Prevalence of hepatitis C virus infection according to the year of birth: identification of risk groups.

Hepatitis C virus (HCV) screening according to the year of birth is recommended is some countries based on epidemiological data. The aim of this study was to analyze anti-HCV prevalence among people born between 1905 and 2015 in Argentina. Patients attending a tertiary care hospital in Buenos Aires, Argentina, from 2001 to 2015, who had a determination of anti-HCV, were included. Of 22,079 patients analyzed, 1,152 (5.2%; 95% confidence interval [CI]: 4.9%-5.5%) patients showed positive anti-HCV and 729 (3.3%; 95% CI: 3.1%-3.5%) patients showed detectable viremia. Three risk groups were identified (HCV prevalence): low-risk group-outpatient clinics/emergencies (2.8%); intermediate-risk group-in-patients (8%); and high-risk group-dialysis/transplants (27.2%). In the low-risk group, being born in 1973 or before was identified as a cut-off value for the risk of anti-HCV acquisition (area under the receiver-operator characteristic curve: 75.1 [95% asymptotic CI: 0.732-0.770; p < 0.001]). Ninety-one patients born after 1973 (0.8%) showed positive anti-HCV versus 457 individuals born in 1973 or before (5.8%), p < 0.001. In this group, positive anti-HCV was observed in 252 females (2.1%) and 296 males (4.1%), p < 0.001. In a multivariate analysis adjusted for gender, alanine-aminotransferase levels and HIV coinfection, being born in 1973 or before was independently identified as a risk for positive anti-HCV (adjusted odds ratio: 14.234 [95% CI: 9.993-20.277]; p < 0.001). People born in 1973 or before without other risk factors should be included in screening programs to link the highest possible number of HCV-infected patients to appropriate care and treatment.

Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study.

OBJECTIVE: To investigate the relationship between hypogonadism and mortality in aged hospitalized male patients. DESIGN: A 5-year prospective observational study was conducted. Gonadal function was assessed at hospital admission and mortality was registered in the follow-up period. PATIENTS AND METHODS: We studied all patients≥65 years admitted for any reason during 2010 and 2011. Serum T concentrations were quantified in all patients. Hypogonadism was defined by the presence of serum T levels<200 ng/dl. Number of deaths and all-cause and cardiovascular (CV) mortality were registered until December 31(st), 2014. RESULTS: During the study 150 patients were admitted and 103 (68.7%) of them died during follow-up. Hypogonadism was positively associated with mortality (P=0.036). The percentage of hypogonadal patients was significantly (P=0.02) higher in the group of patients who died in hospital compared with those who died after hospital discharge and those who survived. CV disease was the main cause of death in 52 patients (50.5%). Kaplan-Meier analysis showed a median survival time for all-cause mortality of 2.0 (0-16.5) months and 21.0 (5.0-33.2) months for patients with and without hypogonadism, respectively (P<0.001). Similar findings were found when analyzing mortality due to CV disease (P=0.009). Hypogonadism was a strong independent predictor for all-cause (adjusted multivariate analysis, HR 3.35; 1.55-7.23, P=0.002) and CV mortality (HR 2.14; 1.18-3.86, P=0.012). CONCLUSIONS: Hypogonadism discovered during hospitalization is associated with in-hospital and long-term mortality in elderly male patients and predicts both all-cause mortality and CV mortality in this population.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

OBJECTIVE: Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. PATIENTS AND METHODS: 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. RESULTS: Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. CONCLUSION: Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Breath-ammonia testing of healthy subjects and patients with cirrhosis.

BACKGROUND: Hepatic encephalopathy (HE) is a serious neuropsychiatric complication in both acute and chronic liver disease. AIMS: To establish the utility of a portable noninvasive method to measure ammonia in the breath of healthy subjects and patients with HE. METHODS: The study included 106 subjects: 44 women and 62 men, 51 healthy and 55 cirrhotic. The breath ammonia was measured with an electrochemical sensor and expressed in parts/billion (ppb). RESULTS: The breath ammonia in healthy subjects had an average value of 151.4 ppb (95% confidence interval [CI]: 149.4-153.4) and the average value in cirrhotic patients was 169.9 ppb (95% CI: 163.5-176.2) (P < 0.0001). In cirrhotic patients with and without HE, the corresponding values were 184.1 ppb (95% CI: 167.7-200.6) and 162.9 ppb (95% CI: 158.8-167.0), respectively (P = 0.0011). Ammonia levels ≥ 165 ppb permitted a differentiation between healthy and cirrhotic subjects; the area under the receiver operating characteristic (ROC) curve for the ammonia-level values in cirrhotic versus control patients was 0.86 (95% CI: 0.79-0.93). In cirrhotic patients, ammonia levels ≥ 175 ppb permitted the distinction between patients with and without HE; the area under the ROC curve in cirrhotic patients with versus without HE was 0.83 (95% CI: 0.73-0.94). CONCLUSION: A portable sensor for measuring breath ammonia can be developed. If the results of the present study are confirmed, breath-ammonia determinations could produce a significant impact on the care of patients with cirrhosis and could even include the possibility of self-monitoring.

Effectiveness of entecavir in chronic hepatitis B NUC-naive patients in routine clinical practice.

INTRODUCTION: Registration studies showed entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B virus (HBV), but its effectiveness in routine clinical practice is unknown. MATERIALS AND METHODS: Sixty-nine HBeAg positive and negative NUC naïve chronic HBV patients were treated with ETV for 110 weeks. 63% were HBeAg positive, 16% were cirrhotics, mean HBV-DNA was 7.09 log IU/ml and mean ALT was 157 IU/ml. RESULTS: Sixty-one (88%) patients achieved undetectable DNA, with 46%, 77% and 100% virological response rates at week 24, 48 and 96 of treatment, respectively. Thirty-seven (84%) patients in the HBeAg-positive population achieved undetectable DNA, with 67% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-four (96%) patients in the HBeAg-negative population achieved undetectable DNA, with 91% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-three (53%) patients cleared HBeAg and 19 (44%) patients seroconverted to antiHBe positive status; seven (10%) patients cleared hepatitis B surface antigen and five (7%) patients developed antiHBs. At the end of the study, 10 patients successfully stopped therapy: nine HBeAg positive (four developed antiHBs positive) and one HBeAg negative. None of the patients had primary non-response. ETV resistance was not tested. None of the patients developed hepatocellular carcinoma, underwent liver transplantation or died because of liver-related events. No serious adverse events were reported. CONCLUSION: The ETV monotherapy showed high virological response rates, a favourable safety profile for NUC-naive HBeAg-positive and negative patients treated in routine clinical practice.

Serum thyrotropin concentration is an early marker of normalization of low triiodothyronine syndrome in aged hospitalized patients after discharge.

OBJECTIVES: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. METHODS: A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4 (FT4), and free T3 (FT3) were evaluated in every patient both after admission and 1 month after discharge. RESULTS: At entry, both serum TSH [median (interquartile range), 2.19mU/l (0.89-2.31)] and FT4 (mean±SD, 16.7±3.4 pmol/l) concentrations were into the normal range, whereas serum FT3 concentrations were low (3.3±0.7 pmol/l). After discharge TSH and FT4 concentrations remained normal and FT3 low. However, both serum TSH [2.53 mU/l (1.24-3.33); p<0.01] and FT3 (3.7±1.0 pmol/l; p<0.001) concentrations significantly increased. Most patients (no.=124, 84.9%) showed the euthyroid sick syndrome (ESS). After discharge, ESS diminished to 76 (52.1%) subjects. Patients who normalized thyroid function tests showed significantly lower TSH values at entry compared with those who persisted with altered thyroid function tests [1.27 mU/l (0.69-1.89) vs 1.69mU/l (0.96-2.91), p<0.05]. Logistic regression analysis showed that serum levels of TSH at admission was the only variable negatively related to normalization of thyroid function [odds ratio 0.730; confidence interval 95%, 0.567-0.940; p=0.01). CONCLUSIONS: About 35%of aged patients hospitalized for acute illness spontaneously normalize their thyroid function tests 1 month after discharge, mainly due to the correction of ESS. Serum TSH levels at admission seem to be the only variable negatively related to normalization of thyroid function at this time.

Alterations in thyroid function tests in aged hospitalized patients: prevalence, aetiology and clinical outcome.

BACKGROUND: Thyroid dysfunction is common in aged people and has recently been associated to mortality. AIMS: Our aims have been (1) to assess the prevalence of alterations in thyroid function tests in hospitalized patients over age 60 years and (2) to study the relationship between thyroid functional status and mortality during hospitalization. METHODS: We studied a group of 447 patients (62% women), aged 61-101 year, hospitalized during 2005. Thyroid dysfunction was assessed by measuring serum concentrations of thyrotrophin (TSH), free thyroxine (FT4), and free thriiodothyronine (FT3). Thyroid autoimmune status was evaluated through thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies quantification. RESULTS: Twenty-one patients (4.7%, 19 women) showed previously known thyroid dysfunction. 332 patients (74.3%) showed alterations in thyroid function tests. Euthyroid sick syndrome (ESS) was the derangement more frequently found (n = 278, 62.2%). After excluding ESS patients, 60 patients (13.4%) showed thyroid dysfunction: overt hypothyroidism, 14 (3.1%); subclinical hypothyroidism, 25 (5.6%); overt hyperthyroidism, 11 (2.5%), and subclinical hyperthyroidism, 10 patients (2.2%). Thyroid autoimmunity was positive in only 4.0% and 2.3% of patients, for TPOAb and TgAb, respectively. The presence of alterations in thyroid function tests was positively associated with the age of the patients and mortality during hospital stay (P < 0.001). Serum levels of FT3 were negatively related to death during hospitalization (OR 0.56; CI 95%, 0.38-0.81; P < 0.01). CONCLUSIONS: About three quarters of patients admitted in our geriatric unit exhibited alterations in thyroid function tests. This finding was associated with elevated age and poor prognosis. The reduction of FT3 values was a powerful predictor for mortality during hospitalization in elderly patients.

Hepatitis C virus infection and outcome of renal transplantation.

Chronic hepatitis B and C viruses (HBV and HCV) are common problems in renal transplant patients. There is no uniform agreement regarding their influence on graft outcomes and patient survival. We evaluated the influence of anti-HCV and hepatitis B surface antigen-positive status; gender; age>49 years at the time of transplantation; alanine aminotransferase elevation; acute rejection; type of graft; number of transplants; and maintenance/induction immunosuppressive treatment on both graft and patient survivals among a population transplanted in our center between 1991 and 2004. Univariate analysis showed that anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. Over the age of 49 years at the time of transplantation, anti-HCV-positive status, cadaveric donor, kidney-pancreas transplantation, and three-drug immunosuppressive therapy were associated with diminished patient survival. Upon multivariate analysis, reduced patient survival was associated with the same variables as in the univariate analysis: anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. In our experience, anti-HCV-positive compared with anti-HCV-negative status was associated with a reduced graft (56% vs. 75%; P=.0002) and patient survival (68% vs. 83%; P=.0028).

Hepatocellular carcinoma in renal transplant patients.

INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B (HBV) and C viruses (HCV), are a common problem in renal transplant patients. Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases, incidence in the renal transplant cohort is higher than in the general population (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the incidence of HCC, its clinical presentation, the treatments, and the relation to chronic viral hepatitis among the population transplanted at our center between January 1980 and December 1998 and followed to August 2003. RESULTS: During the study period, six recipients among 534 renal transplants displayed HCC (incidence 1.12% of the entire population and 2.29% of patients with chronic viral hepatitis). Among the cohort five were men, and all had chronic viral hepatitis: three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to 244) months after transplantation. All patients presented with abnormal liver function tests and tumors larger than 5 cm. Four had more than three tumors and three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients received no treatment (survivals 1, 1, and 4 months); two patients, chemoembolization (survival 6 and 12 months); and one, surgical ethanol injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION: HCC in renal transplant recipients is a common complication among patients with chronic viral hepatitis. The outcome was poor because HCC was detected at an advanced stage. Screening strategies for early diagnosis must be prospectively evaluated.

[Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]. / Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un transplantado renal con hepatitis crónica B y C asintomática.

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90% of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.

Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un transplantado renal con hepatitis crónica B y C asintomática. / [Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90

of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.

[Fulminant hepatic failure. Atypical form of cardiac failure presentation]. / Falla hepática fulminante. Forma atípica de presentación de insuficiencia cardíaca.

Congestive liver disease can be one of the clinical aspects of chronic heart failure. Fulminant hepatic failure can be a consequence of ischemic liver disease secondary to cardiogenic shock. We report a patient with chronic heart failure who was admitted to our hospital presenting general malaise with abnormal liver function tests, prothrombin time and renal failure. The study of viral and autoimmune liver diseases were negative. She did not consume hepatotoxic drugs. She presented encephalopathy without initial evidence of shock. On the fourth day, she presented clinical deterioration compatible with cardiogenic shock. Laboratory abnormalities were similar to those seen in congestive and ischemic liver disease. The patient died 24 hours later. The histology showed congestive and ischemic liver disease. There are several reports of chronic liver diseases without a clear etiology, caused by constrictive pericarditis or restrictive myocardiopathy. In this case, the patient presented fulminant hepatic failure without clear evidence of progressive heart failure. We emphasize the importance of cardiac diseases as possible causes of liver diseases without another clear explanation.

Falla hepática fulminante. Forma atípica de presentación de insuficiencia cardíaca. / [Fulminant hepatic failure. Atypical form of cardiac failure presentation]

Congestive liver disease can be one of the clinical aspects of chronic heart failure. Fulminant hepatic failure can be a consequence of ischemic liver disease secondary to cardiogenic shock. We report a patient with chronic heart failure who was admitted to our hospital presenting general malaise with abnormal liver function tests, prothrombin time and renal failure. The study of viral and autoimmune liver diseases were negative. She did not consume hepatotoxic drugs. She presented encephalopathy without initial evidence of shock. On the fourth day, she presented clinical deterioration compatible with cardiogenic shock. Laboratory abnormalities were similar to those seen in congestive and ischemic liver disease. The patient died 24 hours later. The histology showed congestive and ischemic liver disease. There are several reports of chronic liver diseases without a clear etiology, caused by constrictive pericarditis or restrictive myocardiopathy. In this case, the patient presented fulminant hepatic failure without clear evidence of progressive heart failure. We emphasize the importance of cardiac diseases as possible causes of liver diseases without another clear explanation.