he has examined in his vast practice during the last ten years. I had found at the autopsy, that in majority of the ALA patients, the colon was normal. This should be confirmed by young gastroenterologists by doing routine colonoscopies and biopsies in patients presenting with ALA. If the colon is found to be normal,[2 5 6 12] research should be done to identify whether there is any different strain of E-Histolytica which affects only the liver!
When I wrote my monograph, the incidence of autopsy rate of ALA in my hospital was more than 1()() per year! ! Now we hardly ever hear of a death of a patient due to ALA! If so how will research work on ALA continue? I think imaging specialists have lot more responsibility now. In future sonologists like Nitin Chaubal will be able to enlighten us more on the evolution of ALA with the help of their modern machines! !

The following topics connected to ALA need more attention.
Incidence of ALA because of the widespread use of nitroimidazoles (in so called colonic amoebiasis, irritable bowel syndrome, giardiasis, duodenal ulcer, leucorrhoea, most of the abdominal surgeries, etc.) has come down markedly. The extent of this needs to be reported. Amrapurkar has reported his experience in this issue. However it is not clear whether all patients were observed by him in Bombay Hospital. The following are reports from other top specialists of Mumbai (Personal communication). Chitnis, a thoracic physician from Jaslok Hospital and Gupta, a senior thoracic surgeon from St. George’s and Nanavati Hospital have not seen a single case of pleuro pulmonary or pericardial amoebiasis in the last ten years, when the latter used to operate on about five patients per year in the past. Motwani from Jaslok Hospital and Manchanda from Breach Candy Hospital, both senior surgeons who used to treat 10 to 12 patients of ALA per year, have not seen a single ALA patient for the last 2 to 3 years! Nagori a surgeon from Bombay Hospital has seen only 10 cases of ALA in the last seven years (2 with rupture - one in the chest and the other in the peritoneal cavity). Lalit Kapoor a senior surgeon in the suburbs of Mumbai during the last 10 years sees about five cases of ALA every year. Desai HG, a senior gastroenterologist of Jaslok Hospital still sees about 15 cases of ALA every year. Undre, a senior surgeon with very large practice (covering a large population) still sees about 20 to 30 abscesses every year. Since his patients have no facilities of obtaining reports of serological tests, he taps all his patients for diagnostic purposes and more so, believes in therapeutic aspiration of all abscesses. However, in the last three years, he had not a single case of acute abdomen due to ruptured ALA. ALA has become a rarity in the autopsy room and this needs to be reported. All autopsied patients should be properly studied, to define resistance to metronidazole which may have been detected.

Clinical features of right lobe abscess [7,8,14]:
I have noticed that nowadays a number of patients have been presenting with the complaint of only fever. Many confirm presence of pain in the right trapezius area or discomfort in right upper abdomen, only on direct questioning! Though the incidence of ALA in alcoholics remains high, it is a rarity to have a patient of ALA with a past history of a bloody dysentery! Intercostal tenderness and point tenderness are rarely witnessed in a patient with ALA. Bulges of the chest wall or even bulging abscesses or superficial abscesses are rarely seen. With modern imaging techniques and the clearer anatomy of the liver lobes, no further work has been done to confirm or refute the diagnosis of a junctional abscess which I had described earlier. Posterior abscesses are becoming rare and I have never seen a specialist aspirating an abscess posteriorly in the manner I have described. Sure enough, not many inferior surface abscesses which used to present after rupturing into the peritoneum, have been now described with early diagnosis and the recommendation as to which site requires aspiration.
With modern imaging, the diagnosis of pleuro-pulmonary amoebiasis (PPA) should have improved markedly! What ever I have shown in the autopsy pictures could now be very well seen in a living person And with early diagnosis, the results of management of pleuro-pulmonary amoebiasis should have improved dramatically! I have not seen enough reports to confirm this assumption. Many more cases of pulmonary amoebiasis of the upper lobe, which I had described in my monograph - should have been picked up by now! I have not seen a single report!
With modern bronchoscopic drainage, the prognosis of PPA should have improved markedly without surgery ! If bronchoscopic aspirations, lavages and brushings could be done to look for AFB, pneumocystis carinii or fungi, a gastroenterologist should certainly have shown the presence of amoebae in these specimens to make a rapid and early diagnosis of PPA! !
It should have been possible by now to refute the diagnosis of pulmonary amoebiasis without liver involvement as described in the old literature of which I found no evidence after studying hundreds of autopsies. Nor have I seen any case report described with the help of modern imaging where there was an "independent" ALA with PPA, without a continuous spread as demonstrated in my monograph with an autopsy proof.

Left lobe abscess - More work should have been reported on left lobe abscesses which carry more mortality. I could describe six cases of USS LLL ALA syndrome, (uncomplicated superficial superior lateral left lobe amoebic liver abscess syndrome) because in my large private practice I routinely use dark room fluoroscopy and this was regularly used in our teaching institution. [4,15,19] A raised poorly mobile left dome of the diaphragm is the earliest sign of this syndrome in a patient presenting with fever and pain in the left hypochondrium before the abscess ruptures into the pericardium. With the arrival of modern imaging techniques, more such patients should have been described by now. I have not still seen a single case report in the last twenty years except the last one which I wrote about thirteen years ago. [15 ]
With the arrival of 2-D echo cardiography, colour doppler studies and MRI and with a safer pericardial tapping, more cases of "sympathetic non-suppurative" amoebic pericarditis should have been described. With the additional help of TEE, it should have been proved by now that the entity of amoebic constrictive pericarditis does not exist. With the help of modern CT scan of chest and upper abdomen, more work should have appeared on left sided pleuro-pulmonary amoebiasis.

Multiple amoebic liver abscesses (MALA) - I had described that with modern imaging often multiple small ALAs are detected in a patient of a so called a single large ALA. The prognosis in such patients remains very good. [3 16,20] Patients having multiple "large" abscesses have a poor prognosis. I am still looking forward to see a few reports of such patients where the prognosis has improved because of better facilities involving accurate tapping under sonographic guidance and modern percutaneous catheter drainage. And what about the entity of multiple small ALAs where I had shown that the mortality is hundred per cent and which often occurs in a patient of fulminating amoebic colitis. In the last two decades, I have not seen a single case report of such a patient who has recovered with the help of modern diagnosis and management. Amrapurkar's three patients of multiple abscesses quoted in this issue fall in the first category where prognosis remains excellent. Regarding multiple small ALAs "without" accompanying amoebic colitis, the prognosis remains excellent. [20 ]

Serological tests
If pus is not aspirated, the other method of confirming the diagnosis of ALA is serology. [10] Since I wrote my monograph twenty years ago, only a few isolated labs are doing IHA test. The readings of this test often vary in different laboratories. We often see "Anamnestic reactions" which were in the past described in Widal reaction occurring in fever patients. Thus we have often seen IHA positive in 1 :10,000 in patients of PUO without finding ALA! ! [10] The false positives are quite high and we definitely need the help of some other "specific" test like CE or FA or Gel diffusion test to doubly confirm amoebic aetiology, though this may not be necessary in straight forward cases. Also as Amrapurkar has suggested, the old diagnostic titre of 1:256 suggested by me should now be 'updated' to 1:512. The Elisa test which I described twenty years back, has only been able to match the sensitivity of IHA - nothing more and nothing less. In real difficult situations of differential diagnosis of hepatoma, a positive IHA test has often misguided us.

Regarding the role of modern imaging (which has advanced rapidly in the last twenty years), my experience is that sonography is good enough to confirm your "clinical" diagnosis of ALA. But when it comes to an incidental finding or in differential diagnosis of hepatoma, sonography, CT scan or MRI are not conclusive in diagnosing ALA.

Recurrent ALA: After reviewing the literature, I had described an isolated case of a patient who had ALA on three different occasions, in three different sites. During the second recurrence, his sigmoidoscopy was done and was normal. And since then, I have seen three more patients (two of them were seamen), who had a second illness of ALA with normal sigmoidoscopy appearances. All these patients had received colonic luminicides after the treatment of ALA. If this is proved by a few more reports by present day gastroenterologists, then it can be more convincing that colonic and hepatic amoebiasis are not correlated! And if so, the treatment of luminal amoebicides offered to patients of ALA should be considered outdated.

After I wrote on superficial ALA, I was looking forward to more literature on this subject with the arrival of modern imaging techniques! Somehow the sonographers often do not oblige (unless asked for) by pointing that the patient has a superficial abscess rather than intra-hepatic!

Surprisingly, after l described eighteen patients[l7,l8] of solid ALA. there has been hardly any literature on this subject. In my series, sonography (at that time) was just beginning to be available. Now that sonography and other imaging has arrived, I would have expected much more literature on this subject. After I have shown this entity in an experimental model, I would have liked to see gastroenterologists, contradict presence of this entity. If Nitin Chaubal's studies prove that it is only a phase in the early evolution of the abscess, how will one explain the reproduction of autopsy pictures of patients who died of ALA, in my monograph?

Silent ALA - I had stressed by a single case report, that the real "silent" ALA is the one which mimics hepatoma and where the silent features of fever, hepatic pain and tenderness are absent. The patient complains only of poor health, poor appetite, and loss of weight with other symptoms and signs of chronic illness (like anaemia etc). The fact is that since then I have seen more than a dozen patients [9,11] where an SOL in the liver is discovered but the differential diagnosis between a hepatoma and ALA is not sorted out by the imaging specialists. In fact, most of the times these specialists have given a wrong diagnosis!! I have made it a principle to do the following tests to get an accurate diagnosis.
A positive IHA in high dilution with a negative HBsAg test and normal alpha fetoprotein favours the diagnosis of ALA. But here too, I have been eluded with false positive IHA in hepatoma. And then on asking for FNAC and FNAB, the diagnosis was confirmed in majority of the patients. I have seen ALA being wrongly diagnosed because of the brownish colour of the pus which was aspirated from the liver mass and the presence of so called "E-Histolytica" in the aspirated material when in fact the patient had necrotising malignant masses in the liver!! It is important to remember that all the above tests are not fool proof. A necrotic malignant mass looks like amoebic pus. Many cells in this pus look like immobile E-Histolytica. Incidence of hepatoma is increasing day by day. Incidence of ALA is reducing day by day. Tllc fact remains that ALA is curable, while hepatoma is a fatal disease. The only way to differentiate hepatoma from ALA should be:

1. Clinical history specially of a known HBs Ag carrier.
2. Taking into consideration all false positive and negative blood tests.
3. Relying less on imaging results.
4. Findings of tapping, FNAC, FNAB and microscopy to be given equal value and not to be considered 100 per cent fool proof.
5. In difficult cases to do laparoscopy and to take multiple biopsies from different areas of the mass.

Regarding the chapter on my finding of pulmonary tuberculosis in patients having ALA, I was expecting many reports on this combination after the AIDS epidemic occurred. I expect to see this combination more often in patients of AIDS. Some of my colleagues who have seen more incidence of hepatic tuberculous abscesses in AIDS, are likely to see the combination of ALA and tuberculous liver abscesses in future. Twelve years back I had pointed out that solid tuberculous abscess of the liver mimics ALA. [I7]
When I mentioned the confusion in the terminology of ALA between the following terms - latent abscess, silent abscess, occult abscess, subclinical abscess, chronic abscess, residual abscess, recurrent abscess, relapse of an abscess, resistant abscess and refractory abscess - I expected that over years, this confusion will be cleared and there would be plenty of reports to remove most of the above obsolete terminology from the literature (just like Amoebic hepatitis).

The medical management and the role of aspiration:
Twenty years ago I had mentioned that most patients respond to drugs alone and aspiration is not required. In fact, in retrospect one could say with conviction that thousands of patients in India who were diagnosed as having "Amoebic hepatitis", must have had small ALAs, which responded to anti-amoebicidal dmgs [20] (which in olden days were Injection of emetine and chloroquine tablets) and the other patients had some other or no liver disease. Of course, nitroimidazole group of drugs are easy to administer unlike injections of Emetine. Also unlike the long duration of chloroquine therapy, this therapy can be finished in two to ten days. But I must see more reports to convince me that Injections of emetine and chloroquine phosphate have no more role to play in this disease - an impression given by modern gastroenterologists and pharmaceutical firms. For this answer, I would like the drug trials to be conducted on patients having:

1. Left lobe abscesses
2. Multiple large ALA
3. Multiple small ALA in a patient having acute fulminating dysentery
4. Pleuro - pulmonary amoebiasis
5. Pericardial amoebiasis
6. Ruptured and complicated ALA
7. So called resistant or refractory ALA

Till then I still feel that one day Injection Emetine will come back exactly like Digoxin had a come back in patients of congestive cardiac failure even with sinus rhythm!! Similarly instead of giving intestinal luminicides to any patient of ALA, may be a six weeks course of Chloroquine will prevent the relapses though these are very uncommon. Already, I find that most of the specialists and gastroenterologists are using a combination of metronidazole and chloroquine.
Regarding the role of aspiration the modern days are of "invasiveness". The gastroenterologists have accepted invasiveness in the form of gastroscopies, colonoscopies and ERCP. A simple aspiration of ALA is being discouraged in these days of invasiveness. Today the main stress should be on the recovery time and an early return to work. Most of the reports including Amrapurkar's report in this issue do not discuss this aspect. Laparoscopic removal of the gall bladder is still being practised, when in fact reports are available that patients in whom gall bladder is removed by minimal invasive surgery only take one to two days more to go home! Invasive Cardiologists are now doing primary angioplasty in a case of myocardial infarction! Chest Physicians are putting a drain in most of the patients of pneumothorax or pleural effusions - all this invasiveness to hasten the recovery.
May be the same principle should apply to ALA. There is no doubt that most of the ALA will respond to drugs. But if a single aspiration can hurry the process even by a day or two, then in the modern days of invasiveness is needling of the liver something to be afraid of ? [1] The bonus which doctors will get will be availability of the pus for a quick diagnosis. Also academic study of the pus could be done to find future criteria to differentiate ALA from:

1. Single pyogenic liver abscess (most of which also respond to metronidazole)
2. Fungal abscesses
3. Tuberculous abscesses [l7]

Regarding percutaneous drainage I am not impressed by it because although it is supposed to be safer, it is "slow" and the duration of drainage is long. But certainly in a patient having ALA with prerupture syndrome it would be ideal.
Finally. in future all autopsies of patients dying of ALA should be conducted very carefully. If possible the pus should be sent to molecular laboratories to isolate amoebic antigen7 etc. Drug resistance should be studied in these patients. The typing of E-Histolytica should be studied. No longer should they be considered as routine autopsies but a lot of enthusiasm should be generated on finding out "why did the patient of ALA die?" When after seeing a few hundred deaths in patients having ALA. I was inspired to write a monograph on the subject (when I was a practising physician and a clinical cardiologist and not a gastroenterolgoist)7 today, after twenty years of my wnting the monograph, my soul will be hurt if a single patient of ALA should die ! !

REFERENCES

1. Kapoor OP, Undre AR. Amoebic Osteomyelitis an intl ogellic complication of amoebic liver abscess. BHJ I 988; 30 ( I ): 5-6.
2. Kapoor OP. Can you diagnose "chronic intestinal amoebiasis"'? BHJ I988; 30 (2): 33.
3. Kapoor OP. Multiple amoebic liver abscesses. BHJ 1989; 31 (1): 127-28.
4. Kapoor OP, Allirtldh Kohli. Illlagillg of an amoebic liverabscess. BHJ 1989; 31 (2): 123-25.
5. Kapoor OP. Are you sure it is amoebiasis and not Giardiasis? BHJ 1989; 31 (2): 103- 105.
6. Kapoor OP. Non-clinical amoebiasis. BHJ 1989; 31 (3): 93-94.
7. Kapoor OP. Amoebic liver abscess, Editorial. BHJ 1990; 32 (1): 5-7.
8. Kapoor OP. Surgical amoebiasis - treatment is often conservative. BHJ 1990; 32 (3): 128-33.
9. Kapoor OP. A typical presentation of amoebic liver abscess, Editorial. BHJ 1991; 33 (2).
10. Kapoor OP. Anamnestic reaction of blood test of IHA for amoebiasis. BHJ 1992; 34 (1): I 85.
11. Kapoor OP. Is amoebic liver abscess a silent disease? BHJ 1992; 34(1) :98.
12. Kapoor OP. Does the entity of amoeba exist? BHJ 1996; 38 (1): 164.
13. Kapoor OP. Does the entity of amoebic hepatitis exist. BHJ 1994; 36 (4): 219.
14. Kapoor OP. Problems in the diagnosis of amoebic liver abscess - illustrative cases, Bulletin of Jaslok Hospital. Oct 1980; 5 (2): 91-101.
15. Kapoor OP. USSS LLL ALA. Syndrome, Bulletin of Jaslok Hospital. July 1983; 8 (1): 28-31.
16. Kapoor OP. Multiple amoebic liver abscesses are more common than a single amoebic liver abscess and less serious than thought initially, Bulletin of Jaslok Hospital. Oct 1984; 9 (2): 37-38.
17. Kapoor OP. Solid tuberculoma of the liver a close differential diagnosis of solid amoebic liver abscess, Bulletin of Jaslok Hospital. April 1985; 9 (4): 44-45.
18. Kapoor OP. Solid amoebic liver abscess, Bulletin of Jaslok Hospital. April 1985; 9 (4): 46-47.
19. Kapoor OP. Splenic abscess of the upper pole - A very close differential diagnosis of left lobe superior surface amoebic liver abscess, Bulletin of Jaslok Hospital. July 1985; 10 (1): 42-44.
20. Kapoor OP. Amoebic hepatitis. Nonentity proved by Modem Imaging Bulletin of Jaslok Hospital. Oct 1984; 9 (2): 35-36.