This systematic review and network meta-analysis compared the efficacy of different drug treatments for type 1 hepatorenal syndrome. The analysis included 13 randomized controlled trials comparing terlipressin to placebo or other drugs like norepinephrine. The results showed moderate evidence that terlipressin may reduce short-term mortality compared to placebo. Terlipressin and norepinephrine were both found to be more effective at reversing hepatorenal syndrome compared to midodrine plus octreotide. However, the evidence was limited by the small sizes and short follow-ups of the included studies. Larger, higher quality trials are still needed to evaluate the real-world effectiveness and safety of terlipressin for treating type 1 hepatorenal

1. Shivaom Chaurasia
Resident
Internal Medicine

2. Facciorusso A. et al
Lancet Gastroenterol Hepatol 2016 December 1, 2016

3. INTRODUCTION
Type 1 hepatorenal syndrome:
 is a functional, potentially reversible, form of acute kidney
injury
 caused by haemodynamic imbalances in end-stage liver disease
 is a life-threatening complication of decompensated liver
cirrhosis
 Mortality > 80% at 3 months and median survival < 4 weeks.
 Few data exist for the comparative efficacy of the drugs,
particularly in improving survival.
 Pressing need for effective pharmacological treatments to
improve survival and reverse HRS.

4. AIM
 To compare the efficacy of different management strategies for
type 1 hepatorenal syndrome.

5. STUDY DESIGN
Systematic review and network meta-analysis

6. INCLUSION CRITERIA
 RCTs
 Age > 18 yrs
 Decompensated cirrhosis and type 1 hepatorenal syndrome
 Albumin recipient as treatment

7. EXCLUSION CRITERIA
Studies
 Observational studies
 Trials exclusively of patients with type 2 HRS
 Trials comparing different routes of therapy of same drug
 Cross-over trials without washout period, and
 Trials of experimental, unapproved therapies
Patients
 With active infection

8. OUTCOMES
Primary outcome:
• Reduction in short-term mortality
Secondary outcomes:
 Reversal of HRS (defined as decrease of sr. creatinine level ≤ 1.5
mg/dL)
 Recurrence of HRS after initial reversal, and
 Incidence of treatment-related adverse events

9. METHODS

10.  For this systematic review and network meta-analysis,
they searched MEDLINE In-Process & Other Non-
Indexed Citations, Embase, Cochrane Central Register
of Controlled Trials, Scopus, and Web of Science for
papers published up to June 9, 2016.
 They did pairwise and network meta-analyses to
produce odds ratios (ORs) and 95% CIs. We used the
GRADE criteria to appraise quality of evidence.

12. All trials were two-arm
controlled trials–
i) six compared terlipressin
with placebo,
ii) four compared terlipressin
with nor adrenaline,
iii) one compared terlipressin
with midodrine plus
octreotide,
iv) one compared terlipressin
with dopamine plus
furosemide,
v) and one compared
noradrenaline with
midodrine plus octreotide.

16. Pairwise meta-analysis of drugs efficacy to reduce mortality (A)

17. Pairwise meta-analysis of drugs efficacy to reverse hepatorenal syndrome (B)

18. RESULTS

19.  Moderate-quality evidence might support the use of
Terlipressin over Placebo for reduction of short-term
mortality (OR 0·65, 95% CI 0·41–1·05).
 Low-quality evidence supported the use of
Noradrenaline, Midodrine + Octreotide, and Dopamine
plus furosemide over Placebo to reduce mortality.
 No Odds ratio for any of the comparisons versus placebo
were significant.

20.  Moderate-quality evidence supported the use of
Terlipressin over Midodrine + Octreotide (OR 26·25, 95%
CI 3·07–224·21) to reverse HRS.
 Low-quality evidence supported the use of
Noradrenaline over Placebo (4·17, 1·37–12·50) and over
Midodrine + Octreotide (10·00, 1·49–50·00) for this
outcome.
 A median of 16% (range 5–20) of Terlipressin-treated
patients, and 33% (range 6–40) Noradrenaline-treated
patients with reversal of HRS had recurrence on
discontinuation of therapy.

21.  A median of 8% (range 4–22) Terlipressin-treated patients
required discontinuation of therapy due to serious
adverse events.

22. STRENGTH
 First network meta-analysis of all drug interventions for type 1
HRS to reduce mortality.

23. LIMITATIONS
 Paucity of direct head-to-head comparative trials
 Trials were generally small with low event rates
 Network meta analyses limitations
 Most studies had a small sample size and a short follow-up
 Treatment-related adverse events were poorly reported

24. CONCLUSION
 Terlipressin with albumin might reduce short-term mortality
compared with Placebo in patients with type 1 HRS.
 Terlipressin with albumin and Noradrenaline with albumin
are both superior to Midodrine plus octreotide with albumin
for reversal of HRS.
 Future pragmatic clinical trials of Terlipressin with albumin
are warranted to evaluate real-world eff ectiveness and safety in
patients with type 1 HRS.

25. THANK YOU