Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review.

BACKGROUND AND AIMS: The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS: A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS: Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION: Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

Prevalence and risk factors of fatty liver in Portuguese adults.

BACKGROUND: Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period. MATERIALS AND METHODS: A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years). Participants were evaluated after 12-hour fasting. Anthropometric data, past history including alcohol consumption, and associated diseases were registered. Blood samples were collected for biochemical testing. Dietary intake was evaluated using a semi-quantitative food frequency questionnaire. Presence of FL was evaluated using ultrasound, and NAFLD was diagnosed after exclusion of other causes for liver disease. RESULTS: Adjusted prevalence of FL and NAFLD was 37.8% and 17.0%, respectively. FL individuals were older, more frequently males, with increased probability of having obesity, diabetes or harmful alcohol consumption (HAC). NAFLD individuals were also older, but had a similar sex distribution and an increased probability of obesity and diabetes. In both groups, no differences were found regarding dietary pattern or physical activity. During the same time period, nonalcoholic steatohepatitis (NASH) liver-related deaths in Portugal were 0.105/100 000, while alcohol-related liver disease mortality was 6.790/100 000. CONCLUSION: The large spectrum of FL was present in more than one third of the population, although only less than half could be classified as NAFLD. Other significant risk factors, such as HAC, are probably implicated in FL, explaining the low NASH-related mortality compared with the high alcohol-related mortality during the same time period.

Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

BACKGROUND & AIMS: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. METHODS: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index ≥30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. RESULTS: We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm3 and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis. CONCLUSIONS: In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.

Identifying palliative care needs in a Portuguese liver unit.

BACKGROUND & AIMS: Chronic liver disease is a major worldwide cause of morbidity and mortality. Palliative care policies are not clearly established in chronic liver disease. The NECPAL CCOMS-ICO© (NECesidades PALiativas/Palliative Needs) is a tool to identify palliative care needs, including a section for liver disease. AIM: The aim of this study was to identify palliative care needs in liver patients hospitalised in a tertiary referral Liver Unit. METHODS: Single-centre prospective observational study. One hundred and twenty patients with cirrhosis were included and NECPAL questionnaire was applied to all patients in a 7-month period. RESULTS: 84.2% of patients were considered as requiring palliative intervention; however, clinicians identified those needs only in 65.8% of the cases and caregivers in 6.7% of the cases; less than 8% of the patients were referred for palliative care consultation. An excessive use of healthcare resources (positive answer to question 3) was strongly associated with a positive need for palliative care (positive NECPAL): OR 7.305, CI 95% 2.54-20.995, P < .001). An excessive use of healthcare facilities has a sensitivity of 84.2% and a specificity of 42.1% for prediction of a positive NECPAL result (AUC 0.710, 95% CI 0.570-0.850, P = .004). CONCLUSIONS: The NECPAL CCOMS-ICO© represents a feasible and easy-to-use tool to identify palliative care needs in patients with chronic liver disease.

No Evidence for Lower Levels of Serum Vitamin D in the Presence of Hepatic Steatosis. A Study on the Portuguese General Population.

Introduction and aims: Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, paralleling the pandemic of obesity and diabetes, and represents an important burden. Nutrition knowledge is fundamental, in prevention, evolution and treatment of NAFLD. Association of low serum levels of vitamin D (VD) with several diseases, including NAFLD, has been emphasized in the last decade. We evaluated how serum levels of VD correlate with the presence of hepatic steatosis, and VD intake, in a random sample of the Portuguese adult population. Methods: Participants underwent a dietary intake inquiry, using a semi-quantitative food frequency questionnaire representative of the usual intake over the previous year. Anthropometric measures, blood tests and ultrasound were done. Hepatic steatosis was quantified according to Hamaguchi's ultrasonographic score (steatosis defined by a score ≥ 2). Results: We recruited 789 adult individuals, 416 males (52.7%), mean age of 49.9 ± 17.0 years (18-79). Prevalence of hepatic steatosis was 35.5%, and after exclusion of excessive alcohol consumption, 28.0%. Mean VD serum levels were 26.0 ± 9.8 ng/ml and 68.4% participants had serum VD levels below 30 ng/ml. Mean serum levels of VD were not significantly different between participants with steatosis vs. no steatosis: 25.2±8.7 vs. 26.4±10.3 ng/ml, respectively (p=0.071). There was no correlation between VD serum levels and VD intake, measured by the FFQ, r=0.075 (p= 0.383). Conclusions: In spite of a high prevalence rate, there was no evidence that decreased VD serum levels were associated with hepatic steatosis. No significant correlation was found between VD dietary ingestion and VD serum levels.

A rare cause of acute liver failure- a case report.

BACKGROUND: Acute liver failure (ALF) induced by diffuse metastatic disease has rarely been reported. CASE PRESENTATION: We present a 51-years-old woman with relevant clinical history for breast cancer. The patient was admitted in the emergency department with jaundice, dark urine and pale stools. She was on the 10th day of hormonotherapy for recurrence of breast cancer, diagnosed 7 years previously. Usual causes of acute liver failure were excluded, all drugs were stopped and the imaging studies performed were positive only for steatosis. Nonetheless, ALF progressed and the patient died 4 days later. Autopsy demonstrated a massive intrasinusoidal infiltration of the liver by breast cancer cells. CONCLUSION: We highlight a rare cause of ALF. Although uncommon, physicians should be alert for this situation as the diagnosis can be challenging and the imaging studies can remain normal.

How good is controlled attenuation parameter and fatty liver index for assessing liver steatosis in general population: correlation with ultrasound.

BACKGROUND & AIMS: Liver steatosis measurement by controlled attenuation parameter (CAP) is a non-invasive method for diagnosing steatosis, based on transient elastography. Its usefulness as screening procedure for hepatic steatosis in general population has not been previously evaluated. The aim of this study was to evaluate the diagnostic accuracy of CAP and fatty liver index (FLI) for detection and quantification of steatosis in general population. METHODS: Recruitment was done from a prospective epidemiological study of the general adult population. Steatosis was evaluated using CAP, FLI and ultrasound (US). Steatosis scored according to Hamaguchi's US scoring, from 0 (S0) to 6 (S6) points. Hepatic steatosis defined by score ≥2 (S≥2) and moderate/severe steatosis by score ≥4 (S≥4). Performance of CAP and FLI for diagnosing steatosis compared with US was assessed using areas under receiver operating characteristic curves (AUROC). RESULTS: From 219 consecutive individuals studied, 13 (5.9%) excluded because of failure/unreliable liver stiffness measurements. Steatosis prevalence: S≥2 38.4% and S≥4 12.1%. CAP significantly correlated with steatosis (ρ = 0.73, P < 0.0001), steatosis score (ρ = 0.76; P < 0.0001), FLI (ρ = 0.69), waist circumference (ρ = 0.62), body mass index (ρ = 0.55), triglyceride (ρ = 0.49), HOMA-IR (ρ = 0.26), alcohol consumption (ρ = 0.24) and cholesterol (ρ = 0.19), not with liver stiffness measurements. Using CAP and FLI, AUROC's were 0.94 (95% CI 0.91-0.97, P < 0.001) and 0.91 for S≥2; 0.95 (95% CI 0.90-0.99, P < 0.001) and 0.93 for S≥4 respectively. Optimal cut-off value of CAP and FLI were 243 dB/m and 48 for S≥2; 303.5 dB/m and 62 for S≥4 respectively. CONCLUSION: Controlled attenuation parameter and FLI seem promising tools for screening and steatosis quantification in the general population. Larger studies are needed for validation.

Influence of COVID-19 on Patients with Esophageal Varices under Prophylactic Endoscopic Band Ligation Therapy.

Background and Objectives: Endoscopic band ligation (EBL) plays a critical role in patients with clinically significant portal hypertension, as variceal eradication (VE) is essential to prevent further variceal upper gastrointestinal bleeding (GI). The emergence of COVID-19 has led to a dramatic reduction in endoscopic activity. Our study aimed to evaluate the effect of COVID-19 on VE, GI, and 6-month mortality of patients treated with prophylactic EBL therapy. In addition, our goal was to identify the risk factors for our proposed outcomes. Methods: A single-center retrospective cohort study included patients with esophageal varices treated with prophylactic EBL therapy between 2017 and 2021. To demonstrate the impact of COVID-19 on two independent groups on prophylactic EBL therapy with 1 year of follow-up, March 2019 was selected as the cut-off date. Clinical, laboratory, and endoscopic data were recovered from electronic reports. Results: Ninety-seven patients underwent 398 prophylactic EBL sessions, 75 men (77.3%) with mean age 59 ± 12 years. Most achieved VE (60.8%), 14.4% had GI bleeding post-therapy, and 15.5% died at 6 months. The rate of variceal obliteration was significantly lower in the pandemic group (40.9% vs. 77.4% in the pre-pandemic group, p = 0.001). Mean number of EBL sessions and pandemic group were independently associated with incomplete VE, while MELD-Na, portal vein thrombosis and failed VE were identified as risk factors associated with mortality at 6 months. Conclusions: Almost 60% of patients in the pandemic group failed to eradicate esophageal varices. Failure to achieve this result conferred a higher risk of GI bleeding and death at 6 months, the latter also significantly associated with the MELD-Na score and portal vein thrombosis. Our study is among the first to demonstrate the impact of COVID-19 in patients receiving prophylactic EBL therapy.

Introdução e objetivos: A laqueação elástica endoscópica (LEE) é crucial nos doentes com hipertensão portal clinicamente significativa, uma vez que permite a erradicação das varizes esofágicas (EVE) que, por sua vez, previne a hemorragia digestiva varicosa. Com o início da pandemia COVID-19, a atividade endoscópica foi drasticamente reduzida. Com este estudo pretendemos avaliar a influência da COVID-19 na EVE, hemorragia gastrointestinal (GI) e mortalidade aos 6 meses dos doentes sob LEE profilática, assim como identificar os seus fatores de risco. Métodos: Estudo de coorte monocêntrico e retrospetivo que incluiu doentes com varizes esofágicas sob LEE profilática entre 2017 e 2021. Para demonstrar o impacto da pandemia COVID-19 em dois grupos independentes sob LEE profilática durante um ano de follow-up, a escolha da data-limite foi Março de 2019. Os dados clínicos, laboratoriais e endoscópicos foram obtidos a partir dos relatórios eletrónicos. Resultados: Noventa e sete doentes cumpriram 398 sessões de LEE, 75 homens (77,3%), com idade média de 59 ± 12 anos. A maioria dos doentes obteve EVE (60,8%), 14,4% desenvolveu hemorragia GI e 15,5% faleceu nos primeiros 6 meses pós-terapêutica. A taxa de EVE foi significativamente inferior no grupo pandémico (40,9% vs. 77,4% no grupo pré-pandémico, p = 0.001). O número médio de sessões de LEE e o grupo pandémico foram independentemente associados à EVE incompleta; enquanto MELD-NA, trombose da veia porta e falha na EVE foram identificados como fatores de risco associados à mortalidade aos 6 meses. Conclusão: Cerca de 60% dos doentes no grupo pandémico não conseguiu erradicar as varizes esofágicas. A EVE incompleta aumenta o risco de hemorragia GI e mortalidade aos 6 meses, esta última também associada de forma significativa ao score MELD-Na e TVP. O nosso estudo foi pioneiro na demonstração do impacto da pandemia COVID-19 nos doentes sob LEE profilática.

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

Improving dietary patterns in patients with nonalcoholic fatty liver disease.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is the liver epidemic of our time. Diet strongly influences its development and should be a component of any treatment plan. It is crucial to standardize diet recommendations in an evidence-based manner. RECENT FINDINGS: Calorie restriction per se seems beneficial regardless of macronutrients composition. However, fat consumption, mainly cholesterol and saturated fatty acids are particularly steatogenic. There is increasing evidence that fructose, mainly consumed as soft drinks, is highly deleterious to the liver. Controversial results regarding modest alcohol consumption, suggest that although alcohol should not be advised, it should not be strictly forbidden. Recent studies suggest beneficial effects of coffee and tea in NAFLD. SUMMARY: Patients with NAFLD should have an individualized diet recommendation, in order to lose at least 7% of their weight if overweight, reducing caloric intake, mainly at cost of cholesterol and saturated fatty acids. Simple sugars should be avoided, and soft drinks discouraged.

Do MAFLD Patients with Harmful Alcohol Consumption Have a Different Dietary Intake?

The term metabolic-associated fatty liver disease (MAFLD) has been proposed to define positively fatty liver disease in the form associated with metabolic risk factors. The aim of this study was to assess the dietary intake of MAFLD and explore a possible relationship between its inflammatory characteristics (assessed by Dietary Inflammatory Index-DII®), the degree of liver fibrosis (assessed by transient elastography), and the amount of alcohol intake. MAFLD patients were included (n = 161) and were classified, according to the amount of alcoholic intake, as MAFLD without alcohol intake (n = 77) and MAFLD with alcohol intake (n = 84), with 19 presenting harmful alcoholic consumption. Dietary intake was 1868 ± 415 kcal/day and did not present differences in energy or nutrient intake based on the presence of metabolic comorbidities. Patients with MAFLD and alcohol intake consumed significantly more energy and presented a tendency for higher intake of carbohydrates and sugar. Patients with harmful alcohol intake presented a higher intake of total fat and cholesterol compared with moderate alcohol intake. There were no differences in DII® based on fibrosis severity or the amount of alcohol consumption. This work contributes to the characterization of baseline dietary intake in MAFLD patients, paving the way to design more suited dietary interventional trials.

Severe acute autoimmune hepatitis: How to early predict who will not respond to corticosteroids and needs urgent liver transplantation?

BACKROUND: In acute severe autoimmune hepatitis (AS-AIH), the early identification of predictors of non-response to corticosteroids and the optimal timing for liver transplantation (LT) remains controversial. AIMS: To determine early predictors of non-response to corticosteroids and to assess the usefulness of severity scores, namely the recently developed SURFASA. METHODS: Retrospective multicentre cohort study including consecutive patients admitted for AS-AIH between 2016 and 2020. Definitions- response to corticosteroids: LT-free survival at 90 days (D90); SURFASA score: -6.8 + 1.92x(D0-INR)+1.94xINR[(D3-D0)/D0]+1.64xbilirubin[(D3-D0)/D0]. RESULTS: We included 26 patients [median age 56 (45-69) years; 22 (84.6%) women]. All patients underwent corticosteroid therapy. Overall survival reached 73%. amongst the non-responders, 2 (7.8%) underwent LT and 5 (19.2%) died. The interval between admission and initiation of corticosteroids was not different between responders and non- responders [13 (7-23) vs. 8 (3-10), P:0.06], respectively. SURFASA and MELD-Na+ (D3) scores showed an AUROC of 0.96 (0.87-1) and 0.92 (0.82-0.99), respectively, for prediction of non-response. SURFASA >-2.5 had a sensitivity of 85.7% and a specificity of 100% and MELD-Na+ (D3) >26 had sensitivity of 85.7% and a specificity of 78% for the prediction of non-response. CONCLUSIONS: SURFASA and MELD-Na+ at D3 scores are useful in early identification of non-responders to corticosteroids.

Predictive factors for long-term survival in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIMS: Sorafenib, used for advanced-stage hepatocellular carcinoma (HCC), has an overall survival (OS) of 10 months. However, some patients have better response and long-term survival (LTS). Aims to assess predictive factors for LTS. METHODS: Retrospectively reviewed 77 advanced HCC patients, starting sorafenib treatment between 2007 and 2016, with LTS (OS ≥24 months) as primary endpoint. Univariate and multivariable analysis of clinical variables were performed in order to identify predictive factors for LTS. RESULTS: Patients: seventy (90.9%) males; median age: 65 years (39-82). All had cirrhosis mostly HCV infection (n = 32, 41.6%). Majority were Child-Pugh class A (n = 50, 64.9%); median MELD-Na: 11 (6-30). Multinodular HCC: 74% (n = 57); portal vein invasion (PVI): 50.6% (n = 39); extrahepatic spread: 18.2% (n = 14). Median time between HCC diagnosis and sorafenib start: 3.3 months (0-37.6). Median OS: 13 months [95% confidence interval (CI) 8.2-17.8]. Twenty-five (32.5%) patients were considered LTS, with amedian OS: 52.3 months (95% CI 17.1-87.4). Multivariable analysis identified Child-Pugh class A [odds ratio (OR) 11.1, 95% CI 1.78-69.54] and absence of PVI (OR 7.88, 95% CI 1.56-39.8) as independent predictors of LTS. Sub-analysis of Child-Pugh class A: absence of PVI (OR 7.13, 95% CI 1.69-30.2) and alpha-fetoprotein <400 ng/ml (OR 5.82, 95% CI 1.18-28.75) independently related to LTS. CONCLUSION: Despite global short median OS, sorafenib treatment is associated with longer than 2-year survival in a sub-group, more likely in compensated liver disease and absence of PVI.

What Is the Role of the New Index Relative Fat Mass (RFM) in the Assessment of Nonalcoholic Fatty Liver Disease (NAFLD)?

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of adiposopathy. Recently, a new score was developed to estimate body fat percentage (relative fat mass, RFM). We aimed to evaluate the value of RFM in predicting the presence and severity of NAFLD, compared with other anthropometric measurements. METHODS: RFM, body mass index (BMI), and other anthropometric measurements were evaluated in two cohorts of subjects: a cohort from a Portuguese prospective epidemiological study (e_Cor) and morbidly obese patients with biopsy-proven NAFLD. We evaluated if RFM and BMI were related with the presence and severity of liver disease, which was assessed by noninvasive tools in the first cohort and by liver histology in the morbidly obese cohort. The independence of relations found in univariate analysis was assessed with multivariable logistic regression analysis. RESULTS: In the general population cohort, 744 subjects (48% male) were enrolled. BMI-defined obesity was present in 23% and RFM-defined obesity in 86%. Insulin resistance (IR) related with BMI-defined obesity (OR 4.37 [2.16-8.84]) and weight (OR 1.05 [1.02-1.08]) in men, and waist circumference (WC) (OR 1.07 [1.03-1.11]) in women. Dyslipidemia and hypertension related with RFM-defined obesity in men (OR 2.96 [1.36-6.47] and OR 5.37 [1.31-22.06], respectively). Ultrasound-diagnosed NAFLD in 33% related with weight in men (OR 1.03 [1.003-1.06] and WC in women (OR 1.06 [1.02-1.10]). In men, ALT elevation related with weight (OR 1.04 [1.02-1.07]). In women, advanced fibrosis (estimated by NAFLD Fibrosis Score) associated with BMI-defined obesity (OR 42.43 [3.61-498.13]). In the morbidly obese cohort, 152 subjects were enrolled, of whom 84% were female, 37% had steatohepatitis, and 9.4% had advanced fibrosis. Adiponectin associated inversely and leptin positively with RFM in men. The severity of steatosis increased linearly with BMI and WC in women. Higher BMI associated with steatohepatitis in women and advanced fibrosis in men. CONCLUSION: RFM-defined obesity better predicted dyslipidemia and hypertension (though not IR) and adipokine imbalance; however, it did not add value to BMI-defined obesity in predicting NAFLD or liver injury.

Acute Liver Failure due to Trazodone and Diazepam.

Most antidepressant agents have the potential to cause liver injury, even at therapeutic doses. Nevertheless, drug-induced liver injury (DILI) from antidepressant agents is a rare event. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. We describe a rare case of a 63-year-old man presenting with acute liver failure after 3 months of trazodone and diazepam administration at normal therapeutic doses, requiring liver transplantation. This report should increase physicians' awareness of this complication and call attention to the regular monitoring of liver tests in patients taking trazodone, in order to prevent life-threatening complications.

A maioria dos antidepressivos tem o potencial de causar lesão hepática, mesmo em doses terapêuticas. Contudo, a hepatite tóxica por antidepressivos é um evento raro. Não existe forma de prevenir a hepatite tóxica, mas a sua gravidade pode ser minimizada com o diagnóstico precoce e a retirada antecipada do fármaco. Apresentamos um caso raro de um homem de 63 anos com insuficiência hepática aguda após 3 meses de terapêutica com trazodona e diazepam em doses terapêuticas, com necessidade de transplante hepático. Com este caso pretende-se alertar os clínicos para a possibilidade desta entidade e da necessidade de monitorização regular das provas hepáticas em doentes sob tratamento com trazodona, de forma a prevenir morbilidade e mortalidade.

Hepatitis B and C prevalence in Portugal: disparity between the general population and high-risk groups.

BACKGROUND AND AIMS: The prevalence of anti-HCV and HBsAg in Portugal has been shown to be elevated in high-risk groups, such as intravenous drug-users and incarcerated individuals. However, in the general population, prevalence remains largely unknown. The aims of this study were to estimate the prevalence of anti-HCV and HBsAg in the general Portuguese population and identify associated risk factors. MATERIALS AND METHODS: We carried out a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serology for HBsAg, anti-HBc, anti-HBs, and anti-HCV was performed. Anti-HCV-positive individuals were tested for HCV RNA by PCR. RESULTS: Of 1685 participants, 50.6% were men, mean age 50.2±18.3 years. In terms of hepatitis C, the prevalence of anti-HCV was 0.54% [95% confidence interval (CI): 0.2-0.9] and 0.12% (95% CI: 0.0-0.3) were viremic, with peak prevalence among individuals 35-64 years of age (0.8%), men (0.8%), and individuals from Lisbon and Tagus Valley region (1.9%).In terms of hepatitis B, the estimated prevalence of HBsAg was 1.45% (95% CI: 0.9-2.0). A higher prevalence was found in individuals who were 35-64 years old (2.2%), in men (2.5%), and in the Northern region (2.6%).The presence of positive serological markers of hepatitis C virus and hepatitis B virus infection did not correlate with elevated aminotransferases, race, place of birth, and alcohol consumption. CONCLUSION: These results suggest a low endemicity for both hepatitis B and hepatitis C in the general population, in contrast to a very high prevalence in risk groups, thus suggesting that targeted screening to high-risk groups may be more cost-effective than general population screening.