Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use.

BACKGROUND: α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC. METHODS: In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL). RESULTS: AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels increased with decreasing degrees of HCC differentiation (P < .0001). CONCLUSIONS: Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice.

Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy.

OBJECTIVES: We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs). METHODS: Patients with EE and NERD underwent combined impedance-pH monitoring. Normal values were defined on the basis of previously collected data from 48 HVs. We evaluated distal esophageal acid exposure time (AET), number and type of reflux episodes (acid, nonacid), acid and bolus clearance times, proximal extension of reflux episodes, and symptom association probability (SAP). RESULTS: Distal AET (percentage time, pH<4) was higher (P<0.01) in 58 EE patients (median 7.4%, 25-75th percentile 4.2-9.9%) compared with 168 NERD patients (4.2% (1.2-6.4%)) and 48 HVs (0.7% (0.2-1.4%)). Patients with EE and NERD had a higher (P<0.01) number of acid reflux episodes compared with HVs (51 (37-66) vs. 34 (22-51) vs. 17 (8-31); P<0.05), but a similar number of nonacid reflux episodes (22 (15-39) vs. 23 (15-38) vs. 18 (14-26); P=NS). The percentage of reflux episodes reaching the proximal esophagus was higher (P<0.01) in EE patients (57% (45-73%)) than in NERD patients (45% (36-60%)) and HVs (33% (19-46%)). A positive SAP for heartburn or regurgitation was found in 161 of 168 (96%) NERD and 54 of 58 (93%) EE patients (P=NS). CONCLUSIONS: Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.

[Possible connection between gastroesophageal reflux and interstitial pulmonary fibrosis in patients with systemic sclerosis]. / Correlazione tra reflusso gastroesofageo e fibrosi interstiziale polmonare in pazienti affetti da sclerosi sistemica.

Interstitial lung disease represents the main cause of morbidity and mortality in patients with systemic sclerosis. The mechanisms leading to interstitial lung disease are poorly understood and thus current strategies have little effect on this progressive and fatal disease. Therefore, it appears relevant the importance to assess the possible risk factors involved in its pathogenesis. Previous studies in vivo and in vitro suggested that pulmonary fibrosis can occur after repeated aspiration of small amounts of gastric contents over long periods of time. Recently, our group observed that patients with systemic sclerosis and pulmonary fibrosis have a more severe degree of gastroesophageal reflux with a greater number of reflux events and a higher percentage of reflux episodes reaching the proximal esophagus, causing an increasing risk of microaspiration, compared to patients with systemic sclerosis without lung involvement. Further larger controlled studies are necessary to evaluate whether or not the development of interstitial lung disease in systemic sclerosis patients can be prevented by treating gastroesophageal reflux.

Biopsychosocial predictors of interferon-related depression in patients with Hepatitis C.

OBJECTIVES: The aim of this study is to examine the role of different bio-psycho-social risk factors for the onset of depression among patients with Hepatitis C (HCV) treated with Interferon alpha (IFN). MATERIAL AND METHODS: Patients with HCV were recruited and assessed prospectively at baseline and after 4, 8, and 24 weeks since the start of IFN treatment. Assessments included the Hamilton Depression and Anxiety Rating Scales (HAM-D and HAM-A), Toronto Alexithymia Scale, Temperament Evaluation of the Memphis, Pisa, Paris and San Diego, 110 item version (TEMPS-A), Young Mania Rating Scale and other assessment tools. Sociodemographic and clinical factors were entered as predictors in logistic regression models, with early-onset depression (4 weeks) or persistent depression (24 weeks) as the outcomes. RESULTS: Early-onset depression was predicted by preexisting depressive symptoms' severity (baseline HAM-D scores: OR=1.24; 95% CI: 1.03, 1.50; p=0.03) and by the presence of additional physical comorbidities (OR=3.74; 95% CI: 1.12, 12.5; p=0.03). Persistent depression was predicted by additional physical comorbidities (OR=7.75; 95% CI: 1.33, 45.0, p=0.02), depressive temperament (OR=8.95; 95% CI: 1.32, 60.6; p=0.03) and, at trend-level, by unknown mode of HCV contagion (OR=5.21; 95% CI: 0.89, 30.4; p=0.07). CONCLUSIONS: The incidence of IFN-related depression is associated with factors related to patients' physical and temperamental characteristics. Further research should include comprehensive biopsychosocial assessments to improve the early detection and treatment of vulnerable patients in the real clinical world.

Peg-interfon alpha-2a and low-dose ribavirin for treatment of hepatitis C virus infection in patients with sickle-cell anemia in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Data regarding the safety and efficacy of antiviral therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) in patients with sickle-cell disease (SCD) and hepatitis C virus (HCV) infection are scanty. In this study, our aim was to evaluate the safety and efficacy of antiviral therapy with PEG-IFN and low-dose RBV in patients with SCD and chronic HCV infection receiving hydroxyurea in Saudi Arabia. DESIGN AND SETTINGS: This was a prospective interventional study conducted between January 2009 and September 2012 at the outpatient departments of Haematology and Hepatology/Gastroenterology of a tertiary care hospital in Saudi Arabia. PATIENTS AND METHODS: We studied 8 treatment-naive patients (5 males, 63%) with chronic hepatitis C and SCD receiving hydroxyurea who were treated with PEG-IFN alpha-2a (180 micro g weekly) and low-dose RBV (200 mg daily). Early virological response (EVR) and sustained virological response (SVR) rates were assessed in all patients. RESULTS: All patients were infected with HCV genotype 1 (n=6.8%) or 4 (n=22%). EVR was obtained in 3 patients (38%) and SVR in 6 patients (7%). During the study, there was no increase in the number of blood units transfused and emergency visits due to painful crises. CONCLUSION: in Saudi Arabian patients with SCD and chronic HCV infection on hydroxyurea, PEG-IFN and low-dose RBV treatment proved to be efficacious and safe.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.

INTRODUCTION: Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. AIM: To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. METHODS: Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. RESULTS: Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. CONCLUSION: Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.

Overweight is a risk factor for both erosive and non-erosive reflux disease.

INTRODUCTION: Studies have reported that the association between overweight and erosive oesophagitis is very strong, whilst seeming less consistent with non-erosive reflux disease. AIM: We have hypothesized that this difference may be due to the heterogeneity of endoscopy-negative population. METHODS: We studied 81 patients with erosive oesophagitis, 48 controls and 295 endoscopy-negative patients classified by impedance-pH-testing as: (1) pH-POS (abnormal acid exposure); (2) hypersensitive oesophagus (normal acid exposure/SAP+); (3) functional heartburn (normal acid exposure/SAP-). Body mass index was also calculated. RESULTS: Mean body mass index was significantly higher (p<0.05) in erosive oesophagitis than in endoscopy-negative patients as a whole and controls [27 (18-40) vs. 25 (16-48) vs. 23 (16-34)]. However, the separation of endoscopy-negative patients showed that mean body mass index was higher (p<0.05) in those with increased acid exposure time [26 (18-45)] than in hypersensitive oesophagus [24 (16-48)]. The former subgroup was similar to erosive oesophagitis, whilst the latter one to both functional heartburn [23 (16-34)] and controls (p=ns). Increased body mass index represented a risk factor for erosive oesophagitis (odds ratio 1.4; 95% confidence interval, 1.2-1.6) and non-erosive reflux disease pH-POS subgroup (odds ratio 1.35; 95% confidence interval, 1.2-1.5). CONCLUSION: Our study shows that overweight represents an important risk factor for erosive oesophagitis and pH-POS non-erosive reflux disease and not for hypersensitive oesophagus and functional heartburn. This provides an explanation for the previously reported lesser role of this variable in non-erosive reflux disease population.