Microbiome Restoration after Rifaximin Treatment in Patients with Severe Alcoholic Hepatitis

( Soon Sun Kim ),( Jung Woo Eun ),( Hyo Jung Cho ),( Do Seon Song ),( Chang Wook Kim ),( Young Seok Kim ),( Sung Won Lee ),( Yoon-Keun Kim ),( Jinho Yang ),( Jinhee Choi ),( Hyung Joon Lim ),( Jae You 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Severe alcoholic hepatitis (SAH) is the most aggressive form of alcohol-related liver disease with high mortality. The gut microbiome is an emerging therapeutic target in alcohol- related liver disease. We aimed to investigate the fecal microbiome composition in patients with SAH and determine microbiome recovery after rifaximin treatment in gut bacteria (BTs) and bacteria derived-extracellular vesicles (EVs). Methods: A total of 24 patients with SAH and 24 healthy controls were prospectively enrolled. Additional fecal samples were collected after 4 weeks in 8 patients with SAH who received the rifaximin treatment. Metagenomic profiling was assessed using 16S ribosomal RNA amplicon sequencing. Results: Fecal microbiomes of patients with SAH had lower a-diversity and higher ß-diversity than those of healthy controls in both BT and EV. Metagenomic profiling demonstrated Ba cilli, Lactobacillales, and Veillonella were significantly increased in BT of patients with SAH and Veillonella, Veillonella parvula group, and Lactobacillales were significantly increased in EV of patients with SAH. Eubacterium_g23, Oscillibacter, and Clostridiales decreased in BT of patients with SAH and Eubacterium_ g23, Oscillibacter, and Christensenellaceae decreased in EV of patients with SAH. After rifaximin treatment, 17 taxa in BT and 23 taxa in EV were significantly restored in patients with SAH. In common, Veillonella and Veillonella parvula group increased in patients with SAH and decreased after rifaximin treatment, and Prevotella and Prevotellaceae decreased in patients with SAH and increased after rifaximin treatment. Conclusions: In an analysis of fecal microbiomes of patients with SAH, we demonstrated SAH related dysbiosis and improvement after rifaximin. These taxa are likely to be a candidate for the therapeutic target for the treatment of SAH.

Efficacy of and Resistance to Rifaximin-based Quadruple Therapy in Helicobacter pylori Eradication

Hyun Soo Kim,Hyuk Yoon,신동우,Dong Jun Oh,Mingu Kwon,Yoon Jin Choi,Cheol Min Shin,Young Soo Park,Nayoung Kim,Dong Ho Lee 대한상부위장관ㆍ헬리코박터학회 2020 Korean Journal of Helicobacter Upper Gastrointesti Vol.20 No.3

Background/Aims: The treatment options for Helicobacter pylori (H. pylori) infection are in a state of flux: traditional triple therapies have started to fail, and new treatments are unable to achieve optimal eradication rates. Rifaximin and rifabutin are new antibiotics. The aim of this study was to evaluate the efficacy and safety of adding rifaximin to the standard triple regimen and of a rifabutin- based triple regimen as a rescue therapy for H. pylori eradication. Materials and Methods: We enrolled 27 H. pylori-positive patients who were treated with a proton pump inhibitor, amoxicillin, clarithromycin, and rifaximin for 14 days. H. pylori eradication was assessed by a 13C-urea breath test performed 4 weeks after therapy completion. The efficacy of the therapy was based on intention-to-treat (ITT) and per-protocol (PP) analysis. We also investigated the resistance rate, compliance, and side effects associated with rifaximin therapy. Minimal inhibitory concentrations and resistance to rifabutin were evaluated using the agar dilution method. Results: Of the 27 patients, 22 completed the treatment protocol with 100% compliance; five patients withdrew. The ITT and PP eradication rates for the rifaximin-containing quadruple therapy were 70.4% (19/27) and 86.3% (19/22), respectively. Adverse events were observed in five of 22 patients (22.7%). The resistance rates to rifaximin and rifabutin were 66.7% (2/3) and 0% (0/3), respectively. Conclusions: The findings of this study show the limitations of rifaximin-based quadruple therapy and suggest the benefits of a rifabutin- based rescue regimen in South Korea.

Determination of Rifaximin Treatment Period According to Lactulose Breath Test Values in Nonconstipated Irritable Bowel Syndrome Subjects

배수현,이광재,김영상,김규남 대한의학회 2015 Journal of Korean medical science Vol.30 No.6

Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects’ symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.

The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury

문원,임상욱,정연순,허육문,박선자,박무인,김성은,김재현,정경원 고신대학교(의대) 고신대학교 의과대학 학술지 2022 고신대학교 의과대학 학술지 Vol.37 No.4

Background: Radiotherapy improves overall survival in patients with abdominopelvic malignancies. However, the toxic effects of radiation restrict the maximum dose that can be given, and there are no well-established preventive or therapeutic strategies. This study was conducted to evaluate whether rebamipide, sucralfate, and rifaximin have a suppressive effect on acute ionizing radiation (IR)-induced inflammation in the intestines of mice.Methods: Thirty-six ICR mice were divided into a vehicle-treated group with sham irradiation; a vehicle-treated group with irradiation; rebamipide, sucralfate, or rifaximin-treated groups with irradiation; and a rebamipide-treated group with sham irradiation. The expression of proinflammatory, anti-inflammatory, proapoptotic, and antiapoptotic factors was investigated.Results: The downregulated expression of nicotinamide phosphoribosyltransferase by IR was attenuated by all drugs (p<0.05). All drugs suppressed the IR-induced activation of NF-κB and phosphorylation of MAPKs (p<0.05) and attenuated the production of TNF-α, IL-1β, and IL-6 in response to IR (p<0.05). The administration of all drugs markedly attenuated IR-induced increases in iNOS, COX-2, and PGE2 (p<0.05), as well as [Ca2+] oscillations that were increased by IR. The expression of proapoptotic genes and antiapoptotic genes was suppressed and induced, respectively, by all drugs. IR treatment increased the release of cytochrome C, which was attenuated by all drugs (p<0.05). All drug treatments resulted in a significant decrease in the expression of caspase-3 and caspase-7 (p<0.05), which were both upregulated following IR treatment.Conclusions: The administration of rebamipide, sucralfate, or rifaximin prior to radiation therapy may prevent or attenuate acute radiation-induced enterocolitis.

대한간학회지 제6차 춘계학술대회 초록집 : 구연 ; 간성뇌병증에 의한 과암모니아혈증의 치료에 있어서 Rifaximin과 Lactulose의 효능 및 안전성 비교

박인서 ( Park In Seo ),김명환 ( Kim Myeong Hwan ),한광협 ( Han Gwang Hyeob ),백용한 ( Baeg Yong Han ),문병수 ( Mun Byeong Su ),윤석화 ( Yun Seog Hwa ),이관식 ( Lee Gwan Sig ),전재윤 ( Jeon Jae Yun ),문영명 ( Mun Yeong Myeong ) 대한간학회 2000 Clinical and Molecular Hepatology(대한간학회지) Vol.6 No.1(S)

Rifaximin Prolongs Overall Survival in Cirrhotic Patients Experiencing Hepatic Encephalopathy

( Seong Hee Kang ),( Jeong-ju Yoo ),( Jeong -hoon Lee ),( Yun Bin Lee ),( Young Youn Cho ),( Hyeki Cho ),( Eun Ju Cho ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung-hwan Yoon ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Recent studies suggested that rifaximin might decrease the risk of other portal hypertension-related complications by controlling small intestinal bacterial overgrowth. However, overall effect of rifaximin on cirrhotic patients has not been well evaluated in a large-scale cohort study. In this study, we aimed to evaluate whether rifaximin could prolong overall survival (OS) and reduce the risk of various cirrhotic complications other than hepatic encephalopathy (HE). Methods: This retrospective study included 1,443 patients: 390 patients receiving rifaximin plus lactulose (the rifaximin group) and 1,053 patients receiving lactulose alone (the control group) for HE at a tertiary hospital in Korea. Primary endpoint was Overall survival (OS) and secondary endpoints included recurrence of HE, the development of spontaneous bacterial peritonitis (SBP), and variceal bleeding. Results: The median follow-up period duration was 18.1 weeks (interquartile range, 7.0-76.0 weeks). During this time period, 788 (86.0%) patients died: 170 (43.5%) in the rifaximin group and 618 (58.7%) in the control group. In patients without hepatocellular carcinoma (HCC) (n=527), rifaximin significantly prolonged OS (adjusted hazard ratio (aHR) =0.728, 95% CI=0.563-0.941, P=0.015) after adjustment for age and Child-Pugh class (Figure 1). Rifaximin also significantly reduced the risk of recurrent HE (aHR=0.407, P<0.001), SBP (aHR=0.367, P<0.001), and variceal bleeding (aHR=0.392, P<0.001); but not HRS (aHR=0.856, P=0.372). In patients with HCC (n=916), rifaximin treatment failed to prolong OS (aHR=0.937, P=0.454) and to reduce the risk of recurrent HE (aHR=0.767, P=0.175). However, rifaximin treatment significantly reduce the risk of SBP (aHR=0.461; P<0.001) and variceal bleeding (aHR=0.584, P=0.002) also in patients with HCC. The risk of C.difficile-associated diarrhea was not significantly different between groups (aHR=0.169; P=0.085). Conclusions: In patients who experienced HE, rifaximin treatment significantly prolongs overall survival and reduces the risk of developing SBP, and variceal bleeding as well as recurrent HE, particularly in populations without HCC.

Rifaximin Treatment in Patients with Severe Alcoholic Hepatitis; A Multicenter, Open-Label, Pilot Randomized Controlled Trial

( Do Seon Song ),( Jin Mo Yang ),( Young Kul Jung ),( Hyung Joon Yim ),( Hee Yeon Kim ),( Chang Wook Kim ),( Soon Sun Kim ),( Jae Youn Cheong ),( Hae Lim Lee ),( Sung Won Lee ),( Jeong-joo Yoo ),( San 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: The short-term mortality of severe alcoholic hepatitis (SAH) is very high, but there are no effective treatments to improve short-term mortality other than corticosteroid. This study investigated the effects of rifaximin treatment in patients with SAH. Methods: In an open-label trial, patients with SAH (Maddrey’s discriminant function≥32) were randomized to rifaximin or control group, each added to corticosteroid or pentoxifylline for 4 weeks. Randomization was stratified by SAH treatment. Liver transplantation free survival was evaluated. (NCT02485106) Results: Total 49 patients were enrolled in this study (29 in control and 20 in rifaximin group). The mean Model for End-stage Liver Disease (MELD) score were 24.4 and 27.8 in control and rifaximin group (P=0.083). Rifaximin treatment was tolerable and only 1 patients stopped due to adverse event. There were no differences in 3-month and 6-month mortality between two groups (P=0.576 and P=0.239, respectively). Corticosteroid group had higher 3-month and 6-month survival than pentoxifylline group (P=0.03 and P=0.016, respectively). When stratified by SAH treatment, there were no significant 3-month and 6-month survival between control and rifaximin treatment (P=0.516 and P=0.937 in corticosteroid group and P=0.948 and P=0.620 in pentoxifylline group, respectively). Cox Proportional hazard model showed that MELD score, white blood cell count, C-reactive protein were significant factors for 6-month survival, and MELD score was only independent factor for 6-month survival (Hazard ratio 1.188, P=0.001). Conclusions: In patients with SAH, adding rifaximin to corticosteroid or pentoxifylline was tolerable but had no survival benefit. MELD score was only significant factor for short-term mortality.

Increased Risk of Bacterial Infection in Cirrhotic Patients with Acute Variceal Bleeding Who Were Treated with Prophylactic Rifaximin

( Wook Hyun Yeo ),( Eileen L. Yoon ),( Hyung Gi Bae ),( Yu Ri Hwang ),( Seong Eun Park ),( Jong Ho Lee ),( Ji Young Park ),( Jung Min Choi ),( Tae Joo Jeon ),( Won Chang Shin ),( Won-choong Choi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Prophylactic antibiotic use for spontaneous bacterial peritonitis or hepatic encephalopathy is common in decompensated cirrhotic patients with low level of ascitic protein and poor liver function. There is controversy whether prolonged antibiotic use is related with increased risk of bacterial infection other than SBP. We investigated whether the prophylactic use of rifaximin is associated with increased infection risk in cirrhotic patients. Methods: We reviewed the charts of 160 cirrhotic patients with acute variceal bleeding between 2009 and 2015 and compared the use rate of prophylactic rifaximin in infection group and non-infection group within 1, 3, and 6 months off-treatment. Results: Among 160 patients, 105 patients developed bacterial infection within a year follow-up. Ironically the rate of rifaximin use was higher in the infection group than non-infection group in 1, 3, 6 months off-treatment (p<0.001). MELD score were similar in both groups of patients. Prophylactic rifaximin was the only independent predictor of infection in 1 and 3 months off-treatment and odd ratios (OR) were 8.00/5.00 for 1month (p<0.001)/3months (p<0.001). Thrombocytopenia (OR 0.992, p=0.009) and rifaximin use (OR 2.963, p=0.002) were predictors of infection in 6 months off-treatment. However, types of infection were not significantly different between two groups. Conclusions: Prophylactic use of rifaximin after intravenous antibiotics in cirrhotic patients with acute variceal bleeding increased the risk of bacterial infections. Further study about gains & losses of prophylactic rifaximin are needed, especially in patients with various types of developed infection.

Effect of Rifaximin on Hepatic Fibrosis in Bile Duct-ligated Rat Model

SeungKakShin ( 신승각 ),OhSangKwon ( 권오상 ),JongJoonLee ( 이종준 ),YeonHoPark ( 박연호 ),CheolSooChoi ( 최철수 ),SungHwanJeong ( 정성환 ),DuckJooChoi ( 최덕주 ),YunSooKim ( 김연수 ),JuHyunKim ( 김주현 ) 대한소화기학회 2017 대한소화기학회지 Vol.70 No.5

Background/Aims: The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model. Methods: The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain. Results: In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (μg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis. Conclusions: Rifaximin did not reduce inflammation and fibrosis in bile duct-ligated rat model. (Korean J Gastroenterol 2017;70:239-246)

Effect of Rifaximin on Hepatic Fibrosis in Bile Duct-ligated Rat Model

신승각,권오상,이종준,박연호,최철수,정성환,최덕주,김연수,김주현 대한소화기학회 2017 대한소화기학회지 Vol.70 No.5

Background/Aims: The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model. Methods: The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain. Results: In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (μg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis. Conclusions: Rifaximin did not reduce inflammation and fibrosis in bile duct-ligated rat model.