Table 2.

Comparative analysis on studies on interstitial cystitis.

Study	Number of patients	Study design	Median age	Hyaluronic acid dose	Regimen	Follow up (months)	Outcome parameters	Results
Leppilahti et al. [2002]	11	PCS	64 (51–76)	40 mg	Four weekly instillations after bladder hydrodistension	NR	VAS pain score Urinary frequency	75% decrease
								26% decrease
							ICAM-1 expression1	Increased in nonresponders
Daha et al. [2005]	48 32 with Cmax < 350 cc (group1)	PCS	54 (22–82)	40 mg	Ten weekly instillations	16	VAS pain score	Improvement
								84% group 1
	16 with Cmax > 350 cc (group2)2							87% group 2
								Especially in patients with a Cmax reduction ≥ 30% after 0.2 KCl test
Gupta et al. [2005]	38	PCS		40 mg	Six weekly doses and choice to continue monthly in responders		ICSI	55% of patients improved after six doses
							ICPI	(74% and 23% of patients with positive and negative respectively, PST test)
Kallestrup et al. [2005]	20	PCS	34–80	40 mg	Four weekly plus two monthly instillations. Choice to continue instillations for responders	36	VAS pain score	Reduction in pain score about 2.2-fold after 3 months and 5.2 after 3 years with a decrease of analgesic use Reduction in urinary frequency not observed
							Urinary frequency
							Use of analgesic
Theoharides et al. [2008]	252	PCS	(18–69)	10 mg	Oral ingestion four capsules/day	12	VAS score	About 50% reduction
Cervigni et al. [2008]	23	PCS	46 (20–65)	40 mg (1.6%)	Weekly for 20 weeks then 2 weeks for 4 weeks and then monthly for 3 months	8	Voiding diary	Significant Improvement in all parameters
				plus chondroitin sulphate (2%)			VAS pain score
							ICSI
							ICPI
							PUF
Riedl et al. [2008]	121	PCS	49 (17–83)	40 mg	Weekly instillation until improvement not observed (median instillations for patient 12)		VAS score	Mean VAS score reduction
							Quality of life score	(3.5 posttreatment versus 8.5 pretreatment)
Ahmad et al. [2008]	23	CCS	53 (25–81)	40 mg	Two monthly bladder hydrodistension plus hyaluronic acid instillation. Then further treatment depending on initial response (average six treatments in responders)	16	Bladder capacity	Improvement in mean bladder capacity (492 ml versus 776 ml)
Shao et al. [2010]	47 with functional bladder capacity < 200 ml	RCT	55 (27–76)	40 mg	Four weekly plus two monthly after hydrodistension	9	Mean void per days	Hyaluronic acid and heparin might maintain or prolong the effect of hydrodistention in patients with interstitial cystitis
							VAS pain score
							Bladder capacity after hydrodistension

¹ICAM-1 (intracellular adhesion molecule-1) is one of the identified cell receptors for hyaluronic acid.

²Cmax > 350 ml with 0.9% Na solution is not considered a diagnostic criterion for diagnosis of interstitial cystitis. CCS, case control study; CSI, interstitial cystitis symptom index; ICPI, interstitial cystitis problem index; ICSI, interstitial cystitis symptom index; PCS, prospective cohort study; PST, potassium sensitivity test; PUF, pelvic pain and urgency/frequency symptom scale; RCT, randomized controlled trial; VAS, visual analogue scale.