Significant Alcohol Intake Research Articles

228 - Improvement of mitochondrial function in steatohepatitis by olive oil consumption: role of nitro fatty acids

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by excessive fat deposition in hepatocytes in the absence of significant alcohol intake. We decided to evaluate the effects on NAFLD of extra virgin olive oil (EVOO) consumption and the role that nitro-fatty acids (NO2-FA) present or formed during digestion in EVOO may have. We postulate that NO2-FA, due to its well-characterized pleiotropic anti-inflammatory properties, could spare mitochondria form the deleterious effects of high fat diet (HFD), contributing to the health benefits associated with EVOO consumption. Accordingly, we analyzed liver mitochondrial function in mice fed with HFD and supplemented with 10% EVOO (w/w) in the absence or presence of nitrite. We have been demonstrated that gastric conditions i.e EVOO plus nitrite at acidic pH favor NO2-FA formation (PLOS One 2014). HFD mice supplemented with EVOO plus nitrite exhibited lower increase in body weight than HFD controls or even animals under normal diet, in addition to a decreased accumulation of fat liver. Liver mitochondrial function was studied by high resolution respirometry. The HFD mice group supplemented with EVOO plus nitrite showed the best mitochondrial respiratory control ratio (RCR). When looking for electron transport respiratory chain complexes activities, complexes II and V were significantly improved by EVOO supplementation and even better in the presence of nitrite. As part of the antioxidant/anti-inflammatory actions of NO2-FA, liver hemoxygenase-1 (HO-1) expression increased in the EVOO/nitrite condition. Plasma NO2-FA levels were lower in the condition of HFD when compared to normal diet while increased in the HFD plus EVOO/nitrite condition suggesting an association between NO2-FA formation by EVOO and the observed improvement of mitochondrial function.

The Hepatic Steatosis Index Is Not Accurate in Predicting the Presence of Fatty Liver Disease in Patients With Hepatitis C Who Achieve Sustained Virologic Response

Introduction: The treatment for chronic hepatitis C virus (HCV) infection has been revolutionized by direct acting antivirals with sustained virologic response (SVR) rates of 95% or higher. However, recent data suggest that nonalcoholic fatty liver disease (NAFLD) may affect up to 50% of patients who achieve SVR based on the presence of steatosis that was determined by controlled attenuation parameter (CAP). Unfortunately, CAP technology is not available for the majority of community providers that treat HCV due to cost. The aim of this study was to assess the utility of the readily available hepatic steatosis index (HSI) in predicting post-SVR NAFLD. Methods: All adult patients treated in our clinic for HCV with SVR and had CAP performed with laboratory/clinical data to calculate HSI were included in this study. Patients with significant alcohol intake and those with HCV genotype 3 infection were excluded. CAP was measured using FibroScanTM by an experienced operator and a cutoff of 248 dB/m was used. Patients fasted for 4 hours prior to CAP measurements. CAP was considered the gold standard to determine post-SVR NAFLD. HSI was calculated using the following variables (ALT, AST, BMI, diabetes and gender) with a cutoff of 36 or higher to predict steatosis. C statistics were performed to assess the accuracy of HSI. Results: A total of 96 patients achieved SVR and had both CAP and HSI done. The mean age was 59 ±11 years, 49% were male and 86% had genotype 1 HCV infection. Based on CAP cutoff value of 248 dB/m, 48/96 (50%) of patients had post-SVR NAFLD. Using HSI cutoff ≥36 for post-SVR NAFLD and in comparison to CAP, HSI had sensitivity of 50%, NPV of 58.6%, specificity of 70.83%, and PPV of 63.1%. Fourteen patients with no evidence of NAFLD on CAP would have been classified incorrectly as having NAFLD based on HSI and 24 patients with NAFLD based on CAP would have been missed by using HSI. Overall, the area under the ROC curve for HSI was poor at 0.604 (95% CI, 0.507-0.700). Conclusion: Post-SVR NAFLD is common in patients who are cured from HCV. HSI had poor performance in this setting, therefore; other readily available noninvasive score that can be used by clinicians are urgently needed to determine the presence of post-SVR NAFLD.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography.

Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

Transcatheter Closure of Pulmonary Arteriovenous Malformation to Facilitate Treatment of Pulmonary Arterial Hypertension

A 60-year-old Caucasian woman was admitted to our institution with new onset progressive dyspnea for 2 to 3 weeks and worsening of chronic lower extremity edema or abdominal distension. She had a history of cirrhosis (significant alcohol intake and hepatitis C), portal hypertension, and an

Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

Background and aimHIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools.MethodsHIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis.Results202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01–1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50–3.79; p<0.001) were independent predictors of NASH.ConclusionsNASH, diagnosed by a non-invasive diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV mono-infected individuals, particularly in the presence of insulin resistance and elevated ALT.

Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study

There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population. A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis. Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030). In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk. In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events.

Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India.

The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity. Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child's class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood. Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.

Association of non-alcoholic fatty liver disease with cardiovascular disease and subclinical atherosclerosis.

Non-alcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of significant alcohol intake, use of steatogenic medication, or hereditary disorders. It is a common cause of chronic liver disease with a worldwide estimated prevalence ranging from 6.3% to 33%. The NAFLD is considered a hepatic manifestation of the metabolic syndrome. Insulin resistance and increased oxidative stress are central to pathogenesis of NAFLD, and risk factors include metabolic syndrome, diabetes mellitus, obesity, lack of physical activity, smoking, and high fat diet. NAFLD is associated with higher mortality as compared to the general population with cardiovascular disease being the most common cause of death. The NAFLD is associated with a higher prevalence of subclinical atherosclerosis as evidenced by odds of higher coronary artery calcification, higher average and maximum carotid intima-media thickness. It is also associated with stiff arteries as evidenced by higher cardio-ankle vascular index and higher brachial-ankle pulse wave velocity. Increasing evidence has linked NAFLD with atherosclerotic cardiovascular diseases. The NAFLD is associated with a higher prevalence of coronary artery disease (CAD), more severe CAD, poor coronary collateral development, and higher incidence of coronary events. The NAFLD is also associated with ischemic stroke. Studies have shown that the association between NAFLD and atherosclerotic cardiovascular diseases is independent of shared risk factors.

Impact of Non-alcoholic Fatty Liver Disease on Chronic Hepatitis B Infection

Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are frequent liver diseases with substantial morbidity and mortality. How often do these two diseases occur together? Does hepatitis B virus protect or promote concurrent fatty liver? How does concurrent fatty liver influence the clinical outcomes of CHB? We summarized the latest evidence to tackle all these clinically significant questions. Concurrent fatty liver in CHB without significant alcohol intake is a common and increasingly alarming problem. Patients with CHB have a lower chance of fatty liver than the general population, but the underlying mechanism remains to be further explored. Clinical impacts of concurrent fatty liver among CHB patients, in terms of treatment response, fibrosis and cirrhosis progression, liver cancer risk, and mortality, are still debatable. Concurrent fatty liver in CHB is a common and clinically relevant condition.

Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B.

Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non-alcoholic fatty liver disease pandemic. The risk of HBV-related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis. We conducted a retrospective cohort study on a liver biopsy cohort of HBV-infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non-alcoholic fatty liver disease-related candidate genes (ADIPOQ, APOC3, GCKR, LEPR, PNPLA3, and PPARG). Among 270 HBV-infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis (P = 0.016) and PNPLA3 rs738409 CG/GG genotype (P = 0.002). At a median follow-up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52-34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30-11.84; P = 0.013) were independent factors predicting HCC development. Concurrent fatty liver is common in HBV-infected patients and an independent risk factor potentiating HBV-associated HCC development by 7.3-fold. The risk of HBV-related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.

Can Alcoholic Liver Disease and Nonalcoholic Fatty Liver Disease Co-Exist?

Nonalcoholic fatty liver disease (NAFLD) by definition would require exclusion of significant alcohol intake. Present study was aimed to assess the prevalence of various components of metabolic syndrome (MS) in patients with alcoholic cirrhosis (AC) and to study the affect of its presence on the severity of liver disease, testing the hypothesis if alcoholic liver disease (ALD) and NAFLD could co-exist. In a retrospective analysis of 16 months data, 81 patients with AC were analysed for the prevalence of MS. The diagnosis of AC was based on the history of alcohol intake, clinical examination, serum biochemistry, hematological parameters, exclusion of other causes of chronic liver disease, imaging and upper gastrointestinal endoscopy. Severity of liver disease was assessed by Child-Turcott-Pugh (CTP) score. MS was assessed as per the ATP III criteria and the affect of MS on CTP score was evaluated. All 81 patients with AC were male [mean age 50.9±9.5, mean CTP score 8.38±1.66]. But for three patients (3.7%) all other 78 patients (96.3%) with AC had at least one component of MS. Forty-three (53.0%) patients had full blown MS with three or more components of MS. Sixty-one (75.30%) patients were either overweight [22 (27.1%)] or obese [39 (48.1%)], with a mean BMI of 25.35±3.86kg/m2. Type II DM was present in 40 (25%) and 28 (34.5%) patients were hypertensive. Twenty-two (27.2%) patients had hypertriglyceridemia and 52 (64.2%) had low HDL. Eleven (13.6%) patients had Child's A cirrhosis, 46 (56.8%) had Child's B and 24 (29.6%) patients had Child's C cirrhosis. Even though not significant statistically, patients with Child's C cirrhosis (17, 70.83%) had higher presence of MS in comparison to Child's A (7, 63.6%) and B (19, 41.3%) cirrhosis. MS is common in patients with AC. Presence of MS may be contributing towards severity of liver disease in these patients indirectly suggesting the co-existence of ALD and NAFLD.

Alcohol misuse—a national pandemic: an investigation to identify whether implementing an alcohol brief intervention service would benefit patients attending an oral and maxillofacial (OMFS) department

• Ayrshire and Arran has significant alcohol intake resulting in a large number of alcohol-related hospital admissions.

Liver fat: a relevant target for dietary intervention? Summary of a Unilever workshop.

Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5% of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose-effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.

Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. HIV-infected persons without viral hepatitis are at increased risk of NAFLD. Nevertheless, data on NAFLD in HIV monoinfection are scarce. We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography and associated controlled attenuation parameter (CAP) in unselected HIV-infected adults without significant alcohol intake or viral hepatitis coinfection. NAFLD was defined as CAP at least 238 dB/m. Significant liver fibrosis and cirrhosis were defined as transient elastography measurement at least 7.1 and 13 kPa, respectively. Predictors of NAFLD and significant liver fibrosis were determined using logistic regression analysis. A total of 300 consecutive patients (mean age 50 years, 77% men; mean CD4 cell count 570 cells/μl, 90% on antiretrovirals) were included as a part of a routine screening program. Transient elastography with CAP identified NAFLD and significant liver fibrosis in 48 and 15% of cases, respectively. NAFLD was independently associated with BMI more than 25 kg/m [adjusted odds ratio (aOR) 4.86, 95% confidence interval (CI) 2.55-9.26] and elevated alanine aminotransferase (ALT) (aOR 3.17, 95% CI 1.43-7.03). Independent predictors of significant liver fibrosis were diabetes (aOR 5.84, 95% CI 1.91-17.85), elevated ALT (aOR 3.30, 95% CI 1.27-8.59) and current use of protease inhibitors (aOR 3.96, 95% CI 1.64-9.54). NAFLD and significant liver fibrosis diagnosed by transient elastography with CAP are major comorbidities in unselected HIV monoinfected persons on antiretroviral therapy, particularly if metabolic conditions and elevated ALT coexist. Noninvasive screening for NAFLD should be implemented in this population to establish early interventions and prevent complications.

Noninvasive Assessment of Liver Fibrosis By Transient Elastography and FIB4/APRI for Prediction of Treatment Response in Chronic Hepatitis C—An Experience from a Tertiary Care Hospital

Liver fibrosis and its sequel cirrhosis represent a major health care burden, and assessment of fibrosis by biopsy is gradually being replaced by noninvasive methods. In clinical practice, the determination of fibrosis stage is important, since patients with advanced fibrosis have faster progression to cirrhosis and antiviral therapy is indicated in these patients. To assess the role of transient elastography (TE) and compare it with APRI and FIB4 for predicting liver fibrosis and assessing the effect of host and viral factors on fibrosis and treatment outcome in CHC patients. In a retrospective analysis, 330 CHC patients underwent liver stiffness measurement (LSM) by TE and tests needed for calculating APRI and FIB4 scores at baseline. 228 patients received a combination of Pegylated IFN-based antiviral therapy and were analyzed for therapeutic response. The study included 330 patients (median age 39 years [range 18-67]), predominantly males (n=227, 68.8%) with baseline LSMs. The median liver stiffness was 7.8kPa (range 3.2-69.1kPa). LSMs and its thresholds for severe fibrosis progression (≥9.5kPa) and cirrhosis (≥12.5kPa) were significantly higher in patients with age ≥40 years, diabetes mellitus, and patients with significant alcohol intake (P=0.003 to P<0.001). By taking TE as a reference, the diagnostic accuracy of FIB4 scores for predicting cirrhosis (AUROC 0.896) was good (+LR 13.4) compared to APRI (AUROC 0.823) with moderate likelihood ratio (+LR 6.9). Among 228 treated patients the SVR rate in genotype 3 was 70% versus 57.8% in genotype 1. Fibrosis score F4 (P=0.023) and HCV genotype (P=0.008) were independent predictors of SVR. The study shows that LSM by TE and fibrosis assessment by FIB4/APRI scores can be used with fair reliability to predict fibrosis and treatment response in patients with CHC infection.

Man With Abdominal Swelling

A 46-year-old man presented to the emergency department with abdominal swelling for 2 weeks. He had a history of hepatitis C that he treated with milk thistle for 20 years. He denied significant alcohol intake. His vital signs were normal and his examination revealed a distended abdomen that was tympanic to percussion with mild tenderness. Paracentesis was performed and milky white fluid was aspirated (Figure 1). Chylous ascites. The patient received intravenous antibiotics and was admitted for suspected spontaneous bacterial peritonitis. Peritoneal fluid analysis showed normal white cell counts and Gram stain results and triglyceride levels of 2,196 mg/dL. Computed tomography (CT) of the abdomen and pelvis showed a para-aortic mass with chylous ascites (Figure 2). Biopsy of the mass confirmed a diagnosis of lymphoma. Chylous ascites is an uncommon finding, typically caused by disturbance of the lymphatic system1Browse N.L. Wilson N.M. Russo F. et al.Etiology and treatment of chylous ascites.Br J Surg. 1992; 79: 1145Crossref PubMed Scopus (177) Google Scholar because of a mass or blunt trauma. Lymphomas are the malignancy responsible for most cases of chyloperitoneum.2Press O.W. Press N.O. Kaufman S.D. Evaluation and management of chylous ascites.Ann Intern Med. 1982; 96: 358-364Crossref PubMed Scopus (277) Google Scholar The grim prognosis of chylous ascites as a result of lymphoma makes prompt diagnosis with lymph node biopsy or laparotomy imperative.2Press O.W. Press N.O. Kaufman S.D. Evaluation and management of chylous ascites.Ann Intern Med. 1982; 96: 358-364Crossref PubMed Scopus (277) Google Scholar Surgery, chemotherapy, or radiation should soon follow.2Press O.W. Press N.O. Kaufman S.D. Evaluation and management of chylous ascites.Ann Intern Med. 1982; 96: 358-364Crossref PubMed Scopus (277) Google Scholar

Challenges in the Management of Laryngeal Cancer in Ile-Ife: Any Emerging Pattern?

Background : We undertook this study to detect emerging pattern in the challenges in managing patients with laryngeal cancer in our setting. Methodology : We review the 16 patients with histologically confirmed laryngeal carcinoma managed at the Otorhinolaryngology Head and Neck surgery Department of Obafemi Awolowo University Teaching Hospitals complex between 1 st January 2008 and 31 st December 2013. Result : There were 11 males and 5 females with mean age of 58.0 years. Three (18.8%) patients who were all males had history of smoking. History of significant alcohol intake was found in 4 (25.0 %) males and 1 (6.3%) female. Fifteen (93.8%) patients presented as an emergency with airway obstruction necessitating emergency tracheostomy. Eight (50.0%)patients had total laryngectomy as primary treatment modality and 1 (6.25%) patient had radical radiotherapy as her primary treatment modality. Six (37.5%) patients refused further treatments after their initial emergency Tracheostomy, Laryngoscopy and Biopsy and were subsequently lost to follow up. One (6.35%) patient died before commencement of definitive treatment. Among the laryngectomy group, 2 (12.5%) died on admission, 2 (12.5%) was lost to follow up and1 (6.25%) had stoma recurrence; Three (18.75%) patients are alive. All the patients with loco-regional failure had it within 18 months with only 1 (6.25%) survival at 2 years. Conclusion : Late presentation and treatment refusal remain the major challenges in this study. There is thus an urgent need for health education to promote early presentation.

Abstract 2973: Exome sequencing of 243 liver tumors identifies new mutational signatures and potential therapeutic targets

Abstract Background and Aims: Hepatocellular carcinoma (HCC) is a heterogeneous disease mainly developing in chronic liver disease and caused be a variety of etiologies. Hepatocarcinogenesis is a multi-step process in which pre-cancerous lesions can ultimately transform into advanced liver cancer. Genomic analyses promise to unravel the mutagenic processes in order to identify molecular profiles and to optimize personalized patient care. Methods: We performed exome sequences of 243 liver tumors from European patients (France, Italy and Spain), associated with cirrhosis (F4, n = 118), fibrosis (F2+F3, n = 46), or non-fibrotic livers (F0+F1, n = 79). Cirrhosis-associated tumors presented different stages along HCC progression: 7 dysplastic macronodules, 7 early, 17 small and progressed, 58 classic, and 29 poor-prognosis HCC. Tumors were categorized by varying risk factors: Significant alcohol intake (41%), HCV (26%), non-alcoholic steatohepatitis (18%), HBV (14%), hemochromatosis (7%), no known etiology (11%). Results: We identified 8 mutational signatures of which 6 (Signatures 1A, 1B, 4, 5, 6, and 16) were previously validated in a pan-cancer analysis, while 2 (Signatures 23 and 24) are novel. Hierarchical clustering, based on mutational signatures, revealed 6 groups (MSig1 to 6) and 4 singletons which were significantly associated with specific risk factors, mainly combined alcohol/tobacco consumption, and aflatoxin B1. Next, we identified 161 putative driver genes associated with 11 recurrent pathways. Associations of mutations defined 3 groups of genes centered on CTNNB1 (alcohol), TP53 (HBV), and AXIN1. Analyses according to tumor stage progression revealed TERT promoter mutation as an early event whereas FGF/CCND1 amplification, TP53 and CDKN2A alterations, appeared at more advanced stages in aggressive tumors. Altogether, 28% of patients harbored at least one damaging alteration potentially targetable by an FDA-approved drug and 86% by a drug which has been studied in phase I to phase III clinical trials. Conclusions: In conclusion, our study identified relationships between environmental exposures and mutational patterns in HCC as well as the landscape of driver genes and pathways altered in different clinical stages and etiological backgrounds. For patient care, genomic alterations identified in targetable genes will be useful to determine HCC patients that could potentially benefit from targeted treatment in future clinical trials. Citation Format: Kornelius Schulze, Sandrine Imbeaud, Eric Letouzé, Ludmil B. Alexandrov, Julien Calderaro, Sandra Rebouissou, Gabrielle Couchy, Clément Meiller, Jayendra Shinde, Shalini Datta, Frederic Soysouvanh, Anna-Line Calatayud, Roser Pinyol, Laura Pelletier, Charles Balabaud, Alexis Laurent, Jean-Frederic Blanc, Viccenzo Mazzaferro, Fabien Calvo, Augusto Villanueva, Jean-Charles Nault, Paulette Bioulac-Sage, Michael R. Stratton, Josep M. Llovet, Jessica Zucman-Rossi. Exome sequencing of 243 liver tumors identifies new mutational signatures and potential therapeutic targets. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2973. doi:10.1158/1538-7445.AM2015-2973

Radiofrequency Ablation Parameters Correlate With Survival of Patients With Hepatocellular Carcinoma

SignificanceNoticeably the response of HCC tumors with RF heating are varied: some would ablate with shorter time at lower temperatures and others would ablate with longer time at higher temperatures. The objective of this study is to determine the correlation between radiofrequency ablation parameters with survival.MethodologyThis is a retrospective case-control study. Clinical, laboratory and intraprocedure RFA parameters were collected from charts of HCC patients who underwent RFA from January 2009 to June 2013. The patients were arbitrarily grouped as either having “presumed soft HCC tumor” if the highest RF temperature achieved is <60oC and the time to first ablation is <5 minutes, or “presumed hard HCC tumor” if any of the two criteria were not satisfied. Statistical analysis was done for survival functions between “presumed soft HCC tumor” versus “presumed hard HCC tumor” using Kaplan-Meier method.ResultsThere were 88 tumors from 55 patients included in the study analysis. Patients with “presumed soft HCC tumor” have a better survival than those with “presumed hard HCC tumor” (60.63% vs 51.86%) with p-value: 0.011. Low AFP level, lack of significant alcohol intake, absence of portal vein thrombus and a single tumor favor survival.ConclusionPatients with “presumed soft HCC tumor” have higher survival. RFA can be both therapeutic and prognostic in patients with hepatocellular carcinoma. SignificanceNoticeably the response of HCC tumors with RF heating are varied: some would ablate with shorter time at lower temperatures and others would ablate with longer time at higher temperatures. The objective of this study is to determine the correlation between radiofrequency ablation parameters with survival. Noticeably the response of HCC tumors with RF heating are varied: some would ablate with shorter time at lower temperatures and others would ablate with longer time at higher temperatures. The objective of this study is to determine the correlation between radiofrequency ablation parameters with survival. MethodologyThis is a retrospective case-control study. Clinical, laboratory and intraprocedure RFA parameters were collected from charts of HCC patients who underwent RFA from January 2009 to June 2013. The patients were arbitrarily grouped as either having “presumed soft HCC tumor” if the highest RF temperature achieved is <60oC and the time to first ablation is <5 minutes, or “presumed hard HCC tumor” if any of the two criteria were not satisfied. Statistical analysis was done for survival functions between “presumed soft HCC tumor” versus “presumed hard HCC tumor” using Kaplan-Meier method. This is a retrospective case-control study. Clinical, laboratory and intraprocedure RFA parameters were collected from charts of HCC patients who underwent RFA from January 2009 to June 2013. The patients were arbitrarily grouped as either having “presumed soft HCC tumor” if the highest RF temperature achieved is <60oC and the time to first ablation is <5 minutes, or “presumed hard HCC tumor” if any of the two criteria were not satisfied. Statistical analysis was done for survival functions between “presumed soft HCC tumor” versus “presumed hard HCC tumor” using Kaplan-Meier method. ResultsThere were 88 tumors from 55 patients included in the study analysis. Patients with “presumed soft HCC tumor” have a better survival than those with “presumed hard HCC tumor” (60.63% vs 51.86%) with p-value: 0.011. Low AFP level, lack of significant alcohol intake, absence of portal vein thrombus and a single tumor favor survival. There were 88 tumors from 55 patients included in the study analysis. Patients with “presumed soft HCC tumor” have a better survival than those with “presumed hard HCC tumor” (60.63% vs 51.86%) with p-value: 0.011. Low AFP level, lack of significant alcohol intake, absence of portal vein thrombus and a single tumor favor survival. ConclusionPatients with “presumed soft HCC tumor” have higher survival. RFA can be both therapeutic and prognostic in patients with hepatocellular carcinoma. Patients with “presumed soft HCC tumor” have higher survival. RFA can be both therapeutic and prognostic in patients with hepatocellular carcinoma.

Prevalence of and predictive factors for nonalcoholic fatty liver disease in Sudanese individuals with type 2 diabetes: Is metabolic syndrome the culprit?

Background and study aimNon-alcoholic fatty liver disease (NAFLD) is a common global chronic liver condition. The prevalence of NAFLD among individuals with type 2 diabetes is estimated to be as high as 75%. The aim of this study was to determine the prevalence of NAFLD among individuals with type 2 diabetes in Sudan. Patients and methodsThis was a cross-sectional hospital-based study, which was carried out at the Jabir Abu-Elizz diabetic centre in Khartoum; 167 outpatients with type 2 diabetes were enrolled. NAFLD was diagnosed based on ultrasound, following exclusion of significant alcohol intake and secondary causes of liver diseases. NAFLD was defined as hepatic steatosis in the absence of alcohol intake, medication, previous liver disease and negative results for the serological test for hepatitis B and C. Logistic regression analysis was used to determine independent risk factors for the development of NAFLD in individuals with type 2 diabetes. ResultsThe number of female subjects was 89 (53.3%), and most subjects (145, 86.8%) were between the ages of 40 and 70years. The overall prevalence of fatty liver among individuals with type 2 diabetes was found to be 50.3%. Age, duration of diabetes, hypertension and HbA1c levels appeared to have no impact on the prevalence of NAFLD. The possible predictors of NAFLD were overweight, obesity, central obesity, high triglyceride level and low high-density lipoprotein cholesterol (HDL-c) level. A higher prevalence of NAFLD was observed in individuals with three components of the metabolic syndrome. ConclusionNAFLD was observed in half of the diabetic population, and its occurrence correlates positively with metabolic syndrome risk factors.