Background: Chronic hepatitis B virus (HBV) infection is still a global health problem. Even though it is well known that adaptative immune response plays an important role in the pathogenesis of chronic infection, the impact of each immune cell population in liver damage and viral surveillance is still a matter of debate. Our aim was to elucidate the interplay between the immune response and viral activity in the context of liver damage. Methods & Materials: Immunostaining was performed in 23 liver biopsies from CHB treatment naïve patients (40% HBeAg-positive) to:1) characterize liver infiltrate [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (Foxp3+), and CTL (CD8+)] [portal quantification: immunostained/total lymphocytes; lobular quantification: immunostained lymphocytes in 10 fields; (400x)], 2) evaluate the Hepatitis B surface antigen (HBsAg) expression (presence was determined). Inflammatory activity and fibrosis were assessed using the modified Knodell scoring system (Histological Activity Index, HAI) and METAVIR. Results: All studied populations were observed in portal/periportal infiltrates with predominance of Th {Th [0.65 (0.33-0.77)] > CTL [0.54 (0.16-0.74)] > Treg [0.09 (0.00-0.25)] > Th1 [0.07 (0-0.20)] > Th17 [0.05 (0-0.20)]}. However, only CTL were present in the intralobular area [2.77 (0.01-0.25)]. Concerning liver damage, Th17 frequency was increased in cases with more severe fibrosis (p = 0.04), while Th in cases with severe hepatitis (p = 0.02) mostly due to Treg (p = 0.02). The frequency of intralobular CTL also depicted association with severe hepatitis (p = 0.02). Regarding HBV antigen profile, only 62% of cases showed presence of HBsAg, being its absence associated with a higher number of Treg (p = 0.02) and severe hepatitis (p = 0.01). Moreover, HBe Ag-positive cases exhibited higher Treg and Th frequencies (p = 0.0002 and p = 0.037; respectively). Conclusion: Although Treg population was highly represented in the infiltrate, they were not related to liver damage. In contrast, intrahepatic Th17 mediated fibrosis severity. The presence of CTL in the intralobular area may indicate a relationship between them and hepatocytes denoting their contribution to hepatitis severity. Finally, our results suggest that the presence of a regulatory microenvironment enhances viral replication. This hypothesis is supported by the fact that a higher Treg frequency was observed in the context of absence HBsAg as well as among HBeAg-positive cases.

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

Background: Autoimmune hepatitis predominantly affects women.Little is known about presentation and long term prognosis among males.Aim: To evaluate clinical features and outcome of male patients with autoimmune hepatitis compared with females.Patients and Methods: We evaluated 245 consecutive patients with diagnosis of AIH between January 2000 and June 2008 (48 men, 197 women).Diagnosis was established according to the recommendations of the International Autoimmune Hepatitis Group.Prognostic factors of "bad evolution" (death or requirement of liver transplantation) among men were evaluated.Mean follow up: 3.2 years (0.4-7.5).Results: Compared with females, males have higher frequency of fulminant hepatic failure (14.8 vs 6.3%, p < 0.05) and of acute hepatitis as initial presentation (42 vs 27%, p < 0.05), and lower overlap with primary biliary cirrhosis (6.57vs 13.19%, NS).Males presented with lower frequency of "definitive" diagnosis of AIH according to the score of the IAHG (36 vs 63.9%, p < 0.05), lower gammaglobulin levels (1.79±0.64vs 2.23±1.02gr/dL), lower frequency of autoantibodies (67 vs 86%), lower titers of antinuclear antibodies and higher transaminases levels at presentation (398 (48-2980) vs 273 (52-2740) UI/ml, NS).Mean age at presentation was similar (42±23 vs 44±19 years, NS), though females presented a bimodal distribution (1st-2nd and 4th-5th decades) compared to men (2nd to 4th decades).Women more frequently presented with cirrhosis at initial biopsy (21 vs 8%, p < 0.01) and had associated autoimmune conditions (64 vs 17%, p < 0.01).Complete response to steroid treatment was lower among males at 3 and 6 months post treatment.A bad evolution was observed in 25% of men (n = 12) and 17% of women (n = 34).Factors associated with bad prognosis were fulminant presentation, no "definitive" diagnosis of AIH, absence of autoantibodies and no steroid response at 3 months of treatment.Conclusion: AIH in males compared to females has a distinctive clinical presentation and inmunological profile, with less response to steroid therapy and a worse prognosis.

Introduction and Objectives: Early identification of fulminant autoimmune hepatitis could be lifesaving or prevent liver transplantation, but rapid diagnostic and prognostic criteria are lacking. This study aimed to assess the clinical features and outcomes of fulminant AIH. –To analyze prognostic factors related to poor outcomes (requirement of transplantation or death). Materials and Methods: We retrospectively reviewed 307 consecutive patients evaluated for fulminant hepatic failure (1994-June 2020) in our Unit. Patient work-up consisted of viral serologies, autoantibodies, gammaglobulin, drug screening and ceruloplasmin. Since 2003, selected hemodynamically and neurologically stable patients have received a transjugular liver biopsy. Results: 86 patients (28,01%) fulfilled the criteria for fulminant AIH (AIH simplified criteria). Seven were excluded from analysis due to cirrhosis Oral meprednisone 60 mg or via nasogastric tube was started at diagnosis in 67 patients until death, transplantation, recovery or futility. Biochemical and clinical variables were analyzed. One patient developed hyperacute encephalopathy, 33 within 7/28 days post jaundice (41.7 %) and 45 (55.9 %) subacute encephalopathy (>28 days). 63/79 patients died or required liver transplantation (median time 7.8 days,1-34 days). 48 (60 %) patients underwent LT, 16 (20%) patients survived, and 16 (20 %) died without LT. Seven transplanted patients died early post OLT (infectious n=5, neurological complications n=2). Variables associated with bad prognosis were: prothrombin time < 20% or grade IV encephalopathy at steroid initiation, LC+ or LKM-1 +, massive necrosis, no >20% improvement of prothrombin time by day three post-steroids (p<0.05). Patients diagnosed before 2003 had the worst prognosis (87 vs. 71%), probably related to the shorter time to diagnosis since the introduction of biopsy (2.1±1.7 days vs. 4.6±2.1 days, p<0.05). Among patients who recovered, 5/16 were weaned from immunosuppression at a median of 4.5 years of treatment without relapse. Conclusions: The disease course is aggressive, with death or requirement of liver transplantation in 80 % of patients. Early diagnosis and treatment may improve survival.

O22 Aims: To study the outcome of splanchnic and systemic hemodynamics early after living donor liver transplantation. Methods: The influence of hemodynamic changes on liver function was determined as well. Portal vein velocity and diameter were measured prospectively using Doppler-ultrasound in 23 consecutive recipients with cirrhosis, before and 1, 7, 14 and 30 days after living related right lobe liver transplantation. Portal blood flow (PBF) was calculated. Liver function tests were obtained at the same time-periods. Hepatic venous pressure gradient (HVPG) was determined at day 7 and a transyugular liver biopsy was performed. Hemodynamic results were compared with those preoperatively obtained in donors. Results: The mean graft/recipient weight ratio (GRWR) was 1.01±0.23. Fourteen patients were Child B and 9 were Child C. The mean right PBF in recipients at day 1 was significantly higher than in donors (1.55±0.34 vs 0.89±0.26 L/min, p<0.01). The main determinant of elevated PBF in recipients was the increase in right portal vein velocity (86±21 vs 48±13 cm/sec, p<0.01). GRWR did not differ between Child B and C patients. However, PBF was significantly higher in Child C patients (1.61±0.33 vs 1.38±0.35 L/min, p<0.05). PBF decreased significantly at 1 month but did not achieve normal values. When PBF was analyzed in relation to right lobe volume (PBF/RLV), the mean value of this ratio at day 1 significantly correlated with bilirubin value at day 7 (r = 0.78; p<0.01). HVPG at day 7 was increased (8.5±2.7 mmHg) and correlated closely with PBF/RLV at day 1 (r= 0.70; p<0.01). Histological findings were not related to hemodynamic or biochemical changes. Cardiac output was increased at all time-points but did not correlate with PBF or biochemical changes. Conclusions: Portal blood flow markedly increases early after living related right lobe liver transplantation. Changes in splanchnic hemodynamics may influence the outcome of liver function. Doppler ultrasound is a useful tool for the early detection of hemodynamic changes in these patients.

Biliary papillomatosis is a uncommon disease. Because of the high rate of recurrence and the possibility of malignant transformation, liver resection or transplantation was recommended. A case of diffuse bilobar biliary papillomatosis, in a 60 years old patient, responsible for cholangitis, cholestasis and for high portal pressure (esophageal varices grade I and II and hypersplenisme) is reported. The patient had had an external biliary drainage leading to an great loss of hydroelectrolytic component important. Opacification and biopsies under endoscopic control assert the right diagnosis. He was treated by a orthotopic liver transplantation. Post operative course was simple. In the 9th month, it was asymptomatic with a completely satisfactory evolution. The other therapeutic modalities was discussed, as well as the review of the literature.

Measurements of the components of the microwave permeability tensor of ferrites are usually made on very small specimens, such as spheres, discs, or rods, placed in cavities. Using degenerate modes, one can relate the frequency shifts of these modes to the real parts, and the changes in Q to the imaginary parts, of the tensor components. The technique herein described makes use of measurements performed on a ferrite rod placed along the axis of a circular waveguide. Exciting the specimen successively with the two senses of circular polarization, one obtains phase and attenuation information for each of these modes which can then be related by a perturbation treatment back to the real and imaginary parts, respectively, of the tensor components. The variation of phase and attenuation are recorded continuously (but on successive runs) as functions of the changing applied magnetic field. The apparatus used for these purposes will be described and certain novel features pointed out. While this method lacks the advantage of cavity techniques to separate out the dielectric contributions to the phase and attenuation shifts, it does offer a means whereby a fairly large specimen can be examined for its basic parameters in a geometrical configuration often used in applications.