Volume 61 - 1998 - Fasc.2 - Symposium
Ultrasonically guided fine needle puncture of focal liver lesions Review and personal experience
Despite recent advances in diagnostic imaging of the liver, the management of a patient with focal liver lesions often depends on obtaining tissue for histological diagnosis. Ultrasound guided fine needle biopsy is recommended as a safe and reliable method for cyto-histological confirmation of suspected hepatic malignancy. A fine needle is conventionally defined as having an outer diameter = 0.9 mm or = 19 G. Ultrasound guided fine needle aspiration cytology is found reliable for diagnosing malignancy. Limitations of this method are inadequate sampling and limited value in diagnosis of well-differentiated malignant tumours and benign tumours. Ultrasound guided fine needle cutting biopsy allows to obtain tissue for histological examination according to the Menghini technique. Both methods have high sensitivity, specificity and accuracy in detecting malignancy. In a personal series of 50 fine needle aspiration cytologies, a sensitivity for malignancy of 87% was obtained, with a specificity of 100%. The insufficient sampling rate, however, was 10%. Ultrasound guided fine needle trucut biopsy combines the advantages of a fine needle and a better sampling quality ; a lower insufficient sampling rate can be expected without increase in complication rate. Despite the availability of numerous manually operated or (semi-) automated devices, little data have been published up to now on liver lesions. In our hands, it has proven to be a safe and reliable method, with low insufficient sampling rate, allowing correct identification of primary liver malignancies, correct suggestion of the primary source of the majority of metastases and correct identification of most benign liver lesions. Therefore it is considered as the method of choice when focal noncystic liver lesions are to be biopsied.
Treatment of pancreatic pseudocysts by percutaneous drainage. Review and personal experience
Pseudocysts are serious complications of acute and chronic pancreatitis. Asymptomatic pseudocysts require no specific treatment. Symptomatic pseudocysts can be decompressed by surgical, ultrasonographically and endoscopically guided methods. In the absence of randomised prospective trials it can not be stated that one of these techniques is superior to others. Ultrasonographic and endoscopic approaches should be confined to centres with particular expertise in these techniques
Viral hepatitis throughout infancy to adulthood
Epidemiology of hepatitis B and C in Europe
Noncytolytic Mechanisms Involved in Hepatitis B Virus Clearance
Hepatitis B virus mutants in HBsAg positive children
Genetic heterogeneity and properties of hepatitis C virus
Hepatitis C virus (HCV) is a member of the Flaviviridae family. Its genome is a positive single-stranded RNA molecule which comprises three distinct regions : a 5'non coding region, a long open reading frame encoding both the structural and non structural viral proteins, and a 3' non coding region. HCV circulates in infected individuals as complex mixtures of genetically distinct but closely related variants referred to as "quasispecies". The quasispecies nature of HCV genomes appears to play a major role in viral persistence, cell tropism of viral variants, pathogenicity and resistance to antiviral therapy.
Mother-to-infant transmission of hepatitis C
Hepatitis C in children after transfusion : assessment by look-back studies
Look-back studies to identify paediatric patients with post-transfusion hepatitis C have been conducted at several tertiary-care hospitals in Canada. A general look-back study was conducted at the Hospital for Sick Children in Toronto for the time period December 1985 to May 199O.All patients transfused at the Hospital for Sick Children during this time period were identified from hospital Blood Bank records. Letters of notification were sent by registered mail to all recipients excluding those known to have died. In the letter anti-HCV testing was recommended. Letters were mailed to 6332 transfusion recipients ; 4496 letters were delivered. Of these 146 anti-HCV-positive transfusion recipients (92 pts < 18 yrs old; 54 pts > 18 yrs old) were identified. Sixty-four of these patients were definitely transfused only during this time period. Assuming that all notified patients were tested, the minimum prevalence of new infection in this time period was 1.4%. When possible, identified patients were tested for presence of HCV RNA in the serum by RT-PCR. The proportion of patients anti-HCV positive but HCV RNA negative on one or more occasions was similar in both whole cohort and subset : approximately one-third. These data suggest that chronic hepatitis C may be less likely to develop after transfusion in children than in adults.
Natural history of chronic viral hepatitis in childhood
Chronic Hepatitis B virus (HBV) infection in children is commonly associated with Hepatitis B e antigen (HBeAg) seropositivity and histologic features of minimal to moderate hepatitis. Remission of liver disease is the rule following HBeAg to antiHBe seroconversion and clearance of HBV DNA from serum. In intermediate and low endemicity areas chronic HBV infection is usually acquired postnatally, and more than 80% of children are likely to achieve stable remission during the pediatric age. Severe sequelae, namely cirrhosis and HCC, have been observed only in less than 4% of children followed over two decades. In all cases cirrhosis was an early complication. Chronic HCV infection is usually silent in children. The chronicity rate seems to be high (50-80%) in post-transfusion hepatitis C as well as in perinatally acquired infection. HCV-associated liver disease is characterized by fluctuations of ALT which remain below two times the normal in about half of the cases. Liver histology shows minimal to mild hepatitis in the large majority of patients and cirrhosis is rare. Few patients achieve spontaneous remission and progression to a more severe liver disease might occur in adult life.
Hepatitis B and C in Eastern Europe - the current situation
This paper presents the current situation of HBV and HCV infection in Eastern European countries and discusses the differing aspects of epidemiology, transmission, prevention strategies and treatment approaches in these countries.
Risk of hepatitis A superinfection in patients with underlying liver disease
During recent years the outcome of acute hepatitis A in chronic liver disease has been discussed controversially. Data from large hepatitis A epidemics and surveillance data from the United States suggest a significantly higher risk of fatal outcome in patients with chronic hepatitis B. Patients with chronic active hepatitis or liver cirrhosis seem to be at highest risk, while HBsAg carriers may exhibit a benign course of the disease. Patients with chronic hepatitis C also seem to have a significantly higher risk of fulminant hepatic failure when superinfected with hepatitis A. The recently reported unsuspected coincidence of autoimmune markers with a fulminant course of hepatitis A in those patients needs to be confirmed. Vaccination against hepatitis A in patients with chronic liver disease has been shown to be safe and effective.
Hepatitis B : long-term outcome and benefits from mass vaccination in children
Hepatitis B viruses can cause chronic liver diseases in both children and adults. In hyperendemic areas, although most related complications occur during adulthood, nearly half of the primary infection in chronic hepatitis B virus carriers occurs in perinatal period through maternal transmission and the other half are from horizontal transmission mainly through intrafamilial spread or injection using unsteriled needles. Children with chronic hepatitis B virus infection are mostly asymptomatic. They are generally active and growing well with very rare exceptions. Even with acute exacerbation of liver function and active inflammation, jaundice or growth failure is uncommon. Mild histologic abnormalities in the liver begins early in life and may progress to severe liver impairment in later life. Severe liver damage, with bridging hepatic necrosis or fibrosis, or cirrhosis of the liver may occur, but is rare during childhood. Universal immunization program of hepatitis B virus has been proved to be effective in reducing hepatitis B carrier rate for more than 10 folds, and the incidence of hepatocellular carcinoma in children has also been reduced significantly.
Is liver biopsy needed in children with chronic hepatitis ?
Hepatitis virus induced autoimmunity
Interferon : a meta-analysis of published studies in pediatric chronic hepatitis B
Perinatally infected Asian children respond poorly to interferon (IFN) therapy. In contrast, IFN therapy seems to be more effective in Caucasian children who presumably acquired HBV infection later in life. We reviewed seven controlled studies of IFN treatment in children with chronic hepatitis B living in western countries (216 treated, and 200 untreated children). Before treatment all patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B. Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian. Protocols whicl, have been adopted may schematically be divided into protocols which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or a long duration of treatment (12 months). The percentage of treated patients whO. at the end of treatment, lost HBV-DNA (that in most studies corresponded also to HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much higher than that observed in controls (range 8-17% ; mean 11.4%). A better trend is probably observed only in patients who received the treatment for a longer period of time. At the end of treatment, low percentages of patients lost BsAg (range 0-4% ; mean 1.1%) : again higher doses tend to be more effective than lower doses. In some studies IFN has been shown to significantly accelerate the termination of viral replication. Data on longer term outcome of IFN treatment in Caucasian children are scarce and confirm results obtained at short and at medium-term FU either in horizontally either in perinatally infected children. Results from few randomized controlled trials of interferon therapy with prednisone priming in Chinese and Caucasian children were comparable to results obtained without prednisone. In one study steroid priming did not potentiate the effect of IFN, however it existed a tendency of prednisone to improve HBeAg clearance in patients with normal aspartate aminotransferase, and alanine aminotransferase activity lesser than 100 u/l. In most studies, factors positively influencing response rates of IFN treatment are represented by severe inflammation in the basal liver biopsy, high basal levels of serum transaminase, low basal levels of serum HBV-DNA. Vertical trasmission may be considered a factor adversely affecting the response to IFN treatment both in Chinese and Caucasian population. In general in most controlled studies, the majority of responders have shown a significant reduction in hepatic inflammation and transaminase normalization. Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.
Therapy for chronic hepatitis B : nucleoside analogues in adult and pediatric patients
Immunotherapy of chronic hepatitis B by anti HBV vaccine
Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocehular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, their possible side effects and the imtnune-mediated pathology of HBV infection explain the need of new immune therapies in treating HBV infection. Experimental and clinical evidences suggest the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened study, forty-six consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum UBV DNA were given 3 standard injections of the GenHevac B® vaccine at one month interval. Six months after the first injection, 12 patients (26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more than 50%) in HBV DNA titers. Six of these 12 responders received a standard course of a-Interferon (5 MU thrice weekly subcutaneously for 4 months) and all six had still undetectable HBV replication at the end of follow-up. Among the 34 non responders to vaccine, 20 were given a-Interferon and 2 the monophosphate derivate of Vidarabine : 12 of these 22 patients stopped HBV replication and in all 12, vaccine therapy had induced a significant decrease of HBV replication before the antiviral treatment with a decrease of mean serum HBV DNA from 392 pg/ml before to 217 pg/ml after vaccine therapy. In an ongoing controlled study, using the same vaccine schedule, serum HBV DNA disappeared more frequently after 6 months, in patients who were given a preS2/S vaccine (7/35) than in patients who received a S vaccine (1/21) or no vaccine (1/32). In responders to vaccine, an induction of specific proliferative responses was observed and this may contribute to the potential efficacy of anti-HBV vaccine therapy. No side-effect or vaccine-induced escape-mutants occured during the follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 patients (60.9%) who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These results are not different at 6 months and at the end of follow-up from those of 43 HBsAg chronic carriers who were given only an antiviral treatment. Active immune therapy against HBV appears efficient and less expensive than antiviral therapies in stopping HBV replication. Such results need to be confirmed by the completed results of our controlled, randomized trial which is now conducted in our unit.
"Receptor-ligand" based new strategy for treatment of patients with chronic hepatitis B
Treatment of pediatric hepatitis C : results and perspectives
Global status of HB Immunization, 1998
Interferon Treatment for Chronic Hepatitis B or C Infection: Costs and Effectiveness
Introduction : With recognition that resources are limited, health care payers and policy makers have increasingly turned toward economic analyses to determine whether particular therapies are an efficient use of economic resources. Both chronic hepatitis B and C infections can progress to cirrhosis or hepatocellular carcinoma over time. Interferon treatment has been shown to eradicate viremia, but only does so in a proportion of treated patients. It has potential side effects, has no proven long-term benefit on complications and is relatively expensive. Objective : To determine the cost-effectiveness of interferon treatment by estimating the lifelong economic and clinical outcomes associated with interferon therapy versus standard care for patients with either chronic hepatitis B or C infection. Methods: Computer cohort Markov model simulation to project the lifelong impact of the loss of hepatitis B or C viremia resulting from interferon on cirrhosis, life expectancy, and costs. The natural history of hepatitis B and C was based on published studies. Efficacy estimates for the loss of viremia were based on meta-analysis of published data. Using a societal perspective, economic estimates were based on cost of care data for patients with hepatitis and from estimates regarding the frequency of health resource utilization provided by expert panels. Results: For 20 year old patients with either hepatitis B e antigen positive chronic hepatitis or histologically mild chronic hepatitis C infection, interferon should be cost saving, extending life and reducing lifetime expenditures and morbidity. Life expectancy should increase by 4.8 to 3.1 years for patients with chronic hepatitis B or C, respectively. Lifetime costs should be reduced on average by $ 6,300 to $ 6,900 for each patient treated with interferon. Conchision : Chronic infection with hepatitis B or C can result in liver failure and death. Although only effective in a proportion of treated patients, interferon for chronic hepatitis appears to be an efficient use of societal resources so that economic reasons should not limit its use.
Ethical aspects of pediatric therapeutic clinical trials
Treatment with lamivudine for non-immunocompromized patients with chronic hepatitis B
