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1.  Hepatocellular carcinoma markers in the omics era: the glycomic analysis 
Recently, Kamiyama et al. performed N-glycan profile in hepatocellular carcinoma (HCC) using the quantitative N-glycomics procedure by way of glycoblotting technology and using an automated glycan purification system. The study showed significant differences of N-glycans profile between healthy volunteers and liver cancer patients. The glycomic approach showed us the usefulness of new tools for identification and application of a new biomarkers for cancer diagnosis and treatment. These findings reveal a new field for future markers discovery.
PMCID: PMC4273108  PMID: 25568863
Hepatocellular carcinoma (HCC); glycan; glycomic; tumor markers
2.  Gut microbiota in alcoholic liver disease: Pathogenetic role and therapeutic perspectives 
World Journal of Gastroenterology : WJG  2014;20(44):16639-16648.
Alcoholic liver disease (ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.
PMCID: PMC4248208  PMID: 25469033
Alcoholic liver disease; Bacterial translocation; Dysbiosis; Prebiotics; Probiotics; Synbiotic; Gut microbiota; Endotoxin
3.  Individualized Treatment of Genotype 1 Naïve Patients: An Italian Multicenter Field Practice Experience 
PLoS ONE  2014;9(10):e110284.
Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among naïve patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred.
Patients and Methods
621 naïve treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed.
Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir.
Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment.
PMCID: PMC4207756  PMID: 25340799
4.  Laparoscopic Reversal of Hartmann's Procedure: State of the Art 20 Years after the First Reported Case 
Introduction. Aim of the present work is to review the literature to point out the role of laparoscopic reversal of Hartmann procedure. Material and Methods. Number of patients, age, sex, etiology, Hinchey classification, interval between procedure and reversal, position of the first trocars, mean operative time (min), number and causes of conversion, length of stay, mortality, complications, and quality of life were considered. Results. 238 males (52.4%) and 216 females (47.6%) between 38 and 67 years were analyzed. The etiology was diverticulitis in 292 patients (72.1%), carcinoma in 43 patients (10.6%), and other in 70 patients (17.3%). Only 7 articles (22.6%) reported Hinchey classification. The interval between initial procedure and reversal was between 50 and 330 days. The initial trocar was open positioned in 182 patients (43.2%) through umbilical incision, in 177 patients (41.9%) in right upper quadrant, and in 63 patients (14.9%) in colostomy site. The operative time was between 69 and 285 minutes. A total of 83 patients (12.1%) were converted and the causes were reported in 67.4%. The length of stay was between 3 and 12 days. 5 patients (0.7%) died. The complications concern 112 cases (16.4%). Conclusion. The laparoscopic Hartmann's reversal is safer and achieves faster positive results.
PMCID: PMC4158170  PMID: 25210510
5.  Effect of pre- and post-treatment α-fetoprotein levels and tumor size on survival of patients with hepatocellular carcinoma treated by resection, transarterial chemoembolization or radiofrequency ablation: a retrospective study 
BMC Surgery  2014;14:40.
We evaluated treatment modalities and survival in patients with hepatocellular carcinoma (HCC), by pre-treatment and 3-month post-treatment serum alpha-fetoprotein (AFP) levels and pre-treatment tumor diameters.
We retrospectively reviewed 57 patients treated for HCC in our department from January 2002 to December 2012, including their sex, type of hepatitis, Child class, pre-treatment tumor size, pre-treatment levels of albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), red blood cells, hemoglobin, and total bilirubin, pre- and 3-month post-treatment serum AFP, and treatment modality (transarterial chemoembolization, resection or radiofrequency ablation). Survival was analyzed at 1, 3, and 5 years after treatment.
The 57 patients included 44 men and 13 women, of whom 44 had hepatitis C virus (HCV) infection, 3 had hepatitis B virus (HBV) infection, 3 had both HBV and HCV infection, 1 had both HBV and hepatitis D virus infection, and 3 had alcohol-related liver cirrhosis. Both pre- and post-treatment serum AFP levels significantly correlated with recurrent tumor size (P < 0.05 for both). Pre-treatment tumor size did not correlate with recurrent tumor size. Patients who underwent hepatic resection survived significantly longer than those who underwent transarterial chemoembolization or radiofrequency ablation (P < 0.05).
Serum AFP level is useful in diagnosing tumor recurrence and predicting prognosis in HCC patients treated by hepatic resection, transarterial chemoembolization, and radiofrequency ablation. Hepatic resection remains the treatment of choice for HCC in suitable patients.
PMCID: PMC4107750  PMID: 24993566
Hepatocellular carcinoma; Hepatic resection; Transarterial chemoembolization; Radiofrequency ablation; Alpha-fetoprotein; Tumor size; Survival
6.  Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies 
BioMed Research International  2014;2014:203693.
Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.
PMCID: PMC4096380  PMID: 25089265
7.  Acetyl-L-Carnitine Supplementation During HCV Therapy With Pegylated Interferon-α 2b Plus Ribavirin: Effect on Work Performance; A Randomized Clinical Trial 
Hepatitis Monthly  2014;14(5):e11608.
The health status of employees with chronic hepatitis C has major implications for organizations and labour market.
To assess the effects of Acetyl-L-Carnitine administration on work productivity, daily activity, and fatigue in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b and Ribavirin.
Patients and Methods:
In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis, received Pegylated-Interferon-α2b (1.5 mg/kg per week) plus Ribavirin and placebo, while 32 subjects (Group B) received the same dosage of Pegylated-Interferon-α2b plus Ribavirin plus 2g Acetyl-L-Carnitine twice per day, for 12 months. Work productivity loss, impairment in daily activities, presenteeism, absenteeism, have been assessed using the Work Productivity and Activity Impairment questionnaire. We also evaluated severity of fatigue, mental fatigue and physical fatigue.
Significant difference were observed in physical fatigue, mental fatigue and severity of fatigue, aspartate aminotransferase, alanine aminotransferase, and viremia after 12 months treatment. In Group B we observed a significant decrease of presenteeism and daily activity impairment after 6 months, 12 months and at follow up. A significant increase of work productivity was observed after 12 months and at follow up.
Office workers with chronic hepatitis C, treated with Pegylated-Interferon-α2b plus Ribavirin, had work performance loss. In subjects treated with Acetyl-L-Carnitine supplementation we observed increased daily activity and reduced presenteeism and fatigue. Acetyl-L-Carnitinegroup had a smaller reduction of productivity comparing to placebo group.
PMCID: PMC4030263  PMID: 24910702
Acetyl Lcarnitine; Interferon; Ribavirin; Hepatitis C; Fatigue; Quality of Life
8.  Carbohydrate 19.9 Antigen Serum Levels in Liver Disease 
BioMed Research International  2013;2013:531640.
Background. Carbohydrate 19.9 antigen (CA19.9) has been used in the diagnosis and followup of gastrointestinal tumours. The aim of this prospective longitudinal study was the evaluation of CA19.9 levels in patients with chronic hepatitis and hepatic cirrhosis hepatitis C virus and B virus correlated. Materials and Methods. 180 patients were enrolled, 116 with HCV-related chronic liver disease (48% chronic hepatitis, 52% cirrhosis) and 64 with HBV-related chronic liver disease (86% chronic hepatitis, 14% cirrhosis). Patients with high levels of CA19.9 underwent abdominal ecography, gastroendoscopy, colonoscopy, and abdominal CT scan. Results. 51.7% of patients with HCV-related chronic liver disease and 48.4% of those with HBV-related chronic liver disease presented high levels of CA19.9. None was affected by pancreatic or intestinal neoplasia, cholestatic jaundice, or other diseases potentially able to induce Ca19.9 elevations. CA19.9 levels were elevated in 43.3% of HCV chronic hepatitis, in 56.3% of HCV cirrhosis, in 45.1% of HBV chronic hepatitis, and in 58% of HBV cirrhosis. Conclusions. CA19.9 commonly increases in the serum of patients with chronic viral hepatitis. Elevation of CA 19.9 is not specific for neoplastic disease and is related to the severity of fibrosis and to the viral aetiology of hepatitis.
PMCID: PMC3824822  PMID: 24282817
9.  Serum Markers of Intrahepatic Cholangiocarcinoma 
Disease Markers  2013;34(4):219-228.
Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers2- pyruvate-Kinase (TuM2- PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.
PMCID: PMC3809974  PMID: 23396291
Cholangiocarcinoma; tumor markers; CA 19-9; CEA
10.  Potential role of probiotics on colorectal cancer prevention 
BMC Surgery  2012;12(Suppl 1):S35.
Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.
Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.
Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.
PMCID: PMC3499195  PMID: 23173670
11.  Elevated serum levels of Chromogranin A in hepatocellular carcinoma 
BMC Surgery  2012;12(Suppl 1):S7.
During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages.
The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed.
The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001).
Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.
PMCID: PMC3499206  PMID: 23173843
12.  Persistent increase in alpha-fetoprotein level in a patient without underlying liver disease who underwent curative resection of hepatocellular carcinoma. A case report and review of the literature 
Alpha-fetoprotein (AFP) is an oncofetal protein produced by hepatocellular carcinoma (HCC). AFP level can also be elevated in other neoplastic or non-neoplastic conditions. An elevated AFP level has high diagnostic significance for HCC; at a level of >200 ng/mL, the probability of HCC is >90%. The aim of the present paper is to report a patient who underwent curative resection of HCC, who had a persistently elevated AFP level postoperatively but did not develop recurrence during a 2-year follow-up period. A review of the literature is also presented.
Case report
An 82-year-old male was referred following a computed tomography scan showing a 160 mm diameter mass in the left lobe of the liver. This huge mass was diagnosed as HCC, arising in the absence of cirrhosis or viral hepatitis. After tumor removal, the patient’s high AFP level persisted for 2 years.
As steatosis was the only pathological change in the remnant liver, this may have caused the persistently elevated AFP level in this patient.
PMCID: PMC3407768  PMID: 22559879
Alpha-fetoprotein; Hepatectomy; HCC without cirrhosis; HCC
13.  L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-α 2b plus ribavirin 
AIM: To evaluate the efficacy of L-carnitine on alleviating anemia, thrombocytopenia and leukopenia, and minimizing dose reductions in patients with chronic hepatitis C virus (HCV) in treatment with Interferon α (IFN-α) plus ribavirin.
METHODS: Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups. group A (n = 35) received Peg-IFN-α 2b plus ribavirin plus L-carnitine, and group B (n = 34) received Peg-IFN-α and ribavirin for 12 mo. All patients underwent laboratory investigations including: red cell count, hemoglobin, white cell count, platelets, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viremia.
RESULTS: After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8 (IU/L; P < 0.001), ALT 137.9 vs 112.3 (IU/L; P < 0.001), viremia 4.04 vs 2.36 (× 106 copies/mL; P < 0.001), Hb 1 vs 3.5 (g/dL; P < 0.05), red blood cells 0.3 vs 1.1 (× 1012/L; P < 0.001), white blood cells 1.5 vs 3 (× 109/L; P < 0.001) and platelets 86 vs 85 (× 109/L; P < 0.001). The end treatment responders were 18 vs 12 (60% vs 44%) and the non responders were 12 vs 15 (40% vs 50%) [odds ratio (OR) 1.65, 95% CI = 0.65-5.37, P < 0.05]. In group A compared to group B there was a significant improvement of sustained virological response in 15 vs 7 patients (50% vs 25%), while the relapsers were 3 vs 5 (10% vs 18%) (OR 3.57, 95% CI = 0.65-19.3, P < 0.001).
CONCLUSION: L-carnitine supplementations modulate erythropoiesis, leucopoiesis and thrombocytopoiesis, and may be useful in patients treated for HCV. L-carnitine treatment offers the possibility of achieving a sustained virological response while preventing overtreatment.
PMCID: PMC3218156  PMID: 22110268
L-carnitine; Chronic hepatitis C; Anemia; Interferon
14.  Relationship between circulating interleukin-10 and histological features in patients with chronic C hepatitis 
Annals of Saudi Medicine  2011;31(4):360-364.
An imbalance in cytokine production may be involved in the pathogenesis of chronic C hepatitis. The aim of the study was to investigate circulating levels of interleukin-10 (IL-10) in a selected cohort of patients affected by chronic C hepatitis.
Retrospective study based on consecutive hepatitis C virus patients, affected by chronic active hepatitis, attending the general hospital of hepatology unit from June to September 2009
A total of 49 patients with chronic C hepatitis and 20 healthy control subjects similar in gender and age were examined. Circulating IL-10 was assessed by ELISA commercial kit (R and D Systems) in all investigated subjects.
There was no significant difference in IL-10 values between controls and overall patients (P>.05). Nevertheless, among patients, subjects with more severe necroinflammation had higher values than others (P<.001). Moreover, a close relationship was found between IL-10 values and serum aspartate aminotransferase (r=0.61; P<.001).
These findings suggest that IL-10 may be a useful additional marker to assess necroinflammation and to monitor the evolution of liver damage. They also argue for a potential pathophysiological role for IL-10 in the persistence and progression of hepatitis.
PMCID: PMC3156511  PMID: 21808111
15.  Rosuvastatin reduces nonalcoholic fatty liver disease in patients with chronic hepatitis C treated with α-interferon and ribavirin 
Hepatitis Monthly  2011;11(2):92-98.
Nonalcoholic fatty liver disease develops in patients with chronic hepatitis C. Interferon and ribavirin combination therapy is the standard treatment for chronic hepatitis C, but if present, NAFLD can reduce the virological response to anti-HCV therapies.
We determined whether the addition of rosuvastatin to interferon and ribavirin improves the sustained virological response (SVR) and reduces steatosis.
Patients and Methods
This study was a prospective, randomized, open-label trial. Between January 2004 and December 2007, 65 patients with chronic hepatitis (27 women and 38 men, mean age 48 years) aged 32-63 years (median 46 years) were consecutively enrolled. Patients were randomly assigned to receive leukocyte interferon alpha (3 MIU 3 times per week) plus ribavirin (1200 mg per day) for 12 months or interferon alpha and ribavirin at the same dosages plus rosuvastatin (5 mg per day). The primary endpoints were measurements in SVR, liver enzyme, cholesterol, triglyceride, CRP, glucose, and insulin levels; and Homa-IR, fibrosis, and steatosis scores.
After 12 months of treatment, we observed a significant improvement in SVR in 51% of patients who received interferon plus ribavirin plus rosuvastatin compared with 18% of relapsers (OR 1.52; 95% CI = 0.41-5.64; RR 1.13). There were 23 responders (69%) and 10 nonresponders (30%) (OR 1.38; 95% CI = 0.49-16.5; RR 1.11). When comparing interferon plus ribavirin group vs interferon plus ribavirin and rosuvastatin group after 12 months, we observed a significant difference in AST (85.70 vs.106.5.00 IU/ml) (OR 1.2; 95% CI= 0.29-4.94; RR 1.04; p<0.001), ALT (81.80 vs. 126.2 IU/ml) (OR 1.2; 95% CI = 0.29-4.94; RR 1.04; p < 0.001), LDL-cholesterol (0.01 vs. 0.60 mmol/l) (OR 14; 95% CI = 3.98-49.16; p RR 2.96; < 0.001), triglycerides (0.17 vs. 0.2 mmol/l) (OR 20; 95% CI = 4.94-80.89; RR 5.38; p < 0.05), and Viremia (1.8 vs. 2.48 UI/ml, p < 0.05). Mean fibrosis score decreased 0.10 vs. 0.50 (OR 4.5; 95% CI = 0.89-22.66; RR 1.5; p < 0.05), and mean steatosis score declined 0.30 vs. 0.50 (OR 11.2; CI = 2.88-43.53; RR 2.75; p < 0.001).
In HCV patients with NAFLD, the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia, steatosis, and fibrosis without causing side effects.
PMCID: PMC3206670  PMID: 22087124
NAFLD; Ribavirin; Interferon; Hepatitis
16.  Greater severity of new onset asthma in allergic subjects who smoke: a 10-year longitudinal study 
Respiratory Research  2011;12(1):16.
Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma.
Allergic rhinitis subjects with no asthma (n = 371) were followed-up for 10 years and routinely examined for asthma diagnosis. In those who developed asthma (n = 152), clinical severity and levels of asthma control were determined. Among these subjects, 74 (48.7%) were current smokers, 17 (11.2%) former smokers, and 61 (40.1%) never smokers.
When comparing current or past smokers to never smokers they had a higher risk of severe asthma in the univariate analysis, which became non-significant in the multivariate analysis. On the other hand, the categories of pack-years were significantly related to severe asthma in a dose response relationship in both the univariate and multivariate analysis: compared to 0 pack years, those who smoked 1-10 pack-years had an OR(95% CI) of 1.47(0.46-4.68), those who smoked 11-20 pack-years had an OR of 2.85(1.09-7.46) and those who smoked more than 20 pack-years had an OR of 5.59(1.44-21.67) to develop more severe asthma. Smokers with asthma were also more likely to have uncontrolled disease. A significant dose-response relationship was observed for pack-years and uncontrolled asthma. Compared to 0 pack years, those who smoked 1-10 pack-years had an OR of 5.51(1.73-17.54) and those who smoked more than 10 pack-years had an OR of 13.38(4.57-39.19) to have uncontrolled asthma.
The current findings support the hypothesis that cigarette smoking is an important predictor of asthma severity and poor asthma control.
PMCID: PMC3037316  PMID: 21261960
17.  Incidence and causes of neonatal hyperbilirubinemia in a center of Catania 
Aim and scope:
We conducted this study to estimate the incidence of hyperbilirubinemia in a small neonatal care unit in Catania, Italy, and to determine the underlying causes, which would be of value in identifying and implementing strategies to prevent morbidity from this condition.
Management of hyperbilirubinemia remains a challenge for neonatal medicine because of the risk for serious neurological complications related to the toxicity of bilirubin.
From January 2006 to January 2007, we screened 525 newborns born at the Neonatal Care Unit of Valsalva Hospital in Catania, Italy. Infants aged 3–5 days and with unconjugated hyperbilirubinemia were included for assessment if they had a peak serum total bilirubin level exceeding 6 mg/dl (102 μmol/L). Sex, birth weight, gestational age, breast feeding, type of birth, presence of facial bruising (including cephalohematoma) and ABO group were noted. Patients with Toxoplasma or Cytomegalovirus infection, hepatic insufficiency, or suspected drug-induced hyperbilirubinemia were excluded from more detailed analysis.
Our year-long nursery sample examined otherwise healthy-appearing term infants for the prevalence of hyperbilirubinemia (defined as bilirubin levels exceeding 6 mg/dL [11mol/L]). We found hyperbilirubinemia in 19% (100/525). Among the patients with hyperbilirubinemia, almost all (99%) had peak levels of bilirubin <20 mg/dL, levels which are generally considered to be potentially neurotoxic.
In our clinic experience, hyperbilirubinemia was generally a serious medical issue and one whose etiology can usually be well defined.
PMCID: PMC2697514  PMID: 19436609
hyperbilirubinemia; newborns; incidence; breastfeeding

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