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.
Background/Aims: In chronic viral hepatitis, liver biopsy is performed for assessing disease activity and fibrosis. In this study, we evaluated the impact of the size of liver biopsy on the grading ...and staging.
Methods: We selected 161 liver biopsies from patients with chronic types B and C hepatitis on the basis of their length (≥3 cm) and width (1.4 mm). Ishak scoring system was used for grading and staging. The score was blindly repeated reducing the length of the specimen from ≥3 to 1.5 cm and to 1 cm long and width from 1.4 to 1 mm.
Results: Reducing the length of the biopsy led to an increase of cases with mild grades: 49.7% in ≥3 cm, 60.2% in 1.5 cm and 86.6% in 1 cm long specimens (
P<0.001). Similarly, cases staged as having mild fibrosis significantly increased in the shorter specimens: 59% in ≥3 cm, 68.3% in 1.5 cm and 80.1% in 1 cm long specimens (
P<0.001). As for the width, both grade and stage were significantly underscored in the 1 mm samples, regardless of their length.
Conclusions: Liver biopsy size strongly influences the grading and staging of chronic viral hepatitis. The use of fine needles should be discouraged in this setting.
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.
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.
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.
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.
•Serum ANA is detected in 18.1% of the general population and the prevalence increases with age.•Serum ANA is associated with an increased risk of connective tissue disease over 15 years.•Serum ANA is not related to an increased risk of cancer over 15 years.•Serum ANA positivity is not associated with increased mortality over 15 years.
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.
Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
See Editorial on Page 325
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.
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.
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).
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.
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.
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.
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