Dr Samir Mohindra & Dr Manav Wadhawan gives a detailed presentation on the diagnosis, pathopysiology, monitor & treatment of the patients.

1. Hepatorenal syndrome
Samir Mohindra
Manav Wadhawan

2. • Progressive weakness for
5 months
• Productive cough , low
grade fever X 20 days
• Progressive ascites with
decreasing urine output x
15 days
Altered sensorium x 2 days
No GI Bleed/Jaundice
• H/o Treatment with
multiple i.v. antimicrobials
prior to admission for LRTI
• No H/O:
• Prior surgery
• Skin rash
• Blood transfusion
• Unknown drugs
O/E : afebrile, BMI- 24
Pallor +, Icterus +
Edema
Tense ascites
April 2016
78/F,
HTN X 17y
controlled
Dec 2015
5 months

3. Parameters Values
HbsAg/Anti HCV Negative
ANA,ASMA,ALKM1 Negative
S. Ferritin/B12 Normal
Anti Tissue
Tranglutaminase
Antibody
<3.0 au/ml
S . ceruloplasmin 20 mg/dl(N<20-40)
Ascitic fluid analysis High SAAG ascites,
no SBP
Chest X ray Resolving right side
pneumonia
Parameters Values
Hemoglobin 9.8 g/dl
TLC 8.4 x 1000/ul
Platelets 80 x 1000/ul
Total bilirubin 1.2 mg/dl
AST/ALT 74/60
ALP 128
Total s. protein 5.7 g/dl
Albumin 2.7 g/dl
INR 19.2/12.9 (1.6)
Na/K/Cr 108/3.8/2.1
Ig G 1630 mg/dl (N)
TSH 1.84 miu/ ml (N)
HbA1C 5.4 %
Investigations
UGIE – Normal
USG- CLD , PHT, Gross ascites

4. Diagnosis
• Cryptogenic cirrhosis (CTP C , MELD- 20)
• Tense ascites
• HE II (possible precipitants : LRTI, constipation,
hyponatremia)
• AKI with oliguria
? Cause of Renal failure ? AKI ? Underlying CKD
(Hypertension related)

5. How commonly AKI seen in decompensated
cirrhosis ?

6. Audience poll
1. Less than 10%
2. 10-30%
3. 30-50%
4. More than 50%

7. Incidence of AKI (at presentation)
• 15-20% cirrhosis
• 40-50% cirrhosis with ascites
• 2-6 fold increased mortality

8. Types of AKI

9. What percent of AKI in cirrhosis are due to
HRS?
1. <25%
2. 25-50%
3. 50-75%
4. >75%

10. Causes of AKI in pts with cirrhosis
Martín-LlahíM et al, Gastroenterology. 2011;140(2):488.

11. Diagnostic criteia of renal dysfunction in
cirrhosis
• Acute renal failure : Rise in s.creatinine ≥ 50% from
baseline or rise by ≥ 0.3 mg/dL in < 48h
• Chronic kidney disease :GFR < 60ml/min for >3mo
• Acute on chronic renal dysfunction: Rise in
s.creatinine ≥ 50% from baseline or rise by ≥0.3
mg/dl in < 48h in cirrhosis whose GFR < 60ml/min for
>3mo

12. Actuarial probability to survive in cirrhotic
patients with different renal impairments
Adapted from Alessandria et al

13. How to investigate AKI ?
• Urine r/m
• Urine spot sodium
• 24 hour urine protein
• USG abdomen

14. Forms of kidney injury in chronic liver disease

15. Patient’s Reports
S. Na 109
S. Potassium 3.6
S. Creatinine 2.1
24 Hr Na 5.7
24 Hr K 8.6
24 Hr Cr 2.1
24 Hr Albumin 360 mg
Fe Na < 1%
URINE r/m WNL, No casts, RBC- 0-2/hpf, protein -
trace
Urine C/S sterile
Central venous pressure 14 cm
Chest X RAY Right sided pneumonia (RESOLVING)
USG Abdomen/KUB CLD, PHT, Gross ascites, Kidneys- Normal

16. Final diagnosis
• Cryptogenic cirrhosis , CTP B , MELD- 20
• Tense ascites, HRS 2, AKI cause HRS
• No SBP/HE/Bleed
• Hypertension, Concentric LVH, NYHA II

17. HRS
• Volume-unresponsive, refractory prerenal azotemia in
patients with chronic liver disease, characterized by
systemic and splanchnic vasodilatation but profound
renal vasoconstriction, without parenchymal kidney
injury

18. How to diagnose HRS?

19. Diagnostic criteria of HRS
Minor criteria are supportive but not required for the diagnosis
Salerno F et al. Gut 2007;56:1310

20. International club of ascites acute kidney injury
(ICA-AKI)

21. Issues with s.creatinine
• Affected by age, gender, race, body weight
• Malnutrition,muscle wasting,advanced liver disease
• High bilirubin values.
• Increased secretion of creatinine by tubules
• Expanded volume of distribution
Risk of overestimating renal function

22. Types of HRS

23. HRS type1 vs type2
Course Precipitating
event
H/o diuretic
resistant ascites
Prognosis
HRS type1 Doubling of
s.creatinine <2
weeks
>50% cases ± 90d survival<10%
HRS type2 Gradually
progressive
Usually absent Usually present Median suvival
6 mo

24. Actuarial probability to survive in cirrhotic
patients with different renal impairments
Adapted from Alessandria et al

25. Pathophysiology of HRS

27. Potential Role of Bacterial
Translocation and Cytokine
Overproduction on
Splanchnic Arterial
Vasodilatation.

28. How to monitor and treat our patient ?

29. Treatment goals
• Control infection
• Anti hepatic encephalopathy measures
• Treatment for HRS

30. Ideal Treatment of HRS
Improvement of liver function
• Recovery of alcoholic hepatitis1
• Treatment of decompensated hepatitis B with
effective antiviral therapy2
• Recovery from acute hepatic failure
• Liver transplantation
1. Amini M et al. Alcoholic hepatitis 2010: a clinician's guide to diagnosis and therapy. World J Gastroenterol
2010; 16:4905
2, Garg H et al Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B
presenting as acute on­chronic liver failure. Hepatology 2011; 53:774

31. Treatment strategies
• Improve renal perfusion – volume
• Improve renal perfusion – splanchnic
vasoconstriction
• Reverse portal hypertension
– TIPSS
– Liver Transplant

32. Improve intravascular volume
• Albumin
• 1 g/kg per day [100 g maximum] followed by
25 to 50 grams per day until therapy
continued

33. Vasoconstrictor drugs
Drug Dose
Noradrenaline Continuous infusion (0.5 to 3 mg/hr)
Vasopressin Starting at 0.01 units/min and titrating upward
Terlipressin Intravenous bolus (1 to 2 mg every four to six hours)
Midodrine
+ Octreotide
Orally (starting at 7.5 mg and increasing the dose at eight
hour intervals up to a maximum of 15 mg by mouth three
times daily)

34. Response to Terlipressin
1. Less than 10%
2. 10-25%
3. 25-50%
4. More than 50%

35. Terlipressin in HRS
• Multicenter double blinded RCT
• HRS type 1 diagnosed by
ICA criteria (1996)
• Treatment discontinued if
– Treatment failure
– Liver transplantation
– Adverse effects
• If treatment success achieved,
discontinue or continue drug at
investigator discretion till
max. of 14 days
Placebo
Albumin 25g/d
N =56
180 d0 14 d3 d
Terlipressin 1mg q6h
Albumin 25g/d
N =56
Dose increased to 2mg q6h if
Cr decrease <30%
Albumin 100g on day 1
Sanyal A J et al. Gastroenterology 2008; 134(5): 1360

36. Terlipressin in HRS

37. Terlipressin in HRS – Survival benefit
No difference in survival at 180 d
Sanyal A J et al. Gastroenterology 2008; 134(5): 1360

38. Noradrenaline vs Terlipressin
 Equally efficacious
 Adverse events (mostly abdominal pain, chest pain,
or arrhythmia) were significantly more common with
Terlipressin (28 versus 8%)
 Cost of Terlipressin 3X of NE
 NE in ICU

39. Midodrine, octreotide in HRS
• Retrospective study of 60 patients with type 1 HRS treated
with midodrine/octreotide compared with 21 untreated
controls
• Dose of drugs titrated to achieve MAP increase of 15 mmHg
– Octreotide 100 to 200 µg TID subcutaneous
– Midodrine 5, 7.5, 10, 12.5 & 15 mg TID oral
• Outcome measured - HRS reversal & survival at 30 days
Treatment group
n=60
Control group
n=21
P value
Sustained reduction of Cr 24 (40%) 2 (10%) 0.01
Death at 30 days 26 (43%) 15 (71%) 0.03
Esrailian E et al. Dig Dis Sci (2007) 52:742

40. How to manage our patient?

41. What treatment is most appropriate for her ?
• Terlipressin
• Effective but high risk- old age, concentric LVH
• Noradrenaline
• Equally effective, similar safety profile
• TIPS
• H/O HE II +, invasive, require expertise
• Liver transplant
• Curative but MELD 20, old age, low patient
acceptability

42. Albumin 20 gm/day, Terlipressin 2 mg/day in infusion

43. Discharged in June 2016
• Lasix – 40 mg OD
• Aldactone – 50 mg OD
• Remained well till September 2016
• Readmitted 2 days back with ascites & creatinine of
4.2 mg%

44. Case 2
• 52/M, HCV cirrhosis
• HRS-2, Creatinine – 3.2 mg%
• No response to Terlipressin & albumin

45. Treatment options
• TIPSS
• Liver transplant

46. TIPSS in HRS
1. Is it useful?
2. Does it improve survival?
3. Problems?

47. Transjugular intrahepatic portosystemic shunt
TIPS
• Used in the treatment of refractory ascites
• Provide short-term benefit
• Considered only as a last resort in selected patients

48. TIPSS and HRS
Brensing K A et al. Gut 2000;47:288

49. Liver transplantation
• Retrospective analysis of 726 LT patients
• 71 patients fulfilled HRS criteria (ICA 1996) pre transplant
Survival at 1 y Survival at 3 y
With HRS 80.3% 76.6%
Without HRS 90.7% 85.3%
Improvement in renal
function over first month
Lee J P et al. Liver Transplant 2012;18:1237

50. Liver Transplant in HRS – Our data
p=o.13, Log rank test

51. Prevention of HRS
1. Salerno F et al. Clin Gastroenterol Hepatol. 2013;11(2):123
2. Fernández J et al. Gastroenterology. 2007;133(3):818.

52. Take home messages…..
• HRS is second most common form of AKI in cirrhosis
• HRS has a very poor prognosis and high resource
utilization
• Vasoconstrictors & albumin are effective in less than
50% of HRS patients
• TIPSS can be used as a stop gap treatment in
selected group of patients
• Liver transplantation is the only effective treatment
• Prevention of HRS possible in few cases

53. Thank You