Avik Majumdar

Austin Health

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Co-Authors

Geoffrey W. McCaughan

Royal Prince Alfred Hospital

Emmanuel Tsochatzis

The Royal Free Hospital

Simone I. Strasser

Royal Prince Alfred Hospital

Marie Sinclair

Austin Health

Ken Liu

Royal Prince Alfred Hospital

William Kemp

The Alfred Hospital

Stuart K. Roberts

The Alfred Hospital

Adam Testro

Austin Health

Paul Gow

Austin Health

Ammar Majeed

The Alfred Hospital

Cooperative Institutions

University of Sydney

142

Royal Prince Alfred Hospital

124

University of Melbourne

116

University College London

105

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

Monash University

Austin Health

Sun Yat-sen University

Shanghai Jiao Tong University

Austin Hospital

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Continuous outpatient terlipressin infusion for hepatorenal syndrome as a bridge to successful liver transplantation

Hepatology (2014)

Marcus Robertson Avik Majumdar Kent Garrett Greg Rumler Paul Gow

Hepatorenal syndrome (HRS) is a life-threatening yet potentially reversible cause of renal dysfunction occurring in patients with advanced cirrhosis, ascites, and liver failure.1 It is characterized by functional renal impairment due to renal arterial vasoconstriction in the setting of major disturbances in circulatory function.1, 2 There are two forms of HRS: type 1 is characterized by an acute progressive decrease in kidney function with a median survival time of 2 weeks without treatment, whereas type 2 features more stable and less severe kidney failure and longer survival compared with type 1.3 Liver transplantation remains the only effective long-term therapy for HRS.4 Pharmacologic treatment with vasoconstrictors targeted to reverse splanchnic vasodilation, together with albumin, is effective in reversing renal dysfunction in 34%-44% of patients with type 1 HRS and improves survival in this group.4, 5 The European Association for the Study of the Liver (EASL) recommend terlipressin (1 mg/4-6 hourly as intravenous bolus) together with albumin as first-line treatment for patients with type 1 HRS.6 Traditionally, this is done as an inpatient where cardiovascular parameters can be monitored. Multiple case reports now exist describing continuous terlipressin infusion as an alternative to intravenous bolus administration,7, 8 with similar efficacy and often using a lower total dose, representing a potential cost saving.7 We present the first reported case of an outpatient continuous terlipressin infusion for treatment of recurrent HRS as a bridge to successful liver transplantation. A 59-year-old man with Child-Pugh C cirrhosis due to previous alcohol consumption complicated by recurrent encephalopathy, diuretic-resistant ascites, and hepatocellular carcinoma was admitted to our unit with a rapid deterioration in renal function. This was on a background of three recent admissions with type 1 HRS. On each previous occasion he was treated successfully with bolus administration of terlipressin as per EASL guidelines, resulting in a return of his renal function to baseline (Fig. 1). A terlipressin infusion, consisting of 3 mg terlipressin in 50 mL 5% dextrose delivered by a GemStar pump at a rate of 2.1 mL/h through a peripherally inserted central venous catheter was begun. Dextrose was chosen as the solute based on evidence that it was superior to normal saline at maintaining optimal pH for terlipressin.9 The patient initially received a terlipressin infusion as an inpatient, enabling the dose to be titrated and the patient to be screened for complications. During this time the patient's serum creatinine returned to his baseline level (Fig. 1). On day 6 the patient was discharged home with an ambulatory terlipressin infusion under the supervision of our Hospital-in-the-home program. The patient was reviewed in an outpatient clinic twice per week and had renal function monitored at each visit. This continued for a further 22 days at which time the patient underwent successful liver transplantation. Both outpatient terlipressin infusion and inpatient bolus terlipressin were well tolerated by our patient with no adverse effects noted; larger studies would address whether there is a difference in overall adverse events between the two modes of delivery. Posttransplantation, a renal-sparing immunosuppression regimen consisting of basiliximab, mycophenolate mofetil, and low-dose tacrolimus was implemented. The patient was discharged 10 days posttransplantation with a serum creatinine of 117 μmol/L and has remained stable to day 120 postoperation (Fig. 1). Liver transplantation remains the mainstay of therapy for type 1 HRS; however, vasoconstrictor therapy with terlipressin is recognized as an effective short-term treatment.4, 5 Terlipressin is traditionally given using a bolus regimen in a hospital setting. This case illustrates the successful use of a continuous outpatient terlipressin infusion in a patient with type 1 HRS over a 4-week period as a bridge to liver transplantation, demonstrating that in the appropriate clinical scenario and under close supervision, outpatient terlipressin is feasible, and in this case efficacious and well tolerated.

Terlipressin

Bolus (digestion)

Liver disease

10.1002/hep.27154

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Citations (20)

Su1027 SX-ELLA DANIS STENT FOR THE MANAGEMENT OF REFRACTORY VARICEAL BLEEDING IN CHRONIC LIVER DISEASE: A MULTI-CENTER AUSTRALIAN AND NEW ZEALAND EXPERIENCE

Gastrointestinal Endoscopy (2020)

Saad Khan David Rowbotham Andre Chong Avik Majumdar Campbell White

Refractory (planetary science)

Liver disease

10.1016/j.gie.2020.03.1873

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Citations (0)

Editorial: optimising hepatitis B vaccine response in inflammatory bowel disease—time to get some skin in the game

Alimentary Pharmacology & Therapeutics (2022)

Madeleine Gill Avik Majumdar

LINKED CONTENT This article is linked to Ko et al papers. To view these articles, visit https://doi.org/10.1111/apt.16970 and https://doi.org/10.1111/apt.17069

Inflammatory Bowel Diseases

10.1111/apt.17044

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Citations (1)

Improved survival of cirrhotic patients with infections in Australian and New Zealand ICUs between 2005 and 2017

Liver International (2022)

Ammar Majeed Michael Bailey William Kemp Avik Majumdar Rinaldo Bellomo

Changes in outcomes of cirrhotic patients admitted to intensive care units (ICUs) with infections are poorly understood. We aimed to describe changes over time in outcomes for such patients and to compare them to other ICU admissions.Analysis of consecutive admissions to 188 ICUs between 2005 and 2017 as recorded in the Australian and New Zealand Intensive Care Society Centre for Outcome and Research Evaluation Adult Patient Database.Admissions for cirrhotic patients with infections accounted for 4645 (0.6%) of 813 189 non-elective ICU admissions. Hospital mortality rate (35.5%) was significantly higher compared with other cirrhotic patients' admissions (28.5%), and other ICU admissions for infection (17.1%, p < .0001), and increased to 52.2% in the presence of acute-on-chronic liver failure (ACLF). Hospital mortality in cirrhotic patients' ICU admissions for infection decreased significantly over time (annual decline odds ratio, 0.97; 95% CI, 0.95-0.99, p = .002). There was a comparable reduction in-hospital mortality rates over time in other ICU admissions for infections and other cirrhotic patients' ICU admissions. However, mortality rates did not change over time in the ACLF subgroup. Median hospital and ICU length of stays for cirrhotic patients' ICU admissions for infections were 12.1 and 3.5 days, respectively, and decreased significantly by 1 day every 4 years in-hospital survivors(p < .0001).Hospital mortality in ICU admissions for cirrhotic patients with infection is double that of non-cirrhotic patients with infection but has declined significantly over time. Outcomes in the subgroup with ACLF remained poor without significant improvement over the study period.

10.1111/liv.15285

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Citations (2)

Are liver transplant centres critical for the critically ill patient with cirrhosis?

Journal of Hepatology (2019)

Avik Majumdar Stuart K. Roberts David Pilcher

Chronic liver disease

Etiology

Liver disease

10.1016/j.jhep.2019.05.007

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The holy grail of a biomarker for “liver function”

Clinical Liver Disease (2016)

Avik Majumdar Massimo Pinzani

Watch a video presentation of this article Watch the interview with the author The past decade has given rise to many innovations in hepatology, particularly in the fields of noninvasive fibrosis assessment and viral hepatitis. Comparatively, advances in the functional assessment of the liver have progressed at a much slower rate. It is an ambitious proposal to develop a single unifying biomarker to assess global liver function, but one that highlights the inadequacies of current methods of assessment. A major impediment to the pursuit of this “holy grail” is the broad range of functions performed by the liver. Moreover, liver function per se is only one determinant of prognosis in chronic liver diseases, with portal hypertension and hepatocarcinogenesis being two other major factors. For this reason, any progress in the pure functional assessment of the liver has been made predominantly in the settings of acute liver failure and the preoperative assessment for liver resection. This brief review aims to discuss the current and future status of the hepatic functional assessment. The primary functions of the liver and corresponding tests are summarized in Table 1. The breadth and heterogeneity of sites of hepatocyte function demonstrate the difficulty in developing a single functional biomarker. Drugs/Toxins (cytochrome P450 function) Endogenous steroids Aminopyrine clearance Bromsulphthalein Caffeine clearance Galactose elimination capacity Indocyanine-green clearance Lignocaine metabolites Molecular imaging techniques Serum ammonia Among the routinely available laboratory tests, only serum albumin, bilirubin, and prothrombin time, or its derivative international normalized ratio, have the capability to assess liver function. Despite widespread and frequent use, these basic tests have drawbacks (Table 2). To improve practical utility, these tests have been combined with other biochemical or clinical parameters to devise clinical scores to stratify prognosis in chronic liver disease, the most common being Child-Turcotte-Pugh and the Model for End-Stage Liver Disease. Although originally derived for other purposes, both of these scores are currently used with the endpoints of mortality or transplantation in mind, rather than liver function in absolute terms.1, 2 Additional biochemical measures of liver function have been investigated in acute liver failure, such as arterial ammonia and lactate, of which the latter has been incorporated into prognostic scores such as the King's College Hospital criteria.3, 4 However, these are of limited use in the chronic disease setting. Quantitative methods of assessing liver function have traditionally focused on the excretory capacity of the liver. Bromsulphthalein clearance was first described for this purpose in 1924; however, its use was discontinued in the 1970s because of a high perceived risk for anaphylactic reactions.5 Indocyanine green (ICG) clearance and galactose elimination capacity have since superseded bromsulphthalein and are described later in this article. Other excretory tests that have been described include caffeine clearance and lidocaine metabolite formation.6 Quantitative methods have not yet been adopted to routine clinical practice because of their lack of specificity and dependence on specialized equipment, and thus are mainly used in research or referral centers. The clearance of ICG has been used to assess functional hepatocyte mass, although originally designed to estimate hepatic blood flow using the Fick equation. ICG binds to albumin, alpha1-lipoproteins, and beta-lipoproteins and is entirely excreted by the liver into the bile.5 ICG test results are commonly expressed as the plasma disappearance rate (ICG-PDR) or the percentage retained 15 minutes after intravenous bolus injection (ICG-R15) of ICG at doses of 0.5 mg/kg. These parameters can be quantified with serial arterial or venous blood sampling or using noninvasive pulse densitometry. Several cutoff values have been reported in the literature for safe hepatic resection, with ICG-PDR greater than 15% per minute or ICG-R15 less than 15% generally considered as cutoffs for normal values. ICG testing may be affected by hepatic blood flow variations caused by thrombosis or intrahepatic shunting, and competitive inhibition by excessive bilirubin. Furthermore, ICG uptake by hepatocytes can be reduced in inflammatory states because of the effect on the expression of transporting polypeptides.7, 8 Galactose elimination capacity quantifies the metabolic function of the liver. Essentially, an intravenous load of 0.5 mg/kg galactose is administered, which undergoes phosphorylation within hepatocytes. The elimination capacity is measured with serial serum samples between 20 and 50 minutes postinjection. Galactose elimination capacity has been correlated with clinical outcomes in chronic liver disease and fulminant hepatic failure. However, a number of shortcomings exist, particularly during liver regeneration where there is an increased requirement for galactose in membrane glycoproteins. Furthermore, a prolonged fasting state may result in galactose being converted into glucose and ultimately lead to false results.6 Breath tests are infrequently used and involve an oral or intravenous load of a radiolabeled substance (e.g., 13C- or 14C-aminopyrine,9 14C-galactose) that is predominately metabolized in the liver. Exhaled carbon dioxide (CO2) is collected in an alkaline medium at serial intervals and the activity of 14CO2 is measured. This provides a semiquantitative value when compared with the endogenous production of CO2. These tests required specialized equipment and have little additional value over routine liver biochemical assessment.10 99mTc-diethylenetriamine-pentaacetic acid-galactosyl human serum albumin scintigraphy and 99mTc-mebrofenin hepatobiliary scintigraphy are two molecular imaging techniques that are able to assess the regional variability of hepatic blood flow and functional hepatocyte mass. These methods are of particular use in the assessment before hepatic resection and provide more information than computed tomography volumetry or ICG clearance alone. However, the uptake of 99mTc-mebrofenin is affected by chronic cholestasis, and 99mTc-diethylenetriamine-pentaacetic acid-galactosyl human serum albumin scintigraphy is only approved for use in Japan thus far.6 To maximize utility, the ideal “liver function test” should not only assess function but should also predict the clinical outcomes of patients. Functional tests should be correlated with severity of portal hypertension and hard clinical endpoints such as clinical decompensation and mortality to achieve this. ICG clearance has already been investigated in the detection of esophageal varices.11 Other sequelae of cirrhosis, such as the risk for hepatocarcinogenesis, may be more difficult to correlate with liver function. However, combining noninvasive fibrosis assessment techniques with functional testing may be an innovative way forward. The routine assessment of liver function is still primarily based on basic biochemical and coagulation tests. Although clearance-based functional tests have been used in the hepatic surgical assessment of patients, these are yet to translate to the standard evaluation of patients with liver disease. The discovery of a reliable biomarker for liver function that correlates with clinical outcomes is yet to be found, but certainly is a “holy grail” worth searching for.

Liver function

Indocyanine Green

Viral Hepatitis

Steatohepatitis

Holy Grail

10.1002/cld.554

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Citations (4)

Non‐invasive Assessment of Fibrosis and Cirrhosis

Avik Majumdar Massimo Pinzani

This chapter provides an overview of the available non-invasive tests, their use, and limitations. The tools available for non-invasive assessment of fibrosis range from simple scores calculated from routine laboratory parameters or more complex serum biomarkers, to elastography techniques to measure liver stiffness. These methods aim to overcome the disadvantages inherent in liver biopsy/histology and hepatic venous pressure gradient (HVPG) measurement. Non-invasive tests were developed initially to detect two histopathological endpoints: significant fibrosis and cirrhosis. Generally, the METAVIR or Ishak systems have been used in chronic viral hepatitis and have formed the basis for validation of non-invasive tests. Non-invasive tests allow a series of measurements to be made. They can therefore provide a dynamic picture of stability, progression and, in theory, regression of the chronic disease process. This is in contrast to both liver biopsy and HVPG measurement.

Hepatic fibrosis

Transient elastography

Liver disease

10.1002/9781119237662.ch7

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DECLINING MORTALITY OF CIRRHOTIC PATIENTS REQUIRING ADMISSION TO INTENSIVE CARE UNITS FOR SERIOUS INFECTIONS: A BI-NATIONAL COHORT STUDY

Hepatology (2019)

Ammar Majeed Michael Bailey Avik Majumdar William Kemp Rinaldo Bellomo

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An essential accessory

BMJ Open Gastroenterology (2021)

David Prince Radha Popuri Avik Majumdar

A young adult male was referred for a second opinion of deranged liver biochemistry. He initially presented two years prior with abdominal pain, lethargy and fevers due to a segment two pyogenic liver abscess. He received empirical antibiotic therapy to resolution. Computed tomography for abscess follow-up revealed an intrahepatic inferior vena cava thrombus. He was anti-coagulated with warfarin. He was lupus anticoagulant positive and had a highly positive beta-2 glycoprotein antibody on serial measurement and was diagnosed with anti-phospholipid syndrome. On current review, the patient had no clinical stigmata of chronic liver disease. There were dilated veins on the supraumbilical abdominal and chest walls. There was mild hepatomegaly but no splenomegaly. Laboratory investigations revealed mildly cholestatic liver function tests with hyperbilirubinaemia (40μmol/L) but no liver synthetic dysfunction. Serological screening did not reveal any cause of chronic liver disease. The patient underwent multiphase abdominal CT and formal hepatic venography. What is the diagnosis and describe the hepatic venous outflow?

Lethargy

Liver disease

10.1136/bmjgast-2021-000770

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IDDF2019-ABS-0196 Long term outcomes of utilizing donation after circulatory death grafts in liver transplantation – an australian 12-year cohort study

V.N. Sastry Keval Pandya Mara Teresa Panlilio Claire West Susan Virtue

Background

Organ shortage for liver transplantation (LT) is a major problem worldwide. Use of donation circulatory death donors (DCD) has been one strategy to expand the donor pool; however, data on long term outcomes in DCD graft recipients are mixed. We studied the characteristics, utilization and recipient outcomes of DCDs.

Methods

We retrospectively studied adults who underwent deceased LT between 2006–2018. Donor and recipient data at LT and recipient outcomes were collected from a prospective database. Criteria for DCD selection at our center include all of the following: donor age <50years, BMI <30kg/m², and circulatory arrest within 30minutes of treatment withdrawal in otherwise suitable liver donors. The primary outcome of interest was graft survival (time to retransplantation or death).

Results

During the study period (median follow-up 50.6months), 739 donors were utilized for LT with 53 (7.2%) being DCDs. Compared to donation after brain death donors (DBDs), DCDs were younger (30 vs. 50years), more likely to have history of predonation cardiac arrest (71.2% vs. 34.8%), had longer intubation time (3 vs. 2days), less inotrope requirements (32.7% vs. 7.8% on no agents) and higher AST (59 vs. 46U/L) (median values presented, all P<0.01). DCDs had shorter cold ischemia time (5.75 vs. 6.85hours, P=0.005) and higher donor risk index (Feng et al. 2006) (1.68 vs. 1.56, P<0.001). As per our unit policy, recipients of DCD grafts were less likely to be PSC (1.9 vs. 9.0%, P=0.076) or retransplant patients (0 vs. 6%, P=0.067). Similarly, DCD recipients did not receive split grafts (0 vs. 15.3%, P<0.001). The proportion of DCDs among utilized grafts increased from 4.8% (2006–2009) to 7.8% (2010–2012) and remained stable afterward. 157 patients experienced graft loss during follow-up (31 retransplants, 126 deaths). DCD grafts had similar long term graft survival compared to DBDs, although DCDs recipients with high preLT MELD (>20) appeared to have worse outcomes (figure 1).

Conclusions

Long term outcomes of DCD grafts are similar to DBD grafts especially when matched with appropriately selected recipients (first transplant, nonPSC patients with low MELD).

Economic shortage

10.1136/gutjnl-2019-iddfabstracts.14

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Citations (1)