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 18 October 2017

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Classical Case Studies

HepatologyLiver diseases

Drugs and the liver

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P Beddy, P Neary, T Leong, D McNamara, M Jeffers, FBV Keane New Zealand green lipped mussel extract (Perna canaliculus) induction of hepatic impairment.
P Beddy, P Neary, T Leong, D McNamara, M Jeffers, FBV Keane, 17 September 2003

Summary

We report an extremely rare adverse effect of the ingestion of the homeopathic product of the New Zealand green lipped mussel (Perna canaliculus). Our case is the first reported in the literature of non-granulomatous cholestatic hepatitis associated with P. canaliculus extract ingestion. The jaundice resolved upon cessation of self medication.

Introduction

The extract of the New Zealand green lipped mussel, Perna canaliculus, is primarily composed of lyprinol, and has been therapeutically advocated due to its’ anti-inflammatory effects [1]. Several randomized clinical studies have demonstrated efficacy in patients with osteoarthritis, rheumatoid arthritis and asthma [2-4]. Reported adverse effects include disease progression, dyspepsia, flatulence and nausea.

There is only 1 previously reported case of granulomatous hepatitis secondary to this green lipped muscle extract in a patient on a concurrent non-steroidal anti-inflammatory drug [5]. We report a case with different pattern of hepatitis associated with green lipped muscle extract.

Case Report

A 74-year-old lady was admitted complaining of dysphagia, anorexia, jaundice, and pruritis. She had noticed dark urine for several days and scleral icterus of 24 hours duration prior to admission. She had no history of foreign travel, trauma, blood transfusion, significant alcohol intake or cholelithiasis.

She was taking green lipped mussel extract at a dose of 1 tablet daily for the last 1 and a half years for osteoarthritis. Her drug history only revealed a 5 day course of co-amoxiclav 3 months ago.

Her husband and 2 sisters had died of liver disease for which no apparent cause had been found. They had never taken green lipped mussel extract.

Physical examination revealed marked icterus, palmar erythema and a soft hepar palpable 1 cm below the costal margin. There was no evidence of ascites or encephalopathy. The prothrombin time was normal.

Initial laboratory investigations demonstrated an eosinophilia and liver function tests confirmed a mixed hepatocellular and cholestatic jaundice picture (Table 1). An abdominal ultrasound, CT Abdomen and an MRCP were normal. Viral screen, tumor markers, auto-antibodies and a metabolic screen for 1 antitrypsin deficiency, hemochromatosis and Wilson’s disease were negative.

A gastroscopy revealed esophagitis. Eesophageal biopsies confirmed acute inflammation.

We proceeded to do an ultrasound guided liver biopsy. The liver architecture was normal. There was centrilobular cholestasis. The portal tracts contained a mixed inflammatory infiltrate including neutrophils, eosinophils and lymphocytes but there was no evidence of interface hepatitis. Ductulitis was present. No granulomas were present. Focal lobular inflammation was present.

The overall pattern of injury was consistent with drug induced liver damage (Figure 1).

Figure 1
Hematoxylin and eosin stain of liver biopsy. There is centrilobular cholestasis. The portal tracts contain a mixed inflammatory infiltrate including neutrophils, eosinophils and lymphocytes but there is no evidence of interface hepatitis. Ductulitis is also present.

The histological pattern was not typical of co-amoxiclav induced liver damage. This would also be consistent with the timing of co-amoxiclav use. It was thus concluded that the liver damage was related to her green lipped mussel extract.

The green lipped mussel extract was stopped on her admission. She was given omeprazole for her esophagitis, chlorpheneramine for her pruritus and ursodeoxycholic acid for her abnormal liver function tests. Her liver function tests improved over the following 50 days (Table 1).

Discussion

New Zealand green lipped mussel extract (P. canaliculus) is a lipid rich organic agent. The anti-inflammatory properties described are due to the oil, lyprinol, extracted from the mussel [1].

Lyprinol inhibits leukotriene B4 biosynthesis by monocytes and also inhibits prostaglandin E2 production by activated macrophages [6,7]. The activation of the 5-lipoxygenase pathway also up-regulates the expression and release of CD 23 and the respiratory burst pathway of human monocytes [6]. These 3 activities may account for its’ anti-inflammatory properties.

Prostaglandin E2 down-regulates osteoclast function and is targeted by the Cox–2 inhibitors in the treatment of osteoarthritis [8].

Finally lyprinol increases monocyte functional activity as reflected by increased respiratory burst pathway activity and may also account for some of the disease modifying properties of this compound [6].

Our case of hepatitis secondary to New Zealand green lipped mussel extract differed in histological findings to the previously reported case. This had demonstrated moderate distortion of the hepatic architecture and the hepatic lobules exhibited numerous epitheliod granuloma with giant cells and focal necroses [5]. There was also coincidental endoscopic findings of esophagitis, which has not been previously reported.

The fact that she had a family history of liver disease of unknown etiology may suggest a pre-disposition to hepatotoxic effects of drugs. The rarity of these cases must indicate that other endogenous triggering factors are necessary for this side effect to become clinically obvious and that it may manifest differently in disparate individuals.

Importantly this case also highlights the need for increased awareness among clinicians for the potential side effect of over-the-counter products and alternative medications.

This article was first published on GastroHep.com on 17 September 2003.

References

  1. Sinclair AJ, Murphy KJ, Li D. Marine lipids: overview "new insights and lipid composition of Lyprinol". Allerg Immunol (Paris) 2000; 32(7): 261-71.
  2. Gibson SLM, Gibson RG. The treatment of arthritis with a lipid extract of Perna canaliculus: A randomised trial. Compl Ther Med 1998; 6: 122-6.
  3. Halpern GM. Anti-inflammatory effects of a stabilized extract of Perna canaliculus (Lyprinol). Allerg Immunol (Paris) 2000; 32(7): 272-8.
  4. Emelyanov A, Fedoseev G, Krasnoschekova O Abulimity A, Trendeleva T, Barnes PJ. Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial. Eur J Respir 2002; 20(3): 596-600.
  5. Ahern MJ, Milazzo SC, Dymock R. Granulomatous hepatitis and Seatone. Med J Aust 1980; 2: 151-2.
  6. Dugas B. Lyprinol inhibits LTB4 production by human monocytes. Allerg Immunol (Paris) 2000; 32(7): 284-9.
  7. Miller T, Wu H. In vivo evidence for prostaglandin inhibitory activity in New Zealand green-lipped mussel extract. N Z Med J 1984; 97(757): 355-7.
  8. Tomita M, Li X, Okada Y, Woodiel FN, Young RN, Pilbeam CC, Raisz LG. Effects of selective prostaglandin EP4 receptor antagonist on osteoclast formation and bone resorption in vitro. Bone 2002; 30(1): 159-163.


Table 1 Laboratory investigations

Day 1 3 9 12 17 50
Bilirubin (umol/L) 95* 126* 243* 312* 244* 17
Alkaline phosphatase (iu/L) 338* 437* 493* 513* 364* 89
Alanine aminotransferase (iu/L) 309* 259* 240* 203* 148* 25
Gamma glutamyl transpeptidase (iu/L) 311* 378* 527* 520* 271* 69

*Raised


Contact information

Dr Peter Beddy MB, BAO, BCh, BA.
Senior House Officer, Department of Surgery, Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland
pbeddy@eircom.net

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