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.
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
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.
11.
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.
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.
