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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 4  |  Page : 151-154

Dual or single risk factor in acute liver failure

Department of Hepatology, SRIHER, Chennai, Tamil Nadu, India

Date of Submission21-Feb-2021
Date of Decision16-Apr-2021
Date of Acceptance15-May-2021
Date of Web Publication24-Sep-2021

Correspondence Address:
Jayanthi Venkataraman
Department of Hepatology, SRIHER, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ghep.ghep_6_21

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Acute liver failure (ALF) is a medical emergency. We report a case of ALF due to paracetamol overdose in a patient with pregnancy-related transient hepatic venous outflow obstruction, managed conservatively. The patient made a complete recovery 6 months later.

Keywords: Acute liver failure, Budd–Chiari syndrome, pregnancy, prothrombotic state

How to cite this article:
Varanasi BY, Kedarishetty CK, Mu K, Selvan TS, Venkataraman J. Dual or single risk factor in acute liver failure. Gastroenterol Hepatol Endosc Pract 2021;1:151-4

How to cite this URL:
Varanasi BY, Kedarishetty CK, Mu K, Selvan TS, Venkataraman J. Dual or single risk factor in acute liver failure. Gastroenterol Hepatol Endosc Pract [serial online] 2021 [cited 2022 Sep 30];1:151-4. Available from: http://www.ghepjournal.com/text.asp?2021/1/4/151/326637

  Introduction Top

Acute liver failure (ALF) is a medical emergency in day to day practice associated with high mortality. A detailed clinical history focusing on aetiology would help the clinician in making an early diagnoses of ALF and thereby triage an appropriate management. We report a case of ALF due to paracetamol overdose in a patient with pregnancy related Budd Chiari syndrome, managed conservatively.

  Case Report Top

A 22-year-old nurse presented in May 2019 with fever, anorexia, nausea and vomiting for a week, jaundice (noncholestatic) for 4 days, and generalized anasarca and loss of consciousness for a day. Urine output was normal. The patient had taken paracetamol 650 mg (7 tablets) for a period of 3 days (equivalent to 4.5 g per day) for fever and generalized body ache. There was no history of taking alternative system of medication. There was no history of abdominal pain or gastrointestinal (GI) bleed. The patient was a primi and had a cesarean section 6 weeks before admission, and recovery was uneventful. She had no comorbidities, no history of blood transfusion, and had not taken any oral contraceptive pills in the past. She was born of nonconsanguineous marriage.

On examination, her Glasgow Coma Score was 3/15, with bilateral pupils 3 mm showing a sluggish response and no anisocoria. She required mechanical ventilation at admission. Her pulse rate was 76 per minute and regular in rhythm, blood pressure was 120/70 mmHg, and mean arterial pressure was 77 mmHg with a respiratory rate of 26 per minute. The patient was deeply icteric with bilateral edema of the lower extremities. There was no Kayser–Fleischer ring, superficial lymphadenopathy, or thyromegaly. On systemic examination, the liver span was 12 cm with shifting dullness, and the spleen was not palpable. Cardiovascular and respiratory systems were normal. Working diagnosis was considered as hyperacute liver failure, paracetamol induced with icterus to encephalopathy interval of 3 days, complicated by ascites and Grade 4 hepatic encephalopathy (overt, episodic, Grade III–IV, precipitated by paracetamol intake). This can be deleted as this is being discussed ahead.


At admission hemoglobin was 11 g/dL, total white cell count was 7200 cells/mm3 and platelet count was 2,04,000 cells/cu mm; serum electrolytes and renal function tests were normal. [Table 1] shows the follow-up of liver biochemistry, international normalized ratio (INR), and serum ammonia during hospitalization. Baseline serum albumin was 2.4 g/dL with an albumin–globulin ratio of 0.70; serum alkaline phosphatase: 147 U/L, and serum gamma-glutamyltransferase: 68 U/L. Viral markers for acute hepatitis A, B, and E and autoimmune markers (serum antinuclear antibody, serum anti-smooth muscle antibody, and serum liver–kidney microsomal type) were negative. Thyroid function tests, serum ceruloplasmin, 24-h urine copper, and serum creatinine phosphokinase were normal. Ascitic fluid analysis showed a high serum ascitic fluid gradient and a normal cell count and no spontaneous bacterial peritonitis.
Table 1: Follow-up of laboratory parameters during intensive care management

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Ultrasound and Doppler study showed coarse echotexture of the liver, normal portal vein flow velocity, and absent flow in the right hepatic vein. The middle and left hepatic veins were normal. There were no communicating collaterals within the liver. There was moderate ascites. Computed tomography [Figure 1] of the brain showed an effaced sulcus suggestive of cerebral edema. Contrast-enhanced computed tomography (CECT) of the abdomen [Figure 2]a and [Figure 2]b showed a shrunken and collapsed liver, irregular surface margins, splenomegaly with gross ascites, and attenuated hepatic veins.
Figure 1: Computed tomography brain showing effaced sulcus

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Figure 2: (a and b) Computed tomography abdomen showing a collapsed liver with irregular margins in portal venous phase and delayed arterial phase

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Differential diagnosis at this stage included acute liver failure (ALF) due to paracetamol overdose with an underlying Budd–Chiari syndrome (BCS) (pregnancy-related transient hypercoagulable state), acute sinusoidal obstruction syndrome due to paracetamol toxicity (centrizonal necrosis) with hepatic outflow tract obstruction (centrizonal congestion and necrosis), and acute-on-chronic liver failure due to paracetamol toxicity supervening on underlying chronic liver disease (BCS).

The patient was intubated and started on prophylactic antibiotics after cultures (blood and urine), and N-acetyl cysteine in the regularly scheduled dose was given. She received two cycles of low-volume plasma exchange, and serum sodium was maintained between 145 and 155 meq/dL. Nutrition was maintained by Ryle's tube feeds. Over the next 3 days, the patient showed an improvement in neurological signs, with appropriate awakening, and response to commands. The tense ascites which ensued on day 5 required large-volume paracentesis on two occasions during hospital stay. Upper GI endoscopy showed mild portal hypertensive gastropathy; there were no esophageal or fundal varices. Prothrombotic work was essentially normal, except for a mild increase in homocysteine levels.

She was discharged on normal diet with salt restriction, furosemide 20 mg, and spironolactone 50 mg once a day; no beta-blockers were introduced. Pregnancy state being a reversible prothrombotic state, anticoagulation was not recommended. The patient's relatives were counseled regarding the need for liver transplant as she continued to have abnormal liver biochemistry and prolonged INR and persistent ascites at the time of discharge.

On follow-up at 6 months, the patient was totally asymptomatic. The liver biochemistry and INR returned to normal values. CECT abdomen showed mild alteration in echotexture of the liver; the portal and hepatic venous outflow systems were normal; liver and spleen sizes were normal [Figure 3]. FibroScan showed a 5.2 KPa fibrosis (F1) score and steatosis of 182 db/m. The patient was, however, cautioned of a possible recrudescence of similar symptoms in subsequent pregnancy.
Figure 3: Computed tomography abdomen post 6 months

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She has subsequently conceived in August 2020 and is on close follow-up with a monthly Doppler study of the hepatic and portal venous systems at her native place. Hence, our final diagnosis is likely ALF due to paracetamol toxicity with or without added pregnancy-related thrombophilia state causing transient hepatic venous outflow obstruction.

  Discussion Top

ALF is a syndrome of rapidly progressive hepatic dysfunction associated with a high risk of mortality. The defining features of ALF are hepatic encephalopathy, coagulopathy, and jaundice in patients with the absence of an underlying liver disease. All the three features were present in our patient at the time of presentation.

The patient had consumed an overdose of paracetamol for fever and had an underlying hepatic vein occlusion at 6 weeks (puerperium) postpartum. Both the risk factors affect the centrizonal regions of the liver lobule. The hepatocytic damage following paracetamol overdosage causes submassive necrosis and collapse of reticulin in zone 3, and the major hepatic venous outflow tract obstruction causes centrizonal congestion and pericentral hepatocyte necrosis. Thus, the two hits in one go in the patient (paracetamol toxicity and hepatic venous outflow obstruction) are the most likely insults that are responsible for the ALF. The tense ascites with rapid re-accumulation requiring large-volume paracentesis can be explained by occlusion to the hepatic venous outflow system. One other explanation for the gross ascites in our patient could be due to sinusoidal collapse caused by liver cell dropout, a well-known phenomenon in acute hepatitis.[1] Despite the 2 hits, transaminases did not show the expected rise of 400-fold elevation of the upper limit of normal.

The minimal dose of acetaminophen that produces liver injury varies from 4 to 10 g. Our patient had taken 4.5 g per day for 3 days. This was in the background of a pregnancy-related thrombophilic state resulting in obstruction to the hepatic venous outflow system. Recent studies have shown mild derangement of liver biochemistry with even 1 g of acetaminophen taken 6 hourly by healthy volunteers.[2] While most patients have transaminase levels that are often elevated up to 400 times the upper limit of normal, some may have mild elevations, metabolic acidosis, or isolated hypoprothrombinemia. Our patient had lower levels and may be related to lower dose of paracetamol. Nonintentional acetaminophen overdose (as in the case), when exposed for several days, manifests as more advanced encephalopathy at presentation.

Female sex hormones are associated with an increase in BCS in women on oral contraceptives.[3] It is also well known that pregnancy is a hypercoagulable physiological state and during puerperium, i.e. until 6 weeks after delivery. Studies have shown a high risk for thrombosis to continue even as long as 12 weeks after delivery.[4] This hypercoagulable state is responsible for the association of pregnancy with BCS. The prevalence ranges from 6.8% to 16% in different series.[5],[6],[7],[8]

A significant number of these patients have an underlying thrombophilia, i.e., either inherited or acquired with at least two risk factors.[8] Raotou et al.[8] concluded that BCS is unlikely to occur in the absence of underlying prothrombotic state. Further, a high prevalence of protein S deficiency has been documented during pregnancy, and this is likely to be an important risk factor in predisposing pregnant women to BCS.[9],[10]

There has always been a debatable discussion whether pregnancy is itself a risk factor for BCS?[8] Thus, pregnancy being a prothrombotic state can trigger BCS in women with an underlying prothrombotic condition. The most common clinical presentations of BCS associated with pregnancy are acute and are due to thrombosis of the suprahepatic veins with obstruction of the outflow tract. Pathologically, this causes centrizonal congestion and pericentral necrosis.

Our patient had transient features of outflow tract obstruction with absent flow in two of the three major hepatic veins. This is most likely related to major liver cell dropout resulting in portal hypertension[1] rather than due to a thrombotic occlusion of the major hepatic veins which was not seen on CECT. With clinical and biochemical recovery at 6 months, the radiological findings reversed with a normal Doppler study and CECT indicating a transient occlusion of hepatic veins and not due to BCS.

ALF can occur due to more than one etiological factor, in this case overdose of paracetamol and hypercoagulable state due to pregnancy. Complete clinical recovery, with normalcy of liver biochemistry and liver imaging including the hepatic venous outflow system 6 months posthospitalization, suggests that the patient did indeed have ALF and not acute on chronic liver failure. Management in this case was reversal of paracetamol toxicity with N-acetyl cysteine and supportive care including plasma exchange.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Valla D, Flejou JF, Lebrec D, Bernuau J, Rueff B, Salzmann JL, et al. Portal hypertension and ascites in acute hepatitis: Clinical, hemodynamic and histological correlations. Hepatology 1989;10:482-7.  Back to cited text no. 1
Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: A randomized controlled trial. JAMA 2006;296:87-93.  Back to cited text no. 2
Valla D, Le MG, Poynard T, Zucman N, Rueff B, Benhamou JP. Risk of hepatic vein thrombosis in relation to recent use of oral contraceptives. A case-control study. Gastroenterology 1986;90:807-11.  Back to cited text no. 3
Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014;370:1307-15.  Back to cited text no. 4
Khuroo MS, Datta DV. Budd-Chiari syndrome following pregnancy. Report of 16 cases, with roentgenologic, hemodynamic and histologic studies of the hepatic outflow tract. Am J Med 1980;68:113-21.  Back to cited text no. 5
Ren W, Li X, Jia J, Xia Y, Hu F, Xu Z. Prevalence of Budd-Chiari syndrome during pregnancy or puerperium: A systematic review and meta-analysis. Gastroenterol Res Pract 2015;2015:13.  Back to cited text no. 6
Dilawari JB, Bambery P, Chawla Y, Kaur U, Bhusnurmath SR, Malhotra HS, et al. Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature. Medicine (Baltimore) 1994;73:21-36.  Back to cited text no. 7
Rautou PE, Plessier A, Bernuau J, Denninger MH, Moucari R, Valla D. Pregnancy: a risk factor for Budd-Chiari syndrome? Gut 2009; 58:606-8.  Back to cited text no. 8
Comp PC, Thurnau GR, Welsh J, Esmon CT. Functional and immunologic protein S levels are decreased during pregnancy. Blood 1986;68:881-5.  Back to cited text no. 9
Lim W, Eikelboom JW, Ginsberg JS. Inherited thrombophilia and pregnancy associated venous thromboembolism. BMJ 2007;334:1318-21.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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