Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials

Levy, Cynthia

doi:10.1002/hep.31702

Cited by 3 publications

(4 citation statements)

References 10 publications

(13 reference statements)

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“…Besides, a significant proportion of patients showed improvements on histologic features and cholangiopathy[ 22 ]. Conversely, in a recent retrospective study on a large cohort of children with PSC the authors did not show improvement in outcomes of children treated with OVT or UDCA compared to those with “no treatment”[ 23 ], although several limitations were recorded in the study design[ 24 ]. The median OVT dose in Deneau et al [ 23 ]’s study was 21 mg/kg/d, which was substantially lower than the 50 mg/kg/d typically used in our and others’ studies[ 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

Use of oral vancomycin in children with autoimmune liver disease: A single centre experience

Giorgio¹,

Tulone²,

Nicastro³

et al. 2021

WJH

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BACKGROUND Previous reports showed some beneficial effect of oral vancomycin treatment (OVT) in children with primary sclerosing cholangitis; conversely, the experience in patients with other autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), is scant. AIM To assess the response to immunosuppressive treatment (IS) and to OVT in children diagnosed with AILD. METHODS Retrospective study of children diagnosed with AIH (normal biliary tree at cholangiography) and ASC (abnormal biliary tree at cholangiography) in the last 10 years. All underwent standard immunosuppressive therapy (IS), but non-responders received also OVT. Biochemical remission [normal aspartate aminotransferase (AST)] and immunological remission (normal IgG and negative autoantibodies) rates and Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index were assessed and compared during the follow up. RESULTS 75 children were included [69% female, median age 10.5 years (5.6-13.4 years), AIH = 54, ASC= 21]. Sixty-three patients (84%, AIH = 52, ASC = 11) were treated with standard IS and 61 achieved biochemical remission, whereas 12 not responding to IS [16%, F = 75%, median age 13.5 years, (12.2-15.7), 10 with ASC] required OVT and 8 achieved biochemical remission. Overall OVT increased the biochemical remission rate of the whole group of AILD patients from 81% (61/75) to 92% (69/75). Median values of AST, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) decreased significantly after OVT start ( P < 0.05). Complete normalization of livers enzymes (AST, ALT and GGT) was observed in 6/12 patients (50%). Decrease in SCOPE index score was reported in 5/12 patients (42%). At last follow up (median of 4.4 years, range 0.6-13.8 years) all 75 patients are alive, 6 (8%, 1 with ASC) successfully discontinued medications, 1 (with ASC) required liver transplantation. CONCLUSION Children with AIH and ASC respond well to IS treatment. OVT may represent a valuable treatment option to achieve biochemical remission in patients not responding to standard IS. These promising preliminary results suggest that a prospective study is indicated to define the efficacy of OVT in AILD.

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Section: Discussionmentioning

confidence: 99%

Use of oral vancomycin in children with autoimmune liver disease: A single centre experience

Giorgio¹,

Tulone²,

Nicastro³

et al. 2021

WJH

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“…In recent years, the incidence of PSC has increased, but intestinal flora research has also expanded, resulting in antimicrobial therapy based on intestinal flora modulation and FMT as potential PSC treatment options[ 87 ]. Studies have found that antibiotics, probiotics, and FMT improve intestinal flora disorders, thereby treating PSC (Table 2 )[ 88 , 89 ].…”

Section: Targeted Intestinal Flora Modulation For Psc Treatmentmentioning

confidence: 99%

Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value

Li¹,

Gou²,

Zhang³

et al. 2022

World J Gastroenterol

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Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.

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“…Complications take up to 10 years to develop, but the authors’ median follow‐up was just 4.2 years. The subsequent editorial ( 2 ) noted the limitations of a retrospective, propensity‐matched study and argued cogently for the need to replace empiric practice with data from well‐planned randomized controlled trials (RCTs).…”

mentioning

confidence: 99%

“…Complications take up to 10 years to develop, but the authors' median followup was just 4.2 years. The subsequent editorial (2) noted the limitations of a retrospective, propensitymatched study and argued cogently for the need to replace empiric practice with data from well-planned randomized controlled trials (RCTs).The authors' findings are discrepant with the experience of others. A prospective study in 45 pediatric patients over a median of 2.7 years showed improvement not only in biochemical findings, histologic findings, and symptoms of ulcerative colitis (UC) but also in magnetic resonance cholangiopancreatography in 26 of 34 patients.…”

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confidence: 99%

Letter to the Editor: Oral Vancomycin Versus No Therapy for Pediatric Primary Sclerosing Cholangitis

et al. 2021

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In their recent study addressing efficacy of oral vancomycin (OVT) and ursodeoxycholic acid (UDCA) compared with no therapy in pediatric primary sclerosing cholangitis (PSC), Deneau et al. state that "OVT and UDCA are not effective treatments for PSC in children." (1) Their study shows that the null hypothesis of no effect has not been rejected; a real effect might have been present but missed. Complications take up to 10 years to develop, but the authors' median followup was just 4.2 years. The subsequent editorial (2) noted the limitations of a retrospective, propensitymatched study and argued cogently for the need to replace empiric practice with data from well-planned randomized controlled trials (RCTs).The authors' findings are discrepant with the experience of others. A prospective study in 45 pediatric patients over a median of 2.7 years showed improvement not only in biochemical findings, histologic findings, and symptoms of ulcerative colitis (UC) but also in magnetic resonance cholangiopancreatography in 26 of 34 patients. (3) A systematic review supports clinical efficacy in patients with PSC who are 16 years and older. (4) Although Deneau et al. attempted to construct a control group through retrospective matching, that method cannot correct for hidden covariates, which include the OVT brand, (5) adjustments of the dose to the level of disease activity, adherence, or genetic and microbiome differences among patients.The effects of OVT on colitis are often dramatic. The relief from diarrhea and fatigue have transformed the lives of many of our patients, with substantial improvement of UC symptoms within days or weeks being shown. Deneau et al. apparently recommend against vancomycin therapy without regard to these effects.We do not agree that the study by Deneau et al. justifies the blanket statement that OVT is not effective for PSC/UC in children. The editorial authors recommend an individualized, informed-consent process, and we agree completely. OVT should remain an empiric option in the individualized management of children with this heterogeneous liver and bowel disease that results in significant morbidity and mortality and has a paucity of treatment options. Good RCTs are urgently needed.

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Oral Vancomycin or Ursodeoxycholic Acid for Pediatric Primary Sclerosing Cholangitis? The Uncontroversial Need for Randomized Controlled Trials

Cited by 3 publications

References 10 publications

Use of oral vancomycin in children with autoimmune liver disease: A single centre experience

Use of oral vancomycin in children with autoimmune liver disease: A single centre experience

Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value

Letter to the Editor: Oral Vancomycin Versus No Therapy for Pediatric Primary Sclerosing Cholangitis

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