This document discusses hepatorenal syndrome (HRS), an acute kidney injury that can occur in patients with cirrhosis and liver failure. It provides updates on diagnostic criteria and classifications of HRS subtypes. The pathophysiology of HRS involves increased blood flow to the gut, decreased central blood volume, and kidney vasoconstriction. Risk factors include advanced cirrhosis and bacterial translocation. Terlipressin with albumin is the standard treatment and can reverse HRS, though noradrenaline is also effective with fewer side effects. The timing of renal replacement therapy and role of liver transplantation in HRS are also reviewed.

1. Hepatorenal
Syndrome
Update on
Dr. Ye’ Htet Aung
28-7-20 (Tuesday)

2. Hepatorenal syndrome
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3. Hepatorenal syndrome
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5. Hepatorenal syndrome
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6. Previous Diagnostic criteria for HRS (2007 )

7. 2015 ICA revised criteria

8. New classification of HRS subtypes

9. New classification of HRS subtypes

10. HRS-AKI

11. HRS-NAKI

12. AKI Phenotypes in Cirrhosis
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14. Tubular Injury Biomarkers
Urinary Biomarkers
• IL-8
• Kidney injury molecule-1 (KIM-1)
• Neutrophil gelatinase-associated lipocalin (NGAL)
• Albumin
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Significantly higher in ATN
patients

15. Urinary NGAL
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16. Fractional excretion of Na+ (FENa)
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17. Algorithm for workup and management of AKI

19. Pathophysiology

20. Advanced
Cirrhosis
Impaired liver
function
Portal
hypertension
Increased
splanchnic
blood flow
Increased
cardiac
output
Systemic
vasodilation
Decreased
central blood
volume
Systemic
inflammatory
response

21. Pathophysiology of HRS
Increased splanchnic blood flow
Decreased central blood flow
Activation of vasoconstrictor system
Kidney vasoconstriction – decreased GFR

22. What is new in Pathophysiology of HRS?
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Not only Circulatory dysfunction
but also Systemic inflammation
Bacterial translocation

23. Bacterial translocation (BT)
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26. Risk factors
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27. Prognosis
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28. Prevention of HRS
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29. Role of prophylactic Antibiotics and Albumin
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31. ß-blockers in HRS
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32. ß-blockers in HRS (Cont:)
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33. ß-blockers in HRS (Cont:)
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34. NSAIDs
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35. ACEI & ARBs
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36. Aminoglycosides
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37. Diuretics
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38. Pharmacologic Therapy
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Vasoconstrictor + Albumin

39. How to give Terlipressin
• IV Bolus starting dose 0.5-1mg every 4-
6hr
• Maximum dose 2mg every 4hr in non-
responder (reduction of baseline Cr-
<25%)
• Continuous infusion of Terlipressin 2-
12mg/day
• (Single Study) as efficacious as Bolus
administration
• Lower rates of adverse effects
Standard Method
• Treatment should be maintained until complete response or maximum of 14days in
cases of partial or nonresponse
Alternative Method

40. Adjustment of dose
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41. Adjustment of dose
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42. Complete response or Partial response
• Complete response – Within 0.3 mg of patient baseline sCr
• Partial response – regression of AKI stage to a final SCr ≥0.3 mg/dl
of patient baseline sCr
• For a maximum of within 14 days

43. Side effects of Terlipressin
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• Ischaemic complications have been reported in up to 45–46% of patients when the drug was
delivered by IV boluses.
• The rate of discontinuation because of side effects, mainly cardiovascular, is around 20%.

44. Noradrenaline
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45. Both HRS-1 & HRS-2

46. 40 patients with
HRS-1
N=20
NA 0.5-1mg/hr +
Albumin
N=20
Terlipressin 0.5-2mg
6hrly +Albumin
Until reversal or completion of 15 days of Tx

47. Results
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Serum Creatinine Group A (NA) Group B (TP)
Day 4 2.4 ± 1.2 mg/dL 2.5 ± 1.5 mg/dL
Day 8 1.6 ± 1.2 mg/dL 1.8 ± 0.9 mg/dL
Day 15 1.0 ± 0.4 mg/dL 1.2 ± 0.5 mg/dL
Responders

48. 46 HRS-1
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Terlipressin
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NA
RCT,
India
2011
HRS reversal could be achieved in 9 (39.1%) patients in group A and 10 (43.4%) patients in group B
(p = 0.764).
Noradrenaline is as safe and effective as terlipressin, but less expensive in the treatment of HRS

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NA is inferior to Terlipressin

50. Terlipressin vs Noradrenaline in HRS
RCT (New Delhi, India) 2016
• Terlipressin (2-12 mg/day; n = 60) • Noradrenaline (0.5-3.0 mg/h; n = 60).
Terlipressin Vs NA
• Compared to noradrenaline, terlipressin achieved
Greater day 4 (26.1% vs. 11.7%; p = 0.03)
Greater day 7 (41.7% vs. 20%; p = 0.01) response

51. Reversal of HRS was also better with terlipressin (40% vs. 16.7%; P = 0.004)
Significant reduction in the requirement of RRT (56.6% vs. 80%; P = 0.006)
and
Improved 28-day survival (48.3% vs. 20%; P = 0.001).
Adverse events limiting use of drugs were higher with terlipressin than
noradrenaline (23.3% vs. 8.3%; P = 0.02), but were reversible.

52. Midodrine + Octerotide + Albumin
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53. Summary of RCTs of vasoconstrictor therapy in HRS-1

54. Role of Terlipressin in HRS-2 or HRS-NAKI
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55. Role of Terlipressin in HRS-2 or HRS-NAKI
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56. Role of Albumin
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57. Role of Albumin
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58. Role of Albumin
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60. Role of TIPSS in HRS
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61. Renal Replacement Therapy
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62. Ideal Timing for RRT?
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• As AKI

63. Albumin dialysis
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189
ACLF patients
95
Albumin dialysis
94
Standard dialysis
2003-2009 Europe

64. Liver Transplantation (LT)
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65. Liver Transplantation (LT)
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66. US data
2002-2010
LT centre
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who received acute RRT <90days before LT
9% kidney non-recovery & need chronic RRT
2112 adult deceased-donor LT-alone recipients3.6 % renal non-recovery and need chronic RRT
Who did not received RRT before LT

67. Simultaneous Liver-Kidney Transplantation
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68. Organ Procurement and Transplantation Network selection criteria for
simultaneous liver and kidney transplantation (2017)
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69. Organ Procurement and Transplantation Network selection criteria for
simultaneous liver and kidney transplantation (2017) Cont.
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70. Treatment Recommendations (EASL) 2018
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