Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.

Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma.

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America.

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real-clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real-world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child-Pugh B at baseline and one patient died due to multi-organ failure. Follow up HCV-RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child-Pugh A cirrhosis in non-European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child-Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.

Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice.

BACKGROUND AND AIMS: Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. MATERIAL AND METHODS: We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response. RESULTS: A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported. CONCLUSION: Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.

Validation of the number connection test for identifying patients with minimal hepatic encephalopathy.

OBJECTIVES: Hepatic encephalopathy is a serious neuropsychiatric complication in advanced liver disease. The affected patients exhibit alterations in psychomotor and intellectual functions. The aims of this study were to identif the set ofnormal values for the number connection tests (NCT-A and NCT-B) in a population of volunteers without liver disease, to compare the values from this reference population with those from patients with cirrhosis without hepatic encephalopathy. MATERIALS AND METHODS: This study was performed in two referral hospitals in an urban setting from the city of La Plata. We evaluated the Number Connection Tests in 112 healthy subjects and 30 patients with cirrhosis without manifestations of hepatic encephalopathy. Time for performing the tests was measured in seconds. Results were compared according to age, gender, level of education and fine motor skills in both groups. RESULTS: Mean age in the control group was 45.3years; 56 (50%) were women. Mean age in the cirrhotic group was 54.5 years; 8 (27%) were women. In the control group, the mean time for completing NCT-A and NCT-B was 60 s +/- 36s and 140 s +/- 60 s, respectively. In the cirrhotic group, the mean time for completing NCT-A and NCT-B was 114 s +/- 64 y 232 s +/- 87 s, respectively (P = 0.00001 for both tests). 56.6% of cirrhotic patients took more than 2 SD to perform the NCT-A and 53.3%, more than 2 SD to perform the NCT-B. CONCLUSION: We have obtained reference values for NCT-A and NCT-B completing times in our healthy population. Cirrhotic patients without overt hepatic encephalopathy took double time than controls to complete NCT-A and NCT-B and over half of our patients would have minimal hepatic encephalopathy.

Genetic variation in interleukin-28B predicts SVR in hepatitis C genotype 1 Argentine patients treated with PEG IFN and ribavirin.

BACKGROUND AND AIMS: Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-α/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown. MATERIAL AND METHODS: IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts' biochemical, histological and virological predictors of response. RESULTS: We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 IU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively). CONCLUSION: IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.

Efficacy, tolerability and safety in the treatment of chronic hepatitis C with combination of PEG-Interferon - Ribavirin in daily practice.

BACKGROUND: Efficacy and safety of Pegylated Interferon alfa (PegIFN)-Ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) in routine clinical practice seems to be comparable with results of randomized-controlled trials. AIMS: To evaluate the efficacy, tolerability and safety of CHC treatment with PegIFN + RBV in .real world. patients in Argentina and to analyze factors associated with SVR. METHODS: Medical records of patients treated according to current guidelines from 2001 to 2008 were reviewed. RESULTS: 235 patients were included and 80.8% completed treatment. Discontinuation occurred in 7.6% due to adverse events (AE), and 1.2% dropped-out treatment. Overall SVR was 60.8%. Multivariate analysis demonstrated that being naive (p 0.031) and low basal viral load (p 0.006) were associated with SVR, whereas F3-F4 (p 0.001) and elevated ALT (p 0.023) were associated with non-response. 80% of planned doses completed was associated with 74% SVR (p <0.001). At least one AE was reported in 93.6% of the patients: neutropenia in 27.6%, thrombocytopenia in 15.3%, anemia in 38.7%, psychiatric symptoms in 63.4%, thyroid dysfunction in 10.2%. CONCLUSION: Efficacy, tolerability and safety of treatment of CHC in daily practice in Argentina are similar to those reported in randomized controlled trials.

Etiology of hepatocellular carcinoma in Argentina: results of a multicenter retrospective study.

Incidence and etiology of hepatocellular carcinoma (HCC) are variable around the world, depending mainly on theprevalence ofchronic hepatitis B carriers in each region. No study has been published analyzing epidemiological features of patients with HCC in Argentina. The aim of this retrospective study was to describe demographical and etiological results in a series of 587 consecutive patients with HCC diagnosed in 15 Hepatology and Gastroenterology Units distributed all around our country. Seventy-two per cent of patients were male, the median age was 62 years (interquartile range 55-68 years), and 93% had cirrhosis. Regarding to etiological data (fully available in 551 cases), main etiologies were chronic alcoholism in 229 patients (41.6%) (the sole risk factor in 182, associated to HCVin 35 and to HBV in 12); hepatitis C in 223 patients (40.5%) (the sole risk factor in 181, associated to alcoholism in 35 and to HBV in 7); hepatitis B in 74 patients (13.4%) (the sole risk factor in 55, associated to alcoholism in 12 and to HCV in 7); cryptogenic cirrhosis in 51 patients (9.2%). There were significant differences in percentages of genders between main groups: males were highly predominant in alcoholic cirrhosis (93%), hepatitis B (87%) and HCV plus alcohol (94%), compared to 63% in cryp togenic cirrhosis and 49% in hepatitis C (p<0.01). There were no differences in age at presentation between the main etiologies. In conclusion, the main causes of HCC in Argentina are alcoholic cirrhosis and hepatitis C (76% of cases). A majority of patients with HCC in our country are cirrhotics, males, and in their 6th or -7th decades of life.

Alanine-aminotransferase: an early marker for insulin resistance?

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis B and C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female > or = 15 and > or = 19 U/L; male > or = 17 and > or = 23 U/I, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5% of women and 14.5% of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.

Alanine-aminotransferase: an early marker for insulin resistance? / Alanino-aminotransferasa: un marcador temprano de resistencia a la insulina?

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis Band C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female < or = 15 and < or = 19 U/L; male < or = 17 and < or = 23 U/l, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5 percent of women and 14.5 percent of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.

En una muestra poblacional, luego de excluir a quienes consumían alcohol y drogas hepatotóxicas y a los infectados con virus B y C de la hepatitis, investigamos si la alanino-aminotransferasa (ALT), o transaminasa glutámico pirúvica (TGP), se asociaba con el síndrome metabólico y con resistencia a la insulina y si esta asociación se explicaba por enfermedad hepática grasa no alcohólica (NAFLD). La muestra (432 mujeres y 119 varones) se dividió por los percentilos (P) 50 y 75 de la distribución de ALT (mujeres < o = 15 y < o = 19 U/l; varones < o = 17 y < o = 23 U/l, respectivamente). Las mujeres a partir del P50 de ALT tuvieron valores más altos de índice triglicéridos (TG)/HDLc (p=0.029), glucemia (p=0.028) y de la valoración del modelo homeostático de insulino-resistencia (HOMA-IR) (p=0.045); a partir del P75 tuvieron valores más altos de presión arterial sistólica (PAS) (p=0.036), presión arterial diastólica (PAD) (p=0.018), TG (p=0.024), índice TG/HDLc (p=0.028), glucemia (p=0.004) y HOMA-IR (p=0.001). Los varones a partir del P50 de ALT tuvieron valores más altos del índice de masa corporal (p=0.017) y del índice (TG/HDLc (p=0.048); a partir del P75 mostraron valores más bajos de HDLc (p=0,042). Sólo 16.5 porciento de las mujeres y 14.5 porciento de los varones, a partir del P75 de ALT, mostraron aumento del brillo hepático en la ecografía. Este trabajo muestra, en mujeres, asociación temprana de ALT con el índice TG/HDLc y el HOMA-IR. Dado que estos dos últimos son predictores independientes del riesgo cardiovascular se debería prestar atención a los valores de ALT cercanos al límite superior aun en ausencia de NAFLD y de obesidad.

Alanine-aminotransferase: an early marker for insulin resistance? / Alanino-aminotransferasa: un marcador temprano de resistencia a la insulina?

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis Band C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female < or = 15 and < or = 19 U/L; male < or = 17 and < or = 23 U/l, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5 percent of women and 14.5 percent of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.(AU)

En una muestra poblacional, luego de excluir a quienes consumían alcohol y drogas hepatotóxicas y a los infectados con virus B y C de la hepatitis, investigamos si la alanino-aminotransferasa (ALT), o transaminasa glutámico pirúvica (TGP), se asociaba con el síndrome metabólico y con resistencia a la insulina y si esta asociación se explicaba por enfermedad hepática grasa no alcohólica (NAFLD). La muestra (432 mujeres y 119 varones) se dividió por los percentilos (P) 50 y 75 de la distribución de ALT (mujeres < o = 15 y < o = 19 U/l; varones < o = 17 y < o = 23 U/l, respectivamente). Las mujeres a partir del P50 de ALT tuvieron valores más altos de índice triglicéridos (TG)/HDLc (p=0.029), glucemia (p=0.028) y de la valoración del modelo homeostático de insulino-resistencia (HOMA-IR) (p=0.045); a partir del P75 tuvieron valores más altos de presión arterial sistólica (PAS) (p=0.036), presión arterial diastólica (PAD) (p=0.018), TG (p=0.024), índice TG/HDLc (p=0.028), glucemia (p=0.004) y HOMA-IR (p=0.001). Los varones a partir del P50 de ALT tuvieron valores más altos del índice de masa corporal (p=0.017) y del índice (TG/HDLc (p=0.048); a partir del P75 mostraron valores más bajos de HDLc (p=0,042). Sólo 16.5 porciento de las mujeres y 14.5 porciento de los varones, a partir del P75 de ALT, mostraron aumento del brillo hepático en la ecografía. Este trabajo muestra, en mujeres, asociación temprana de ALT con el índice TG/HDLc y el HOMA-IR. Dado que estos dos últimos son predictores independientes del riesgo cardiovascular se debería prestar atención a los valores de ALT cercanos al límite superior aun en ausencia de NAFLD y de obesidad. (AU)

[Liver damage in workers exposed to hydrocarbons]. / Daño hepático en trabajadores expuestos a hidrocarburos.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the occurrence of hypertransaminasemia (hTAMSemia) as an indicator of liver damage and to establish the association of this hepatotoxicity with exposure to aromatic hydrocarbons (benzene, toluene, and xylene [BTX]) among workers in a petrochemical company. PATIENTS AND METHOD: The medical records of 167 industrial employees, 95 with hydrocarbon exposure (EHCs) and 72 without exposure (NEHCs) were reviewed. Age, sex, number of years employed, body mass index, and biochemical and hematological parameters were evaluated. Employees with previous liver disease, diabetes mellitus, or alcohol intake (> 50 g/day) were excluded. In employees with hTAMSemia, we performed a proteinogram and hepatic ultrasonography and tested blood samples for prothrombin and hepatitis B and C markers. Within this subgroup, 3 workers were excluded (due to serum markers of hepatitis B virus in 2 and refusal to participate in 1), leaving a total of 92 in the EHC group. Finally, the working environment was screened for volatile contaminants. RESULTS: Twenty-seven employees from the EHC group (29.4%) and 1 from the NEHC group (1.4%) had hTAMSemia (p = 0.001). The remaining biochemical tests and parameters measured showed no significant differences between the two groups. Comparison between the EHC subgroup of 27 workers showing hTAMSemia and the remainder of the EHC group with normal values (65 workers) revealed no differences in the other parameters measured. Of the 27 workers of the former subgroup, 14 (51.9%) showed ultrasonographic images compatible with a fatty liver. One worker (1.4%) in the NEHC group showed hTAMSemia and ultrasonography compatible with fatty liver. The environmental levels of BTX during the 9 months of the study remained below the maximum values permitted by law in Argentina (benzene, 1.5 ppm., toluene 10 ppm and xylene 18.5 ppm). The odds ratio of developing hTAMSemia in the EHC group was 27.7 (p = 0.002). CONCLUSIONS: Occupational exposure to aromatic hydrocarbons may cause liver damage. The liver is more vulnerable to these hydrocarbons than bone marrow. These conclusions would argue for a modification of the environmental regulations currently in force within the petroleum refineries in Argentina.

Daño hepático en trabajadores expuestos a hidrocarburos / Liver damage in workers exposed to hydrocarbons

Fundamento y objetivos: Investigar la presencia de hipertransaminasemia, como expresión bioquímica de daño hepático, y correlacionarla con la exposición a hidrocarburos (benceno, tolueno y xileno BTX) en trabajadores de una empresa petroquímica. Pacientes y método: Se revisaron las historias clínicas de 167 empleados, 95 expuestos (GE) y 72 no expuestos (GNE), y se evaluaron los siguientes parámetros: edad, sexo, antigüedad laboral, índice de masa corporal y pruebas bioquímicas. Se excluyó a los que presentaban hepatopatía previa, diabetes mellitus o ingesta de alcohol > 50 g/día. En los que se halló hipertransaminasemia se realizaron las siguientes pruebas: proteinograma, protrombina, anti-HBc, HBsAg, anti-VHC y ecografía hepática. Tres operarios comprendidos en el GE fueron excluidos, 2 por presentar marcadores séricos de virus de hepatitis B y otro por haber decidido no participar en el estudio; en definitiva, el GE quedó constituido por 92 trabajadores. Se midieron los contaminantes ambientales. Resultados: Veintisiete individuos del GE (29,4%) y uno del GNE (1,4%) presentaron hipertransaminasemia (p = 0,001). El resto de las pruebas bioquímicas, hemograma y de los otros parámetros analizados no mostraron diferencias entre ambos grupos. Iguales parámetros se evaluaron entre GE1 (ALAT normal) y GE2 (elevada) sin hallarse diferencias. En la ecografía se halló compatibilidad con hígado graso en 14 (51,9%) de los 27 pacientes del GE2. Un individuo (1,4%) del GNE presentó alanino-aminotransferasa elevada y ecografía compatible con hígado graso. Los valores de compuestos orgánicos volátiles ambientales resultaron inferiores a las 5 ppm exigidas durante los 9 meses que duró el estudio (benceno 1,5 ppm, tolueno 10 ppm, y xileno 18,5 ppm). La odds ratio para desarrollar hipertransaminasemia en el GE fue de 27,7 (p = 0,002). Conclusiones: La exposición laboral a hidrocarburos volátiles puede ocasionar daño hepático. El hígado, según nuestros hallazgos, aparece como más vulnerable a los hidrocarburos volátiles que la médula ósea. Estas conclusiones deberían servir para modificar las normas de tolerabilidad ambiental vigentes en las refinerías de Argentina

Background and objectives: The aim of this study was to investigate the occurrence of hypertransaminasemia (hTAMSemia) as an indicator of liver damage and to establish the association of this hepatotoxicity with exposure to aromatic hydrocarbons (benzene, toluene, and xylene [BTX]) among workers in a petrochemical company. Patients and method: The medical records of 167 industrial employees, 95 with hydrocarbon exposure (EHCs) and 72 without exposure (NEHCs) were reviewed. Age, sex, number of years employed, body mass index, and biochemical and hematological parameters were evaluated. Employees with previous liver disease, diabetes mellitus, or alcohol intake (> 50 g/day) were excluded. In employees with hTAMSemia, we performed a proteinogram and hepatic ultrasonography and tested blood samples for prothrombin and hepatitis B and C markers. Within this subgroup, 3 workers were excluded (due to serum markers of hepatitis B virus in 2 and refusal to participate in 1), leaving a total of 92 in the EHC group. Finally, the working environment was screened for volatile contaminants. Results: Twenty-seven employees from the EHC group (29.4%) and 1 from the NEHC group (1.4%) had hTAMSemia (p = 0.001). The remaining biochemical tests and parameters measured showed no significant differences between the two groups. Comparison between the EHC subgroup of 27 workers showing hTAMSemia and the remainder of the EHC group with normal values (65 workers) revealed no differences in the other parameters measured. Of the 27 workers of the former subgroup, 14 (51.9%) showed ultrasonographic images compatible with a fatty liver. One worker (1.4%) in the NEHC group showed hTAMSemia and ultrasonography compatible with fatty liver. The environmental levels of BTX during the 9 months of the study remained below the maximum values permitted by law in Argentina (benzene, 1.5 ppm., toluene 10 ppm and xylene 18.5 ppm). The odds ratio of developing hTAMSemia in the EHC group was 27.7 (p = 0.002). Conclusions: Occupational exposure to aromatic hydrocarbons may cause liver damage. The liver is more vulnerable to these hydrocarbons than bone marrow. These conclusions would argue for a modification of the environmental regulations currently in force within the petroleum refineries in Argentina

[Liver dysfunction in recipients of hematopoietic stem cells. Impact on mortality]. / Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas. Impacto sobre la mortalidad.

Liver disease is a well-known cause of early morbidity and mortality affecting 80% of patients receiving allogeneic bone-marrow transplantation (BMT). Drug toxicity, veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), and fungal, bacterial, and viral infections are the most frequent hepatic complications during this period. The aim of this retrospective study was to determine the prevalence and etiology of liver disease and its impact on mortality as well as to assess the predictive value of pre BMT hepatic biochemical tests on the subsequent occurrence of acute and/or chronic GVHD and patient mortality. Of a total of 236 patients who underwent allogeneic BMT, 82 were analysed. Liver dysfunction was found in 88%. The causes of liver disease were: acute GVHD, 40.2%; chronic GVHD, 15.9%; unknown, 9.8%; sepsis, 7.3%; hepatotoxicity, 6.1%; VOD, 3.7%; acute hepatitis and disease recurrence, 2.4%. The mortality rate was 37%. We found acute liver failure (ALF) in 10% of the deaths (8 patients). The causes of ALF in these cases were acute GVHD progression in 5, herpetic hepatitis in 1, disease recurrence in 1, and VOD in 1. The correlation coefficients indicating positive predictive values of pre BMT hepatic biochemical tests for the subsequent occurrence of acute GVHD, chronic GVHD, and mortality were 0.27, 0.14, and 0.43, respectively. There was no significant difference between patients with abnormal or normal pre BMT liver function tests in the frequency of acute and chronic GVHD or mortality.

Disfunción hepática en el trasplante de celulas progenitoras hematopoyéticas. Impacto sobre la mortalidad. / [Liver dysfunction in recipients of hematopoietic stem cells. Impact on mortality]

Liver disease is a well-known cause of early morbidity and mortality affecting 80

of patients receiving allogeneic bone-marrow transplantation (BMT). Drug toxicity, veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), and fungal, bacterial, and viral infections are the most frequent hepatic complications during this period. The aim of this retrospective study was to determine the prevalence and etiology of liver disease and its impact on mortality as well as to assess the predictive value of pre BMT hepatic biochemical tests on the subsequent occurrence of acute and/or chronic GVHD and patient mortality. Of a total of 236 patients who underwent allogeneic BMT, 82 were analysed. Liver dysfunction was found in 88

. The causes of liver disease were: acute GVHD, 40.2

; chronic GVHD, 15.9

; unknown, 9.8

; sepsis, 7.3

; hepatotoxicity, 6.1

; VOD, 3.7

; acute hepatitis and disease recurrence, 2.4

. The mortality rate was 37

. We found acute liver failure (ALF) in 10

of the deaths (8 patients). The causes of ALF in these cases were acute GVHD progression in 5, herpetic hepatitis in 1, disease recurrence in 1, and VOD in 1. The correlation coefficients indicating positive predictive values of pre BMT hepatic biochemical tests for the subsequent occurrence of acute GVHD, chronic GVHD, and mortality were 0.27, 0.14, and 0.43, respectively. There was no significant difference between patients with abnormal or normal pre BMT liver function tests in the frequency of acute and chronic GVHD or mortality.

Ascitis / Ascites

La ascitis puede ocurrir como una manifestación clinica de ciertas enfermedades hepáticas como una complicación de la hipertensión portal, o bien obedecer a otras causas. Aproximadamente el 85 por ciento de las ascitis son secundarias a hipertensión portal, 10 por ciento a neoplasias, 2 por ciento a tuberculosis, 1 por ciento a enfermedades pancreáticas y el 2 por ciento restante a causas poco frecuentes. La paracentesis confirma la ascitis y posibilita el análisis bioquímico y citológico del líquido, lo cual resulta de extraordinaria importancia para el diagnóstico etiológico diferencial y a su vez permite establecer o excluir la presencia de "peritonitis bacteriana expontanea" y eventualmente instaurar el tratamiento para prevenirla. El gradiente sero-ascitico de albumina > de 1.1 g/dl identifica las ascitis por hipertensión portal con una exactitud del 96,7 por ciento. Para una manejo terapeutico racional de los pacientes cirróticos con ascitis, se debe recordar que en ellos siempre hay disminución de la resistencia vascular sistemica, oliguria, retención renal de sodio y agua y expansión del volúmen plasmático. Esta aumentada la secreción de hormona antidiuretica y tienen dificultad para excretar agua libre. El filtrado glomerular depende de la producción renal de prostaglandinas que intentan compensar la vasoconstricción de la microcirculación renal.