Pneumococcal vaccination status among cirrhotic patients in Italy: a neglected topic.

To date, few reports have evaluated the pneumococcal vaccination status in cirrhotic patients. No data are available for European countries. We have explored this topic and the potential independent predictors motivating lack of vaccination in Italy. Between January 1st and June 30th 2022, 1419 cirrhotic patients of any etiology were consecutively enrolled in an observational, prospective study at 8 referral centers in Italy. Adjusted odds ratios (ORs) for the association with lack of vaccination were evaluated by multiple logistic regression analysis. Overall vaccine coverage was 17.9% (8.9% in patients < 65 years of age and 27.1% in those aged ≥ 65 years; p < 0.001). Among the 1165 unvaccinated patients, 1068 (91.7%) reported lack of information regarding vaccination as the reason for not having undergone vaccination. Independent predictors associated with lack of vaccination were age < 65 years (OR 3.39, CI 95% 2.41-4.76) and a higher number of schooling years (OR 2.14, CI 95% 1.58-2.91); alcoholic etiology resulted only marginally associated (OR 1.91, CI 95% 1.03-3.52). These findings establish evidence on how pneumococcal vaccination status in Italy is largely suboptimal among cirrhotic patients. These results raise concern, considering the severe outcomes of pneumococcal infection in patients with chronic liver diseases.

Low influenza vaccination coverage in subjects with liver cirrhosis. An alert waiting for winter season 2020-2021 during the COVID-19 pandemic.

We have evaluated flu vaccine coverage and variables associated with the lack of vaccination in cirrhotic subjects with particular attention to the cirrhosis etiology. Cirrhotic subjects consecutively referring to eight Italian centers were prospectively enrolled for a 6-month period in 2019. Subjects were asked if they had received a flu vaccine in the last 12 months. Multiple logistic regression analysis was performed to identify independent predictors of lack of vaccination. A total of 818 cases were recruited. The overall vaccine coverage was 39.6% (26.9% in those younger than 65 years and 51.9% in those older than 64 years; p < 0.001). Age < 65 years (odds ratio [OR] = 2.38; 95% confidence interval [CI] = 1.68-3.36), alcoholic etiology (OR = 2.40; 95% CI = 1.49-3.85), birth abroad (OR = 2.7; 95% CI = 1.10-6.61), and residence in South/Sardinia island (OR = 1.66; 95% CI = 1.14-2.42) all resulted independent predictors of the likelihood of lack of vaccination. The lack of information regarding the vaccine as the reason for no vaccination was reported by 71.4% of foreigners and by 34.7% of natives (p < 0.001). In conclusion, much work still should be done to improve coverage among groups at higher risk of lack of vaccination identified in this survey. The ongoing SARS-CoV-2 pandemic may represent one more alert for improving seasonal flu vaccine coverage to avoid further stress to the National Health System.

Chronic hepatitis B virus infection in Italy during the twenty-first century: an updated survey in 2019.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25-5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02-2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9-4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Rheumatoid factor and anti-citrullinated peptide antibodies in the general population: hepatitis B and C virus association and 15-year-risk of rheumatoid arthritis.

OBJECTIVES: The study aimed to determine the prevalence of rheumatoid factor (RF) and anti-citrullinated peptides (ACPA), to estimate the association with hepatitis B (HBV) or C (HCV) virus infections and the 15-year risk of developing RA in a large cohort from a Northern Italian region. METHODS: In 1998, 15,907 subjects between the ages of 18 and 75 were randomly selected 1:4 for HBV and HCV testing; more recently, we tested a subgroup of sera for RF (n=2196) and ACPA (n=2525). Administrative databases were searched after 15 years for incident RA diagnoses occurring between 1998 and 2013. RESULTS: RF was positive in 8.1% of cases with 10% of RF-positive subjects having HBsAg (p=0.004) and 9% anti-HCV. ACPA were detected in 4.8% of subjects with 5% of the ACPA-positive subjects having HBsAg and 5.9% anti-HCV. Older subjects had higher positivity rates for both RF and ACPA. HBsAg and anti-HCV were detected in 5.5% and 4.3% of sera, respectively. Over 15 years, 10 RA cases were recorded (9 women, median age at diagnosis 52 years) with RF previously positive in 2/10 and ACPA in 5/10 cases. RF and ACPA were associated with relative risks for developing RA of 5.7 (adjusted for HBsAg status; 95% CI 1.2-26.3) and 13.2 (95% CI 3.8-46.3), respectively. CONCLUSIONS: Our data in a large cohort from an unselected general population confirm a higher risk of RA development associated with ACPA compared to RF. HBV exposure correlates with RF but not with ACPA positivity.

Migratory flow and hepatitis delta infection in Italy: A new challenge at the beginning of the third millennium.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P < .001). HDV-RNA was checked in 63 (80.8%) of the 78 anti-HDV+ subjects, and 49 (77.8%) tested positive. Compared to non-natives, Italians were more likely males (male/female 1.6 vs 0.6; P < .05) and older (median age 57 years vs 46 years; P < .05). Multivariate analysis showed that non-natives (OR = 6.02; CI 95% = 3.06-11.84) and cirrhosis (OR 9.6; CI 95% = 5.39-17.30) were independently associated with anti-HDV positivity. A remarkable changing pattern in some characteristics of anti-HDV-positive subjects was observed over 1987-2019: a decreasing male/female ratio, an increasing mean age and proportion of cirrhotic subjects. Anti-HDV prevalence decreased from 7.4% to 6.4% among Italians, increasing from 12.2% to 26.4% among non-natives during 2001-2019. Hence, HDV infection in Italians is further decreasing and mostly affects old people and subjects with advanced disease reflecting a survival effect. Conversely, non-natives are sixfold more likely anti-HDV-positive with an increasing trend. Migratory flow may be a new challenge for HDV infection at the beginning of the third millennium.

Focus on histological abnormalities of intrahepatic vasculature in chronic viral hepatitis.

BACKGROUND & AIMS: The histological intrahepatic microvasculature lesions have not been deeply investigated outside the setting of portal hypertension. The aim of this study was to analyse the type and the prevalence of microvasculature abnormalities and their correlation with inflammatory activity, fibrosis stage and tissue markers of fibrogenesis, angiogenesis and oxidative DNA damage in liver biopsies obtained from patients with chronic viral hepatitis. METHODS: Seventy-four liver biopsies from untreated patients affected by hepatitis B (22 cases) and C (52 cases) were included. The presence of microvascular changes was correlated with (i) the severity of the activity and fibrosis; (ii) immunohistochemical markers of angiogenesis (CD34) and hepatic stellate cells activation (alpha-smooth muscle actin); (iii) a tissue marker of oxidative damage (8-OHdG adducts). RESULTS: Sixty-five out of 74 biopsies (87.8%) showed vascular lesions. Portal angiomatosis was the most prevalent (62.2%) and it was associated with, on 1 side, the fibrosis stage at both univariate (P < .0001) and multivariate analysis (P = .01, OR = 9.4 [1.6-54]) and, on the other, with angiogenesis (P = .05) and hepatic stellate cells activation (P = .002). Interestingly, 36/46 cases with portal angiomatosis were at early/intermediate fibrosis stage. The hepatic stellate cells activation was also associated with the presence of aberrant periportal vessels (P = .01). CONCLUSIONS: The histological alterations of intrahepatic microvasculature, usually seen in cirrhosis and portal hypertension, occur in chronic viral hepatitis even at early/intermediate fibrosis stages. Their correlation with angiogenesis and fibrogenesis supports a possible involvement in disease progression.

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy.

BACKGROUND: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). METHODS: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. RESULTS: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014). CONCLUSION: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study.

BACKGROUND AND AIM: The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). MATERIAL AND METHODS: A total of 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. RESULTS: The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6% to 33.2%. Regarding the age class 0-33 (fully covered by HBV vaccination in 2014), the rate of inactive carriers decreased from the 21.7% in 2001 to 5.9% in 2014, that of chronic hepatitis from 17.5% to 5.2% and that of cirrhosis cases from 26.4% to 4.1%. Instead, in the over-60 age group the rate of inactive carriers increased from 22.8% to 41.2% and that of chronic hepatitis from 16.8% to 46%; the rate of patients with cirrhosis ranged from 5% to 8% in different studies. CONCLUSION: Twenty-three years after the introduction universal HBV vaccination in Italy, the clinical presentation of CLD had shown a shift toward older ages and more severe diseases.

Obliterative portal venopathy without portal hypertension: an underestimated condition.

BACKGROUND & AIMS: Obliterative portal venopathy without portal hypertension has been described by a single study in a limited number of patients, thus very little is known about this clinical condition. This study aimed to investigate the prevalence of obliterative portal venopathy and its clinical-pathological correlations in patients with cryptogenic chronic liver test abnormalities without clinical signs of portal hypertension. METHODS: We analysed 482 liver biopsies from adults with non-cirrhotic cryptogenic chronic liver disorders and without any clinical signs of portal hypertension, consecutively enrolled in a 5-year period. Twenty cases of idiopathic non-cirrhotic portal hypertension diagnosed in the same period, were included for comparison. Histological findings were matched with clinical and laboratory features. RESULTS: Obliterative portal venopathy was identified in 94 (19.5%) of 482 subjects and in all 20 cases of idiopathic non-cirrhotic portal hypertension: both groups shared the entire spectrum of histological changes described in the latter condition. The prevalence of incomplete fibrous septa and nodular regenerative hyperplasia was higher in the biopsies of idiopathic non-cirrhotic portal hypertension (P = 0.006 and P = 0.002), a possible hint of a more advanced stage of the disease. The two groups also shared several clinical laboratory features, including a similar liver function test profile, concomitant prothrombotic conditions and extrahepatic autoimmune disorders. CONCLUSION: Obliterative portal venopathy occurs in a substantial proportion of patients with unexplained chronic abnormal liver function tests without portal hypertension. The clinical-pathological profile of these subjects suggests that they may be in an early (non-symptomatic) stage of idiopathic non-cirrhotic portal hypertension.

COVID-19 vaccination among cirrhotics in Italy: High coverage and effectiveness of 3 doses versus 2 in preventing breakthrough infection and hospitalization.

BACKGROUND AND AIMS: Few reports, all retrospective, have evaluated vaccine coverage against COVID-19 infection in cirrhotic subjects. No data are available for European Countries. We aimed to explore this topic and potential independent predictors of lack of vaccination. METHODS: Between January 1st and June 30th 2022, 1512 cirrhotic subjects of any etiology were consecutively enrolled in an observational - prospective study in 8 referral centers in Italy. Adjusted Odds Ratios (O.R.) for the association with lack of vaccination and with occurrence of breakthrough infection were evaluated by multiple logistic regression analysis. RESULTS: Overall vaccine coverage was 89.7% (80% among people born abroad). Among the 1358 vaccinated people, 178 (13.1%) had a breakthrough infection; of them 12 (6.7%) were hospitalized, but none died. Independent predictors associated with lack of vaccination were birth abroad, age <65 years and lower years of schooling. Child stage B/C was the only independent predictor of breakthrough infection. Occurrence of breakthrough infection was more likely reported in subjects who received 2 doses of vaccine than in those who received 3 doses (33.9% versus 9.0%; P<0.001). CONCLUSION: High vaccine coverage against COVID-19 infection is observed among cirrhotic subjects in Italy. Vaccine is effective in preventing severe outcomes. Three doses are more effective than two, even in cirrhotic subjects. LAY SUMMARY: This large cohort study evidenced high vaccine coverage against COVID-19 infection among cirrhotic subjects in a European country and the effectiveness of vaccine in preventing severe outcomes. Three doses of vaccine are more effective than two in preventing breakthrough infection and hospitalization. Informative campaigns targeting people younger than 65 years of age and those with lower years of schooling may increase these excellent results.

Hepatitis B vaccine coverage and risk factors for lack of vaccination in subjects with HBsAg negative liver cirrhosis in Italy: still, much work should be done.

BACKGROUND: in Italy, Hepatitis-B-vaccine is advised and provided free-of-charge for subjects with chronic liver disease (CLD), including liver cirrhosis. AIMS: to evaluate HB-vaccine-coverage and variables associated with lack of vaccination in cirrhotic patients with particular attention to cirrhosis' etiology. METHODS: cirrhotic patients of any etiology (excluding HBsAg+) referring to 8 tertiary-centers were prospectively enrolled for a-six-months-period in 2019. Subjects were asked if they received HB-vaccine previously. Multiple-logistic-regression-analysis was performed to identify independent predictors of lack of vaccination. RESULTS: 731 cases were recruited. Overall-vaccine-coverage was 16.3% (23.7% in those younger than 65y, 10.0% in those older than 64y; p<0.001). Lack of information was the most frequent reason (78.5% of cases) reported by the 608 unvaccinated subjects, without statistical difference by area-of-birth (77.3% in Italians, 80.0% in people-born-abroad). Age>64 y (OR: 4.27; CI 95%: 2.52-7.24), educational level<9 years (OR: 3.52; CI 95%: 2.10-5.90), residence in South/Sardinia (OR 2.52; CI 95%:1.45-4.39), birth-abroad (OR 5.09; CI 95%: 1.07-24-.17), and Child grade B/C(OR 2.68; CI 95%: 1.35-5.33) all resulted independent predictors of likelihood of lack of vaccination. CONCLUSIONS: Vaccination-rate in cirrhotic patients results very low. Vaccine-coverage implementation in these subjects, is warranted. Vaccine should be provided in early CLD, when immunization is most effective.

Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.

BACKGROUND: Little is known about the efficacy, safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis Cvirus (HCV) infection and histologically proven fully established cirrhosis. We aimed here to evaluate the safety of this regimen in such patients and to identify baseline and on-treatment predictors of a sustained virological response (SVR). METHODS: Patients with histologically proven, HCV-induced cirrhosis were randomized to receive pegylated interferon-alpha2b (PEG-IFN-alpha2b; 1.0 microg/kg/week, n=56; group A) or recombinant interferon-alpha2b (IFN-alpha2b; 3 million IU three times/week, n=36; group B), each in combination with a weight-based dose of ribavirin (800-1,200 mg/day) for up to 48 weeks. The primary endpoint of the study was the assessment of SVR, defined as undetectable HCV RNA 24 weeks after treatment cessation. RESULTS: Overall, 40% (37/93) of patients attained SVR: 44% (25/57) in group A and 33% (12/36) in group B (P=0.31). SVR rates were significantly higher in genotype 2/3 patients than in genotype 1 patients (69% versus 25%; P<0.0001). Platelet count at baseline, rapid virological response, and early virological response were predictors of SVR. Twelve patients discontinued treatment because of an adverse event and 20 patients required ribavirin dose reduction for the management of anaemia. CONCLUSIONS: PEG-IFN-alpha2b plus ribavirin for 48 weeks is an efficacious and well-tolerated treatment regimen for patients with HCV-induced cirrhosis. Although SVR rates were more satisfactory in genotype 2/3 than in genotype 1 patients, our study identified additional predictors of response that could allow physicians to better manage treatment in this 'difficult-to-cure' subset of patients.

Pathology of idiopathic non-cirrhotic portal hypertension.

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.

BACKGROUND: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. OBJECTIVE: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. DESIGN: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis. RESULTS: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex. CONCLUSIONS: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology.

BACKGROUND: Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. AIM: To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. PATIENTS: Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. RESULTS: The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02). CONCLUSIONS: Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p<0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012).

Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years.

The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43±13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58±13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥1:160 (HR 14.19, 95% CI 3.07-65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75-1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94-2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk.

The overlap syndrome between primary biliary cirrhosis and primary sclerosing cholangitis.

BACKGROUND: The overlap syndrome between primary biliary cirrhosis and primary sclerosing cholangitis is an extremely rare condition that has been reported in only six published cases so far. METHODS: Here we report two cases showing the clinical manifestations of both primary biliary cirrhosis and primary sclerosing cholangitis. RESULTS: In one case the overlap condition was associated with psoriatric arthritis, and the patient successfully underwent dual treatment with ursodeoxycholic acid and the anti-tumour necrosis factor-alpha agent adalimumab. In the second case, the predominant condition was, initially, an antimitochondrial antibody-negative primary biliary cirrhosis with progressive course towards end-stage liver disease; the patient then developed either antimitochondrial antibody positivity or changes in the biliary tree compatible with primary sclerosing cholangitis. CONCLUSIONS: These two cases add information on a controversial issue in the literature, and indicate the importance of recognizing a possible overlap syndrome to optimize treatment.

Occult hepatitis B virus in liver tissue of individuals without hepatic disease.

BACKGROUND/AIMS: While many data are available concerning occult hepatitis B virus (HBV) infection in patients with hepatic disorders, there is little information about this cryptic infection in individuals without liver disease. The aim of this study was to investigate the prevalence of occult HBV in the general population by examining liver specimens from a large series of HBV-surface-antigen negative individuals with no clinical and biochemical evidence of liver disease. METHODS: The presence of HBV DNA was evaluated by testing, through polymerase chain reaction techniques, DNA extracts from 98 liver-disease-free individuals who underwent liver resection or needle biopsy during abdominal surgery. Sixteen of them were anti-HBV-core antigen (anti-HBc) positive and 82 were HBV serum-marker negative. All patients were negative for antibody to hepatitis C virus. RESULTS: Occult HBV infection was revealed in 16 of the 98 cases (16.3%). In particular, 10/16 anti-HBc positive (62.5%) versus 6/82 (7.3%) HBV-seronegative individuals were occult carriers (p<0.0001). CONCLUSIONS: This study revealed that about 1/6 of the Italian general population might be carriers of occult HBV infection, and this condition is significantly associated with the anti-HBc positive status.

Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.

BACKGROUND & AIMS: Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. METHODS: We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. RESULTS: Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in 1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in 142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. CONCLUSIONS: In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.