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Article: Outcomes following renal transplantation in patients with chronic hepatitis C based on severity of fibrosis on pre-transplant liver biopsy.

Dbouk, Nader / Parekh, Samir

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia

2013 Volume 24, Issue 4, Page(s) 682–687

Abstract: Data regarding long-term outcomes following renal transplantation in patients with hepatitis C virus (HCV) infection have been controversial. Our aim was to determine whether there is a difference in outcomes between patients with HCV and more advanced ... ...

Abstract	Data regarding long-term outcomes following renal transplantation in patients with hepatitis C virus (HCV) infection have been controversial. Our aim was to determine whether there is a difference in outcomes between patients with HCV and more advanced fibrosis on pretransplant biopsy and those with minimal or no fibrosis. Patients were divided according to the severity of fibrosis and their outcomes (including acute rejection, chronic rejection, re-initiation of dialysis, progression of liver disease and mortality) were compared. Thirty-one patients with minimal or no fibrosis (Scheuer stages 0 and 1: Group-A) and 10 patients with more advanced fibrosis (Scheuer stages 2 and 3: Group-B) were included in the final data analysis. Acute rejection occurred in 29% (9/31) of the patients with minimal and 30% (3/10) of the patients with advanced fibrosis (P = 0.95), while chronic allograft nephropathy occurred in 6.5% (2/31) of the patients without and 50% (5/10) of the patients with fibrosis (P = 0.006). None of the patients without fibrosis required re-initiation of dialysis compared with 50% (5/10) of the patients with fibrosis (P <0.05). Median graft survival was 46 months and 18 months for patients with minimal and advanced fibrosis, respectively. There were four deaths among patients with advanced and three deaths among patients with minimal fibrosis (P = 0.04). Our data suggests that patients with chronic HCV and more advanced fibrosis on liver biopsy who undergo a renal transplant have a higher incidence of chronic rejection, graft failure and mortality following renal transplant compared with those with minimal fibrosis.
MeSH term(s)	Biopsy ; Female ; Fibrosis ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/surgery ; Humans ; Kidney Transplantation ; Liver/pathology ; Male ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome
Language	English
Publishing date	2013-06-29
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	1379955-1
ISSN	1319-2442
ISSN	1319-2442
DOI	10.4103/1319-2442.113847
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Article ; Online: Impact of pretransplant antinuclear antibody and antismooth muscle antibody titers on disease recurrence and graft survival following liver transplantation in autoimmune hepatitis patients.

Dbouk, Nader / Parekh, Samir

Journal of gastroenterology and hepatology

2012 Volume 28, Issue 3, Page(s) 537–542

Abstract: Background and aims: Disease recurrence following transplantation occurs in 20-45% of patients with autoimmune hepatitis (AIH). Factors associated with an increased risk of recurrence include human leukocyte antigen (HLA) DR3 and HLA DR4 positivity, ... ...

Abstract	Background and aims: Disease recurrence following transplantation occurs in 20-45% of patients with autoimmune hepatitis (AIH). Factors associated with an increased risk of recurrence include human leukocyte antigen (HLA) DR3 and HLA DR4 positivity, inadequate immunosuppression, and severity of inflammation in the native liver. Titers of several autoantibodies can be elevated in patients with AIH, including antinuclear antibody (ANA) and antismooth muscle antibody (SMA); however, it is unclear whether or not the degree of elevation influences the risk of disease recurrence following transplantation. Methods: We conducted a retrospective study to evaluate the potential impact of pretransplant titers on post-transplant outcomes for patients with AIH. Sixty-three patients with AIH who underwent 72 liver transplants between 1 January 1989 and 1 January 2009 were included, with a median follow up of 10 months. Patients were divided into group A (ANA or SMA ≥ 1:160) and group B (titers ≤ 1:160). Results: There was no significant difference in the recurrence rates or death between patients in groups A and B, respectively. Only race appeared to impact outcomes, with African American patients having a higher incidence of death and recurrent disease post-transplant compared to other ethnicities. Conclusions: Based on our findings, pretransplant ANA and SMA levels do not appear to impact recurrence rates or outcomes following liver transplantation for AIH.
MeSH term(s)	Adult ; African Americans ; Antibodies, Antinuclear/blood ; Autoantibodies/blood ; Biomarkers/blood ; Female ; Fluorescent Antibody Technique, Indirect ; Follow-Up Studies ; Graft Survival/immunology ; Hepatitis, Autoimmune/ethnology ; Hepatitis, Autoimmune/immunology ; Hepatitis, Autoimmune/mortality ; Hepatitis, Autoimmune/surgery ; Humans ; Liver Transplantation/immunology ; Logistic Models ; Male ; Middle Aged ; Preoperative Period ; Recurrence ; Retrospective Studies ; Survival Analysis ; Treatment Outcome
Chemical Substances	Antibodies, Antinuclear ; Autoantibodies ; Biomarkers ; anti-liver kidney microsome antibody
Language	English
Publishing date	2012-04-02
Publishing country	Australia
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632882-9
ISSN	1440-1746 ; 0815-9319
ISSN (online)	1440-1746
ISSN	0815-9319
DOI	10.1111/j.1440-1746.2012.07125.x
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Article ; Online: Outcomes following renal transplantation in patients with chronic hepatitis C based on severity of fibrosis on pre-transplant liver biopsy

Nader Dbouk / Samir Parekh

Saudi Journal of Kidney Diseases and Transplantation, Vol 24, Iss 4, Pp 682-

2013 Volume 687

Abstract	Data regarding long-term outcomes following renal transplantation in patients with hepatitis C virus (HCV) infection have been controversial. Our aim was to determine whether there is a difference in outcomes between patients with HCV and more advanced fibrosis on pretransplant biopsy and those with minimal or no fibrosis. Patients were divided according to the severity of fibrosis and their outcomes (including acute rejection, chronic rejection, re-initiation of dialysis, progression of liver disease and mortality) were compared. Thirty-one patients with minimal or no fibrosis (Scheuer stages 0 and 1: Group-A) and 10 patients with more advanced fibrosis (Scheuer stages 2 and 3: Group-B) were included in the final data analysis. Acute rejection occurred in 29% (9/31) of the patients with minimal and 30% (3/10) of the patients with advanced fibrosis (P = 0.95), while chronic allograft nephropathy occurred in 6.5% (2/31) of the patients without and 50% (5/10) of the patients with fibrosis (P = 0.006). None of the patients without fibrosis required re-initiation of dialysis compared with 50% (5/10) of the patients with fibrosis (P <0.05). Median graft survival was 46 months and 18 months for patients with minimal and advanced fibrosis, respectively. There were four deaths among patients with advanced and three deaths among patients with minimal fibrosis (P = 0.04). Our data suggests that patients with chronic HCV and more advanced fibrosis on liver biopsy who undergo a renal transplant have a higher incidence of chronic rejection, graft failure and mortality following renal transplant compared with those with minimal fibrosis.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
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Article ; Online: C-peptide in diabetes: A player in a dual hormone disorder?

Dakroub, Ali / Dbouk, Ali / Asfour, Aref / Nasser, Suzanne A / El-Yazbi, Ahmed F / Sahebkar, Amirhossein / Eid, Assaad A / Iratni, Rabah / Eid, Ali H

Journal of cellular physiology

2024

Abstract: ... protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species ...

Abstract	C-peptide, a byproduct of insulin synthesis believed to be biologically inert, is emerging as a multifunctional molecule. C-peptide serves an anti-inflammatory and anti-atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C-peptide protects endothelial cells by activating AMP-activated protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia-induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase-3 activity and promoting expression of B-cell lymphoma-2. Additionally, C-peptide suppresses platelet-derived growth factor (PDGF)-beta receptor and p44/p42 mitogen-activated protein (MAP) kinase phosphorylation to inhibit vascular smooth muscle cells (VSMC) proliferation. It also diminishes leukocyte adhesion by virtue of its capacity to abolish nuclear factor kappa B (NF-kB) signaling, a major pro-inflammatory cascade. Consequently, it is envisaged that supplementation of C-peptide in T1DM might ameliorate or even prevent end-organ damage. In marked contrast, C-peptide increases monocyte recruitment and migration through phosphoinositide 3-kinase (PI-3 kinase)-mediated pathways, induces lipid accumulation via peroxisome proliferator-activated receptor γ upregulation, and stimulates VSMC proliferation and CD4
Language	English
Publishing date	2024-02-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.31212
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Article ; Online: Increase of reactive oxygen species contributes to growth inhibition by fluconazole in Cryptococcus neoformans.

Dbouk, Nadir Hani / Covington, Madison Bailey / Nguyen, Kenny / Chandrasekaran, Srikripa

BMC microbiology

2019 Volume 19, Issue 1, Page(s) 243

Abstract: Background: Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal ... ...

Abstract	Background: Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal drug fluconazole (FLC) can induce oxidative stress in C. neoformans by increasing the production of reactive oxygen species (ROS), as presence of the antioxidant ascorbic acid (AA) could reverse the inhibitory effects of FLC on C. neoformans. However, in Candida albicans, AA has been shown to stimulate the expression of genes essential for ergosterol biosynthesis. Hence, the contribution of ROS in FLC-mediated growth inhibition remains unclear. Results: In order to determine whether counteracting ROS generated by FLC in C. neoformans can contribute to diminishing inhibitory effects of FLC, we tested three other antioxidants in addition to AA, namely, pyrrolidine dithiocarbamate (PDTC), retinoic acid (RA), and glutathione (GSH). Our data confirm that there is an increase in ROS in the presence of FLC in C. neoformans. Importantly, all four antioxidants reversed FLC-mediated growth inhibition of C. neoformans to various extents. We further verified the involvement of increased ROS in FLC-mediated growth inhibition by determining that ROS-scavenging proteins, metallothioneins (CMT1 and CMT2), contribute to growth recovery by PDTC and AA during treatment with FLC. Conclusion: Our study suggests that ROS contributes to FLC-mediated growth inhibition and points to a complex nature of antioxidant-mediated growth rescue in the presence of FLC.
MeSH term(s)	Antifungal Agents/pharmacology ; Ascorbic Acid/pharmacology ; Cryptococcus neoformans/drug effects ; Cryptococcus neoformans/growth & development ; Cryptococcus neoformans/metabolism ; Fluconazole/pharmacology ; Fungal Proteins/genetics ; Gene Expression Regulation, Fungal/drug effects ; Glutathione/pharmacology ; Metallothionein/genetics ; Microbial Viability/drug effects ; Pyrrolidines/pharmacology ; Reactive Oxygen Species/metabolism ; Thiocarbamates/pharmacology ; Tretinoin/pharmacology
Chemical Substances	Antifungal Agents ; Fungal Proteins ; Pyrrolidines ; Reactive Oxygen Species ; Thiocarbamates ; pyrrolidine dithiocarbamic acid (25769-03-3) ; Tretinoin (5688UTC01R) ; Fluconazole (8VZV102JFY) ; Metallothionein (9038-94-2) ; Glutathione (GAN16C9B8O) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2019-11-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1471-2180
ISSN (online)	1471-2180
DOI	10.1186/s12866-019-1606-4
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Article ; Online: Genetic contribution to high temperature tolerance in Cryptococcus neoformans.

Stempinski, Piotr R / Zielinski, Jessica M / Dbouk, Nadir H / Huey, Elizabeth S / McCormack, Ellen C / Rubin, Alexander M / Chandrasekaran, Srikripa / Kozubowski, Lukasz

Genetics

2021 Volume 217, Issue 1, Page(s) 1–15

Abstract: The human fungal pathogen Cryptococcus neoformans relies on a complex signaling network for the adaptation and survival at the host temperature. Protein phosphatase calcineurin is central to proliferation at 37°C but its exact contributions remain ill- ... ...

Abstract	The human fungal pathogen Cryptococcus neoformans relies on a complex signaling network for the adaptation and survival at the host temperature. Protein phosphatase calcineurin is central to proliferation at 37°C but its exact contributions remain ill-defined. To better define genetic contributions to the C. neoformans temperature tolerance, 4031 gene knockouts were screened for genes essential at 37°C and under conditions that keep calcineurin inactive. Identified 83 candidate strains, potentially sensitive to 37°C, were subsequently subject to technologically simple yet robust assay, in which cells are exposed to a temperature gradient. This has resulted in identification of 46 genes contributing to the maximum temperature at which C. neoformans can proliferate (Tmax). The 46 mutants, characterized by a range of Tmax on drug-free media, were further assessed for Tmax under conditions that inhibit calcineurin, which led to identification of several previously uncharacterized knockouts exhibiting synthetic interaction with the inhibition of calcineurin. A mutant that lacked septin Cdc11 was among those with the lowest Tmax and failed to proliferate in the absence of calcineurin activity. To further define connections with calcineurin and the role for septins in high temperature growth, the 46 mutants were tested for cell morphology at 37°C and growth in the presence of agents disrupting cell wall and cell membrane. Mutants sensitive to calcineurin inhibition were tested for synthetic lethal interaction with deletion of the septin-encoding CDC12 and the localization of the septin Cdc3-mCherry. The analysis described here pointed to previously uncharacterized genes that were missed in standard growth assays indicating that the temperature gradient assay is a valuable complementary tool for elucidating the genetic basis of temperature range at which microorganisms proliferate.
MeSH term(s)	Calcineurin/genetics ; Calcineurin/metabolism ; Cell Membrane/metabolism ; Cryptococcus neoformans/genetics ; Cryptococcus neoformans/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Mutation ; Septins/genetics ; Septins/metabolism ; Thermotolerance/genetics
Chemical Substances	Fungal Proteins ; Calcineurin (EC 3.1.3.16) ; Septins (EC 3.6.1.-)
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1093/genetics/iyaa009
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Article: Assessment of the PHQ-9 as a screening tool for depression in patients with chronic hepatitis C.

Dbouk, Nader / Arguedas, Miguel R / Sheikh, Aasim

Digestive diseases and sciences

2007 Volume 53, Issue 4, Page(s) 1100–1106

Abstract: Background and objectives: We examined the test characteristics of the PHQ-9, a new screening tool that has been validated in the general population but not amongst patients with hepatitis C virus (HCV).: Methods: The PHQ-9, CES-D and BDI-II ... ...

Abstract	Background and objectives: We examined the test characteristics of the PHQ-9, a new screening tool that has been validated in the general population but not amongst patients with hepatitis C virus (HCV). Methods: The PHQ-9, CES-D and BDI-II questionnaires were administered to 129 consecutive patients with chronic HCV attending a specialty clinic between August 2005 and April 2006. Results: Approximately 52% of participants reported symptoms suggesting depression. Prevalence of depression was 62% using the BDI-II, 75% per the PHQ-9 and 72% per the CES-D. We observed a strong correlation between the BDI-II, CES-D and PHQ-9 in patients on and off interferon. Scores on the three questionnaires were only moderately associated with symptoms reported by the patients. There was moderate agreement between the CES-D and BDI-II and slight agreement between both these questionnaires and the PHQ-9. Scores on the PHQ-9 correlated strongly with scores on the CES-D and BDI-II and moderately with patients' symptoms.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/therapeutic use ; Depressive Disorder/diagnosis ; Depressive Disorder/etiology ; Female ; Health Status Indicators ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/psychology ; Humans ; Interferons/therapeutic use ; Male ; Mass Screening ; Middle Aged ; Psychological Tests ; Reproducibility of Results ; Surveys and Questionnaires
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2007-10-13
Publishing country	United States
Document type	Controlled Clinical Trial ; Journal Article
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-007-9985-z
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Article: Hepatic encephalopathy: a review of its pathophysiology and treatment.

Dbouk, Nader / McGuire, Brendan M

Current treatment options in gastroenterology

2006 Volume 9, Issue 6, Page(s) 464–474

Abstract: Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease. The presence of HE is a poor prognostic sign, with 1-year mortality rates of almost 60%. There is much debate ... ...

Abstract	Hepatic encephalopathy (HE) is a broad spectrum of neuropsychiatric manifestations usually affecting individuals with end-stage liver disease. The presence of HE is a poor prognostic sign, with 1-year mortality rates of almost 60%. There is much debate about the underlying mechanisms that result in this syndrome; however, elevated plasma and central nervous system ammonia levels are considered key factors in its pathogenesis. Initial evaluation of the patient presenting with overt HE should include a careful search for predisposing factors, including underlying infection, gastrointestinal (GI) bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and excessive use of benzodiazepines, psychoactive drugs, or alcohol. The mainstay of treatment for many years has been nonabsorbable disaccharides, particularly lactulose. Alternative treatments, which usually are second line in patients who do not respond to lactulose, include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention. Accepted treatments for HE are associated with significant unpleasant side effects, including diarrhea, renal failure, neuropathy, and other GI disturbance. Newer therapies are still in development, and most are awaiting human trials in order to confirm their benefit. These include manganese chelators, L-carnitine, N-methyl-d-aspartate receptor antagonists, blood purification dialysis system, and an intravenous combination of sodium benzoate and phenylacetate.
Language	English
Publishing date	2006-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2057334-0
ISSN	1534-309X ; 1092-8472
ISSN (online)	1534-309X
ISSN	1092-8472
DOI	10.1007/s11938-006-0003-x
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