Jaundice in a case of amoebic liver abscess which was once considered to be a rare occurrence is being recognised and studied more frequently during last few years. The mechanism of jaundice in amoebic liver abscess has been a subject of controversy for long and has evoked the. interest of research workers all over the world. The prognostic implications of jaundice in cases of amoebic liver abscess are also being investigated with interest.

Incidence
The incidence of jaundice in amoebic liver abscess as reported by different workers shows a wide variation. Phillips,¹ Manson-Bahr,² Craig³ and Chatterjee,^1-4 while setting forth the clinical features of amoebic liver abscess, described jaundice as uncommon and mild when present. Manson-Bahr² considered presence of jaundice as a feature against the diagnosis of hepatic amoebiasis. On the whole, the older literature emphasised the rarity of jaundice in amoebic liver abscess. Similar views continue to be expressed in some of the recent text books on liver diseases,⁵ tropical diseases⁶ and other publications.⁷ However, the incidence of jaundice in amoebic abscess reported in recent literature is higher as seen by the work of Chhetri et al⁸ (6%), Subramaniam et al⁹ (7.8%), Lamont and Pooler¹⁰ (10.1%), Vakil et al¹¹ (15%), Salako¹² (22%) and Aptekar and Sood¹³ (22.2%).
We have found the incidence of jaundice quite higha4 (23.1%), though Kamat et al¹⁵ had the highest incidence (28%) in their series. Facilities for liver function tests are more widely available now. This probably accounts for the reports of higher incidence of jaundice in the more recent series. Many of these patients do not have clinical icterus. This accounts for the wide variation of incidence of jaundice reported by different observers. In our series,¹⁴ we observed that in as many as 43.5% cases, jaundice was sub-clinical and detected only on biochemical tests. Obviously these cases were missed in the days prior to the availability of liver function tests. Greater awareness of this phenomenon may also have led to its more frequent recognition.¹⁴ It must also be kept in mind, however, that in the series in which higher incidence of jaundice was reported, the cases studied were of a more serious nature, who had been hospitalised, aspirated, operated or who succumbed to the disease. There still exists a large number of cases of hepatic amoebiasis seen in private practice, who respond well to antiamoebic drugs and in whom no further attempt is made to aspirate the abscess, nor are any liver function tests carried out. Therefore, the true incidence of jaundice in amoebic liver abscess is difficult to estimate.
The abundance of reports in recent literature makes it also clear that presence of deep jaundice is not incompatible with the diagnosis of amoebic liver abscess. According to Alkan et al¹⁶ jaundice is comparatively frequent and deep when a left lobe abscess perforates into the lesser sac. Rarely a patient with amoebic liver abscess can present as a case of obstructive jaundice. This may be due to compression of the common bile duct by the amoebic liver abscess.¹⁷ Desai et al¹⁸ reported four cases of amoebic liver abscess presenting with obstructive -jaundice. Zulfiqar Haider and Aziza Rasuls¹⁹ also reported a case of amoebic liver abscess with serum bilirubin of 15 mgs. Their case and one of Desai's case had superior surface amoebic liver abscess of the right lobe. We have come across two cases of single large abscess in the upper part of the liver with serum bilirubin of 14 and 16 mgs. respectively. However, we have seen clinical jaundice with serum bilirubin of about 5 to 10 mgs. more often in patients with multiple abscesses. In one of our patients with obstructive jaundice whose serum bilirubin was 11.5 mgs., liver scan confirmed the presence of two abscesses . Since on two occasions, not more than 25 mls. of thick brownish pus could be aspirated and the jaundice was not subsiding, laparotomy was done. The antero-inferior liver abscess was adherent to the gall bladder and had leaked its contents into it (Fig. 22). The second posterior abscess was also drained. The patient recovered without any stormy post-operative course and the icterus subsided very rapidly after the surgery. Highest level of 30 mgs. of serum bilirubin was recorded in one of the patients of Desai et al.¹⁸ At autopsy this patient had a huge abscess of the right lobe. Jaundice was possibly due to peri-and intraductal adhesions producing partial or complete obstruction of the biliary ducts.

Mechanism of jaundice
Jaundice in a case of amoebic liver abscess may be due to hepatocellular dysfunction or intrahepatic biliary obstruction.²⁰
An enlarging amoebic abscess may compress upon or distort a large hepatic duct and produce obstructive jaundice. Cases of this nature, proved at abdominal exploration or post-mortem, have been reported.^21-23 Hence there is no doubt that such a mechanism exists. However, such a phenomenon can be responsible for jaundice in only (a small proportion of cases of amoebic liver abscess. Compression of the common bile duct or involvement of the gall bladder as in our case, may be responsible in a few cases. An inferior surface amoebic abscess is more likely to be associated with such a complication.
On analysis of the results of liver function tests in amoebic abscess, it has been found by many workers, that the most frequent abnormal finding is elevation of serum alkaline phosphatase.²⁴ In a large number of these cases, elevation of serum alkaline phosphatase was not accompanied by corresponding degree of jaundice. Such a disparity in the liver function tests can be explained by obstruction to portions of intrahepatic biliary system, without diffuse hepatocellular damage. According to Salako,¹² the situation is comparable to that produced by ligation of portions of intrahepatic biliary system in experimental animals.^25,26 In these animals serum alkaline phosphatase was found to be elevated without corresponding elevation of serum bilirubin. While conjugated bilirubin is readily excreted by kidney and cleared from the blood, serum alkaline phosphatase accumulates in the blood and produces this disparity. Brem,²⁷ Virant vatti,²⁸ Kini and Imbichi²⁴ and Haider et al²⁹ als feel that intrahepatic biliary obstruction is the bas of deranged liver function in patients of amoebic liver abscess.
Recently, Datta et al^30-32 in an attempt to study the mechanism of jaundice in patients of amoebi liver abscess have made the following observations

1. The survival of chromium labelled red bloc cells was normal in these patients and there was no evidence of haemolysis and increased bilirubin.³³
2. There was significant elevation of the co jugated bilirubin fraction.³⁰
3. Bilirubin UDP-glucuronyl transferase enzyme activity was normal in patients of amoebic liver abscess with or without jaundice.³⁴
4. Activity of BSP-glutathione conjugating enzyme was reduced in patients of amoebic liver abscess regardless of the presence of jaundice.³⁵
5. BSP-excretion studies showed that the storage capacity which represents the ability of uptake and storage of BSP by liver cells was well preserved but the rate of BSP excretion by the hepatic parenchymal cells into the biliary system was significantly reduced.³⁰

On the basis of these observations they concluded that jaundice in amoebic liver abscess is a result of defective excretion of bilirubin by hepatic cells into the biliary tree.
There have been other reports explaining the jaundice on the basis of hepatocellular dysfunction. In our series¹⁴ we found that elevation of serum alkaline phosphatase was present only in 66% cases of abscess with jaundice. We also found that cases without jaundice had normal transaminase levels, while they were elevated in approximately two thirds of the cases of abscess with jaundice. The close parallelism in the incidence of elevation of serum alkaline phosphatase (66%), transaminases (approximately 60%) and hypoproteinaemia (70%) in amoebic abscess with jaundice, led us to believe that there was a "common pathologic denominator" of diffuse hepatocellular damage. Kamat et al ¹⁵ observed that the results of liver function tests in cases of jaundice in amoebic abscess were characterised by significant derangement of such serum protein levels as hypoalbuminaemia, elevated globulin levels and a high percentage of abnormal globulin precipitation tests. These abnormalities were strongly suggestive of hepatocellular damage. They showed that even after clinical improvement following therapy, return of the serum proteins electrophoretic pattern to normal was quite slow indicating extensive hepatocellular involvement. In their series of ²¹ cases of amoebic liver abscess, biliary obstruction was not a significant factor contributing to jaundice.
El-Zayadi et al³⁶ and Ramachandran et al³⁷ have found that hypoalbuminaemia and elevation of serum alpha₁ and alpha₂ globulins were uniformly present in all the cases of amoebic liver abscess studied by them. Such a high incidence of hypoalbuminaemia cannot be accounted for by poor nutrition alone, as has been suggested by some other workers.³⁰ Cholestasis when present is not sufficiently prolonged to produce widespread hepatic damage in all the cases. Hence it is likely that hepatic amoebiasis does produce hepatocellular damage and impairment of liver function which accounts for the hypoalbuminaemia, while the elevation of serum alpha₁ and alpha₂ globulins is probably due to reticuloendothelial reaction. ^36,37
Thus, there seems to be no unanimity regarding the mechanism of jaundice. A few cases are due to a major hepatic duct obstruction by an inferior surface abscess near the hilum. In some cases, jaundice is probably due to diffuse hepatocellular damage and dysfunction. In the remaining cases it is probably due to a combination of more than one factor.
Datta et al have observed that cases of amoebic liver abscess with jaundice are characterised by acute onset and absence of intercostal tenderness.³⁰ Such observations have not been confirmed by other workers. But as stated earlier, we have often seen patients with small multiple amoebic liver abscesses who present with acute onset, and have no local intercostal tenderness but often have jaundice.

Role of other factors in the pathogenesis of jaundice in amoebic liver abscess

1. Site of abscess. An abscess near the inferior surface of the liver is more likely to distort or compress a major hepatic duct and produce jaundice. Datta et al have demonstrated this by post-mortem injection of dye into the biliary tree.^30,38 However, their belief³⁹ that in every case of abscess with jaundice there is either a large abscess in the right lobe or near the inferior surface in the hilar region, lacks confirmation by others and the author. Abscesses at other sites have no specific relation to jaundice.
2. Size and number of abscesses. In case of a large abscess or multiple abscesses, there is a greater degree of destruction of liver parenchyma and corresponding degree of impairment of liver function. Hence the reported incidence of jaundice is higher in large abscesses" We have also observed higher incidence of jaundice in patients having multiple large abscesses.⁴⁰
3. Previous status of liver function. If liver function is previously impaired by alcoholism, an episode of viral hepatitis or any other disease, the superadded amoebic abscess would be associated with greater incidence of jaundice¹⁴
4. Secondary infection. Diffuse 'toxic' damage to the liver due to secondary infection has been described as a cause of jaundice in amoebic abscess but not supported by adequate proof.

Mortality
The mortality of amoebic liver abscess with associated jaundice is reported to be higher than in patients without it.^11,14,41 As has already been discussed, presence of jaundice is usually associated with more severe affection of the liver. It may cause general debility and sometimes even lead to hepatic encephalopathy. If jaundice is due to an inferior surface abscess, the risk of abdominal complications is also higher. All these factors contribute to the higher mortality of amoebic liver abscess associated with jaundice.

References

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