Pub Date : 2018-10-24eCollection Date: 2018-01-01DOI: 10.2147/HMER.S160616
Zohair Ahmed, Jinma Ren, Adam Gonzalez, Umair Ahmed, Saqib Walayat, Daniel K Martin, Harsha Moole, Sherri Yong, Sean Koppe, Sonu Dhillon
Aim: The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies.
Methods: This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset.
Results: Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (P<0.05). Regression formula for prediction of cirrhosis was generated and a novel index was subsequently created. The diagnostic performance of the novel index for predicting cirrhosis was assessed using the receiver operating characteristic curve. The new index had significantly higher AUROC (0.83, 95% CI: 0.79-0.87) than Fibro-Q (0.80, 95% CI: 0.76-0.85), FIB4 (0.79, 95% CI: 0.74-0.83), APRI (0.74, 95% CI: 0.69-0.78), and AAR (0.72, 95% CI: 0.67-0.78).
Conclusion: The novel index had the highest AUROC curve when compared with current indices and can be applied to all etiologies of chronic liver disease.
{"title":"Universal Index for Cirrhosis (UIC index): The development and validation of a novel index to predict advanced liver disease.","authors":"Zohair Ahmed, Jinma Ren, Adam Gonzalez, Umair Ahmed, Saqib Walayat, Daniel K Martin, Harsha Moole, Sherri Yong, Sean Koppe, Sonu Dhillon","doi":"10.2147/HMER.S160616","DOIUrl":"https://doi.org/10.2147/HMER.S160616","url":null,"abstract":"<p><strong>Aim: </strong>The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies.</p><p><strong>Methods: </strong>This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset.</p><p><strong>Results: </strong>Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (<i>P</i><0.05). Regression formula for prediction of cirrhosis was generated and a novel index was subsequently created. The diagnostic performance of the novel index for predicting cirrhosis was assessed using the receiver operating characteristic curve. The new index had significantly higher AUROC (0.83, 95% CI: 0.79-0.87) than Fibro-Q (0.80, 95% CI: 0.76-0.85), FIB4 (0.79, 95% CI: 0.74-0.83), APRI (0.74, 95% CI: 0.69-0.78), and AAR (0.72, 95% CI: 0.67-0.78).</p><p><strong>Conclusion: </strong>The novel index had the highest AUROC curve when compared with current indices and can be applied to all etiologies of chronic liver disease.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S160616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36781760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-28eCollection Date: 2018-01-01DOI: 10.2147/HMER.S154842
Motaz Fathy Saad, Saleh Alenezi, Haifaa Asker
Chronic hepatitis C virus (HCV) infection is a leading cause of death, especially in immunocompromised patients. The lack of clear prevalence data in the Middle East makes it difficult to estimate the true morbidity and mortality burden of HCV. In Kuwait, estimating the burden of disease is complicated by the constant flow of expatriates, many of whom are from HCV-endemic areas. The development of new and revolutionary treatments for HCV necessitates the standardization of clinical practice across all healthcare institutions. While international guidelines from the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) do address this evolving treatment landscape, the cost-driven treatment prioritization of patients by these guidelines and unique HCV genotype presentation in the Kuwaiti population prompted the development of a more tailored approach. The predominant HCV genotypes prevalent in Kuwait are genotypes 4 and 1. The Kuwait Hepatology Club (KHC), comprising hepatologists across all major institutions in Kuwait, conducted several consensus meetings to develop the scoring criteria, evaluate all current evidence, and propose screening, diagnosis, and treatment suggestions for the management of HCV in this population. While these treatment suggestions were largely consistent with the 2016 AASLD and 2015 EASL guidelines, they also addressed gaps in the unmet needs of the Kuwaiti population with HCV.
{"title":"Expert opinion on the management of hepatitis C infection in Kuwait.","authors":"Motaz Fathy Saad, Saleh Alenezi, Haifaa Asker","doi":"10.2147/HMER.S154842","DOIUrl":"https://doi.org/10.2147/HMER.S154842","url":null,"abstract":"Chronic hepatitis C virus (HCV) infection is a leading cause of death, especially in immunocompromised patients. The lack of clear prevalence data in the Middle East makes it difficult to estimate the true morbidity and mortality burden of HCV. In Kuwait, estimating the burden of disease is complicated by the constant flow of expatriates, many of whom are from HCV-endemic areas. The development of new and revolutionary treatments for HCV necessitates the standardization of clinical practice across all healthcare institutions. While international guidelines from the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) do address this evolving treatment landscape, the cost-driven treatment prioritization of patients by these guidelines and unique HCV genotype presentation in the Kuwaiti population prompted the development of a more tailored approach. The predominant HCV genotypes prevalent in Kuwait are genotypes 4 and 1. The Kuwait Hepatology Club (KHC), comprising hepatologists across all major institutions in Kuwait, conducted several consensus meetings to develop the scoring criteria, evaluate all current evidence, and propose screening, diagnosis, and treatment suggestions for the management of HCV in this population. While these treatment suggestions were largely consistent with the 2016 AASLD and 2015 EASL guidelines, they also addressed gaps in the unmet needs of the Kuwaiti population with HCV.","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S154842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36628197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-12eCollection Date: 2018-01-01DOI: 10.2147/HMER.S140711
Nadia Savy, David Brossier, Catherine Brunel-Guitton, Laurence Ducharme-Crevier, Geneviève Du Pont-Thibodeau, Philippe Jouvet
Acute hyperammonemia may induce a neurologic impairment leading to an acute life-threatening condition. Coma duration, ammonia peak level, and hyperammonemia duration are the main risk factors of hyperammonemia-related neurologic deficits and death. In children, hyperammonemia is mainly caused by severe liver failure and inborn errors of metabolism. In an acute setting, obtaining reliable plasma ammonia levels can be challenging because of the preanalytical difficulties that need to be addressed carefully. The management of hyperammonemia includes 1) identification of precipitating factors and cerebral edema presence, 2) a decrease in ammonia production by reducing protein intake and reversing catabolism, and 3) ammonia removal with pharmacologic treatment and, in the most severe cases, with extracorporeal therapies. In case of severe coma, transcranial Doppler ultrasound could be the method of choice to noninvasively monitor cerebral blood flow and titrate therapies.
{"title":"Acute pediatric hyperammonemia: current diagnosis and management strategies.","authors":"Nadia Savy, David Brossier, Catherine Brunel-Guitton, Laurence Ducharme-Crevier, Geneviève Du Pont-Thibodeau, Philippe Jouvet","doi":"10.2147/HMER.S140711","DOIUrl":"https://doi.org/10.2147/HMER.S140711","url":null,"abstract":"<p><p>Acute hyperammonemia may induce a neurologic impairment leading to an acute life-threatening condition. Coma duration, ammonia peak level, and hyperammonemia duration are the main risk factors of hyperammonemia-related neurologic deficits and death. In children, hyperammonemia is mainly caused by severe liver failure and inborn errors of metabolism. In an acute setting, obtaining reliable plasma ammonia levels can be challenging because of the preanalytical difficulties that need to be addressed carefully. The management of hyperammonemia includes 1) identification of precipitating factors and cerebral edema presence, 2) a decrease in ammonia production by reducing protein intake and reversing catabolism, and 3) ammonia removal with pharmacologic treatment and, in the most severe cases, with extracorporeal therapies. In case of severe coma, transcranial Doppler ultrasound could be the method of choice to noninvasively monitor cerebral blood flow and titrate therapies.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S140711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36522482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-09-10eCollection Date: 2018-01-01DOI: 10.2147/HMER.S137209
Mithat Gunaydin, Asudan Tugce Bozkurter Cil
Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive cholestatic liver diseases which are subgrouped according to the genetic defect, clinical presentation, laboratory findings and liver histology. Progressive liver fibrosis, cirrhosis, and end stage liver disease (ESLD) may eventually develop. PFIC was first described in Amish descendants of Jacob Byler, therefore it was originally called Byler disease. But it can be seen anywhere on the globe. This review summarizes the main features of the subtypes of the disease and discusses the current available diagnosis, conservative and surgical therapeutic options.
{"title":"Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment.","authors":"Mithat Gunaydin, Asudan Tugce Bozkurter Cil","doi":"10.2147/HMER.S137209","DOIUrl":"https://doi.org/10.2147/HMER.S137209","url":null,"abstract":"<p><p>Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive cholestatic liver diseases which are subgrouped according to the genetic defect, clinical presentation, laboratory findings and liver histology. Progressive liver fibrosis, cirrhosis, and end stage liver disease (ESLD) may eventually develop. PFIC was first described in Amish descendants of Jacob Byler, therefore it was originally called Byler disease. But it can be seen anywhere on the globe. This review summarizes the main features of the subtypes of the disease and discusses the current available diagnosis, conservative and surgical therapeutic options.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S137209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36511860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed Khaled Tawfik, Amal Helmy, Mohamed Yousef, Sabry Abou-Saif, Abdelrahman Kobtan, Eman Asaad, Sherief Abd-Elsalam
Objectives: The aim of the work was to assess the level of copeptin as a surrogate marker predicting the severity of liver diseases and its major complications.
Patients and methods: This was a cross-sectional study that included 40 patients and 10 controls and was performed in Tanta University Hospital between June 2016 and November 2016. The studied cases were divided into five groups: group I (10 patients): compensated cirrhosis; group II (10 patients): cirrhosis with gastrointestinal hemorrhage due to portal hypertension; group III (10 patients): cirrhosis with hepatorenal syndrome; group IV (10 patients): cirrhosis with liver cell failure; and group V (10 controls): normal healthy individuals.
Results: Regarding serum copeptin in the studied groups, copeptin showed a significant decrease in group I vs group II' group I vs group III, and group I vs group IV; and there was a significant increase in group II vs group III' group II vs group IV' group II vs control' group III vs control, and group IV vs control. No significance was detected between group I vs control and group III vs group IV.
Conclusions: Copeptin is a novel marker for the determination of prognosis of liver cirrhosis. There is significant association between serum level of copeptin and complications of liver cirrhosis.
{"title":"Copeptin as a novel marker predicting prognosis of liver cirrhosis and its major complications.","authors":"Ahmed Khaled Tawfik, Amal Helmy, Mohamed Yousef, Sabry Abou-Saif, Abdelrahman Kobtan, Eman Asaad, Sherief Abd-Elsalam","doi":"10.2147/HMER.S174267","DOIUrl":"10.2147/HMER.S174267","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of the work was to assess the level of copeptin as a surrogate marker predicting the severity of liver diseases and its major complications.</p><p><strong>Patients and methods: </strong>This was a cross-sectional study that included 40 patients and 10 controls and was performed in Tanta University Hospital between June 2016 and November 2016. The studied cases were divided into five groups: group I (10 patients): compensated cirrhosis; group II (10 patients): cirrhosis with gastrointestinal hemorrhage due to portal hypertension; group III (10 patients): cirrhosis with hepatorenal syndrome; group IV (10 patients): cirrhosis with liver cell failure; and group V (10 controls): normal healthy individuals.</p><p><strong>Results: </strong>Regarding serum copeptin in the studied groups, copeptin showed a significant decrease in group I vs group II' group I vs group III, and group I vs group IV; and there was a significant increase in group II vs group III' group II vs group IV' group II vs control' group III vs control, and group IV vs control. No significance was detected between group I vs control and group III vs group IV.</p><p><strong>Conclusions: </strong>Copeptin is a novel marker for the determination of prognosis of liver cirrhosis. There is significant association between serum level of copeptin and complications of liver cirrhosis.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S174267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36490773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-08-28eCollection Date: 2018-01-01DOI: 10.2147/HMER.S160351
Antoine Abou Rached, Selim Abou Kheir, Jowana Saba, Salwa Assaf, Georges Kassis, Yuri Sanchez Gonzalez, Olivier Ethgen
Purpose: To analyze the hepatitis C virus (HCV) burden in Lebanon and the value of comprehensive screening and treatment for different age groups and fibrosis stages.
Methods: We used a multicohort, health-state-transition model to project the number of HCV genotype 1 and 4 patients achieving a sustained virologic response 12 weeks after treatment or progressing to compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver-related death (LrD) from 2016 to 2036. In the low/medium/high screening scenarios, the proportion of patients screened for HCV was projected to increase to 60%/85%/99%, respectively, by 2036. We analyzed four treatment strategies: 1) no treatment, 2) all-oral direct-acting antivirals (DAAs) given to F3-F4 (CC) patients only, 3) all-oral DAAs to F2-F3-F4 (CC) patients, and 4) all-oral DAAs to all fibrosis patients.
Results: Low, medium, and high HCV screening scenarios projected that 3,838, 5,665, and 7,669 individuals will be diagnosed with HCV infection, respectively, from 2016 to 2036, or 40% of those aged 18-39 years, and 60% of those aged 40-80 years. With no treatment, the projected number of patients reaching CC, DCC, HCC, or LrD in 2036 was 899, 147, 131, and 147, respectively, for the 18-39 years age group. For the 40-80 years age group, these projections were substantially greater: 2,828 CC, 736 DCC, 668 HCC, and 958 LrD. The overall economic burden without treatment reached 150 million EUR. However, introducing DAAs for F0-F4 patients was projected to increase the proportion of remaining life-years spent in sustained virologic response 12 weeks after treatment by 43% and 62% compared to DAAs given at F2-F4 or F3-F4 only, respectively.
Conclusion: An enhanced screening policy combined with broader access to DAAs can diminish the future clinical and economic burden of HCV in the Lebanese population and, for the middle-aged and elderly, provide the greatest health benefit with net cost savings.
{"title":"Hepatitis C in Lebanon: the burden of the disease and the value of comprehensive screening and treatment.","authors":"Antoine Abou Rached, Selim Abou Kheir, Jowana Saba, Salwa Assaf, Georges Kassis, Yuri Sanchez Gonzalez, Olivier Ethgen","doi":"10.2147/HMER.S160351","DOIUrl":"https://doi.org/10.2147/HMER.S160351","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze the hepatitis C virus (HCV) burden in Lebanon and the value of comprehensive screening and treatment for different age groups and fibrosis stages.</p><p><strong>Methods: </strong>We used a multicohort, health-state-transition model to project the number of HCV genotype 1 and 4 patients achieving a sustained virologic response 12 weeks after treatment or progressing to compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver-related death (LrD) from 2016 to 2036. In the low/medium/high screening scenarios, the proportion of patients screened for HCV was projected to increase to 60%/85%/99%, respectively, by 2036. We analyzed four treatment strategies: 1) no treatment, 2) all-oral direct-acting antivirals (DAAs) given to F3-F4 (CC) patients only, 3) all-oral DAAs to F2-F3-F4 (CC) patients, and 4) all-oral DAAs to all fibrosis patients.</p><p><strong>Results: </strong>Low, medium, and high HCV screening scenarios projected that 3,838, 5,665, and 7,669 individuals will be diagnosed with HCV infection, respectively, from 2016 to 2036, or 40% of those aged 18-39 years, and 60% of those aged 40-80 years. With no treatment, the projected number of patients reaching CC, DCC, HCC, or LrD in 2036 was 899, 147, 131, and 147, respectively, for the 18-39 years age group. For the 40-80 years age group, these projections were substantially greater: 2,828 CC, 736 DCC, 668 HCC, and 958 LrD. The overall economic burden without treatment reached 150 million EUR. However, introducing DAAs for F0-F4 patients was projected to increase the proportion of remaining life-years spent in sustained virologic response 12 weeks after treatment by 43% and 62% compared to DAAs given at F2-F4 or F3-F4 only, respectively.</p><p><strong>Conclusion: </strong>An enhanced screening policy combined with broader access to DAAs can diminish the future clinical and economic burden of HCV in the Lebanese population and, for the middle-aged and elderly, provide the greatest health benefit with net cost savings.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S160351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36490772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Among the various risky complications of liver cirrhosis, refractory ascites is associated with poor survival of cirrhotics and persistently worsens their quality of life (QOL). Major clinical guidelines worldwide define refractory ascites as ascites that cannot be managed by medical therapy either because of a lack of response to maximum doses of diuretics or because patients develop complications related to diuretic therapy that preclude the use of an effective dose of diuretics. Due to the difficulty in receiving a liver transplantation (LT), the ultimate solution for refractory ascites, most cirrhotic patients have selected the palliative therapy such as repeated serial paracentesis, transjugular intrahepatic portosystemic shunt, or peritoneovenous shunt to improve their QOL. During the past several decades, new interventions and methodologies, such as indwelling peritoneal catheter, peritoneal-urinary drainage, and cell-free and concentrated ascites reinfusion therapy, have been introduced. In addition, new medical treatments with vasoconstrictors or vasopressin V2 receptor antagonists have been proposed. Both the benefits and risks of these old and new modalities have been extensively studied in relation to the pathophysiological changes in ascites formation. Although the best solution for refractory ascites is to eliminate hepatic failure either by LT or by causal treatment, the selection of the best palliative therapy for individual patients is of utmost importance, aiming at achieving the longest possible, comfortable life. This review briefly summarizes the changing landscape of variable treatment modalities for cirrhotic patients with refractory ascites, aiming at clarifying their possibilities and limitations. Evolving issues with regard to the impact of gut-derived systemic and local infection on the clinical course of cirrhotic patients have paved the way for the development of a new gut microbiome-based therapeutics. Thus, it should be further investigated whether the early therapeutic approach to gut dysbiosis provides a better solution for the management of cirrhotic ascites.
{"title":"Management of refractory cirrhotic ascites: challenges and solutions.","authors":"Hiroshi Fukui, Hideto Kawaratani, Kosuke Kaji, Hiroaki Takaya, Hitoshi Yoshiji","doi":"10.2147/HMER.S136578","DOIUrl":"https://doi.org/10.2147/HMER.S136578","url":null,"abstract":"<p><p>Among the various risky complications of liver cirrhosis, refractory ascites is associated with poor survival of cirrhotics and persistently worsens their quality of life (QOL). Major clinical guidelines worldwide define refractory ascites as ascites that cannot be managed by medical therapy either because of a lack of response to maximum doses of diuretics or because patients develop complications related to diuretic therapy that preclude the use of an effective dose of diuretics. Due to the difficulty in receiving a liver transplantation (LT), the ultimate solution for refractory ascites, most cirrhotic patients have selected the palliative therapy such as repeated serial paracentesis, transjugular intrahepatic portosystemic shunt, or peritoneovenous shunt to improve their QOL. During the past several decades, new interventions and methodologies, such as indwelling peritoneal catheter, peritoneal-urinary drainage, and cell-free and concentrated ascites reinfusion therapy, have been introduced. In addition, new medical treatments with vasoconstrictors or vasopressin V2 receptor antagonists have been proposed. Both the benefits and risks of these old and new modalities have been extensively studied in relation to the pathophysiological changes in ascites formation. Although the best solution for refractory ascites is to eliminate hepatic failure either by LT or by causal treatment, the selection of the best palliative therapy for individual patients is of utmost importance, aiming at achieving the longest possible, comfortable life. This review briefly summarizes the changing landscape of variable treatment modalities for cirrhotic patients with refractory ascites, aiming at clarifying their possibilities and limitations. Evolving issues with regard to the impact of gut-derived systemic and local infection on the clinical course of cirrhotic patients have paved the way for the development of a new gut microbiome-based therapeutics. Thus, it should be further investigated whether the early therapeutic approach to gut dysbiosis provides a better solution for the management of cirrhotic ascites.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S136578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36316806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-18eCollection Date: 2018-01-01DOI: 10.2147/HMER.S135337
Elias Kouroumalis, Demetrius Samonakis, Argyro Voumvouraki
Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.
{"title":"Biomarkers for primary biliary cholangitis: current perspectives.","authors":"Elias Kouroumalis, Demetrius Samonakis, Argyro Voumvouraki","doi":"10.2147/HMER.S135337","DOIUrl":"https://doi.org/10.2147/HMER.S135337","url":null,"abstract":"<p><p>Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S135337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36262909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-05-04eCollection Date: 2018-01-01DOI: 10.2147/HMER.S130103
Nimisha Sulejmani, Syed-Mohammed Jafri
Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection. Efficacy of grazoprevir/elbasvir has been proven in patients with cirrhosis, patients who have previously failed treatment with peginterferon and ribavirin (RBV), patients with end-stage renal disease and patients with HIV co-infection. Data have shown a high barrier to resistance despite the presence of resistance-associated substitutions. Grazoprevir/elbasvir represents a very promising regimen for treatment of HCV infection. This review provides a summary of pharmacology, efficacy, and safety of grazoprevir/elbasvir for the treatment of HCV infection.
{"title":"Grazoprevir/elbasvir for the treatment of adults with chronic hepatitis C: a short review on the clinical evidence and place in therapy.","authors":"Nimisha Sulejmani, Syed-Mohammed Jafri","doi":"10.2147/HMER.S130103","DOIUrl":"10.2147/HMER.S130103","url":null,"abstract":"<p><p>Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection. Efficacy of grazoprevir/elbasvir has been proven in patients with cirrhosis, patients who have previously failed treatment with peginterferon and ribavirin (RBV), patients with end-stage renal disease and patients with HIV co-infection. Data have shown a high barrier to resistance despite the presence of resistance-associated substitutions. Grazoprevir/elbasvir represents a very promising regimen for treatment of HCV infection. This review provides a summary of pharmacology, efficacy, and safety of grazoprevir/elbasvir for the treatment of HCV infection.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S130103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-04-27eCollection Date: 2018-01-01DOI: 10.2147/HMER.S158053
Shahinul Alam, Jhumur Ghosh, Golam Mustafa, Mohammad Kamal, Nooruddin Ahmad
Background/purpose: Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin.
Materials and methods: In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year. Patients from both groups were encouraged to exercise moderately and advised to avoid saturated fat, excessive sugar, soft drinks, fast food, and refined carbohydrates to reduce weight.
Results: Steatosis improved in the SL group (from 2.3±0.6 to 1.2±0.8; P=0.000) and the L group (from 2.1±0.6 to 1.6±0.9; P=0.008), ballooning decreased from 1.8±0.6 to 1.3±06 (P=0.002) in the SL group, but not in the L group. Nonalcoholic fatty liver disease activity score (NAS) attenuated in both groups: the SL group (from 5.8±0.9 to 3.9±1.4; P=0.000) and the L group (from 5.3±0.6 to 4.6±1.2; P=0.009). NAS improvement was much higher in the SL group (1.9±1.4) than in the L group (0.7±1.1) (P=0.006), with NAS improving by ≥2 in 13 patients from the SL group and five patients from the L group (P=0.01). Improvement was irrespective of diabetes. Regression analysis explored that sitagliptin had odds of 6.38 and weight reduction had odds of 4.51 for NAS reduction.
Conclusion: Sitagliptin 100 mg once daily for 1 year ameliorates NAS by improving steatosis and ballooning, irrespective of diabetes. Sitagliptin has stronger efficacy than that of weight reduction.
{"title":"Effect of sitagliptin on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis patients: a 1-year randomized control trial.","authors":"Shahinul Alam, Jhumur Ghosh, Golam Mustafa, Mohammad Kamal, Nooruddin Ahmad","doi":"10.2147/HMER.S158053","DOIUrl":"https://doi.org/10.2147/HMER.S158053","url":null,"abstract":"<p><strong>Background/purpose: </strong>Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin.</p><p><strong>Materials and methods: </strong>In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year. Patients from both groups were encouraged to exercise moderately and advised to avoid saturated fat, excessive sugar, soft drinks, fast food, and refined carbohydrates to reduce weight.</p><p><strong>Results: </strong>Steatosis improved in the SL group (from 2.3±0.6 to 1.2±0.8; <i>P</i>=0.000) and the L group (from 2.1±0.6 to 1.6±0.9; <i>P</i>=0.008), ballooning decreased from 1.8±0.6 to 1.3±06 (<i>P</i>=0.002) in the SL group, but not in the L group. Nonalcoholic fatty liver disease activity score (NAS) attenuated in both groups: the SL group (from 5.8±0.9 to 3.9±1.4; <i>P</i>=0.000) and the L group (from 5.3±0.6 to 4.6±1.2; <i>P</i>=0.009). NAS improvement was much higher in the SL group (1.9±1.4) than in the L group (0.7±1.1) (<i>P</i>=0.006), with NAS improving by ≥2 in 13 patients from the SL group and five patients from the L group (<i>P</i>=0.01). Improvement was irrespective of diabetes. Regression analysis explored that sitagliptin had odds of 6.38 and weight reduction had odds of 4.51 for NAS reduction.</p><p><strong>Conclusion: </strong>Sitagliptin 100 mg once daily for 1 year ameliorates NAS by improving steatosis and ballooning, irrespective of diabetes. Sitagliptin has stronger efficacy than that of weight reduction.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2018-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HMER.S158053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36080738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}