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 antiHCV 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

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 analyze 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 one side, the fibrosis stage at both univariate (p <0.0001) and multivariate analysis (p = 0.01, OR = 9.4 [1.6-54]) and, on the other, with angiogenesis (p= 0.05) and hepatic stellate cells activation (p = 0.002). 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 = 0.01). 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

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