AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided in...AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.展开更多
Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are...Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.展开更多
AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty...AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk(odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI(patients-14/93 and controls-7/138; P = 0.009) and NEI ethnicities(patients-17/163 and controls-7/109; P = 0.01). CONCLUSION Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants.展开更多
Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinica...Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH;moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.展开更多
Annually,10%of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis(LVP)is a frequently used therapeutic procedure.LVP,although a safe method,is associated with circulatory dy...Annually,10%of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis(LVP)is a frequently used therapeutic procedure.LVP,although a safe method,is associated with circulatory dysfunction in a significant percentage of patients,which is termed para-centesis-induced circulatory dysfunction(PICD).PICD results in faster reaccumulation of ascites,hyponatremia,renal impairment,and shorter survival.PICD is diagnosed through laboratory results,with increases of>50%of baseline plasma renin activity to a value≥4 ng/mL/h on the fifth to sixth day after paracentesis.In this review,we discuss the pathophysi-ology and prevention of PICD.展开更多
Favipiravir,an antiviral,was given restricted emergency use approval to treat coronavirus disease 2019(COVID-19)in many countries.While the clinical efficacy of favipiravir in COVID-19 remains uncertain,the approval w...Favipiravir,an antiviral,was given restricted emergency use approval to treat coronavirus disease 2019(COVID-19)in many countries.While the clinical efficacy of favipiravir in COVID-19 remains uncertain,the approval was based on findings from in vitro studies and a clinical trial.1 Limited data from studies of the Ebola virus and influenza disease showed a favorable safety profile.2 Herein,we provide the first report of drug-induced liver injury(DILI)due to favipiravir in patients treated for COVID-19.展开更多
Aim:Nonselective beta‐blockers(NSBBs)can reduce the incidence of complications in patients with cirrhosis and prolong survival.The safety and efficacy of NSBBs in real‐world settings in patients with acute‐on‐chro...Aim:Nonselective beta‐blockers(NSBBs)can reduce the incidence of complications in patients with cirrhosis and prolong survival.The safety and efficacy of NSBBs in real‐world settings in patients with acute‐on‐chronic liver failure(ACLF)identified by the Asian Pacific Association for the Study of Liver criteria are unknown.This study aimed to assess the safety and efficacy of NSBBs in patients with Asian Pacific Association for the Study of Liver(APASL)‐defined ACLF Methods:In this retrospective,multicenter study,patients with ACLF with complete 30 days follow‐up from January 2019 to December 2021 were included.The primary objective was to compare 30‐day mortality among standard of care(SOC)and NSBB(+SOC)groups.The secondary objectives were to compare the incidence of infection,variceal bleed,and recompensation among both the groups.Results:A total of 346 patients were included.Only 26%(n=89)of them received NSBBs,while 74%(n=257)received only SOC.On Kaplan-Meier analysis,the incidence of mortality was 21%(95%confidence interval[CI]:16.20-26.50)in SOC group compared to only 8%(95%CI:3.22-15.53)in NSBB group at Day 30(p=0.005).Similarly,mortality in SOC group was 63%(95%CI:56.81-69.00)compared to 46%(95%CI:35.44-57.00)in NSBB group at 1 year(p=0.001).NSBB therapy could not reduce the incidence of infections or variceal bleed.Forty‐seven percent of patients in the SOC group and 73%of patients in the NSBB group(p<0.001)recompensated.Carvedilol was prescribed in 77.5%and propranolol in 22.5%of patients.Conclusions:NSBBs reduce mortality without any effect on infection or variceal bleed in patients with ACLF.However,only one in four ACLF patients are suitable for NSBB therapy.展开更多
基金Supported by Grants from Asian Healthcare Foundation
文摘AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated cirrhosis.METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference(P =0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.
文摘Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.
文摘AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk(odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI(patients-14/93 and controls-7/138; P = 0.009) and NEI ethnicities(patients-17/163 and controls-7/109; P = 0.01). CONCLUSION Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants.
文摘Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH;moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.
文摘Annually,10%of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis(LVP)is a frequently used therapeutic procedure.LVP,although a safe method,is associated with circulatory dysfunction in a significant percentage of patients,which is termed para-centesis-induced circulatory dysfunction(PICD).PICD results in faster reaccumulation of ascites,hyponatremia,renal impairment,and shorter survival.PICD is diagnosed through laboratory results,with increases of>50%of baseline plasma renin activity to a value≥4 ng/mL/h on the fifth to sixth day after paracentesis.In this review,we discuss the pathophysi-ology and prevention of PICD.
文摘Favipiravir,an antiviral,was given restricted emergency use approval to treat coronavirus disease 2019(COVID-19)in many countries.While the clinical efficacy of favipiravir in COVID-19 remains uncertain,the approval was based on findings from in vitro studies and a clinical trial.1 Limited data from studies of the Ebola virus and influenza disease showed a favorable safety profile.2 Herein,we provide the first report of drug-induced liver injury(DILI)due to favipiravir in patients treated for COVID-19.
文摘Aim:Nonselective beta‐blockers(NSBBs)can reduce the incidence of complications in patients with cirrhosis and prolong survival.The safety and efficacy of NSBBs in real‐world settings in patients with acute‐on‐chronic liver failure(ACLF)identified by the Asian Pacific Association for the Study of Liver criteria are unknown.This study aimed to assess the safety and efficacy of NSBBs in patients with Asian Pacific Association for the Study of Liver(APASL)‐defined ACLF Methods:In this retrospective,multicenter study,patients with ACLF with complete 30 days follow‐up from January 2019 to December 2021 were included.The primary objective was to compare 30‐day mortality among standard of care(SOC)and NSBB(+SOC)groups.The secondary objectives were to compare the incidence of infection,variceal bleed,and recompensation among both the groups.Results:A total of 346 patients were included.Only 26%(n=89)of them received NSBBs,while 74%(n=257)received only SOC.On Kaplan-Meier analysis,the incidence of mortality was 21%(95%confidence interval[CI]:16.20-26.50)in SOC group compared to only 8%(95%CI:3.22-15.53)in NSBB group at Day 30(p=0.005).Similarly,mortality in SOC group was 63%(95%CI:56.81-69.00)compared to 46%(95%CI:35.44-57.00)in NSBB group at 1 year(p=0.001).NSBB therapy could not reduce the incidence of infections or variceal bleed.Forty‐seven percent of patients in the SOC group and 73%of patients in the NSBB group(p<0.001)recompensated.Carvedilol was prescribed in 77.5%and propranolol in 22.5%of patients.Conclusions:NSBBs reduce mortality without any effect on infection or variceal bleed in patients with ACLF.However,only one in four ACLF patients are suitable for NSBB therapy.
