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1.
World J Hepatol ; 15(2): 274-281, 2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36926230

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation (LT). Hence, more patients with diabetes mellitus (DM) are undergoing LT, especially, above the age of 65. AIM: To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65. METHODS: We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record. We assessed the impact of DM on short-term outcomes, one-year, post-LT based on the following variables: Survival at one year; acute cellular rejection (ACR) rates; intensive care unit (ICU) and hospital length of stay; and readmissions. RESULTS: Total of 148 patients who are 65 year or older underwent LT during the study period. The mean age is 68.5 ± 3.3 years and 67.6% were male. The median Model for End-stage Liver Disease score at time of transplantation was 22 (6-39), 39% of patients had hepatocellular carcinoma and 77.7% underwent living donor LT. The one-year survival was similar between DM patients and others, 91%. ACR occurred in 13.5% of patients (P = 0.902). The median ICU stay is 4.5-day P = 0.023. The rates of ICU and 90-d readmission were similar (P = 0.821) and (P = 0.194), respectively. CONCLUSION: The short-term outcome of elderly diabetic patients undergoing LT is similar to others. The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

2.
Cancers (Basel) ; 13(24)2021 Dec 07.
Article in English | MEDLINE | ID: mdl-34944792

ABSTRACT

Hepatocellular carcinoma (HCC) occurs in nearly three-quarters of all primary liver cancers, with the majority not amenable to curative therapies. We therefore aimed to re-evaluate the safety, efficacy, and survival benefits of treating patients with drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) compared to the conventional transcatheter arterial chemoembolization (C-TACE). Several databases were searched with a strict eligibility criterion for studies reporting on adult patients with unresectable or recurrent HCC. The pooled analysis included 34 studies involving 4841 HCC patients with a median follow-up of 1.5 to 18 months. There were no significant differences between DEB-TACE and C-TACE with regard to complete response, partial response and disease stability. However, disease control (OR: 1.42 (95% CI (1.03,1.96) and objective response (OR: 1.33 (95% CI (0.99, 1.79) were significantly more effective for DEB-TACE treatment with fewer severe complications and all-cause mortality. The pooled-analysis did not find superiority of DEB-TACE in complete or partial response, disease stability, controlling disease progression, and 30 day or end-mortality. However, results showed that DEB-TACE is associated with a better objective response, disease control, and lower all-cause mortality with severe complications compared to C-TACE treatment. Given that the safety outcomes are based on limited studies with a potential for bias, there was no clear improvement of DEB-TACE over C-TACE treatment.

3.
BMC Gastroenterol ; 21(1): 245, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34074270

ABSTRACT

BACKGROUND: Several trend analyses on liver transplantation (LT) indications have been published in the U.S. and in other countries, but there are limited data on LT indication trends in Saudi Arabia (SA), especially since the availability of direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV). This study aimed to analyze trends in the frequency of LT indications among LT recipients in SA over a 19-year period and examine associations between etiologic-specific trends and clinicodemographic characteristics. METHODS: This retrospective study analyzed clinical and surgical data of adult patients (n = 1009) who underwent LT at the King Faisal Specialist Hospital & Research Center (Riyadh, SA) between 2001 and 2019. Spearman's rank correlation, Poisson regression, and Joinpoint regression analysis were employed to assess changes in LT etiologic trends. RESULTS: In the first period (2001-2010), the main LT indications were HCV (41.9%) and hepatitis B virus (HBV) (21.1%), but nonalcoholic steatohepatitis (NASH) (29.7%) surpassed HCV (23.7%) as the leading LT indication in the second period (2011-2019); and the trends were significant in correlation analyses [incidence rate ratio (IRR) = 1.09 (1.06-1.13) for NASH; IRR = 0.93 (0.91-0.95) for HCV]. In the Joinpoint regression analysis, increases in NASH from 2006 to 2012 (+ 32.1%) were statistically significant, as were the decreases in HCV from 2004 to 2007 (- 19.6%) and from 2010 to 2019 (- 12.1%). Similar patterns were observed in LT etiological comparisons before and after the availability of DAAs and within hepatocellular carcinoma stratifications. CONCLUSIONS: Trends in the epidemiology of LT indications among LT recipients in SA have changed over a 19-year period. Most notably, NASH has eclipsed HCV in the country due to the effective treatment strategies for HCV. These trends in NASH now need an aggressive public health response to minimize and avert future onset of additional clinical and economic strains on health care systems and LT centers in SA.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Adult , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/surgery , Humans , Liver Neoplasms/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/surgery , Retrospective Studies , Saudi Arabia/epidemiology
4.
PLoS One ; 16(5): e0251487, 2021.
Article in English | MEDLINE | ID: mdl-33984017

ABSTRACT

INTRODUCTION: Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors. METHODS: Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (<5%), S1 (5-33%), S2 (33-66%), and S3 (>66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results. RESULTS: Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016-1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively. CONCLUSION: The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies.


Subject(s)
Fatty Liver/diagnosis , Living Donors , Adult , Biopsy , Elasticity Imaging Techniques , Fatty Liver/pathology , Female , Humans , Liver/pathology , Liver Transplantation , Male , Young Adult
5.
World J Hepatol ; 13(3): 375-383, 2021 03 27.
Article in English | MEDLINE | ID: mdl-33815679

ABSTRACT

BACKGROUND: Once daily tacrolimus regimen was found to exhibits similar bioavailability, safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients. AIM: To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients. METHODS: MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95% confidence interval (CI) for dichotomous data. RESULTS: Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups (risk ratio: 1.06, 95%CI: 0.84-1.34, n = 758, I2 = 0%) and also we found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I2 = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups. CONCLUSION: The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.

6.
Transplant Proc ; 53(1): 148-158, 2021.
Article in English | MEDLINE | ID: mdl-33390288

ABSTRACT

BACKGROUND: Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose. BACKGROUND: To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation. METHODS: We searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently. RESULTS: Eight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR. CONCLUSIONS: The analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.


Subject(s)
Everolimus/adverse effects , Immunosuppressive Agents/adverse effects , Liver Transplantation , Renal Insufficiency, Chronic/chemically induced , Calcineurin Inhibitors/adverse effects , Female , Graft Rejection/prevention & control , Humans , Liver Transplantation/adverse effects , Male , Randomized Controlled Trials as Topic , Tacrolimus/adverse effects
7.
Sci Rep ; 10(1): 8825, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32483260

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We prospectively evaluated endothelial function by assessing flow-mediated dilatation (FMD) of the brachial artery in patients with biopsy-proven NAFLD. This prospective study included 139 patients (50 healthy controls, 47 patients with steatosis and 42 patients with steatohepatitis), all of whom were nondiabetic. Patients with long-standing or uncontrolled hypertension, smokers, and morbidly obese patients were excluded. The medians (ranges) for vascular FMD in the steatohepatitis, steatosis, and control groups were 6% (0-37.5%), 10.8% (0-40%) and 13.6% (0-50%), respectively. The control group had a higher average FMD than the NAFLD group (15.13% vs 10.46%), and statistical significance was reached when the control and steatohepatitis groups were compared (13.6% vs 6%, p = 0.027). Average alanine aminotransferase was significantly higher in the steatohepatitis group than in the steatosis and control groups (54 (U/L) vs 31 (U/L), p = 0.008). Cholesterol levels were similar between all groups. In the multivariate analysis, FMD (OR = 0.85, p = 0.035) and high triglycerides (OR = 76.4, p = 0.009) were significant predictors of steatohepatitis. In the absence of major cardiac risk factors, we demonstrated better endothelial function in healthy controls, evidenced by a higher FMD of the brachial artery than that of patients with steatohepatitis.


Subject(s)
Endothelium, Vascular/physiopathology , Heart Diseases/epidemiology , Non-alcoholic Fatty Liver Disease/physiopathology , Adult , Biopsy , Body Mass Index , Brachial Artery/physiopathology , Case-Control Studies , Female , Heart Diseases/etiology , Humans , Insulin Resistance , Male , Metabolic Syndrome/complications , Metabolic Syndrome/physiopathology , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , Prospective Studies , ROC Curve , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Vasodilation
8.
Exp Clin Transplant ; 18(2): 188-195, 2020 04.
Article in English | MEDLINE | ID: mdl-31875463

ABSTRACT

OBJECTIVES: Liver retransplant is considered the only hope for patients with irreversible graft failure after primary transplant. In most Western centers, retransplantis done mainly from deceased donors; so far, only few published studies have reported on outcomes of liver retransplant with living donors. In this study, our aim was to analyze the outcomes of living-donor liver retransplant. MATERIALS AND METHODS: Patients who underwent liver retransplant between February 2011 and February 2019 were included in the study. Preoperative, operative, and postoperative data were analyzed. Results from 2 patient groups were compared: liver retransplant with living donors and liver retransplant with deceased donors. RESULTS: Thirty-two patients underwent liver retransplant (21 adult and 11 pediatric patients). The most common indications for liver retransplant were hepatic artery thrombosis (28.5%) and primary graft nonfunction (23.8%) in adults and hepatic artery thrombosis (45.5%) and chronic rejection (36.4%) in pediatric patients. Seventeen retransplant patients (53.1%) required early retransplant (within 1 mo), mainly due to hepatic artery thrombosis (52.9%) and primary graft nonfunction (35.3%). Late retransplant was mainly due to chronic rejection (40%) and recurrence of primary disease (26.7%). Seventeen patients (53.1%) underwent living-donor retransplant, and 5 donors underwent robotic right hepatectomy. Graft and patient survival rates at 1, 3, and 5 years were 81.3% for living-donor and 51.4% for deceased-donor liver retransplant recipients (P = .08). On multivariate analyses, we observed significant differences between both groups in pretransplant Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores (P = .05), preoperative international normalized ratio (P = .012), and cold ischemia time (P = .046). CONCLUSIONS: The use of living donors for liver retransplant, despite its technical demand, was shown to be a safe and feasible option, especially when there is scarcity of deceased donors.


Subject(s)
Liver Transplantation , Living Donors , Postoperative Complications/surgery , Reoperation , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Reoperation/adverse effects , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
9.
Ann Thorac Med ; 14(3): 179-185, 2019.
Article in English | MEDLINE | ID: mdl-31333767

ABSTRACT

BACKGROUND: After the emergence of new influenza viruses, the morbidity and mortality of viral pneumonia have received a great attention. OBJECTIVES: The objective of this study is to describe the epidemiologic, clinical and laboratory changes, and outcomes of viral pneumonia caused by influenza and the Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. METHODS: In a retrospective cohort study, the medical records of all patients diagnosed with viral pneumonia at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, during the period from January 2012 to December 2015 were screened. Cases who were > 18 years old and were confirmed by a respiratory viral panel to have viral pneumonia either MERS-CoV or influenza viruses were included in the analysis. Sociodemographic, clinical, laboratory, and outcome data were extracted from patients' medical files. The data were analyzed descriptively and inferentially to identify the predictors of poor outcome. RESULTS: A total of 448 patients with confirmed viral pneumonia were included, of those, 216 (48.2%) were caused by influenza A (non H1N1)/influenza B, 150 (33.5%) by H1N1, and 82 (18.3%) by MERS-CoV. The majority of patients presented with fever (82%), shortness of breath (64%), and flu-like symptoms (54.9%), particularly in MERS-CoV infected cases (92%). The peak incidence of viral pneumonia was in early spring and autumn. The mortality rate was 13.8%, and it was significantly higher among MERS-CoV cases. The predictors of death were age > 65 years, male gender, and associated comorbidities particularly diabetes mellitus, hypertension, and chronic kidney diseases. The number of comorbid illnesses was directly related to the increase in mortality in this group of patients. CONCLUSION: Viral pneumonia caused by influenza and MERS-CoV carries a high mortality rate, particularly among MERS-CoV infected cases. Old age, male gender, and comorbid illnesses are predictors of poor outcome. Routine testing for newly emergent viruses is warranted for adults who have been hospitalized with pneumonia.

10.
Sci Rep ; 9(1): 7123, 2019 05 09.
Article in English | MEDLINE | ID: mdl-31073186

ABSTRACT

Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.


Subject(s)
Hepatitis B Surface Antigens/metabolism , Hepatitis B virus/immunology , Hepatitis B, Chronic/genetics , Interleukin-1/genetics , Liver Diseases/virology , Polymorphism, Single Nucleotide , Adult , Aged , Case-Control Studies , Disease Progression , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Liver Diseases/genetics , Male , Middle Aged , Saudi Arabia
11.
Ann Hepatol ; 18(3): 439-444, 2019.
Article in English | MEDLINE | ID: mdl-31040094

ABSTRACT

INTRODUCTION AND AIM: Autoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH. MATERIALS AND METHODS: A multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported. RESULTS: Seventy patients were included. The mean age was 33.8±1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733±463.6), aspartate transaminase (699±423), and total bilirubin (210±181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis. CONCLUSION: Acute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.


Subject(s)
Antibodies, Antinuclear/immunology , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/drug therapy , Immunosuppressive Agents/therapeutic use , Liver Cirrhosis/immunology , Acute Disease , Adult , Alanine Transaminase/blood , Cohort Studies , Disease Progression , Female , Hepatitis, Autoimmune/mortality , Humans , Immunoglobulin G/immunology , Kaplan-Meier Estimate , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Function Tests , Logistic Models , Male , Multivariate Analysis , Prednisone/therapeutic use , Retrospective Studies , Risk Assessment , Saudi Arabia , Severity of Illness Index , Survival Analysis , Tertiary Care Centers
12.
Article in English | MEDLINE | ID: mdl-30406036

ABSTRACT

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B Core Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Liver Cirrhosis/virology , Liver Neoplasms/virology , Mutation, Missense , Adult , Aged , Amino Acid Substitution , Carrier State/virology , Disease Progression , Female , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Saudi Arabia , Young Adult
14.
J Infect ; 76(6): 536-542, 2018 06.
Article in English | MEDLINE | ID: mdl-29742470

ABSTRACT

Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. PATIENTS & METHODS: This observational cohort (n = 213) included GT4 treatment-naïve (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600-1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). RESULTS: The mean age of the overall cohort was 59.6 ±â€¯12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics (P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis (P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). CONCLUSION: LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.


Subject(s)
Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Fluorenes/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Uridine Monophosphate/analogs & derivatives , Adult , Aged , Antiviral Agents/administration & dosage , Benzimidazoles/administration & dosage , Cohort Studies , Female , Fluorenes/administration & dosage , Genotype , Hepacivirus/genetics , Humans , Liver Cirrhosis/virology , Male , Middle Aged , Ribavirin/administration & dosage , Ribavirin/therapeutic use , Sofosbuvir , Sustained Virologic Response , Treatment Outcome , Uridine Monophosphate/administration & dosage , Uridine Monophosphate/therapeutic use
15.
J Clin Gastroenterol ; 52(5): 452-457, 2018.
Article in English | MEDLINE | ID: mdl-28767462

ABSTRACT

INTRODUCTION: The combination of sofosbuvir (SOF) with simeprevir (SMV) or daclatasvir (DCV) is very effective in treating hepatitis C virus (HCV) infection, particularly genotype (GT) 1. However, the data on GT4 are very limited. We aimed to determine the efficacy and safety of SOF in combination with either SMV or DCV in GT4-infected patients. PATIENTS AND METHODS: In this real life, prospective, observational study, HCV (GT4) patients (n=96) were evaluated in 2 groups on the basis of the 12-week treatment regimen they received. Group 1 (n=56) patients were treated with SOF and SMV±ribavirin (RBV), whereas group 2 patients were treated with SOF and DCV±RBV (n=40). The primary efficacy endpoint was sustained virologic response 12, whereas the primary safety endpoint was drug discontinuation or occurrence of grade 3/4 adverse events. RESULTS: The mean age was 49±14.6 years (59.4% men). Cirrhosis was present in 53.6% and 35.0% of groups 1 and 2, respectively, whereas 27 patients (48.2%) in group 1 and 21 patients (52.5%) in group 2 had failed prior interferon-based treatment. The median pretreatment HCV-RNA log10 was 6.1 (3.6 to 7.0) and 6.0 (3.6 to 7.2) IU/mL in groups 1 and 2, respectively. RBV was given to 17 patients (30.4%) in group 1 and 2 patients (5%) in group 2. All patients achieved sustained virologic response 12 (100%). Adverse events occurred in 32% of patients (grade 1 and 2), but none discontinued treatment. One patient died in the SMV group (not related to treatment). CONCLUSIONS: SMV/SOF or DCV/SOF combinations are safe and highly effective in HCV-GT4 treatment. Cirrhosis and failure of prior interferon-based treatment did not influence treatment response.


Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/drug therapy , Adult , Antiviral Agents/adverse effects , Carbamates , Drug Therapy, Combination , Female , Genotype , Hepacivirus/isolation & purification , Hepatitis C, Chronic/virology , Humans , Imidazoles/administration & dosage , Liver Cirrhosis/virology , Male , Middle Aged , Prospective Studies , Pyrrolidines , RNA, Viral/blood , Ribavirin/administration & dosage , Simeprevir/administration & dosage , Sofosbuvir/administration & dosage , Sustained Virologic Response , Treatment Outcome , Valine/analogs & derivatives
16.
Oncotarget ; 8(62): 105115-105125, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29285238

ABSTRACT

Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combinational mutations in HBx gene on the pathogenesis of HCC during progressive stages of liver disease. The patients were categorized into inactive HBV carriers, active carriers, cirrhosis and HCC groups based on disease severity. Male sex, age > 50 years, and high serum alanine aminotransferase level were associated with risk of progressive liver disease. I127T, V131I, and F132Y/I/R mutations showed a significant increasing trend associated with the disease progression to HCC. H94Y and K130M mutations were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed, with significant rising prevalence through progressive clinical phases of liver disease to HCC. Several single and combinational mutations in HBx correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating the progression to HCC. These specific patterns of HBx mutations can be useful in predicting the clinical outcome of HBV-infected patients and may serve as early markers of high risk of developing HCC.

17.
Int J Surg Case Rep ; 35: 82-86, 2017.
Article in English | MEDLINE | ID: mdl-28458144

ABSTRACT

INTRODUCTION: Pulmonary complications after bariatric surgeries are rare but usually serious. They often occur early after surgery but the presentation might be delayed for several months. Gastropleural fistula after bariatric surgery is extremely rare and has been reported in a very small number of patients post sleeve gastrectomy and gastric bypass. CASE PRESENTATION: A 37-year-old lady presented with left sided pleural effusion and empyema 2 years post single anastomosis gastric bypass surgery. She was found to have a large gastropleural fistula and was managed by surgical repair of the fistula with conversion to gastric bypass and decortication of the affected pleura. That resulted in significant clinical improvement and resolution of the empyema. CONCLUSION: Gastropleural fistula is a very rare complication of bariatric surgeries and should be considered in patients who present with chronic or recurrent pulmonary infections.

18.
BMJ Case Rep ; 20172017 May 28.
Article in English | MEDLINE | ID: mdl-28554883

ABSTRACT

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.


Subject(s)
Adenocarcinoma/pathology , Colonic Neoplasms/complications , Endocarditis, Bacterial/complications , Heart Valve Prosthesis/microbiology , Mitral Valve/microbiology , Streptococcus bovis/isolation & purification , Adenocarcinoma/surgery , Aftercare , Aged , Bacteremia , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Colonoscopy/methods , Echocardiography/methods , Female , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/pathology , Streptococcal Infections/complications , Streptococcal Infections/diagnosis , Streptococcal Infections/microbiology , Treatment Outcome
19.
Ann Hepatol ; 15(6): 824-833, 2016.
Article in English | MEDLINE | ID: mdl-27740515

ABSTRACT

 Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.


Subject(s)
Carcinoma, Hepatocellular/genetics , Hepatitis C, Chronic/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Polymorphism, Single Nucleotide , Ubiquitin-Protein Ligases/genetics , Adult , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/virology , Case-Control Studies , Chi-Square Distribution , Disease Progression , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Haplotypes , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/enzymology , Hepatitis C, Chronic/virology , Humans , Linkage Disequilibrium , Liver Cirrhosis/diagnosis , Liver Cirrhosis/enzymology , Liver Cirrhosis/virology , Liver Neoplasms/diagnosis , Liver Neoplasms/enzymology , Liver Neoplasms/virology , Male , Middle Aged , Odds Ratio , Phenotype , Risk Factors , Young Adult
20.
Saudi Med J ; 37(10): 1089-95, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27652359

ABSTRACT

OBJECTIVES: To assess the outcomes of different types of bariatric surgeries in a single newly established private obesity center. METHODS: Retrospectively, we included patients who were entered in the registry for bariatric surgeries in the Obesity Unit, Riyadh National Hospital, Riyadh, Saudi Arabia between January 2013 and September 2014, and completed one year of follow up. Baseline characteristics, percent excess weight loss, and safety data were collected and analyzed. RESULTS: A total of 79 patients were included. Based on the type of surgery, patients were divided into 3 groups: laparoscopic Roux-en-Y gastric bypass (RYGB), laparoscopic minigastric bypass (MGBP), and laparoscopic vertical sleeve gastrectomy (SG). After one year, RYGB and MGB patients lost more weight than SG patients. No mortality, or leak were reported and one patient had reoperation after revision laparoscopic RYGB for bleeding. There was one readmission, while 4 patients visited the emergency room for vomiting and dehydration (2 patients), anemia (one patient), and port site infection (one patient). CONCLUSION: Bariatric surgeries are safe when carried out by an experienced bariatric surgeon in the private sector. The outcome of this series is similar to the published results from large international obesity databases.


Subject(s)
Gastric Bypass/methods , Hospitals, Private , Obesity/surgery , Female , Humans , Male , Saudi Arabia , Weight Loss
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