Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.     

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe

A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.     

Behavioural change in injecting drug users: evaluation of an HIV/AIDS education programme

The results obtained from the training and follow-up of 189 IDUs who participated in a programme consisting of an audiovisual presentation, pre-/post-testing and individual counselling are presented. Syringe sharing decreased from 35% at initial contact to 12% after 6 months. Sexual behaviour proved more resistant to change. However, condom use in at-risk situations increased from 49% to 70%. IDUs under continuous methadone treatment were less likely to engage high risk drug injecting practices than the other IDUs. Results indicate that an educational programme addressed toward risk reduction may determine relevant behavioural change among IDUs.     

The Italian experience on paediatric liver transplantation: 1988-1999 report.

BACKGROUND: Liver transplantation is the treatment of choice for end-stage liver disease in both adult and paediatric patients. The Italian experience in paediatric liver transplantation during the period 1988-1999 is reported herein. PATIENTS AND METHODS: This report concerns 228 liver transplantations performed in 207 patients (100 male, 107 female, mean age 5.1+/-4.4 years) in 11 Italian centres. The mean waiting time on the transplantation list was 6.1+/-8.9 months and the main indications for the procedure were biliary atresia, inborn metabolic disorders, liver cirrhosis, liver neoplasms, Alagille syndrome, and fulminant hepatic failure. RESULTS: The cumulative survival rate was 77%, 76%, 73%, and 71% at 1, 3, 5, and 7 years. The overall prevalence of acute rejection was 54%. Survival was significantly affected by re-transplantation (p=0.0002), by United Network for Organ Sharing 4 status at transplantation (p=0.016), and, among the indications for the procedure, by fulminant hepatic failure (p=0.004). Fifty patients (24%) died during the observation period. The main causes of death were primary non-function of the graft and sepsis CONCLUSIONS: This study shows that liver transplantation in paediatric age, in Italy, is an effective procedure providing a 5-year survival rate comparable to that attained in the largest published series.     

Therapy for chronic hepatitis C. Present status

Interferon (IFN) is the only treatment so far approved world-wide for chronic hepatitis C. Though proof of long term benefit is lacking, metanalyses have provided extrapolations that substantiate the hypothesis that this therapy can modify favourably the natural history of the disease. Results, however, are limited and new forms of therapy, complementary or alternative to IFN, have been developed. Efforts to ameliorate the results of alpha-IFN mono therapy in chronic hepatitis C with new IFNs, or the manipulation of IFN monotherapy so as to obtain the maximum results compatible with tolerance, have not produced a better results than the classical protocols of alpha IFN monotherapy. Important recent therapeutic progress that surpasses and advances the results obtained with single IFN therapy is the combination of IFN with ribavirin, with which overall rates of response have increased three times compared to IFN monotherapy. Combination therapy has become the treatment of choice for IFN naive patients as well as for IFN relapses; it is not efficacious in patients who have not responded to IFN.     

Primary biliary cirrhosis: lung involvement

Abstract: Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p<0.01) and with the presence of circulating anti-centromere antibodies (p<0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome. Prospective studies are needed to evaluate if these abnormalities will eventually lead to clinical symptoms and if their progression could be influenced by different therapeutic regimens for primary biliary cirrhosis.     

Role of coinfection by transfusion-transmitted virus (TTV) in patients with chronic HCV hepatitis

A novel DNA virus, associated with non A-G post-transfusion hepatitis, has been recently discovered. TTV is detectable in acute and chronic liver diseases with a variable incidence. The clinical significance of TTV coinfection in patients with chronic HCV hepatitis has not yet been defined. In this review we report the data regarding the possible pathogenetic role of TTV infection in chronic HCV hepatitis.     

Recurring duodenal ulcer. Evaluation of previous complications as a predictive factor of ulcer recurrence after eradication of Helicobacter pylori

Duodenal ulcer is a chronic disease, punctuated by acute relapses. The pathogenic mechanism in 90-100% of cases is infection by Helicobacter pylori. Two major strains exist of this bacterium: I strain, which secretes a vacuolating cytotoxin (Vac-A), and another protein named cytotoxin-associated (Cag-A) and type II strain, unable to produce both proteins and unable to produce duodenal pathology. We sought to identify the natural history of relapsing duodenal ulcer after cure of the bacterial infection. In particular, we followed the outcome of patients who repeatedly had bled from their recurrent ulcer disease, after success in eliminating the microorganism from the stomach. None of 12 repeated bleeders had an ulcer recurrence after the cure of Helicobacter pylori infection. Only 3 (5%) of 60 frequent relapser had a new episode of duodenal ulcer during a follow-up reinfection by Helicobacter pylori. We demonstrated that the cure of bacterial infection is also the cure of duodenal ulcer recurrence, but for a few cases, in the latter, event one could hypothesize a defect in the production of growth factors (Epidermal Growth Factor, Fibroblast Growth Factor) or of cellular polyamines synthesis. It is important to improve the diagnosis of reinfection by implementing the urea breath test.     

Hepatitis B vaccination: current status

BACKGROUND: Hepatitis B remains a crucial Public Health problem worldwide, with a numerical impact of infected persons and long term sequences higher than other infectious diseases preventable by vaccines. Around 75% of the world population is living in areas where HBV is endemic (Africa, most of south America, eastern Europe, eastern Mediterranean basin, south-eastern Asia, China and Pacific islands except Australia, new Zealand and Japan); 5-15% of these populations are affected by chronic HBV infection. Rates of chronicity depend on the age of exposure to HBV. Newly infected adults generally clear the infection and only about 5% become chronic carriers of the virus. Infected children rarely develop clinical disease but 25-90% become chronic carriers. Over two billions of persons worldwide have been infected in their life and 350 millions are chronic carriers of HBV. About 25% of the chronic carriers will die of cirrhosis or hepatocellular carcinoma. In recent years control of the spread of HBV has been achieved by the large-scale availability of safe and effective vaccines. This review summarizes the current perspective and use of hepatitis B vaccination, with particular attention to implementation needs and results in Italy, the first country that has introduced universal vaccination against hepatitis B.