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Novel Challenges and Therapeutic Options for Digestive and Liver Diseases
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Novel Challenges and Therapeutic Options for Digestive and Liver Diseases

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 16284

Special Issue Editors

Prof. Dr. Daniel Paramythiotis

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Guest Editor
First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
Interests: pancreas; surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Eleni Karlafti

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Guest Editor
Emergency Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
Interests: emergency medicine; internal medicine; diabetes; hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The digestive system is one of the most important systems in the human body, with a major direct and indirect role in homeostasis. The digestive system includes the liver, which plays a crucial role in metabolism, interacting with nutrient stimuli and hormones.

Digestive and liver diseases comprise viral, toxic, autoimmune, inherited and acquired causes, with complex molecular pathogenesis and various risk factors. These disorders have high frequency worldwide, affecting an increasing number of patients. The above raise concern among medical society.

The aim of this Special Issue is to evaluate and discuss novel Challenges and Therapeutic Options for Digestive and Liver Diseases-diagnostic challenges, differential diagnosis, prognosis, treatment, management, pharmacotherapy, and outcome.

We invite colleagues around the world to report their experience and knowledge with original studies, reviews or communications in Novel Challenges and Therapeutic Options for Digestive and Liver Diseases for this Special Issue of our journal in order to support this dominant area.

Dr. Daniel Paramythiotis
Dr. Eleni Karlafti
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • digestive disease
  • gastrointestinal
  • pancreas
  • gallbladder
  • liver disease
  • therapy
  • management
  • microbiota
  • drugs
  • diagnosis

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Published Papers (9 papers)

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Research

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11 pages, 248 KiB  
Article
Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study
by Theodora-Maria Venou, Evangelia Vetsiou, Christos Varelas, Angelos Daniilidis, Kyriakos Psarras, Evaggelia-Evdoxia Koravou, Maria Koutra, Tasoula Touloumenidou, Vasilis Tsolakidis, Apostolia Papalexandri, Fani Minti, Evdokia Mandala, Konstantinos Dinas, Efthymia Vlachaki and Eleni Gavriilaki
J. Pers. Med. 2024, 14(4), 387; https://doi.org/10.3390/jpm14040387 - 3 Apr 2024
Viewed by 1365
Abstract
Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This [...] Read more.
Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
17 pages, 5235 KiB  
Article
The Hemodynamic Profile and Intraoperative Bleeding Impact on Liver Transplant Patients
by Lavinia Nicoleta Brezeanu, Cosmina Elena Jercălău, Catalina Liliana Andrei, Octavian Ceban and Gabriela Droc
J. Pers. Med. 2024, 14(3), 288; https://doi.org/10.3390/jpm14030288 - 8 Mar 2024
Viewed by 1275
Abstract
Liver transplantation is the treatment of choice for end-stage liver disease and despite accumulated experience over the years, improved surgical techniques, better immunosuppression and adequate intensive care management, it still represents the greatest challenge for anesthesiologists. The aim of the study was the [...] Read more.
Liver transplantation is the treatment of choice for end-stage liver disease and despite accumulated experience over the years, improved surgical techniques, better immunosuppression and adequate intensive care management, it still represents the greatest challenge for anesthesiologists. The aim of the study was the characterization of the hemodynamic profile of patients with liver cirrhosis undergoing liver transplantation with the help of the PiCCO system during the three surgical stages, the impact of bleeding on hemodynamic status and correlation between the amount of bleeding, lactate levels, severity scores and survival rate and complications. Another focus of this study was the amount of transfused blood products and their impact on postoperative complications. Our study included 70 patients who underwent liver transplantation in our center and were hemodynamically monitored with the PiCCO system. Data were processed using the Python 3.9 programming language. Results: The mean MELD severity score was 18 points. During surgery, significant variations in the hemodynamic parameters occurred. All patients had a decrease in cardiac output in the anhepatic phase, with 50% presenting a decrease of more than 40%. In total, 78% of patients showed a decrease in the global ejection fraction, with a median value of 30%.Overall, 75% of patients had a total blood loss of less than 6000 mL and 31 patients developed immediate postoperative complications with a 50% probability with blood loss exceeding 6500 mL. Seven patients (10%) did not survive after 30 days. An amount of 5 mmol/L of serum neohepatic lactate determines a 50% probability of complications. Conclusions: Surgical technique causes an important decrease in cardiac output. Intraoperative bleeding has a major impact on outcome and the first month represents a critical period after liver transplantation. Statistical tests describe the probability of 30/90-day survival and the occurrence of complications according to variables such as intraoperative bleeding and MELD severity score. Intraoperative transfusion correlates with the occurrence of postoperative complications. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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18 pages, 6826 KiB  
Article
The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats
by Georgios Geropoulos, Kyriakos Psarras, Maria Papaioannou, Vasileios Geropoulos, Argyri Niti, Christina Nikolaidou, Georgios Koimtzis, Nikolaos Symeonidis, Efstathios T. Pavlidis, Georgios Koliakos, Theodoros E. Pavlidis and Ioannis Galanis
J. Pers. Med. 2024, 14(1), 121; https://doi.org/10.3390/jpm14010121 - 22 Jan 2024
Viewed by 1697
Abstract
Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal [...] Read more.
Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann–Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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10 pages, 1518 KiB  
Article
Endoscopic Transpapillary Stenting for Malignant Hilar Biliary Stricture: Side-by-Side Placement versus Partial Stent-in-Stent Placement
by Koji Takahashi, Hiroshi Ohyama, Yuichi Takiguchi, Motoyasu Kan, Mayu Ouchi, Hiroki Nagashima, Izumi Ohno and Naoya Kato
J. Pers. Med. 2023, 13(5), 831; https://doi.org/10.3390/jpm13050831 - 14 May 2023
Cited by 1 | Viewed by 1719
Abstract
Background/Aims: Endoscopic uncovered metal stent (UMS) placement has been widely performed for unresectable hilar malignant biliary stricture (UHMBS). Two stenting methods are used for the two bile duct branches: side-by-side placement (SBS) and partial stent-in-stent placement (PSIS). However, it remains controversial whether SBS [...] Read more.
Background/Aims: Endoscopic uncovered metal stent (UMS) placement has been widely performed for unresectable hilar malignant biliary stricture (UHMBS). Two stenting methods are used for the two bile duct branches: side-by-side placement (SBS) and partial stent-in-stent placement (PSIS). However, it remains controversial whether SBS or PSIS is superior. This study aimed to compare SBS and PSIS in UHMBS cases with UMS placement in two branches of the IHD. Methods: This retrospective study included 89 cases of UHMBS treated with UMS placement through the SBS or PSIS technique using endoscopic retrograde cholangiopancreatography at our institution. Patients were divided into two groups, SBS (n = 64) and PSIS (n = 25), and compared. Results: Clinical success was achieved in 79.7% and 80.0% in the SBS and PSIS groups, respectively (p = 0.97). The adverse event rate was 20.3% and 12.0% in the SBS and PSIS groups, respectively (p = 0.36). The recurrent biliary obstruction (RBO) rate was 32.8% and 28.0% in the SBS and PSIS groups, respectively (p = 0.66). The median cumulative time to RBO was 224 and 178 days in the SBS and PSIS groups, respectively (p = 0.52). The median procedure time was 43 and 62 min in the SBS and PSIS groups, respectively, which was significantly longer in the PSIS group (p = 0.014). Conclusions: No significant differences were noted in the clinical success rate, adverse event rate, time to RBO, or overall survival between the SBS and PSIS groups, other than the significantly longer procedure time in the PSIS group. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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15 pages, 2321 KiB  
Article
Clinical-Pathological Characteristics of Adenosquamous Esophageal Carcinoma: A Propensity-Score-Matching Study
by Xinxin Xu, Feng Jiang, Yihan Guo, Hu Chen, Jiayi Qian, Leilei Wu, Dong Xie and Guangxia Chen
J. Pers. Med. 2023, 13(3), 468; https://doi.org/10.3390/jpm13030468 - 3 Mar 2023
Cited by 1 | Viewed by 1887
Abstract
There are few studies on esophageal adenosquamous carcinoma (ADSC). Our study intended to investigate the clinical and survival features of ADSC. We included esophageal cancer (EC) data from the Surveillance, Epidemiology, and End Results program database to explore clinical and survival traits. Propensity [...] Read more.
There are few studies on esophageal adenosquamous carcinoma (ADSC). Our study intended to investigate the clinical and survival features of ADSC. We included esophageal cancer (EC) data from the Surveillance, Epidemiology, and End Results program database to explore clinical and survival traits. Propensity score matching (PSM), the multivariate Cox regression model, and survival curves were used in this study. A total of 137 patients with ADSC were included in our analysis. The proportion of ADSC within the EC cohort declined from 2004 to 2018. Besides, results indicated no significant difference in survival between ADSC and SCC groups (PSM-adjusted HR = 1.249, P = 0.127). However, the survival rate of the ADSC group was significantly worse than that of the ADC group (PSM-adjusted HR = 1.497, P = 0.007). For the ADSC group, combined treatment with surgery had a higher survival rate than other treatment methods (all P < 0.001). Surgical resection, radiotherapy, and chemotherapy were independent protective prognostic factors (all P < 0.05). The proportion of ADSC has been declining from 2004 to 2018. The prognosis of ADSC is not significantly different from that of SCC but is worse than that of ADC. Surgery, radiotherapy, and chemotherapy could improve the prognosis of patients. Comprehensive treatment with surgery as the main treatment is more beneficial for some patients. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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Review

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11 pages, 1427 KiB  
Review
Perineal Rectosigmoidectomy (Altemeier’s Procedure) in the Treatment of Strangulated Rectal Prolapse: A Case Series and Literature Review
by Ioannis Mantzoros, Aliki Brenta, Aikaterini-Antonia Bourtzinakou, Ourania Kontaxi, Georgios Gemousakakis, Nikolaos Antoniou, Stefanos Bitsianis, Efstathios Kotidis, Dimitrios Kyziridis, Orestis Ioannidis, Ourania Kerasidou, Anna Gkiouliava, Manousos Pramateftakis and Stamatios Aggelopoulos
J. Pers. Med. 2024, 14(11), 1095; https://doi.org/10.3390/jpm14111095 - 6 Nov 2024
Viewed by 498
Abstract
Background: Rectal prolapse (RP) predominantly affects women over the age of 50 and presents as mucosal, internal, or full thickness prolapse. Strangulated rectal prolapse requires immediate medical intervention, and surgical treatment options include both abdominal and perineal approaches. We aim to present a [...] Read more.
Background: Rectal prolapse (RP) predominantly affects women over the age of 50 and presents as mucosal, internal, or full thickness prolapse. Strangulated rectal prolapse requires immediate medical intervention, and surgical treatment options include both abdominal and perineal approaches. We aim to present a case series of perineal rectosigmoidectomy performed urgently due to strangulation and argue that Altemeier’s procedure is the preferred method for treating strangulated rectal prolapse. Methods: Perineal rectosigmoidectomy, particularly Altemeier’s procedure, is effective for incarcerated cases. Altemeier’s procedure with diverting ileostomy was used in all three patients. Results: All patients were successfully treated, with no recurrence of prolapse and stool incontinence. Conclusions: Altemeier’s procedure is ideal for the treatment of strangulated rectal prolapse. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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16 pages, 641 KiB  
Review
Knockout Genes in Bowel Anastomoses: A Systematic Review of Literature Outcomes
by Georgios Geropoulos, Kyriakos Psarras, Georgios Koimtzis, Massimiliano Fornasiero, Elissavet Anestiadou, Vasileios Geropoulos, Anna Michopoulou, Maria Papaioannou, Kokkona Kouzi-Koliakou and Ioannis Galanis
J. Pers. Med. 2024, 14(6), 553; https://doi.org/10.3390/jpm14060553 - 23 May 2024
Viewed by 1049
Abstract
Background: The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared [...] Read more.
Background: The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared to other tissues. The aim of this systematic review was to summarize all studies with knockout (KO) experimental models in bowel anastomoses, underline any recent knowledge, and clarify further the cellular and molecular mechanisms of the intestinal healing process. A systematic review protocol was performed. Materials and methods: Medline, EMBASE, and Scopus were comprehensively searched. Results: a total of eight studies were included. The silenced genes included interleukin-10, the four-and-one-half LIM domain-containing protein 2 (FHL2), cyclooxygenase-2 (COX-2), annexin A1 (ANXA-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and heparin-binding epidermal growth factor (HB-EGF) gene. Surgically, an end-to-end bowel anastomosis was performed in the majority of the studies. Increased inflammatory cell infiltration in the anastomotic site was found in IL-10-, annexin-A1-, and TAFI-deficient mice compared to controls. COX-1 deficiency showed decreased angiogenesis at the anastomotic site. Administration of prostaglandin E2 in COX-2-deficient mice partially improved anastomotic leak rates, while treatment of ANXA1 KO mice with Ac2-26 nanoparticles reduced colitis activity and increased weight recovery following surgery. Conclusions: our findings provide new insights into improving intestinal wound healing by amplifying the aforementioned genes using appropriate gene therapies. Further research is required to clarify further the cellular and micromolecular mechanisms of intestinal healing. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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Other

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13 pages, 669 KiB  
Systematic Review
HER2 Overexpression in Periampullary Tumors According to Anatomical and Histological Classification—A Systematic Review
by Ioan Cătălin Bodea, Andra Ciocan, Florin Vasile Zaharie, Raluca Bodea, Florin Graur, Ștefan Ursu, Răzvan Alexandru Ciocan and Nadim Al Hajjar
J. Pers. Med. 2024, 14(5), 463; https://doi.org/10.3390/jpm14050463 - 27 Apr 2024
Viewed by 2306
Abstract
Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The [...] Read more.
Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25–30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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21 pages, 5218 KiB  
Systematic Review
Which Is the Best Way to Treat Massive Hemoptysis? A Systematic Review and Meta-Analysis of Observational Studies
by Eleni Karlafti, Dimitrios Tsavdaris, Evangelia Kotzakioulafi, Leonidas Kougias, Georgios Tagarakis, Georgia Kaiafa, Smaro Netta, Christos Savopoulos, Antonios Michalopoulos and Daniel Paramythiotis
J. Pers. Med. 2023, 13(12), 1649; https://doi.org/10.3390/jpm13121649 - 26 Nov 2023
Cited by 3 | Viewed by 2075
Abstract
Introduction: Hemoptysis is one of the most common symptoms of respiratory system diseases. Common causes include bronchiectasis, tumors, tuberculosis, aspergilloma, and cystic fibrosis. The severity of hemoptysis varies from mild to moderate to massive hemoptysis and can easily lead to hemodynamic instability and [...] Read more.
Introduction: Hemoptysis is one of the most common symptoms of respiratory system diseases. Common causes include bronchiectasis, tumors, tuberculosis, aspergilloma, and cystic fibrosis. The severity of hemoptysis varies from mild to moderate to massive hemoptysis and can easily lead to hemodynamic instability and death from suffocation or shock. Nevertheless, the most threatening hemoptysis that is presented to the emergency department and requires hospitalization is the massive one. In these cases, today, the most common way to manage hemoptysis is bronchial artery embolization (BAE). Methods: A systematic literature search was conducted in PubMed and Scopus from January 2017 (with the aim of selecting the newest possible reports in the literature) until May 2023 for studies reporting massive hemoptysis. All studies that included technical and clinical success rates of hemoptysis management, as well as rebleeding and mortality rates, were included. A proportional meta-analysis was conducted using a random-effects model. Results: Of the 30 studies included in this systematic review, 26 used bronchial artery embolization as a means of treating hemoptysis, with very high levels of both technical and clinical success (greater than 73.7% and 84.2%, respectively). However, in cases where it was not possible to use bronchial artery embolization, alternative methods were used, such as dual-vessel intervention (80% technical success rate and 66.7% clinical success rate), customized endobronchial silicone blockers (92.3% technical success rate and 92.3% clinical success rate), antifibrinolytic agents (50% clinical success rate), and percutaneous transthoracic embolization (93.1% technical success rate and 88.9% clinical success rate), which all had high success rates apart from antifibrinolytic agents. Of the 2467 patients included in these studies, 341 experienced rebleeding during the follow-up period, while 354 other complications occurred, including chest discomfort, fever, dysphagia, and paresis. A total of 89 patients died after an episode of massive hemoptysis or during the follow-up period. The results of the meta-analysis showed a pooled technical success of bronchial artery embolization equal to 97.22% and a pooled clinical success equal to 92.46%. The pooled recurrence was calculated to be 21.46%, while the mortality was 3.5%. These results confirm the ability of bronchial artery embolization in the treatment of massive hemoptysis but also emphasize the high rate of recurrence following the intervention, as well as the risk of death. Conclusion: In conclusion, massive hemoptysis can be treated with great clinical and technical success using bronchial artery embolization, reducing mortality. Mortality has now been reduced to a small percentage of cases. Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Digestive and Liver Diseases)
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