Rat hepatitis E virus (Rocahepevirus ratti) in people living with HIV.

Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with hepatitis E virus (HEV; species Paslahepevirus balayani), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%-2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%-0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

Bone alterations in hepatitis C virus infected patients.

BACKGROUND AND AIMS: Most studies have shown that patients with chronic hepatitis C virus (HCV) infection are affected by osteoporosis. However, liver function impairment and deranged nutrition may both play a role in the bone alterations observed. In some works no osteoporosis was found, and some cases of osteosclerosis have been reported. The aim of the study is to assess bone alterations in treatment-naïve, well-nourished HCV patients, in order to discern whether or not HCV infection causes osteoporosis. METHODS: Whole-body bone densitometry and assessment of T-score at lumbar spine and hip were performed to 40 patients and 40 age- and sex-matched controls, with a Lunar Prodigy Advance (General Electric, Piscataway, NJ, USA). All the patients underwent liver biopsy. Nutritional evaluation was performed by subjective nutritional assessment, body mass index (BMI), and densitometric assessment of total lean mass and total fat mass. Serum osteocalcin, osteoprotegerin, RANKL, PTH, crosslaps, vitamin D3, testosterone, IGF-1, and estradiol were determined. RESULTS: Patients did not show differences in total bone mineral density (BMD) or T-score with controls. On the contrary, about a third of them showed positive T scores. Patients showed lower IGF-1, vitamin D3 and testosterone, but higher telopeptide levels, and a trend to higher osteoprotegerin levels. Multivariate analyses disclosed that age, sex, and total lean mass were the only parameters independently related with BMD. CONCLUSIONS: Therefore, chronic HCV infection in well nourished patients with preserved liver function does not cause osteoporosis.

Similar inflammatory response in alcoholic and non-alcoholic sepsis patients.

UNLABELLED: It is well known that alcoholics are prone to severe infections and that the immune system is impaired by chronic ethanol abuse. The aim of this study is to compare serum inflammatory mediators in response to sepsis in chronic alcoholic with sepsis, non-alcoholics with sepsis and non-infected alcoholics. METHOD: We included 25 alcoholics with sepsis, 34 non-alcoholics with sepsis, 34 non-infected alcoholics admitted for programmed withdrawal, and 27 healthy control subjects. After initial evaluation, blood samples were taken for determination of serum cytokine levels. RESULTS: We found similar responses for the inflammatory mediators analyzed among our sepsis patients, regardless of alcohol abuse. The only difference was that alcoholics with sepsis showed lower CRP and G-CSF than non-alcoholic sepsis patients. There were no differences regarding leukocyte count. Alcoholics admitted for programmed withdrawal showed higher IL-6, IFN-γ, IL-10, Il-4 and ICAM-1 serum levels than healthy controls. Serum IL-5 levels were decreased in both alcoholic groups. CONCLUSION: The inflammatory response of alcoholics with sepsis is similar to that of non-alcoholic sepsis patients. However, the low G-CSF levels in alcoholic sepsis patients might suggest a predisposition to infections in alcohol abusers.

Factors involved in the paradox of reverse epidemiology.

BACKGROUND & AIMS: The hypothesis of reverse epidemiology holds that some cardiovascular risk factors, such as obesity, hypercholesterolemia and hypertension, in the elderly or in some chronic diseases are not harmful but permit better survival. However, this phenomenon is controversial and the underlying reasons are poorly understood. OBJECTIVE: To search for factors simultaneously linked to reverse epidemiology and to short or long term survival. METHODS: We included 400 patients, older than 60 years, hospitalized in a general internal medicine unit; 61 died in hospital and 338 were followed up by telephone. RESULTS: Obesity, higher blood pressure and serum cholesterol, besides being related to lower mortality both in hospital and after discharge, were associated with better nutrition and functional capacity, less intense acute phase reaction and organ dysfunction, and lower incidence of high-mortality diseases such as dementia, pneumonia, sepsis or cancer. These associations may explain why obesity and other reverse epidemiology data are inversely related to mortality. Weight loss was related to mortality independently of BMI. Patients with BMI under 30 kg/m(2) who died in hospital showed more weight loss than those who survived; the lower the BMI, the greater the weight loss. In contrast, patients with BMI over 30 kg/m(2) who died in hospital gained more weight than those who survived; the higher the BMI, the greater the weight gain. CONCLUSION: In patients over 60 years of age admitted to an internal medicine ward, obesity did not show independent survival value, being displaced by other nutritional parameters, functional capacity, acute phase reaction, organ dysfunction and diseases with poor prognosis.

Prognostic value of inflammatory markers (notably cytokines and procalcitonin), nutritional assessment, and organ function in patients with sepsis.

OBJECTIVE: Procalcitonin is useful for the diagnosis of sepsis, but its prognostic value regarding mortality is unclear. Our objective was to determine the prognostic value of procalcitonin determined at the onset of sepsis, and to compare it with other markers of inflammatory response, malnutrition and organ dysfunction data. METHODS: We studied 253 hospitalized patients (146 men, 107 women) with a median age of 65 years. Sepsis was defined as infection, and at least two SIRS criteria. We assessed co-morbidities, nutritional status, bacteremia, procalcitonin and other inflammatory markers (PCR, TNF-alpha, IL6, TREM-1, IL-10, IL-1ra, CD14 and LBP), and organ function using the SOFA score. Mortality was assessed at 28 days after onset of sepsis. RESULTS: At day 28, 49 (19%) patients had died. Inflammatory markers showed only moderate predictive value for mortality, with IL-10 and IL-6 being the best predictors. Mortality was mainly related to organ dysfunction indicators (SOFA and Glasgow scores), serum lactate, ferritin and LDH levels, and to nutritional data such as subjective assessment, handgrip strength and serum transferrin levels. The most frequent location of sepsis was the lung, with 140 cases (55%), which showed more comorbidity, worse nutritional status, less frequent bacteremia and lower inflammatory response. When the analysis was limited to patients with non-pulmonary sepsis, organ dysfunction, nutritional status and inflammatory markers showed the best prognostic value. Of the inflammatory markers, procalcitonin showed only moderate predictive value; however it showed the highest correlation with bacteremia and the ability to discriminate non-complicated sepsis from severe forms. CONCLUSION: Procalcitonin only showed moderate predictive value for sepsis-related mortality, being surpassed by organ dysfunction, nutritional status, IL-10 and IL-6. However, it proved useful to discriminate between non-complicated and severe forms of sepsis.

Association of Harris lines and shorter stature with ethanol consumption during growth.

Ethanol consumption may impair bone growth. Transverse radiopaque lines (Harris lines) have been interpreted as manifestations of bone growth arrest due to nutritional stress. It is possible that ethanol consumption during growth leads to Harris lines formation and to a shorter stature. Plain X-ray film of the right tibia was performed to 175 individuals, who were inquired about ethanol consumption, periods of perceived hunger, and protracted illness during growth period (from birth to 18 years of age). Stature was also recorded. Men who drank during growth showed a shorter stature than those who did not (t=3.65, P<.001). Differences were not statistically significant among women (t=0.95). Neither periods of perceived hunger nor illness were associated to differences in stature. Ethanol consumption during growth showed a significant association with the presence of Harris lines (chi(2)=15, P<.001, Odds Ratio [OR]=3.39, confidence interval [CI]=1.81-6.33), an association which was more marked between having two or more Harris lines and drinking during growth (chi(2)=23.19, P<.001, OR=6.04, CI=2.79-13.11) or having three or more lines and drinking during growth (chi(2)=15.93, P<.001, OR=7.41, CI=2.47-22.21). Periods of perceived hunger during growth were also related to the presence of two or more Harris lines (chi(2)=4.66, P=.031, OR=2.055, CI=1.065-3.965), but no association was observed between illness and Harris lines, two or more Harris lines, and three or more Harris lines. Multivariate analysis showed that only ethanol consumption during growth period was associated with Harris lines.

Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response.

UNLABELLED: TREM-1 is an activating receptor expressed on the surface of neutrophils and mature monocytes when stimulated by bacteria or fungi, leading to amplification of the inflammatory response. Our objective is to analyze the prognostic value of serum sTREM-1 levels and other mediators of the inflammatory response, in patients hospitalized for CAP, and to compare its prognostic value with those of advanced age, pneumonia severity scores, Charlson index, nutritional status and severity of sepsis. METHODS: We included 226 patients with CAP, 145 males and 81 females, median age of 74 years. The following tests were performed: arterial blood gases and chest radiography, nutritional assessment, assessment of the severity of the sepsis, Pneumonia Severity Index (PSI) and CURB-65, and mediators of inflammation: TNF alfa, IL-6, IL-10, IL-1ra, LBP, sCD14, CRP, and sTREM-1. Mortality during admittance was defined as the sole end point. RESULTS: Twenty-eight of the two-hundred and twenty-six patients died (12.4%). On univariate analysis advanced age, dehydration, increased Na, low BMI, handgrip strength, serum albumin, prealbumin, IGF-1, lymphocyte count, conscious drowsiness, tachypnea, decreased PaO2, hypotension, creatinine, ASAT, LDH, severity of sepsis, a high PSI or CURB65, TNFalpha, IL-6, IL-10, IL-1ra, and sTREM-1 were related to mortality. Variables with an independent value were IGF-1, CURB-65, TREM-1, advanced age and IL-6. CONCLUSIONS: This study confirms the usefulness of TREM-1 in the diagnosis and prognosis of patients with CAP, which is independent of advanced age, other inflammation markers such as IL-6, severity index for CAP such as CURB-65 or PSI, severity of sepsis and nutritional status including IGF-1.

Rib fractures in chronic alcoholic men: Relationship with feeding habits, social problems, malnutrition, bone alterations, and liver dysfunction.

Rib fractures are common in alcoholics. This high prevalence might be due to ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar lifestyle of the alcoholic with frequent trauma and altercations. In this study we try to discern the role of these factors on rib fracture (assessed on a plain thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics. Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25-dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and corticosterone were measured, and the patients also underwent assessment of bone mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body mass index, triceps skinfold, and brachial perimeter were also determined, and the patients and their families were asked about tobacco consumption, social and familial links, consumption of ethanol by other members of the family, kind of job, and feeding habits. Forty-two male nondrinker sanitary workers of similar age served as controls. Forty of the 81 patients showed rib fractures. There was a statistically significant association between rib fractures and disruption of social and familial links, irregular feeding habits (in bars or pubs, not at home), ethanol consumption by close relatives, and intensity of tobacco consumption, but not between rib fractures and liver function tests, nutritional parameters, or bone mineral density, besides a nearly significant trend (p = .053) with the presence of osteopenia at the femoral neck. Patients with major withdrawal symptoms at admission also presented more frequent rib fractures. We conclude that rib fractures in alcoholics are related to the peculiar lifestyle of these patients rather than to bone alterations, liver dysfunction, or nutritional status.