Longitudinal investigation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older patients in the province of Palermo (Southern Italy) during the early wave of the pandemic.

Introduction: Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in old adults from Southern Italy is little known. This study aims to investigate the mortality risk related to risk factors, therapy and clinical course and to suggest prognostic indicators based on day-to-day follow-up of clinical and laboratory findings. Material and methods: It was designed as a retrospective longitudinal cohort study of adult SARS-CoV-2 patients admitted at Partinico COVID Hospital in Palermo, Southern Italy. Patients were recruited between 4 March and 25 April and followed up until 31 May 2020, day-to-day until death or hospital discharge. Clinical data, laboratory tests and treatment data were extracted from medical records and epidemiologic information was obtained by clinical history and the medical interview. Results: Forty-seven patients (median age = 75 IQR: 59.50-86.00) were followed up during a 87 days observation period, accounting for a total of 1,035 person days. At the end of follow-up, 28 (60%) patients were discharged and 19 (40%) died, so that the estimated incidence density rate was 0.018 deaths per day (18 SARS-CoV-2-related deaths per 1,000 patient days). Diabetes (HR = 8.13, 95% CI: 1.91-34.67), chronic kidney failure (HR = 5.86, 95% CI: 1.36-25.21), dementia (HR = 7.84, 95% CI: 1.80-34.20), and neutrophil/lymphocyte ratio > 7 (HR = 10.37, 95% CI: 2.24-48.14) were found as significant prognostic factors. Conclusions: The joint evaluation of dementia, diabetes, chronic kidney failure and neutrophil/lymphocyte ratio showed an optimal prognostic value already in the first week of follow-up. The day-to-day follow-up provides essential information for clinical monitoring and treatment of the disease in a hospital setting and improves the disease's home management, especially for older patients with frailty.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients.

BACKGROUND: Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. AIM: The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. RESULTS: No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION: Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.

Long-term follow-up of hepatitis C virus-positive patients with persistently normal serum transaminases.

MATERIAL AND METHODS: This study prospectively evaluated the progression of liver disease in a group of anti-HCV-positive patients with persistently normal ALT levels (PNALT) who were HCV-RNA positive. Patients selected for this study were those who presented with PNALT according to the Italian Association for the Study of the Liver (AISF) criteria in the year 1995/96 and underwent liver biopsy. They were divided into two groups according to their ALT evolution. Forty-five patients were included in this study. RESULTS: After a median follow-up time of 180 months twenty-five of them maintained PNALT, but two of these developed liver cirrhosis (LC) in a mean time of 174 and 202 months, respectively. Twenty patients had flares of ALT and three of them developed LC in a mean time of 162-178 months. Twelve of these patients underwent current antiviral treatment; six patients were SVR. At baseline, the 5 patients who progressed to LC had age and BMI significantly higher than patients without LC (P < 0.005 and P < 0.01, respectively). Grading (P < 0.006) and staging (P < 0.003) were also more severe at histology, while serum HDL-C levels were statistically lower (P < 0.002). Comparing patients with flares of transaminases with and without LC, we found a significant difference at baseline for age, BMI, HDL-C, grading and staging (P < 0.05; P < 0.01 and P < 0.003, respectively). CONCLUSION: In HCV-RNA positive patients associated with PNALT the grade of disease activity increased over the years in only half of patients and a higher degree of liver fibrosis at baseline was the major relevant factor for progression.

The health of irregular and illegal immigrants: analysis of day-hospital admissions in a department of migration medicine.

It is difficult to trace full details of the path which irregular or illegal immigrants follow when seeking assistance in the network of the various hospital departments and health structures. The aim of this work was to analyze the health needs of immigrant people by reviewing the types of treatment given to them in the day-hospital of our Department of Migration Medicine. Our study analyzed day-hospital admissions between 2003 and 2009. The patient charts used for managing day-hospital activity were adopted in 2002 in conformity with the "OSI project". From these it is possible to draw up a scale picture of the distribution of each pathology in the immigrant population. The sample population consisted of 1,758 subjects, representing 7.4% of potential users. More than half came from Africa, followed by Asia, and then Europe. Gastroenterological diseases ranked first, with dyspeptic syndromes most frequently diagnosed. Infections and parasitic diseases ranked second, and the most frequent diagnoses were sexually transmitted diseases. Third were diseases of the genitourinary system. Metabolic disorders ranked fourth, among them, more than half of the cases were of diabetes mellitus, in patients from south-east Asia. Diseases of the circulatory system were sixth, with hypertension the most frequent pathology. Our data confirm a marked persistence of the phenomenon known as the "healthy immigrant effect" in these types of patients, as well as the prominent role played by "social determinants" in conditioning the health of immigrants, particularly in the case of some infectious diseases.

Transient elastography: a non-invasive tool for assessing liver fibrosis in HIV/HCV patients.

AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviral therapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (χ(2)(MH) = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected patients (χ(2) = 5, P < 0.03). Also APRI and the FIB-4 index showed more LF in co-infected than in HIV mono-infected patients (P < 0.0001), but not in HCV mono-infected patients. In HIV/HCV co-infected patients, the extent of LS was significantly associated with alcohol intake (P < 0.04) and lower CD4+ cell count (P < 0.02). In HCV patients, LS was correlated with alcohol intake (P < 0.001) and cholesterol levels (P < 0.03). Body mass index, diabetes, HCV- and HIV-viremia were not significantly correlated with LS. In addition, 20% of co-infected patients had virologically unsuccessful HAART; in 50% compliance was low, CD4+ levels were < 400 cells/mm(3) and LS was > 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.

Hepatocellular carcinoma: comparison of two different periods at the same center.

AIMS: To analyze the main etiological factors and some clinical characteristics of patients with HCC at diagnosis and to compare them with those we described ten years ago. METHODS: 179 patients were included in Group 1, while 132 patients were included in Group 2. For all patients age, sex, serum markers of hepatitis B and C viruses, alcohol consumption, serum alpha feto-protein (AFP) levels and the main liver function parameters at HCC diagnosis were recorded. RESULTS: Mean age was 66.0 years for Group 1 and 69.0 for Group 2 (P=0.005). HCV was responsible for 80.3% of HCC cases in Group 2 versus 72% in Group 1 (P=0.005). HBV alone and co-infection of HCV+HBV decreased, but not significantly. In Group 1 only four patients had an underlying normal liver, while in Group 2 no patients showed an underlying normal liver (P=ns). HCC was more frequently associated with Child class A in Group 2 (P=0.0001), whereas in Group 1 it was more frequently associated with class C (P=0.0001). Staging of HCC correlated inversely when patients of Groups 1 and 2 were compared (P<0.03). AFP serum levels were above normal in 72% of cases in Group 1 and in 41.5% in Group 2 (P=0.0001). CONCLUSION: This study shows that over the last decade a number of characteristics of patients with HCC in our region have changed, particularly age at onset of HCC, staging of underlying liver disease and staging of HCC.

Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report.

INTRODUCTION: Visceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus Leishmania and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis. CASE PRESENTATION: In this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy with Liposomal Amphotericin-B the patient recovered and now, 20 months post-treatment, he is well and has regained a good part of the lost weight. CONCLUSIONS: This case taught us that patients with massive splenomegaly, even with a diagnosis of liver cirrhosis, should be investigated for infectious or lymphoproliferative diseases.

Cyclooxygenase-2 expression in chronic liver diseases and hepatocellular carcinoma: an immunohistochemical study .

UNLABELLED: Hepatocarcinogenesis is a multistep process characterized by hepatocyte inflammation, regeneration, and proliferation. These changes are believed to depend on the aberrant expression of various tumor suppressor genes, oncogenes and growth factors. Several studies have shown the involvement of cyclooxygenase-2 (COX-2), the inducible isoform of the enzymes that catalyze prostaglandin synthesis in various aspects of carcinogenesis. COX-2 has been described as being overexpressed in hepatocellular carcinoma (HCC) patients. Using immunohistochemistry, we studied COX-2 expression in different chronic liver diseases (CLD) including nonalcoholic steatohepatitis (NASH), chronic hepatitis (CH), liver cirrhosis (LC), and HCC in a population referred to a tertiary center in western Sicily, an area moderately endemic for CLD. Sixteen NASH, 35 CH, 15 LC, and 21 HCC samples were analyzed. Positive signs of COX-2 were observed in the cytoplasm of hepatocytes and median values were 6 (3-9) for NASH, 7 (3-9) for CH, 6 (4-9) for LC, and 4 (0-7) for HCC. COX-2 expression was significantly lower in HCC than in NASH (P < 0.001), CH (P < 0.0001), and LC (P < 0.0001). In HCC we found a wide range of COX-2 expression: from no expression in poorly differentiated areas to a high expression in well-differentiated ones, with an inverse correlation between COX-2 and tumor grading, according to Edmonson (rho=-0.67, P < 0.0001). IN CONCLUSION: (a) COX-2 expression was significantly lower in HCC than in the other CLD; (b) COX-2 expression inversely correlated with tumor differentiation status. These results suggest that COX-2 expression could be related to the inflammatory phenomena present in the early phases of CLD and eventually to the induction of hepatocarcinogenesis.

Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C.

OBJECTIVES: The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy. METHODS: We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocytes was scored on the basis of: (i) maximum intensity; (ii) dominant intensity; and (iii) extent. RESULTS: No significant differences were found in COX-1 and COX-2 expression in CHC patients divided according to genotype or according to the type of response to combination therapy with pegylated-interferon and ribavirin. The only significant correlations were observed between the dominant intensity of COX-2 and the presence of histological steatosis (P<0.01) and an inverse correlation between COX-2 extent and the viral load (P<0.02). CONCLUSIONS: The lack of correlation between COXs tissue expression and response to antiviral treatment suggests that there is no rationale to adding selective COX inhibitors to increase the efficacy of antiviral therapy, although further studies on larger patient populations are needed. On the contrary, there is a potential application for their use in the prevention and treatment of liver steatosis.

[Abnormal liver function in Mediterranean spotted fever]. / Interessamento epatico in corso di febbre bottonosa del Mediterraneo.

In this study we retrospectively assessed the prevalence of impaired liver function in all 49 patients suffering from Mediterranean Spotted Fever (MSF) consecutively admitted to our department over the last four years. The main parameters of liver function and ultrasound of upper abdomen were performed at entry and at the end of treatment. At admission mean values of transaminases were above the normal limits and significantly higher when compared to mean serum levels at recovery. 55% and 51% of patients had serum values of GOT and GPT, respectively, above the normal limits versus 1% and 2% at the end of treatment. Mean serum values of alkaline phosphatase (AP) were within the normal limits at entry in hospital, but 22 of them had serum values above the normal limits. The same proportion was seen for gamma glutamiltranspeptidase values. Eighteen patients (36.7%) had both transaminases and AP above the normal limits. There were no significant differences among serum values of albumin, bilirubin and gamma globulin before and after therapy. Platelet count, on the contrary, was significantly reduced at admission (p < 0.0001). At ultrasound half of the patients showed hepatomegaly with a hepatitis-like pattern and 39% of patients had splenomegaly. In conclusion, this study confirms previous data from the literature showing a high frequency of liver impairment during the course of MSF, which is usually mild-moderate. In a few cases, however, the increase of transaminases could be serious and the recovery delayed, but never, in our experience, has there been progression toward chronic liver disease.

[Acute renal failure as a complication of transarterial chemoembolization in a patient with hepatocellular carcinoma]. / Insufficienza renale acuta in paziente con carcinoma epatocellulare recentemente sottoposto a chemioembolizzazione transarteriosa.

Transarterial chemoembolization (TACE) is included among the wide therapeutic tools for the treatment of hepatocellular carcinoma (HCC), tumour with high frequency and malignancy. The approach is invasive and, beyond the discomfort for the patient, it is charged by a number of side effects and complications. In this study we report the case of renal acute failure of hypovolemic origin, as a consequence of a TACE in a patient suffering from HCC, occurred after one week of intervention. The different possible mechanisms involved in the pathogenesis of this complication are discussed.

Thyroid sarcoidosis as a unique localization.

Sarcoidosis is a systemic disorder characterized by granulomatous lesions, principally affecting the lungs. There are numerous reports in the literature of an associated involvement of the thyroid, much more frequently in hypothyroid than in hyperthyroid subjects. The present case report refers to a woman presenting with thyroid nodules and normal biochemical levels and thyroid function parameters, while histology revealed sarcoid-type lesions. Subsequent investigations and a long follow-up showed no evidence of involvement of other sites, including the lungs. Consequently, after a long period of normal health associated with the negative results of the examinations, a diagnosis of sarcoidosis limited to the thyroid was proposed, which was cured by thyroidectomy.

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.