Franco Capra

α-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers

Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non-responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis.

Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications

Although a number of studies have demonstrated the influence of ABO blood group on plasma levels of von Willebrand factor (VWF), the nature of this association and its clinical importance is still largely unknown.In this review, the most recent advances in our understanding of the mechanisms by which ABO blood group determines plasma VWF levels and their clinical impact will be discussed.

Chronic hepatitis in multiple virus infection : histopathological evaluation

The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty‐nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The δ‐5‐virus (HDV) was not associated with severe necro‐inflammatory lesions, but HDV‐positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non‐specific for HCV infection, or that these cases represent HCV infection with false‐negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co‐infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear.

The effect of iron depletion on chronic hepatitis C virus infection

Increasing evidence exists that iron overload, a common finding in chronic hepatitis C virus (HCV) infection, plays an important role in the pathophysiology of this disease. The mechanisms by which iron excess induces liver damage along with the benefit of iron depletion via phlebotomy on biochemical and histological outcomes in patients with chronic HCV infection have been discussed in this review. Finally, we focus on the effect of iron reduction on the rate of response to interferon antiviral therapy.

Decreased activity of scavenger enzymes in human hepatocellular carcinoma, but not in liver metastases

SummaryTo investigate the role of oxygen free radicals in hepatocellular carcinoma we assayed tissue scavenger enzymes (superoxide dismutase and selenium-dependent glutathione peroxidase) in liver homogenate, plasma concentrations of vitamins A and E and the serum selenium level from 19 control patients, 23 cases of hepatocellular carcinoma and 18 cases of metastases to liver from different carcinomas. In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver and in metastases-bearing liver; the enzyme activities of the latter tissues were not different from control liver. In contrast, normal liver adjacent to the hepatocellular carcinoma had decreased activity of superoxide dismutase. Serum selenium concentrations were significantly decreased in patients with hepatocellular carcinoma and those with liver metastases, while vitamin A was significantly decreased only in the former. These findings suggest that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.

Altered intestinal function precedes the appearance of bacterial DNA in serum and ascites in patients with cirrhosis: a pilot study.

Objectives Bacterial translocation seems to precede the occurrence of overt bacterial infection in patients with cirrhosis. The presence of bacterial DNA in blood and ascites correlates with bacterial translocation and is frequent in patients with advanced cirrhosis without overt infection. Our aim was to search for bacterial DNA in patients with cirrhosis both with and without ascites, and to study its correlation with abnormal intestinal motility or permeability and the presence of bacterial overgrowth. Methods Blood and ascites samples were obtained on day 1, and blood samples were taken twice a day for the following 3 days. Bacterial DNA was assayed by polymerase chain reaction using universal primers for rRNA 16 s. Oro-caecal transit time and bacterial overgrowth were assessed with Lactulose H2 breath testing. Intestinal permeability was assessed by determining urinary lactulose and mannitol excretion with high performance liquid chromatography. Results We studied seven patients (six were male, age range was 42–78 years). Aetiology was alcohol in four, HCV in two, HBV in one; ascites was present in four and Child−Pugh grade was A in four and B in three. All patients had increased intestinal permeability, six had decreased transit time and one had bacterial overgrowth. In only one patient (with ascites), polymerase chain reaction was positive for bacterial DNA both in ascites and serum for all 4 days on which samples were taken. Conclusion Increased intestinal permeability and abnormal motility were frequent without evidence of bacterial translocation in cirrhosis even without ascites. They are likely to be facilitators for bacterial translocation and thus precede it.

Serum selenium in liver cirrhosis: Correlation with markers of fibrosis

In 55 patients with alcoholic cirrhosis and in 47 healthy individuals we assayed the concentration of selenium in serum (S-Se) by proton induced X-ray emission, the aminoterminal peptide of type III procollagen (NPIIIP) by RIA and the plasma fibronectin (FN) by immuno-nephelometry, together with routine biochemical tests. S-Se was lower in cirrhosis than in controls (0.57, SD 0.20 vs 0.92, SD 0.16 mumol/l; p less than 0.001) and was more reduced in ascitic than in compensated patients (0.50, SD 0.19 vs 0.66, SD 0.17 mumol/l; p less than 0.001). Regression analysis showed a positive correlation of S-Se with serum albumin and FN, whereas necrotic or inflammatory activity seems unrelated to S-Se; a negative correlation was found between S-Se and NPIIIP, suggesting a protective role of selenium against fibrosis.

REVIEW: Liver Transplantation: Making the Best Out of What We Have

Since the first human liver transplantation, carried out in 1963, the procedure has become routine with an excellent outcome in terms of both quality and length of survival. One of the major challenges facing the transplant community is the shortage of donor organs. Possible approaches to overcoming this problem include changes in legislation, setting up of organizational structures, more effective use of marginal donor livers, splitting livers, and the development of living related transplants. Alternative treatments to liver transplantation have been sought, including hepatocyte transplantation, xenotransplantation, liver-directed gene therapy, extracorporeal liver support systems, tissue-engineered organs, and auxiliary partial orthotopic liver transplantation.

Serum laminin P1 in chronic viral hepatitis: correlations with liver histological activity and diagnostic value

Laminin is a major basement membrane-associated, non-collagenous glycoprotein of the extracellular matrix and is deposited in the space of Disse during sinusoidal capillarisation. Laminin P1, a pepsin-resistant fragment originating from the central portion of the cross-shaped laminin molecule, is detectable in serum and has been related to liver fibrosis and portal hypertension. In this study we investigated the behaviour of serum laminin P1, measured by radioimmunoassay, in a homogeneous group of 95 patients suffering from chronic viral hepatitis, types C or B, in order to determine the relationships between serum laminin P1 and each of the main histological aspects of the disease process (i.e. portal-periportal activity, lobular activity and fibrosis), which were assigned numerical scores. Moreover, we computed, at several cut-off levels, the sensitivity, specificity and positive and negative predictive values of laminin P1 in detecting both necroinflammatory activity and fibrosis in the liver. The results show that serum laminin P1 levels parallel the severity of liver disease, the highest laminin concentrations being observed in cirrhotic patients. They suggest also that serum laminin P1 should be considered a marker of the liver disease process as a whole, rather than a marker exclusively linked to fibrosis. Nevertheless, the usefulness of serum laminin P1 measurement, as investigated in this study, seems too limited to be recommended for routine clinical practice.

Procollagen III peptide and fibronectin in alcohol-related chronic liver disease: Correlations with morphological features and biochemical tests

In order to clarify the significance of procollagen III peptide (PIIIP) and fibronectin (FN) blood concentration in alcohol related chronic liver disease (ALD), we have investigated their relationships with histological liver features and biochemical liver tests in 44 ALD patients. PIIIP was measured in serum by radioimmunoassay whereas FN was determined in plasma using an immunonephelometric method. In each liver biopsy, steatosis, portal infiltrate, lobular necro-inflammation, portal fibrosis and lobular fibrosis were semiquantitatively assessed by scoring from 0 to 3. A close correlation of PIIIP was found with morphological features of fibrosis (both of lobular and portal type), but not with necro-inflammation or steatosis. PIIIP was also positively correlated with ALP and GGT and exhibited a good diagnostic value in liver fibrosis. On the contrary, FN did not distinguish between normals and patients and was not correlated with any morphological liver feature or biochemical liver test. We also conclude that serum NP3P effectively reflects liver fibrosis, whereas plasma FN seems not related to any of the main histological aspects of liver damage in ALD.