Background. Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. Aims. To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index.Methods. Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. Results. For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a ‘severity’ component; the second one, accounting for 18% of variance, was interpreted as a ‘profile’ component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution × intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. Conclusion. The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials.

Progression of hepatitis B in patients with lamivudine-resistant strains is slowed down by adefovir dipivoxil (ADV). Whether the time point of ADV administration (genotypic vs. phenotypic resistance) influences the outcome of therapy is unknown. We compared the outcome of ADV therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients with genotypic and phenotypic resistance to lamivudine. Ten milligrams of ADV was administered daily for 2 years to 46 HBeAg-negative patients at the time of phenotypic resistance (group A, >6 log 10 copies/mL of hepatitis B virus [HBV] DNA and high alanine aminotransferase [ALT] levels) and 28 patients at the time of genotypic resistance (group B, 3-6 log 10 copies/mL of HBV-DNA and normal ALT). HBV DNA was assessed every 2 months using Versant 3.0 assay, and lamivudine resistance was confirmed via INNO-LiPA assay in all patients. By month 3, HBV DNA tested negative in all patients from group B compared with only 20 (46%) in group A (P < .0001). The 2-year rates of virological response were 100% in the former patients and 78% in the latter ones (P < .0001). ALT levels remained persistently normal in all group B patients, whereas in group A patients they normalized at rates of 50% at month 6 (P < .0001), 72% at month 12 (P < .01), and 93% at month 24. None of the patients developed ADV resistance or ADV-related side effects. In conclusion, to optimize antiviral treatment in HBeAg-negative patients selecting resistant strains to lamivudine, ADV should be added to lamivudine as soon as genotypic resistance is detected. (HEPATOLOGY 2005;42:1414-1419

The impact of hepatitis C virus (HCV) infection on mortality of patients receiving regular dialysis remains unclear. The assessment of the natural history of HCV in dialysis population is difficult because of the low progression of HCV-related liver disease over time and the reduced life expectancy in patients with end-stage renal disease. The aim of the study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on the survival of patients undergoing maintenance dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. We identified seven studies involving 11 589 unique patients on maintenance dialysis; two (29%) were case-control studies. Pooling of study results demonstrated that presence of anti-HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (aRR) (all-cause mortality) was 1.34 with a 95% confidence interval (CI) of 1.13-1.59. Heterogeneity statistics, R(i) = 0.48 (P-value by Q-test = 0.13). In a sensitivity analysis including only (n = 5) cohort studies, the pooled aRR was 1.38 (95% CI, 1.20-1.59); heterogeneity statistics R(i) = 0.46. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti-HCV-positive than -negative dialysis patients. Our meta-analysis indicates that anti-HCV-positive patients on dialysis have an increased risk of mortality compared with HCV-negative patients. The excess risk of death in HCV-positive patients may be at least partially attributed to chronic liver disease with its attendant complications.

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Objectives: The management of healthcare workers (HCWs) exposed to confirmed cases of coronavirus disease 2019 (COVID-19) is still a matter of debate. We aimed to assess in this group the attack rate of asymptomatic carriers and the symptoms most frequently associated with infection. Methods: Occupational and clinical characteristics of HCWs who underwent nasopharyngeal swab testing for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a university hospital from 24 February 2020 to 31 March 2020 were collected. For those who tested positive and for those who tested positive but who were asymptomatic, we checked the laboratory and clinical data as of 22 May to calculate the time necessary for HCWs to then test negative and to verify whether symptoms developed thereafter. Frequencies of positive tests were compared according to selected variables using multivariable logistic regression models. Results: There were 139 positive tests (8.8%) among 1573 HCWs (95% confidence interval, 7.5e10.3), with a marked difference between symptomatic (122/503, 24.2%) and asymptomatic (17/1070, 1.6%) workers (p < 0.001). Physicians were the group with the highest frequency of positive tests (61/582, 10.5%), whereas clerical workers and technicians had the lowest frequency (5/137, 3.6%). The likelihood of testing positive for COVID-19 increased with the number of reported symptoms; the strongest predictors of test positivity were taste and smell alterations (odds ratio ¼ 76.9) and fever (odds ratio ¼ 9.12). The median time from first positive test to a negative test was 27 days (95% confidence interval, 24e30). Conclusions: HCWs can be infected with SARS-CoV-2 without displaying any symptoms. Among symptomatic HCWs, the key symptoms to guide diagnosis are taste and smell alterations and fever. A median of almost 4 weeks is necessary before nasopharyngeal swab test results are negative.

BACKGROUND & AIMS:Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. METHODS:In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28-87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3-6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. RESULTS:During a median 25 months of follow up (range, 3-39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%-9%). Of patients with de novo HCC, 75% had a single tumor and 82% of these were Barcelona liver cancer stage 0-A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0-9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44-26.47; P [ .01), diabetes (HR, 2.52; 95% CI, 1.08-5.87; P [ .03), LSM (HR, 1.03; 95% CI, 1.01-1.06; P [ .01), and FIB-4 score (HR, 1.08; 95% CI, 1.01-1.14; P [ .01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3year cumulative probability for recurrence was 43% (95% CI, 20%-61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55-10.93; P [ .004).Abbreviations used in this paper: CONCLUSIONS:In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.

SUMMARYBackground: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. Aim: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. Methods: We screened a large cohort (n ¼ 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n ¼ 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. Results: Occult hepatitis B virus infection was absent (zero of 213 ¼ 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P ¼ 0.0001]. No dialysis

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P = .03). Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P < .001). During a median period of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the 21 untreated controls (sustained response: 33% vs. 0; P < .001). Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P = .01), but not in the untreated group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients.