Arab Journal of Gastroenterology 14 (2013) 176–179

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Arab Journal of Gastroenterology

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Case Report

Ischaemic hepatitis precipitated by recurrent episodes of atrial fibrillation

Fahmi Yousef Khan a,⇑, Khaled A. Baagar b

a Department of Medicine, Hamad General Hospital, P.O. Box 3050, Doha, Qatarb Department of Medicine, Hamad General Hospital, Doha, Qatar

a r t i c l e i n f o

Article history:Received 18 February 2012Accepted 2 February 2013

Keywords:CardiomyopathyHepatic congestionIschaemic hepatitis

1687-1979/$ - see front matter � 2013 Arab Journal ohttp://dx.doi.org/10.1016/j.ajg.2013.10.002

⇑ Corresponding author. Tel.: +974 5275989; fax: +E-mail address: fakhanqal@yahoo.co.uk (F.Y. Khan

a b s t r a c t

We report a case of ischaemic hepatitis associated with recurrent fast atrial fibrillation (AF) episodes in a59-year-old male who presented with shortness of breath, nausea and vomiting. The patient had a historyof ischaemic cardiomyopathy. An emergency electrocardiogram showed fast AF with a ventricular rate of190 min�1. The aspartate aminotransferase (AST) level was 2222 U l�1, alanine aminotransferase (ALT)was 1255 U l�1, lactate dehydrogenase (LDH) was 1842 U l�1 and serum creatinine was 150 lmol l�1.An ultrasound of the abdomen showed an enlarged liver with hypoechoic lesions. The patient receiveddigoxin. In the next few days, while liver enzymes and serum creatinine started to return to normallevels, the patient had two attacks of fast AF, each associated with elevated liver enzymes and a concom-itant rise in serum creatinine. The patient was transferred to the intensive care unit to improve control ofhis AF, after which his liver enzymes and renal function gradually returned to normal.

� 2013 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Introduction

Ischaemic hepatitis (IH), also called shock liver or hypoxic hep-atitis, is defined as a diffuse hepatic injury that occurs as a result ofacute hypoperfusion [1]. It is characterised by a transient and oftenmarked elevation of serum hepatic transaminase levels inassociation with centrilobular hepatic necrosis. Serum hepatictransaminases usually increase to 10–300 times the upper limitof normal and most often resolve over 5–25 days [2].

Although patients of all ages can be affected, IH usually occursin elderly individuals with right-side congestive heart failure andlow cardiac output. It usually occurs after periods of haemody-namic instability or hypoxia such as haemorrhage, sepsis,pulmonary embolus, cardiac failure, arrhythmias, acute myocardialinfarction and other causes of respiratory distress. However, manypatients have no documented decrease in their blood pressure [3].In this report, we describe an elderly patient with underlyingischaemic cardiomyopathy who developed IH precipitated byrecurrent episodes of fast atrial fibrillation (AF).

Case history

A 59-year-old male was admitted to our hospital with a 2-dayhistory of shortness of breath associated with nausea, vomitingand fatigue. The patient’s history included hypertension, diabetesmellitus (DM) type II, ischaemic cardiomyopathy, chronic AFand peripheral vascular disease, and he had undergone an

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above-left-knee amputation 3 years ago. Moreover, he had under-gone revascularisation surgery of his right leg 2 years prior to hisadmission. He had no prior history of liver disease and denied alco-hol abuse or exposure to known hepatotoxins. The patient’s cur-rent medications included furosemide, valsartan, isosorbidedinitrate, trimetazidine, prindopril, aspirin, omeprazole, pentoxy-philline, NovoRapid and diclofenac sodium (on demand for jointpain). Upon arrival to the emergency room, the patient was con-scious, oriented, dyspnoeic and restless. His blood pressure was120/84 mmHg, and he had a peripheral pulse of 108 min�1 (irreg-ularly irregular) along with a weak but thick vessel wall, a centralpulse of 180 min�1 and a temperature of 36.8 �C. There were vari-able heart sounds and bilateral lower-limb oedema. Oxygen satu-ration by pulse oximetry was 94% with room air. An emergencyelectrocardiogram (ECG) showed fast AF with a ventricular rateof 190 min�1. A careful review of the patient’s medical recordshowed that his baseline blood pressure was 140–150/90 mmHg.

Blood tests showed a white blood cell (WBC) count of 15,700 ll�1

(62.7% neutrophils and 28.3% lymphocytes), a haemoglobin level of14 g dl�1 and a platelet count of 206,000 ll�1. The levels were2222 U l�1 for aspartate aminotransferase (AST), 1255 U l�1 foralanine aminotransferase (ALT), 1842 U l�1 for lactate dehydroge-nase (LDH), 121 U l�1 for alkaline phosphatase and 34 lmol l�1 fortotal bilirubin. Additionally, the patient’s urea nitrogen level was12.1 mmol l�1, and he showed a serum creatinine level of150 lmol l�1. The international normalised ratio (INR) was 1.7.The cardiac markers were within the normal limit. An emergencychest X-ray showed bilateral pleural effusion with lung congestion.On admission to the ward, the patient was conscious, oriented andafebrile. There was no jaundice or flapping tremor. His blood

sevier B.V. All rights reserved.

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Fig. 2. Clinical course and change in the serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT) and serum creatinine (S. Cr). Markedlyelevated levels of AST and ALT with a concomitant rise in S. Cr are observed witheach fast atrial fibrillation (AF) episode. Although the systolic blood pressure (SBP)was normal, it dropped below baseline during each attack of AF.

F.Y. Khan, K.A. Baagar / Arab Journal of Gastroenterology 14 (2013) 176–179 177

pressure was 130/80 mmHg, with a peripheral pulse of 96 min�1

(irregularly irregular) and a temperature of 36.8 �C. In addition todecreased air flow to both the lungs and variable heart sounds, therewas bilateral lower-limb oedema. Oxygen saturation by pulse oxim-etry was 96% with room air. The serological studies, including testsfor hepatitis A, B, C and E viruses, cytomegalovirus, human immuno-deficiency virus (HIV), Epstein–Barr virus and herpes simplexviruses 1 and 2, were negative. Furthermore, markers related toauto-immune hepatitis were negative. Serial ultrasound of theabdomen showed an enlarged liver with hypoechoic lesions(Fig. 1). Repeated echocardiographic examinations showed an ejec-tion fraction of 26% with global hypokinesia of the left-ventricularwall; the right-ventricular systolic pressure was 47 mmHg.

Laboratory tests performed 2 months before admission showeda urea nitrogen level of 6.6 mmol l�1, a creatinine level of76 lmol l�1, a sodium level of 136 mEq l�1, a potassium level of3.8 mEq l�1, a bicarbonate level of 29 mmol l�1 and a calcium levelof 2.4 mmol l–1. The AST level was 30 U l�1, ALT level was 32 U l�1,alkaline phosphatase level was 84 U l�1, total bilirubin level was14 lmol l�1 and INR was 1.3.

During his stay in the hospital, the patient received ranitidine,valsartan, isosorbide dinitrate, trimetazidine and heparin. Furose-mide was not administered due to renal impairment. Full septicwork-ups including blood and urine cultures were performed, fol-lowing which the patient was given a broad-spectrum antibiotic.His septic work-ups were negative; the liver enzymes declinedbut had not normalised, whereas the serum creatinine leveldeclined towards the normal value.

On the sixth day of hospitalisation, the patient had another fastAF episode with a heart rate of 196 min�1 and a blood pressure of110/70 mmHg associated with high liver enzymes and renalimpairment. Over the next few days, the liver enzymes and serumcreatinine levels declined, but another episode of fast AF with dropin blood pressure (110/70 mmHg) occurred and the same scenariowas repeated (Fig. 2). Acute IH, secondary to liver hypoperfusion,caused by recurrent fast AF episodes then seemed the most likelydiagnosis. The patient was transferred to the intensive care unitto properly control his AF. After good control of his heart ratewas achieved, his liver enzymes and renal function graduallyreturned to normal (Fig. 2).

Fig. 1. Serial sonographic studies were performed after the onset of ischaemic hepatitislesions in the liver. (B) Performed 7 days after admission, the image shows an increasin

Discussion

The incidence of hypoxic hepatitis varies among different stud-ies and is high in cardiac and intensive care units [2,4–6] and lowin internal medicine units [1,7]. The reason for this is not clear. Thisvariability could result from under-reporting cases in internalmedicine units, which can be explained by the fact that numerousstudies in these units are retrospective. Therefore, the majority ofthe hypoxic hepatitis cases are missed because they are transferredto the cardiac or other specialised units.

Understanding hypoxic hepatitis requires an awareness of theliver blood supply and what happens when this supply is dis-rupted. The liver receives 25% of the cardiac output, of whichapproximately two-thirds is supplied via the portal vein and one-third by the hepatic artery [8]. Blood flowing through the liver isdrained via the right, left and middle hepatic veins into the inferiorvena cava, which empties into the right atrium. To protect the liveragainst ischaemia, the hepatic circulation has multiple interactingfactors that attempt to maintain a constant hepatic blood flow inresponse to acute and chronic conditions. These factors include

. (A) Performed in the emergency department, this image shows a few hypoechoicg number of hypoechoic lesions.

178 F.Y. Khan, K.A. Baagar / Arab Journal of Gastroenterology 14 (2013) 176–179

passive expulsion of blood from the large hepatic reservoir into thecentral venous system, the hepatic artery buffer response andhepatorenal reflex [9].

Although the pathophysiology of IH is poorly understood,numerous potential explanations have been suggested. Previously,serious systemic hypotension, which usually occurs during shock,was advocated as the most important pathogenic factor [10,11].Afterwards, a low cardiac output with a reduction in hepatic bloodflow (‘forward failure’) was suggested as a pathogenic factor, evenwithout shock [1,4,6]. Then, several years later, hepatic venous con-gestion (‘backward failure’) was proposed to play a major role in thepathogenesis [12]. Despite the controversy about whether bothmechanisms (forward and backward failure) must be present simul-taneously for acute hypoxic hepatitis to occur [5], the available datasupport the hypothesis that IH is likely to be multifactorial [13].Therefore, it can be concluded that heart failure, particularly right-sided heart failure, which is uniformly present in many patients withIH [12], and passive congestion may be important factors in thepathophysiological process underlying IH. The concomitant occur-rence of conditions such as decreased perfusion, hypoxia or contactwith an endotoxin may precipitate IH [3]. In patients with chronicrespiratory failure, passive congestion of the liver also contributesto a predisposition to hypoxic hepatitis. However, unlike patientswith congestive cardiac failure, IH in these patients is associatedwith progressive hypoxaemia without an acute process [14]. Inour patient, underlying hepatic venous congestion (due to ischaemiccardiomyopathy) and decreased hepatic perfusion (precipitated byfast AF) were the most likely pathogenic factors. Although the bloodpressure readings during the AF attacks were normal, they were be-low the baseline readings (140/90 mmHg), which resulted in de-creased hepatic perfusion. The repetition of the same scenario(elevation of liver enzymes in association with each episode of fastAF and drop in blood pressure) three times during hospitalisationstrongly implicates fast AF as the precipitating factor in this patient.

The clinical presentation of hypoxic hepatitis is highly variable.Unless there is a high index of suspicion, hypoxic hepatitis can bemissed because vomiting and right hypochondrial pain from theenlarged liver may not be prominent features or even present.Hypoxic hepatitis may be an incidental finding during laboratorytesting in the hospital for problems not primarily associated withthe liver. Our patient presented with shortness of breath associatedwith nausea, vomiting and fatigue, which are nonspecific.

Liver biopsy would show pathognomonic centrilobular necrosis,but it was not performed in this case. However, liver biopsy is usu-ally not necessary to confirm the diagnosis of IH [15]. The disorderis usually identified by a marked and reversible elevation in serumaminotransferase levels in the absence of other causes of liverdamage [12]. Although there is no cut-off value that conclusivelydefines hypoxic hepatitis, serum aminotransferase levels >20 timesthe normal upper limit in the appropriate clinical setting have beenaccepted as sufficient for diagnosis [6,12,16]. Other abnormal con-ditions that might be encountered in patients with hypoxic hepa-titis include an early elevation of LDH (12–48 h after theinitiating event) with an ALT/LDH ratio <1.5 [17,18]. Serum creat-inine values are often concomitantly elevated in association withliver enzymes [12]. The INR and bilirubin may increase [2]. The ser-um bilirubin level rarely rises above four times the normal upperlimit, usually beginning its rise after aminotransferase levels havebegun to decline. Serum alkaline phosphatase levels are rarelyhigher than twice the normal upper limit [2,4–6]. Imaging studiesreveal hypoechoic or hypodense lesions that resolve completelywith the reversal of the initiating event [19]. In our patient, therewas a rapid and marked increase in liver enzymes, more than 20times the normal upper limit, with normalisation within 14 days

(from the last episode) and exclusion of viral or hepatotoxic agentsas the cause. Moreover, the LDH level was also elevated, and theALT/LDH ratio was 0.7 (<1.5). As noted, serum creatinine was alsoelevated in association with the liver enzymes.

The most important differential diagnoses to consider in patientspresenting with marked elevation of serum hepatic transaminaselevels (>20 times) are viral hepatitis, toxin- or drug-induced hepati-tis and IH. In our patient, in addition to negative serological tests forthe hepatitis A, B, C and E viruses, the following events strongly sug-gest IH: first, the patient had underlying ischaemic cardiomyopathy,and he denied ingestion of hepatotoxic drugs; second, there was arapid decline in serum aminotransferase levels after the initial risewith each episode of fast AF; third, an early rapid rise in the serumLDH level with an ALT/LDH ratio of <1.5 was observed [18]; fourth,blood tests showed a concomitant rise in serum creatinine level witheach fast AF episode [12]; and fifth, an ultrasound study of the livershowed multiple hypoechoic lesions, which resolved completelywith the reversal of the initiating event [19].

There is no specific therapy for IH. Nevertheless, importantaspects of management include prompt restoration of cardiac out-put and reversal of the underlying cause of the haemodynamicinstability. The prognosis is usually determined by the underlyingaetiology rather than by the subsequent hepatic dysfunction [16].

In conclusion, our case emphasises that physicians should beaware of this syndrome and the possibility of its occurrence evenwith normal blood pressure.

Conflict of interest

The authors declared that there was no conflict of interest.

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