High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study.

BACKGROUND & AIMS: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease. METHODS: This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed. CONCLUSIONS: These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes.

[Acceptability and quality of abdominal ultrasound studies requested by medical professionals]. / Adecuación y calidad de las ecografías abdominales solicitadas por los profesionales de medicina.

OBJECTIVE: To evaluate the acceptability/quality of abdominal ultrasound studies requested by primary care physicians in Barcelona; to develop ultrasound guidelines and assess their impact on acceptability. DESIGN: 2-phase study, one retrospective, descriptive phase evaluating the acceptability/quality of requests (pre-intervention phase) and another to assess the impact of guidelines on acceptability/quality (post-intervention phase). SUBJECTS: Requests for ultrasound studies from January-June 2010 from 10 primary care centers and the same number of requests from the same centers after the intervention. VARIABLES: Pre-intervention phase: reason for consultation and request; presence of diagnostic orientation; results of ultrasound; acceptability/quality of the request. INTERVENTION: design guidelines using the nominal group technique, dissemination of guidelines in the same centers. Post-intervention phase: three months after dissemination analyze the same number of requests assessing the same variables included in the pre-intervention phase. RESULTS: Pre-intervention phase: 1,063 requests, 52.4% women, mean age 52±16years (range 11-94). Post-intervention phase: 1,060 requests, 57.6% women, mean age 54±17years (range 6-91). Main reasons for requests: abdominal pain/discomfort 38.3% (pre-intervention) and 43.1% (post-intervention). Diagnostic orientation in 14.5% (pre-intervention) and 40.8% (post-intervention). Normal ultrasound results in 46.0% (pre-intervention) and 42.3% (post-intervention). Good quality of requests in 42.7% (pre-intervention) and 46.5% (post-intervention). Acceptability of ultrasound: 70.5% (pre-intervention) and 94.1% (post-intervention). The better the quality of the request, the better the acceptability of the studies and the greater the number of pathological conditions identified. CONCLUSIONS: Guidelines for ultrasound improve the quality of requests, diagnostic orientation and acceptability of the studies.

[Non-invasive markers of fibrosis in the diagnosis of non-alcoholic fatty liver disease]. / Marcadores no invasivos de fibrosis en el diagnóstico del hígado graso no alcohólico.

OBJECTIVE: To analyze the utility of three indices to predict hepatic fibrosis in the detection of non-alcoholic fatty liver disease (NAFLD) as a non-invasive method in primary care. DESIGN: We performed a descriptive, cross-sectional, multicenter study with a populational base from 25 primary care centers in the province of Barcelona. PARTICIPANTS: Healthy individuals aged 17 to 83 years randomly selected from the Primary Care Computer System. METHODS: Medical history, physical examination, and blood analyses were used to determine the following predictive indices of fibrosis; HAIR (hypertension, alanine-aminotransferase, insulin resistance); Fatty Liver Index (FLI) (body mass index, gammaglutamyl-transpeptidase, triglycerides, abdominal perimeter) and Lipid Accumulation Product (LAP) (triglycerides, abdominal perimeter), and abdominal echography. RESULTS: We included 702 individuals; 58% were women and the mean age was 53±14 years. The FLI was positive in 30.8%, HAIR was positive in 6.7%, and LAP was positive in 15.5%. Agreement among the three indices ranged from 63.1% to 84.9%, with kappa indices between 0.18 and 0.50. A total of 184 individuals met the echographic criteria of NAFLD, representing a prevalence of 26.29%. The prevalence of NAFLD in patients with positive FLI, HAIR and LAP indices was 46.8%, 68.1% and 56%, respectively. The index with the greatest sensitivity for NAFLD was tFLI≥60 with 84%. Specificity was highest for HAIR and LAP with 97% and 91%, respectively. CONCLUSIONS: FLI, HAIR and LAP are highly prevalent and have been shown to be independent markers for the diagnosis of NAFLD. Because of the lack of concordance between the indices, different prevalences are obtained, thus requiring criteria to be unified in order to obtain a more useful index for the diagnosis of NAFLD.

Using transient elastography to detect chronic liver diseases in a primary care nurse consultancy.

BACKGROUND: Chronic liver diseases (CLDs) are significant causes of death in adults in many countries and are usually diagnosed at late stages. Early detection may allow time for treatment to prevent disease progression. OBJECTIVES: The aim of this study was to assess the feasibility of screening for unrecognized CLDs in a primary care nurse consultancy and report findings from screening. METHODS: Two experienced nurses in a primary care nurse consultancy were trained to perform transient elastography (TE). Subjects aged from 18 to 70 years were identified randomly from the health registry and invited to participate in a feasibility pilot study. Exclusion criteria were past or current history of liver diseases. Nurses collected demographic and clinical data and performed TE tests using Fibroscan to measure liver stiffness; a cutoff score of 6.8 kPa or greater was used as an indicator of the presence of CLD with fibrosis. RESULTS: Accurate measurements were obtained in 495 of 502 participants (98.6%). Prevalence of elevated liver stiffness was observed in 28 of 495 subjects (5.7%). Compared to patients with normal liver stiffness, patients with increased liver stiffness were older, were more frequently male, and had higher frequency of metabolic syndrome. Nonalcoholic fatty liver was the most common cause of CLD. DISCUSSION: Following training in procedures for conducting TE, nurses in a primary care clinic were able to detect unrecognized CLDs in presumably healthy subjects. Early detection of CLDs is feasible in primary care clinics and may facilitate identification of undiagnosed CLD in adults.

TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population.

Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18-75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 ± 12 years; 61% female). Subjects with TSH ≥ 2.5 µIU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH ≥ 2.5 (µIU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively, in subjects with TSH ≥ 2.5 µIU/mL compared with TSH < 2.5 µIU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values ≥ 10 µIU/mL.

Risk of Liver Fibrosis According to TSH Levels in Euthyroid Subjects.

Alterations in thyroid function may contribute to the development of liver fibrosis especially in subjects with non-alcoholic fatty liver disease. This study aimed to investigate the risk of liver fibrosis according to low-normal thyroid function in the general population. We performed a descriptive cross-sectional study in subjects from 18-75 years randomly selected from 16 primary health care centers from 2017-2019. Each subject underwent clinical evaluation, physical examination, blood analysis and transient hepatic elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with fibrosis. We included 1096 subjects (60 ± 11 years; 61% women); 70% had strict-normal thyroid function and 30% had low-normal thyroid function. Low-normal thyroid function was associated with a higher liver stiffness (LS) values: 5.2 vs. 4.8 kPa (p = 0.001) and a greater prevalence of fibrosis: 6.1 vs. 3% (p = 0.016) and 4.3 vs. 2.1% (p = 0.044) for the cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively. After adjustment for potential confounding factors, the risk of fibrosis in subjects with low-normal thyroid function was OR 1.54 (p = 0.213). In conclusion, low-normal thyroid function is associated with higher LS values and a greater risk of liver fibrosis in the general population, being dependent on other metabolic factors.

Adequacy and quality of abdominal echographies requested by primary care professionals.

BACKGROUND: The value of abdominal echography in primary care is great because it is innocuous, inexpensive, easy to perform and provides a great deal of information making this the first examination to be requested in cases of probable abdominal disease. However, too many abdominal echographies are probably requested overcrowding the Departments of Radiodiagnosis with not always justified petitions or with repetition of tests based on little clinical criteria. METHODS/DESIGN: The aim of the study is to evaluate the adequacy and quality of abdominal echographies requested by primary care physicians in the Maresme County (North of Barcelona), develop guidelines for indicating echographies and reevaluate this adequacy after implementing these guidelines.We will perform a two-phase study: the first descriptive, and retrospective evaluating the adequacy and quality of petitions for abdominal echographies, and in the second phase we will evaluate the impact of recommendations for indicating abdominal echographies for PC physicians on the adequacy and quality of echography petitions thereafter.This study will be carried out in 10 primary care centres in the Maresme (Barcelona).1067 abdominal echographies requested by primary care physicians from the above mentioned centres from January 2007 to April 2010 and referred to the Department of Radiology and the same number of applications after the intervention.All the petitions for abdominal echographies requested will be analysed and the clinical histories will be obtained to determine demographic variables, the reason for the visit and for the echography petition and diagnostic orientation, clinical and echographic data, evaluation of the echographies according to the quality and variables characterising the professionals requesting the echographies including: age, sex, laboral situation, length of time in work post, formation, etc.To achieve a consensus of the adequacy of abdominal echography, a work group including gastroenterologists, radiologists and general practitioners will be created following the nominal group. This will allow the design of guidelines for the indication of abdominal echography and posterior evaluation of their impact among physicians by diffusion and posterior reevaluation of the adequacy of the petitions.

Relationship between hypothyroidism and non-alcoholic fatty liver disease in the Spanish population. / Relación entre el hipotiroidismo y el hígado graso no alcohólico en una población española.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries and is considered the hepatic component of metabolic syndrome (MetS). Recently hypothyroidism has been associated with NAFLD but has never been studied in Spain. OBJECTIVES: To analyze the relationship between hypothyroidism (clinical and subclinical) and NAFLD. To determine the association between MetS with NAFLD and hypothyroidism. METHODS: Cross-sectional, retrospective, population study in subjects ≥45 years from primary care centres in Catalonia included in the SIDIAP database. The data was collected between 2009 and 2013. VARIABLES: socio-demographic data, comorbidities, toxic habits, physical examination, analytical tests and diagnosis of MetS. Descriptive analysis and application of statistical tests for the comparison of variables. RESULTS: Sample of 10,116 individuals with a mean age of 61(10) and a predominance of females (63.6%). The prevalence of hypothyroidism was 9.1%, with no significant differences according to the presence of NAFLD (p=.631). Hypothyroidism was associated with higher triglyceride levels and a greater prevalence of obesity (p=.003). Greater alteration of AST was detected in individuals with elevated TSH (p=.012) and decreased levels of T4L (p=.037). Alterations in thyroid hormone levels were not associated with a higher prevalence of NAFLD (TSH p=.072 and T4L p=.447). Hypothyroidism was not considered a risk factor for the development of NAFLD (OR .75; 95% CI: .39-1.44; p=.38). CONCLUSIONS: No association was found between hypothyroidism and NAFLD. Prospective studies are needed to clarify a possible relationship between these two diseases.

Prevalence of Early Chronic Kidney Disease and Main Associated Factors in Spanish Population: Populational Study.

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18-75 years randomly selected from 18 Primary Healthcare centers in the area of Barcelonès Nord and Maresme (Catalunya, Spain). Variables: anamnesis, physical examination, blood pressure, and analysis. EKD was defined with by a glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 and albumin/creatinine ratio (ACR) ≥17 mg/g in men and ≥25 mg/g in women confirmed with two determinations. 2871 individuals: 43% men, mean age 55 years (19-75), 32.2% obese, 50.5% abdominal obesity, 21.1% hypertensive, and 10.6% diabetic. Prevalence of EKD: With one determination 157 individuals (5.5%), 110 men (9%) and 47 women (2.8%); with two determinations 109 individuals (3.8%), 85 men (7%), and 24 women (1.5%). Factors independently associated with the multivariate logistic regression model: Man (OR 3.35), blood pressure ≥ 135/85 mmHg (OR 2.29), BMI ≥ 30 kg/m2 (OR 2.48), glycemia ≥ 100 mg/dL (OR 1.73), smoker (OR 1.67) and age (OR 1.04). The prevalence varies if the diagnosis is established based on one or two analytical determinations, overestimated if only one determination is made and depends on the value chosen to define urine albumin excretion.

[Reasons for not carrying out stem cell transplantation in patients referred to a transplant unit]. / Causas por las que no se realiza el trasplante de progenitores hematopoyéticos en pacientes remitidos a una unidad de trasplante.

BACKGROUND AND OBJECTIVE: Although indications of stem cell transplantation (SCT) are increasing, a transplant may not be performed in all planned cases for several reasons. Our objective was to investigate the reasons for which SCT was not performed in patients referred to a transplant unit. PATIENTS AND METHOD: Pretransplant data of 129 patients consecutively referred to a transplant unit between December 1999 and November 2002 were collected. Frequency and causes of non transplantation were analyzed. Transplanted and non transplanted patient's characteristics were compared. RESULTS: In 119 out of 129 patients, an autologous SCT was indicated and in 10 of them an allogeneic SCT was planned. Mean (SD) age was 46 (14) years (range, 13-69) and 69 (53.5%) were males. One hundred eighteen patients had malignant hematological diseases and 11 had solid tumours. Sixty-one patients showed complete response and 68 had a partial response. At the time of the analysis, 93 SCT had been performed in 90 (69.8%) patients. Autologous SCT was performed in 81 patients (two SCT in one patient) and allogeneic SCT in 10 (two in one patient). Two (1.5%) patients were still awaiting SCT. An SCT was not performed in 37 (28.7%) patients. Causes of non transplantation included: in 12 (32.5%) cases, relapse and/or progression at the time the SCT had been planned; in 12 (32.5%), delay or change in the therapeutic decision; in 9 (24%), poor mobilization; and in 4 (11%), patient's refusal. When delay in SCT was excluded from the analysis, the frequency of no transplant was 19.4%. In 21 (57%) patients of the non-SCT group, peripheral stem cells were previously collected by apheresis. Both groups (SCT and non-SCT) were comparable regarding patients' and disease characteristics except for a more advanced age in the non-SCT group (51 [12] vs 44 [14] years, p<0.005) and status of the disease at the pretransplant visit. CONCLUSIONS: The frequency of not performing an SCT in patients referred to a SCT unit was considerable. Relapses and disease progression and poor mobilization were the main causes for it. Delay was also a relatively common cause.

[Risk factors associated with non-alcoholic fatty liver disease: a case-control study]. / Factores de riesgo asociados a la presencia de hígado graso no alcohólico: un estudio de casos y controles.

BACKGROUND AND OBJECTIVES: To establish the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) and evaluate the influence of each component constituting the metabolic syndrome (MS) and the risk of developing NAFLD. PATIENTS AND METHODS: We performed a multicenter, population-based, observational, analytical study of cases and controls. A case was defined as any patient fulfilling the inclusion criteria and presenting NAFLD by abdominal echography for any reason. A control was randomly selected for each case, from the same health center and of the same age and sex. All the cases underwent anamnesis, physical examination, complete biochemical analyses and determination of MS according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. All the controls also underwent an abdominal echography. RESULTS: We included 327 cases and 377 controls with a mean age of 56 ± 12 years for the cases and of 55 ± 13 years for the controls (range: 17 and 80 years); 52.0% of the cases were males and 49.1% of males were controls. The risk factors associated with NAFLD were obesity (odds ratio [OR] 3.82, 95% confidence interval [95% CI] 2.19-6.66), MS (OR 1.73, 95% CI 1.09-2.75), insulin resistance (OR 3.65, 95% CI 2.18-6.12), and an increase in alanine aminotransferase (ALT) (OR 4.72, 95% CI 2.58-8.61) and gamma glutamyl transferase values (GGT) (OR 1.95, 95% CI 1.14-3.34). The components of the MS best predicting NAFLD were hyperglycemia (OR 1.65, 95% CI1.06-2.56) and triglyceride values (OR 1.75, 95% CI1.13-2.72). CONCLUSIONS: The independent variables associated with NAFLD were obesity, insulin resistance and elevated ALT and GGT. The components of MS best predicting NAFLD were hyperglycemia and an increase in triglyceride values.

Metabolic syndrome and nonalcoholic fatty liver disease in a Spanish population: influence of the diagnostic criteria used.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and it is considered the hepatic component of the metabolic syndrome (MetS). The WHO, the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) have different criteria to define MetS. The aim of this study was to analyze the association between NAFLD and MetS using the three existing criteria. METHODS: Cross-sectional, descriptive population-based study derived from a previous study on the prevalence and factors associated with NAFLD in Spain. RESULTS: A total of 696 individuals [mean age 53 ± 14 years (range 17-83 years)] were included, 59% of whom were women. The prevalence of MetS was 34.2% according to the IDF, 17.7% according to the NCEP and 15.5% according to the WHO. Concordance among the different criteria was between 76 and 87%, with kappa indexes between 0.39 and 0.54. NAFLD was present in 184 individuals according to echographic criteria (prevalence 26.4%). The prevalence of NAFLD among patients with MetS was 43% (IDF), 53% (NCEP) and 64% (WHO). The odds ratio (95% confidence interval) for a logistic regression using NAFLD as a dependent variable varied from 3.44 (2.42-4.88) for IDF to 7.28 (4.68-11.3) for WHO, being 4.28 (2.84-6.43) for NCEP. CONCLUSION: The MetS is quite frequent in the general population, although its prevalence varies considerably according to the criteria used for its definition. The MetS is associated with NAFLD, with the WHO definition being the best to determine its presence, probably because of the inclusion of insulin resistance as a main component. Unification of criteria is needed to adequately compare the prevalence of MetS and its relationship with NAFLD in different population groups.

[Elective inguinal hernioplasty in patients on chronic anticoagulation therapy. Management and outcome]. / Hernioplastia inguinal electiva en pacientes con anticoagulación oral. ¿Son candidatos a cirugía ambulatoria?

BACKGROUND: Perioperative management of patients on anticoagulant therapy increases the complexity of elective inguinal hernia repair. We assessed the safety of our standardised anticoagulation protocol and investigated the outpatient and one day surgery rates. MATERIAL AND METHODS: The records of 1184 patients undergoing elective inguinal hernioplasty between 2005 and 2007 were reviewed; 14 patients on chronic anticoagulation therapy were identified. We used a standard bridging therapy protocol with low-molecular-weight heparins. Outcomes were assessed at 30 days post-procedure and included bleeding, thromboembolic events or death and type of hospital admission. RESULTS: Mean age was 74+/-10 years; 12 (25%) patients were high risk for thromboembolism and 31 (67%) patients were ASA III. Almost all inguinal repairs were performed using a polypropylene mesh; 6 (13%) patients had a surgical site haematoma and there was 1 (2.7%) major bleeding, that was re-operated on. No thromboembolic events or deaths occurred; 11 (23%) patients were treated on an outpatient basis and 16 (34%) on a one day surgery regimen. Mean hospital stay was 2.4+/-5.1 days. CONCLUSIONS: Elective inguinal hernioplasty in patients on chronic oral anticoagulation therapy using a standard bridging protocol is a safe procedure. Chronic anticoagulation therapy is not a contraindication for ambulatory surgery.

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients.

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30 x 10(9)/l. They had received a median of five (2-13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m(2) in four weekly doses in 77 patients, and 12 patients received 1-6 doses. Forty-nine patients (55.1%) reached platelet counts >50 x 10(9)/l; 41 (46%) achieved a complete response (CR; platelets >100 x 10(9)/l), and eight (9%) obtained a partial response (platelets 50-100 x 10(9)/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2-42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.