Jawahar Taunk - Academia.edu (original) (raw)
Papers by Jawahar Taunk
medRxiv (Cold Spring Harbor Laboratory), Jun 25, 2024
Diabetes, Jul 1, 2018
Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, ... more Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were older (median 61 vs. 56 years) and had a higher BMI than nonDM (34.0 vs. 32.0 kg/m2, both p<0.01). The prevalence rates of hypertension (68 vs. 41%), dyslipidemia (42 vs. 25%), CVD (26 vs. 17%) all p <0.001, and cancer (17 vs. 12% p=0.015), were higher in T2DM compared to nonDM. Median ALT in T2DM was lower than nonDM (33 vs. 38 U/L, p<0.001). Among pts with a liver biopsy, advanced fibrosis was seen in 55% of T2DM vs. 35% nonDM, including 38 vs. 19% with cirrhosis, respectively (both p<0.001). Among pts with a biopsy and NAFLD Activity Score total, more T2DM had severe steatohepatitis than nonDM (38 vs. 23% p<0.01). In this large cohort of NASH pts managed in standard clinical practice, pts with T2DM had substantially different clinical profiles compared to nonDM. ALT, only modestly elevated in most pts with NASH, is not a reliable marker for NASH. Diagnosis requires reliance on clinical features and additional testing. Further investigation of independent risk factors and long-term outcomes is ongoing. Disclosure K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc. A.S. Barritt: Consultant; Self; Targetpharma solutions. Consultant; Spouse/Partner; Targetpharma solutions, Takeda Pharmaceuticals U.S.A., Inc., AbbVie Inc.. V. Clark: None. R.J. Firpi: None. S. Klein: Stock/Shareholder; Self; Aspire Bariatrics. Consultant; Self; Pfizer Inc.. Research Support; Self; Merck & Co., Inc., Johnson & Johnson Services, Inc., REMD Biotherapeutics. A. Lok: None. R. Loomba: Research Support; Self; Adheron, Arora, BMS, Daiichi-Sankyo Inc., Galectin, Galmed, GE, Genfit, Gilead, Immuron, Intercept, Kinemed, Madrigal, Merck, NGM, Promedior, Prometheus, Siemens, Sirius, Tobira. Advisory Panel; Self; Arrowhead Research, Conatus, Galmed, Gilead, Intercept, NGM, Nimbus, Octeta, Tobira. Consultant; Self; Alnylam, Bird Rock Bio, BMS, Boehringer Ingleheim, Celgene, Conatus, DeuteRx, Eli Lily, Enanta, Fibrogen, Genkyotex, Gilead, GRI Bio, ISIS, Janssen Inc.Kirin, Madrigal, Metacrine, NGM, Nitto Denko, Pf, Sanofi,Scholar Rock, Shire, Tasly, Viking, Yuhan Pharmaceuticals, Zafgen. L. Malahias: None. B. Neuschwander-Tetri: None. C. Schoen: None. K. Reddy: Advisory Panel; Self; Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc.. Other Relationship; Self; Novartis AG, Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc., Mallinckrodt Pharmaceuticals, Conatus Pharmaceuticals Inc., Intercept Pharmaceuticals, Inc.. J.L. Taunk: None. K. Wyne: Research Support; Self; Sanofi. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. A.J. Sanyal: Stock/Shareholder; Self; Sanyal Bio, Genfit, Durect, Indalo, Exhalenz. Consultant; Self; Gilead, Boehringer Ingelheim, Intercept. Advisory Panel; Self; Galectin, NGM. Consultant; Self; Pfizer.
Cellular Immunology, May 1, 1992
Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have man... more Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocyte types. In contrast to previous studies, SP (IO-* or IO-'* M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838-+ 603 or 3131 f 832 receptors per cell, with a Kd of 0.21 + 0.01 or 0.18 * 0.09 nM, using [3H]SP or '251-SP respectively. No receptors were found , on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity.
Journal of Hepatology, Apr 1, 2014
Clinical Gastroenterology and Hepatology
Alimentary Pharmacology & Therapeutics, 2021
SummaryBackgroundPatients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 compris... more SummaryBackgroundPatients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis.AimsTo investigate the completeness of real‐world NASH‐related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy‐diagnosed NASH and a pragmatic clinical definition of NASH.MethodsLiver pathology reports from 222 patients across 38 TARGET‐NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over‐read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET‐NASH clinically defined NASH: elevated ALT, hepatic st...
Diabetes, 2020
Nonalcoholic fatty liver disease (NAFLD), including its severe form known as steatohepatitis or N... more Nonalcoholic fatty liver disease (NAFLD), including its severe form known as steatohepatitis or NASH, are increasingly common in patients with type 2 diabetes mellitus (T2DM) and can progress to cirrhosis. However, there is limited information on their comorbid medical conditions in “real world” practice. Thus, the disease characteristics of patients with NASH or NASH-cirrhosis (cirrhosis), with or without T2DM, was evaluated in TARGET-NASH, an ongoing longitudinal observational study of patients with NAFLD, who are managed according to local standards at 60 community and academic hepatology and endocrinology practices in the United States. Among 3085 patients enrolled with NASH or cirrhosis, 1645 had NASH (47% T2DM) and 1440 had cirrhosis (72% T2DM). Patients with T2DM were older (median 61 vs. 56 years) and had a higher median BMI (34.0 vs. 32.0 kg/m2, p<0.001) than participants without T2DM. The prevalence of hypertension (88 vs. 62%), dyslipidemia (78 vs. 56%), cardiovascular...
Diabetes, 2018
Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, ... more Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were ol...
Lung India, 2016
kindness for those who are less fortunate. At the end of this incidence, I was touched by how the... more kindness for those who are less fortunate. At the end of this incidence, I was touched by how the workers had sincerely dedicated themselves to both self and societal progress. Through this example, Dr. Singh shows how the power of atonement is more effective than direct punishment. The book is filled with numerous examples of using the power of atonement to deal with day-today absenteeism, lack of empathy, greed, and anger in hospital workers, residents, and medical students. The power of change, hope, and altruism is embodied within each of these examples. Gandhiji was one of the greatest motivators and philosophers of our time. One of his most lasting principles was that "you must be the change you wish to see in the world." It is with this mindset that Dr. Singh has incorporated Gandhi's principals into his own day-today life and is motivating others to do so as well. If you want to better yourself and improve the world around you, this book can provide you with the framework and context you need to make tremendous changes. Read this book, and you will be the change!
The American journal of gastroenterology, 1991
The medical records and liver biopsies of nine sickle cell patients with chronically elevated liv... more The medical records and liver biopsies of nine sickle cell patients with chronically elevated liver function tests were retrospectively reviewed to determine the etiology of chronic liver disease. There were eight women and one man with a mean age of 30 yr. All patients had hemoglobin SS. Eight patients were referred for elevated aminotransferases and one for an elevated alkaline phosphatase. Hemosiderosis was present in all of the biopsies. Two patients had cirrhosis. Chronic hepatitis was noted in two patients, and five patients had cholestasis. Two patients had serologic markers demonstrating HBV exposure but no patients were HBsAg positive. Erythrophagocytosis, sinusoidal dilatation, and Kupffer cell hyperplasia were present in all of the liver biopsies. Transfusion-related causes were the most common significant pathologic findings in our patients, and appeared to be the etiologies of chronic liver disease in sickle cell patients.
Liver International, 2014
Background & AimsThe safety and efficacy of the interferon‐free combination of faldaprevir (NS3/A... more Background & AimsThe safety and efficacy of the interferon‐free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non‐nucleoside polymerase inhibitor), and ribavirin in treatment‐naïve patients chronically infected with HCV genotype‐1 was explored.MethodsSOUND‐C3 was a multicenter, open‐label Phase 2b study. Treatment‐naïve patients chronically infected with HCV genotype‐1a (IL28B CC genotype only; n = 12) and genotype‐1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight‐based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy.ResultsSustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype‐1a and genotype‐1b respectively. All four patients with cirrhosi...
Gastroenterology, 1992
Human intraepithelial lymphocytes are T cells primarily of the CD8+ phenotype located between int... more Human intraepithelial lymphocytes are T cells primarily of the CD8+ phenotype located between intestinal epithelial cells. The cytotoxic and suppressor activities of these lymphocytes are largely unexplored. The spontaneous cytotoxic activity of these cells is evaluated in this study. Jejunal intraepithelial lymphocytes spontaneously lysed a variety of epithelial cell tumor lines (colonic and pancreatic adenocarcinomas and bladder epidermoid carcinoma) but not the highly natural killer-sensitive K-562 cells. Cold target inhibition studies showed that these lymphocytes preferentially bind the DLD-1 colonic adenocarcinoma cells rather than the K-562 cells. Pretreatment of the effector cells with interferon-gamma did not change their cytotoxic activity. The cytotoxic cells are T lymphocytes (expressing CD2, CD3, and CD8). In contrast, the spontaneous cytotoxic activity of peripheral blood lymphocytes is directed against both epithelial cell targets and K-562 cells, is enhanced by inter...
Gastroenterology, 2014
Background: Optimal duration of interferon-free HCV treatment continues to be examined in clinica... more Background: Optimal duration of interferon-free HCV treatment continues to be examined in clinical trials. The SOUND-C2 and -C3 studies assessed the efficacy and safety of 16, 24, 28 and 40 weeks (W) of the interferon-free combination of faldaprevir, deleobuvir ± ribavirin in treatment-naïve patients infected with HCV genotype (GT)-1. Relapse was higher in HCV GT-1a-infected patients treated for 16W with this regimen compared with GT-1b. We examined the relationship between duration of undetectable HCV RNA and virological response in SOUND-C2 and -C3. Methods: Patients received faldaprevir 120 mg QD plus deleobuvir 600 mg BID or TID. A ribavirin-free arm was investigated in SOUND-C2. The relationship between duration of undetectable HCV RNA to the end of treatment and SVR12 was assessed. Results: SVR rates among patients with undetectable HCV RNA at the last ontreatment visit, based on duration of undetectable HCV RNA, are shown . GT-1binfected patients may require less time at undetectable HCV RNA (8-12W) compared with GT-1a patients (>16W) in order to achieve SVR. Regression analysis indicated that duration of undetectable HCV RNA was significantly associated with SVR. Conclusions: Duration of undetectable HCV RNA to end of treatment with this two DAA regimen was associated with SVR. These data suggest that the optimal treatment duration in GT-1b-infected patients is between 8W and 12W plus the time required to reach undetectable HCV RNA. There were
Cellular Immunology, 1992
Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have man... more Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocyte types. In contrast to previous studies, SP (IO-* or IO-'* M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838 -+ 603 or 3131 f 832 receptors per cell, with a Kd of 0.21 + 0.01 or 0.18 * 0.09 nM, using [3H]SP or '251-SP respectively. No receptors were found , on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity. 0
Liver International, 2014
The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibi... more The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.
medRxiv (Cold Spring Harbor Laboratory), Jun 25, 2024
Diabetes, Jul 1, 2018
Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, ... more Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were older (median 61 vs. 56 years) and had a higher BMI than nonDM (34.0 vs. 32.0 kg/m2, both p<0.01). The prevalence rates of hypertension (68 vs. 41%), dyslipidemia (42 vs. 25%), CVD (26 vs. 17%) all p <0.001, and cancer (17 vs. 12% p=0.015), were higher in T2DM compared to nonDM. Median ALT in T2DM was lower than nonDM (33 vs. 38 U/L, p<0.001). Among pts with a liver biopsy, advanced fibrosis was seen in 55% of T2DM vs. 35% nonDM, including 38 vs. 19% with cirrhosis, respectively (both p<0.001). Among pts with a biopsy and NAFLD Activity Score total, more T2DM had severe steatohepatitis than nonDM (38 vs. 23% p<0.01). In this large cohort of NASH pts managed in standard clinical practice, pts with T2DM had substantially different clinical profiles compared to nonDM. ALT, only modestly elevated in most pts with NASH, is not a reliable marker for NASH. Diagnosis requires reliance on clinical features and additional testing. Further investigation of independent risk factors and long-term outcomes is ongoing. Disclosure K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc. A.S. Barritt: Consultant; Self; Targetpharma solutions. Consultant; Spouse/Partner; Targetpharma solutions, Takeda Pharmaceuticals U.S.A., Inc., AbbVie Inc.. V. Clark: None. R.J. Firpi: None. S. Klein: Stock/Shareholder; Self; Aspire Bariatrics. Consultant; Self; Pfizer Inc.. Research Support; Self; Merck & Co., Inc., Johnson & Johnson Services, Inc., REMD Biotherapeutics. A. Lok: None. R. Loomba: Research Support; Self; Adheron, Arora, BMS, Daiichi-Sankyo Inc., Galectin, Galmed, GE, Genfit, Gilead, Immuron, Intercept, Kinemed, Madrigal, Merck, NGM, Promedior, Prometheus, Siemens, Sirius, Tobira. Advisory Panel; Self; Arrowhead Research, Conatus, Galmed, Gilead, Intercept, NGM, Nimbus, Octeta, Tobira. Consultant; Self; Alnylam, Bird Rock Bio, BMS, Boehringer Ingleheim, Celgene, Conatus, DeuteRx, Eli Lily, Enanta, Fibrogen, Genkyotex, Gilead, GRI Bio, ISIS, Janssen Inc.Kirin, Madrigal, Metacrine, NGM, Nitto Denko, Pf, Sanofi,Scholar Rock, Shire, Tasly, Viking, Yuhan Pharmaceuticals, Zafgen. L. Malahias: None. B. Neuschwander-Tetri: None. C. Schoen: None. K. Reddy: Advisory Panel; Self; Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc.. Other Relationship; Self; Novartis AG, Gilead Sciences, Inc., Merck & Co., Inc., AbbVie Inc., Mallinckrodt Pharmaceuticals, Conatus Pharmaceuticals Inc., Intercept Pharmaceuticals, Inc.. J.L. Taunk: None. K. Wyne: Research Support; Self; Sanofi. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. A.J. Sanyal: Stock/Shareholder; Self; Sanyal Bio, Genfit, Durect, Indalo, Exhalenz. Consultant; Self; Gilead, Boehringer Ingelheim, Intercept. Advisory Panel; Self; Galectin, NGM. Consultant; Self; Pfizer.
Cellular Immunology, May 1, 1992
Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have man... more Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocyte types. In contrast to previous studies, SP (IO-* or IO-'* M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838-+ 603 or 3131 f 832 receptors per cell, with a Kd of 0.21 + 0.01 or 0.18 * 0.09 nM, using [3H]SP or '251-SP respectively. No receptors were found , on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity.
Journal of Hepatology, Apr 1, 2014
Clinical Gastroenterology and Hepatology
Alimentary Pharmacology & Therapeutics, 2021
SummaryBackgroundPatients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 compris... more SummaryBackgroundPatients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis.AimsTo investigate the completeness of real‐world NASH‐related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy‐diagnosed NASH and a pragmatic clinical definition of NASH.MethodsLiver pathology reports from 222 patients across 38 TARGET‐NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over‐read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET‐NASH clinically defined NASH: elevated ALT, hepatic st...
Diabetes, 2020
Nonalcoholic fatty liver disease (NAFLD), including its severe form known as steatohepatitis or N... more Nonalcoholic fatty liver disease (NAFLD), including its severe form known as steatohepatitis or NASH, are increasingly common in patients with type 2 diabetes mellitus (T2DM) and can progress to cirrhosis. However, there is limited information on their comorbid medical conditions in “real world” practice. Thus, the disease characteristics of patients with NASH or NASH-cirrhosis (cirrhosis), with or without T2DM, was evaluated in TARGET-NASH, an ongoing longitudinal observational study of patients with NAFLD, who are managed according to local standards at 60 community and academic hepatology and endocrinology practices in the United States. Among 3085 patients enrolled with NASH or cirrhosis, 1645 had NASH (47% T2DM) and 1440 had cirrhosis (72% T2DM). Patients with T2DM were older (median 61 vs. 56 years) and had a higher median BMI (34.0 vs. 32.0 kg/m2, p<0.001) than participants without T2DM. The prevalence of hypertension (88 vs. 62%), dyslipidemia (78 vs. 56%), cardiovascular...
Diabetes, 2018
Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, ... more Nonalcoholic Fatty Liver Disease (NAFLD), ranging from simple steatosis to its more severe form, steatohepatitis (NASH), is an increasingly common problem in patients with T2DM and is associated with progression to cirrhosis and extrahepatic complications (i.e., cardiovascular disease [CVD]). There is limited information on the clinical profile of T2DM patients with NASH in “real world” practice. Accordingly, we studied the clinical profile of participants (pts) with NASH, with or without T2DM (nonDM), enrolled in TARGET-NASH, a large longitudinal observational study of patients with NAFLD followed at 54 sites (39 academic/15 community) across the U.S. Data collected from medical records (including lab data, imaging, pathology, procedures, and outcomes) is sent to a central database utilizing novel data abstraction technology. Among 1743 pts studied to date in TARGET-NASH, 1261 had NASH diagnosed by biopsy or clinical criteria (699 T2DM and 562 nonDM). Pts with T2DM and NASH were ol...
Lung India, 2016
kindness for those who are less fortunate. At the end of this incidence, I was touched by how the... more kindness for those who are less fortunate. At the end of this incidence, I was touched by how the workers had sincerely dedicated themselves to both self and societal progress. Through this example, Dr. Singh shows how the power of atonement is more effective than direct punishment. The book is filled with numerous examples of using the power of atonement to deal with day-today absenteeism, lack of empathy, greed, and anger in hospital workers, residents, and medical students. The power of change, hope, and altruism is embodied within each of these examples. Gandhiji was one of the greatest motivators and philosophers of our time. One of his most lasting principles was that "you must be the change you wish to see in the world." It is with this mindset that Dr. Singh has incorporated Gandhi's principals into his own day-today life and is motivating others to do so as well. If you want to better yourself and improve the world around you, this book can provide you with the framework and context you need to make tremendous changes. Read this book, and you will be the change!
The American journal of gastroenterology, 1991
The medical records and liver biopsies of nine sickle cell patients with chronically elevated liv... more The medical records and liver biopsies of nine sickle cell patients with chronically elevated liver function tests were retrospectively reviewed to determine the etiology of chronic liver disease. There were eight women and one man with a mean age of 30 yr. All patients had hemoglobin SS. Eight patients were referred for elevated aminotransferases and one for an elevated alkaline phosphatase. Hemosiderosis was present in all of the biopsies. Two patients had cirrhosis. Chronic hepatitis was noted in two patients, and five patients had cholestasis. Two patients had serologic markers demonstrating HBV exposure but no patients were HBsAg positive. Erythrophagocytosis, sinusoidal dilatation, and Kupffer cell hyperplasia were present in all of the liver biopsies. Transfusion-related causes were the most common significant pathologic findings in our patients, and appeared to be the etiologies of chronic liver disease in sickle cell patients.
Liver International, 2014
Background & AimsThe safety and efficacy of the interferon‐free combination of faldaprevir (NS3/A... more Background & AimsThe safety and efficacy of the interferon‐free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non‐nucleoside polymerase inhibitor), and ribavirin in treatment‐naïve patients chronically infected with HCV genotype‐1 was explored.MethodsSOUND‐C3 was a multicenter, open‐label Phase 2b study. Treatment‐naïve patients chronically infected with HCV genotype‐1a (IL28B CC genotype only; n = 12) and genotype‐1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight‐based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy.ResultsSustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype‐1a and genotype‐1b respectively. All four patients with cirrhosi...
Gastroenterology, 1992
Human intraepithelial lymphocytes are T cells primarily of the CD8+ phenotype located between int... more Human intraepithelial lymphocytes are T cells primarily of the CD8+ phenotype located between intestinal epithelial cells. The cytotoxic and suppressor activities of these lymphocytes are largely unexplored. The spontaneous cytotoxic activity of these cells is evaluated in this study. Jejunal intraepithelial lymphocytes spontaneously lysed a variety of epithelial cell tumor lines (colonic and pancreatic adenocarcinomas and bladder epidermoid carcinoma) but not the highly natural killer-sensitive K-562 cells. Cold target inhibition studies showed that these lymphocytes preferentially bind the DLD-1 colonic adenocarcinoma cells rather than the K-562 cells. Pretreatment of the effector cells with interferon-gamma did not change their cytotoxic activity. The cytotoxic cells are T lymphocytes (expressing CD2, CD3, and CD8). In contrast, the spontaneous cytotoxic activity of peripheral blood lymphocytes is directed against both epithelial cell targets and K-562 cells, is enhanced by inter...
Gastroenterology, 2014
Background: Optimal duration of interferon-free HCV treatment continues to be examined in clinica... more Background: Optimal duration of interferon-free HCV treatment continues to be examined in clinical trials. The SOUND-C2 and -C3 studies assessed the efficacy and safety of 16, 24, 28 and 40 weeks (W) of the interferon-free combination of faldaprevir, deleobuvir ± ribavirin in treatment-naïve patients infected with HCV genotype (GT)-1. Relapse was higher in HCV GT-1a-infected patients treated for 16W with this regimen compared with GT-1b. We examined the relationship between duration of undetectable HCV RNA and virological response in SOUND-C2 and -C3. Methods: Patients received faldaprevir 120 mg QD plus deleobuvir 600 mg BID or TID. A ribavirin-free arm was investigated in SOUND-C2. The relationship between duration of undetectable HCV RNA to the end of treatment and SVR12 was assessed. Results: SVR rates among patients with undetectable HCV RNA at the last ontreatment visit, based on duration of undetectable HCV RNA, are shown . GT-1binfected patients may require less time at undetectable HCV RNA (8-12W) compared with GT-1a patients (>16W) in order to achieve SVR. Regression analysis indicated that duration of undetectable HCV RNA was significantly associated with SVR. Conclusions: Duration of undetectable HCV RNA to end of treatment with this two DAA regimen was associated with SVR. These data suggest that the optimal treatment duration in GT-1b-infected patients is between 8W and 12W plus the time required to reach undetectable HCV RNA. There were
Cellular Immunology, 1992
Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have man... more Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocyte types. In contrast to previous studies, SP (IO-* or IO-'* M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838 -+ 603 or 3131 f 832 receptors per cell, with a Kd of 0.21 + 0.01 or 0.18 * 0.09 nM, using [3H]SP or '251-SP respectively. No receptors were found , on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity. 0
Liver International, 2014
The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibi... more The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.