Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study.

BACKGROUND: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. METHODS: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. RESULTS: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). CONCLUSIONS: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.

Survival of patients with early hepatocellular carcinoma treated by percutaneous alcohol injection.

BACKGROUND: Once small (<10 mm) nodules, suspicious for hepatocellular carcinoma, are detected in cirrhotics, the European Association for the Study of the Liver guidelines recommend to delay histological confirmation and treatment until they increase in size. AIM: To validate this policy by evaluating survival of 450 cirrhotics in Child-Pugh class A or B with unifocal 'early' hepatocellular carcinoma treated by percutaneous alcohol injection. METHODS: Patients were sorted by nodular size into three groups: < or =10 mm (n = 36, group A), >10 to < or = 20 mm (n = 142, group B) and >20 to < or = 30 mm (n = 272, group C). Overall and tumour-free survivals were estimated by Kaplan-Meier method. RESULTS: In groups A, B and C, mean follow-up was 33 +/- 26, 34 +/- 22 and 35 +/- 25 months (P = 0.89), mean survival time was 63 +/- 54, 57 +/- 48 and 62 +/- 66 months (P = 0.69) and mean tumour-free survival was 44 +/- 47, 46 +/- 58 and 41 +/- 68 months (P = 0.51), respectively. When patients were sorted by Child status, mean survival time was 76 +/- 82 and 38 +/- 29 months in Child A and B (P < 0.0001). CONCLUSIONS: The comparable survival of percutaneous alcohol injection-treated patients with single, early hepatocellular carcinoma sorted by nodular size supports the European Association for the Study of the Liver 'wait-and-see' policy for patients with lesions <10 mm, and suggests that allowing the nodules to grow prior to taking further diagnostic or therapeutic actions would not harm these patients.

The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis.

AIM: The observation of bright liver echo pattern on ultrasound is commonly considered a sign of hepatic steatosis. However, the interference of liver fibrosis on sensitivity and specificity of bright liver echo pattern has caused many to question its effectiveness as a diagnostic tool. The objective of this study was to evaluate the sensitivity, specificity and predictive values of bright liver echo pattern for liver steatosis. PATIENTS AND METHODS: We studied 235 consecutive patients suspected of having liver disease of various aetiologies. Median age was 52 years (range, 17-72 years), and there was a male/female ratio of 1:18. All patients underwent ultrasound examination before liver biopsy and was performed by two operators. The presence or absence of bright liver echo pattern and posterior attenuation or areas with different patterns of fat infiltration were noted. Histologic evaluation was performed and graded by Ishak score. Steatosis was categorised as absent, 0-2%, 3-29% to 30-49% or >50%. RESULTS: Interobserver concordance was high. Bright liver echo pattern was found in 67% of patients with steatosis of any degree and 89% of patients with steatosis of >or=30%. Only three patients without steatosis, who had a low Ishak score, demonstrated bright liver echo pattern on ultrasonography. The sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern for steatosis were 64%, 97%, 96.0% and 65%, respectively. Among the subgroup of patients who had steatosis of >or=30%, the sensitivity, specificity, positive predictive value and negative predictive value of bright liver echo pattern were 91%, 93%, 89% and 94%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of posterior attenuation and/or skip areas associated with bright liver echo pattern for steatosis were 89.7%, 100%, 100% and 92.3%, respectively. Univariate analysis showed bright liver echo pattern to be associated only with steatosis and not with fibrosis. CONCLUSION: We concluded that the presence of bright liver echo pattern is a sign of liver steatosis and that liver fibrosis does not interfere with ultrasound measurements. Posterior attenuation and/or skip areas are closely related to steatosis of >or=30%.

Validity and reliability of the Italian version of the Chronic Liver Disease Questionnaire (CLDQ-I) for the assessment of health-related quality of life.

BACKGROUND: The Chronic Liver Disease Questionnaire is a specific health-related quality of life assessment designed for patients with liver diseases. AIM: The aim of this paper is to report on the validity, reliability and sensitivity to change of the Italian version (Chronic Liver Disease Questionnaire-I) in subjects with HCV infection. SUBJECTS: The Chronic Liver Disease Questionnaire-I was administered to 350 subjects with HCV infection together with the World Health Organization Quality of Life Assessment, abbreviated version, a generic quality of life assessment. METHODS: The instrument was translated from English, backtranslated and reviewed in focus groups in the framework of a large multicentre study. Exploratory factor analysis identified five factors accounting for 65% of the variance of Chronic Liver Disease Questionnaire-I items and only partially overlapping with those found in the original version. RESULTS: The Chronic Liver Disease Questionnaire-I proved to discriminate between subjects with and without comorbid diseases at baseline (t-test = 3.59, p < 0.001). Test-retest reliability was moderate (ICC = 0.60). The Chronic Liver Disease Questionnaire-I was sensitive to change in patients who deteriorated after one month of treatment. Change in the overall Chronic Liver Disease Questionnaire-I score in deteriorated patients was correlated with changes in World Health Organization Quality of Life Assessment, abbreviated version scores in the physical, psychological and environment, but not in the social area. CONCLUSIONS: The Italian version of Chronic Liver Disease Questionnaire is a valid and reliable instrument to be used in cross-sectional and longitudinal studies.

[Effects of a new pharmacological complex (silybin + vitamin-E + phospholipids) on some markers of the metabolic syndrome and of liver fibrosis in patients with hepatic steatosis. Preliminary study]. / Effeto di un nuovo complesso farmacologico (sillibina vitamina E+ fosfolipidi) su alcuni indicatori di sindrome metabolica e di fibrosi epatica in pazienti con epatopatia steatosica. Studio pilota.

AIM: This open preliminary pilot study was aimed to evaluate the effect of a new pharmaceutical complex (silybin+vitamin E+phospholipids - RealSIL-IBI-Lorenzini Pharmaceutical, Italy) on some parameters of metabolic syndrome and of liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD) with or without the contemporaneous presence of hepatitis C virus (HCV)-related chronic hepatitis. METHODS: Eighty five patients were consecutively enrolled in the study and divided in 2 groups; the first group was represented by 59 patients affected by NAFLD, negative for other known causes of chronic liver damage (M/F= 39/20; median age and range: 44 years, 22-76, group A); the second group was represented by 26 patients (M/F=19/7; median age and range 51 years, 20-75, group B) with HCV-related chronic hepatitis associated to NAFLD. Adverse events and drop-outs were absent in all group and compliance at the study was absolute. RESULTS: This open preliminary study shows that the new compound silybin+vitamin E+ phospholipids is active, in vivo, and produces some therapeutic effects in patients with different forms of chronic liver damage. In particular, it improves insulin resistance and plasma levels of markers of liver fibrosis in patients in whom these parameters are particularly altered. CONCLUSIONS: Our data have a role of suggestion to further evaluate, through a controlled trial, a possible therapeutic use of this new compound in the management of patients with NAFLD.

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea.

BACKGROUND AND AIMS: Recent studies suggest a potential relationship between rosacea and Helicobacter pylori (H. pylori) infection or small intestinal bacterial overgrowth (SIBO), but there is no firm evidence of an association between rosacea and H. pylori infection or SIBO. We performed a prospective study to assess the prevalence of H. pylori infection and/or SIBO in patients with rosacea and evaluated the effect of H. pylori or SIBO eradication on rosacea. METHODS: We enrolled 90 patients with rosacea from January 2012 to January 2013 and a control group consisting of 90 patients referred to us because of mapping of nevi during the same period. We used the (13)C Urea Breath Test and H. pylori stool antigen (HpSA) test to assess H. pylori infection and the glucose breath test to assess SIBO. Patients infected by H. pylori were treated with clarithromycin-containing sequential therapy. Patients positive for SIBO were treated with rifaximin. RESULTS: We found that 44/90 (48.9%) patients with rosacea and 24/90 (26.7%) control subjects were infected with H. pylori (p = 0.003). Moreover, 9/90 (10%) patients with rosacea and 7/90 (7.8%) subjects in the control group had SIBO (p = 0.6). Within 10 weeks from the end of antibiotic therapy, the skin lesions of rosacea disappeared or decreased markedly in 35/36 (97.2%) patients after eradication of H. pylori and in 3/8 (37.5%) patients who did not eradicate the infection (p < 0.0001). Rosacea skin lesions decreased markedly in 6/7 (85.7%) after eradication of SIBO whereas of the two patients who did not eradicate SIBO, one (50%) showed an improvement in rosacea (p = 0.284). CONCLUSIONS: Prevalence of H. pylori infection was significantly higher in patients with rosacea than control group, whereas SIBO prevalence was comparable between the two groups. Eradication of H. pylori infection led to a significant improvement of skin symptoms in rosacea patients.

Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.

BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver.

AIM: To define the characteristics of the Italian patient presenting non-alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 305 patients with abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase levels for at least 12 months, with no known cause of chronic liver damage, were consecutively enrolled in the study. Clinical, routine biochemical and liver histology investigations were carried out in all patients. Also evaluated were: (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA test model; and (c) plasma endotoxaemia, total antioxidant plasma capability, tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels. Malondialdehyde and 4-hydroxynonenal content were determined on liver samples from 120 patients. RESULTS: The majority of patients were young overweight or obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and cytokines were only sporadically altered. Total antioxidant plasma capability was decreased in 38.4% of the patients. Eighty percent of the cases had histological steatosis with a mild degree of inflammation and fibrosis. Seven patients had cirrhosis. Lipid peroxidation markers were increased in 90% of the cases, inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at multivariate analysis no single factor was found to be an independent predictor of hepatic lesions. CONCLUSIONS: The typical Italian patient with non-alcoholic fatty liver disease is a young male, obese, not diabetic, with a variable incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define the type of liver damage.

Ultrasound-guided percutaneous ethanol injection: first choice for treatment of hepatocellular carcinoma in the elderly.

Percutaneous ethanol injection (PEI) under ultrasound guidance has recently been proposed as a new therapeutic approach for patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HCC is more frequently observed in elderly subjects. We treated 59 patients (44 males and 15 females, mean age 66 years, age-range 54-77 years). Forty-six patients were in Child A, 12 in Child B and 1 in Child C class. Thirty-nine patients had a single lesion up to 5 cm size; 2 had a single lesion larger than 5 cm, and 18 had 2 or 3 lesions, each smaller than 4 cm. The survival rates after 1, 2, 3 and 4 years for all patients were 92, 73, 54 and 54%, respectively; while for those with only a single lesion amounted to 94, 85, 63, and 63%, for the same years. In this latter group, the survival rates at 1 and 2 years were significantly higher in subjects in the Child A class, than in those who were in Child B and C classes (100 and 95%, against 79 and 63%, respectively, p < 0.05). In the group of patients with multiple lesions the survival rates were 89, 57 and 42% at 1, 2 and 3 years, respectively. We did not have any lethal complications during the procedure of PEI, and only minor complications occurred in 6 patients. During the follow-up, 21 patients developed new lesions, and 6 patients had small local recurrences which were possibly retreated. In conclusion, PEI is a safe and efficient alternative therapy for the management of HCC in LC in elderly subjects.

[Evaluation of the arterial share of portal flow using a scintigraphic technique in patients with liver cirrhosis. Correlations with other parameters of portal hypertension]. / Valutazione della quota arteriosa di flusso portale mediante tecnica scintigrafica in pazienti con cirrosi epatica. Correlazione con altri parametri di ipertensione portale.

This study aimed to measure in semiquantitative terms the arterial-venous ratio of the portal flow using a scintigraphic technique, by means of a simple intravenous injection of a 99mTcDiethylHIDA bolus, a method which was found to be extremely simple and non-invasive, with a good degree of repeatibility. The percentage of arterialisation of the portal flow was found to be higher in cirrhotic patients compared to non-hepatopathic subjects, and among cirrhotic patients it was correlated with the severity of disease, the presence and degree of esophageal varices, and the presence of porto-systemic shunts, assessed using the ammonium chloride test.

Effect of somatostatin on salivary secretion in man.

Intravenous infusion of pentagastrin increases salivary secretion progressively at doses from 1 to 4 micrograms/kg body weight/h. Pentagastrin also stimulates salivary secretion of amylase. Simultaneous administration of somatostatin, at the dose that inhibits gastric secretion of pentagastrin-stimulated HCl, blocks the effect of pentagastrin on salivary flow, while it does not reduce the amylase concentration. The data suggest that different mechanisms underlie the effects exerted by pentagastrin on salivary flow and on the concentration of amylase in saliva.

Diagnosis of hepatocellular carcinoma by fine needle biopsy of portal vein thrombosis.

The authors describe a case of HBsAg positive liver cirrhosis and elevated alpha-fetoprotein value (AFP) where imaging techniques failed to detect focal liver changes. Diagnosis of hepatocellular carcinoma was reached by ultrasound-guided fine needle aspiration biopsy of portal vein thrombosis.

Subcutaneous needle-tract seeding after fine needle aspiration biopsy of pancreatic liver metastasis.

A case of subcutaneous neoplastic seeding after fine needle aspiration biopsy of a pancreatic liver metastasis is reported. Neoplastic seeding is a rare complication after fine needle biopsy (FNB). The seeding appeared 3 months after the biopsy with a subcutaneous hypoechoic nodule; diagnosis was confirmed by fine needle aspiration of the nodule. The neoplastic seeding did not change the outcome of the patient.

Natural history of focal nodular hyperplasia of the liver: an ultrasound study.

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Cholelithiasis in patients with chronic active liver disease: evaluation of risk factors.

The aim of this cross-sectional study was to evaluate the prevalence of gallstones in patients with chronic active liver disease in relation to age, sex, family history of gallstones, number of pregnancies, obesity, diabetes mellitus, aetiology of liver disease and presence or not of cirrhosis. We studied 508 patients (411 with liver cirrhosis and 97 with chronic active hepatitis) by ultrasonography. Overall prevalence of gallstones and previous cholecystectomy was 22.6% and 8.5%, respectively. A higher prevalence of gallstones was found in the subjects studied, matched for sex and age, than in the general Italian population. Univariate analysis of data showed that the prevalence of gallstones is higher in females and increases with age in both sexes and with the progression of liver disease to cirrhosis. No significant association was found between gallstones and lithogenic familiarity, obesity, diabetes mellitus, number of pregnancies and alcohol abuse. In multiple logistic regression analysis of data, female sex, increasing age and cirrhosis in the whole series, age in males and cirrhosis in females proved to be the only independent variables associated with gallstones.

Predictive factors of survival and intrahepatic recurrence of hepatocellular carcinoma in cirrhosis after percutaneous ethanol injection: analysis of 71 patients.

BACKGROUND/AIMS: This study was undertaken to determine the factors predicting survival and intrahepatic recurrence in hepatocellular carcinoma patients treated with percutaneous ethanol injection. METHODS: Seventy-one patients with cirrhosis and hepatocellular carcinoma underwent percutaneous ethanol injection (54 males/17 females; median age 66 years; Child A 54/B 17). Fifty-two patients had a single nodule < or = 5 cm and 19 had multiple nodules, up to three, each one < or = 4 cm. Follow-up ranged from 2-63 months (median 26). RESULTS: Overall survival rates were 89%, 54% and 24% and new lesions recurrence rates 32%, 73% and 81% at 1, 3 and 5 years, respectively. At univariate analysis, monofocal tumor (p<0.05), absence of ascites (p<0.05), complete tumor necrosis at CT-scan or MRI (p<0.01), post-treatment alpha-fetoprotein < or = 10 ng/ml (p<0.05) and Child A class in patients with a single nodule (p<0.05) were associated with higher survival. Presence of tumor capsule at imaging (p<0.05), complete tumor necrosis at CT-scan or MRI (p<0.01) and post-treatment alpha-fetoprotein < or = 10 ng/ml (p<0.01) were associated with lower recurrence rates. At multivariate analysis, basal alpha-fetoprotein (p=0.040) and tumor number (p=0.032) significantly affected survival; stepwise analysis revealed basal alpha-fetoprotein, tumor number and serum albumin (p=0.0012) as the best combination predicting survival. No variable reliably predicted recurrence by multivariate analysis. CONCLUSIONS: In patients with cirrhosis and hepatocellular carcinoma, treated with percutaneous ethanol injection, survival depends on: the severity of the underlying liver disease, uni/multifocality of the tumor and basal alpha-fetoprotein. Presence of a tumor capsule is associated with lower recurrence rates. At post-treatment evaluation, both survival and recurrence rates are positively affected by complete tumor necrosis and alpha-fetoprotein < or = 10 ng/ml.

Decision-making model for a non-invasive diagnosis of compensated liver cirrhosis.

Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this procedure is not without risk to the patients. This study was aimed to evaluate whether clinical, ultrasonographic, and biochemical variables may discriminate between well-compensated liver cirrhosis and non-cirrhotic chronic liver disease. Logistic regression analysis was used to assess the independent predictive value of each variable. Moreover, the post-test probability of the diagnostic variables was converted into "weights" which positively correlated with the likelihood of diagnosis of liver cirrhosis. We applied a decisional rule based on the diagnostic "weight" of each variable to 412 patients, 278 with well-compensated liver cirrhosis and 134 with non-cirrhotic chronic liver disease, diagnosed by liver biopsy with/without laparoscopy. By adding the diagnostic "weights" of each variable, liver cirrhosis and non-cirrhotic chronic liver disease were correctly diagnosed in 67% and 75% of cases, respectively. This result was validated in a split sample of 100 patients (50 with compensated liver cirrhosis and 50 with non-cirrhotic chronic liver disease) randomly selected from the acquisition sample. Based on this data, diagnosis of well-compensated liver cirrhosis can be reached in over 67% of cases without using invasive procedures. However, a prospective study is needed to confirm the clinical reliability of this method.

Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis.

The aim of the present study was to evaluate whether hepatitis C virus plays any role in the development of hepatocellular carcinoma in cirrhotic patients. The role of age, sex, alcohol abuse, and infection by other hepatitic viruses, such as hepatitis B and Delta viruses, was also assessed. We found that mean age and male/female ratio were significantly higher in patients with HCC plus liver cirrhosis than in those with liver cirrhosis alone. Also, the prevalence of HCV infection was found to be higher in HCC patients compared to cirrhotics. Further, by means of multiple logistic regression, we evaluated the independent role of each variable in the development of HCC. Age, male sex, and to a lesser degree, HCV infection, as assessed by anti-HCV positivity, were the only risk factors which significantly correlated with the development of HCC. Moreover, when age and sex were excluded from the statistical model, HCV infection, but not HBV, HDV, and alcohol abuse, appeared to be associated with HCC. In conclusion, based on these data, age and male sex are the most important factors for the development of hepatocellular carcinoma in cirrhotic patients. Hepatitis C virus, at least in the Mediterranean area, may play a role as an additive risk factor of HCC in patients suffering from liver cirrhosis.