Cost-effective analysis of hepatitis A prevention in Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective prevention strategy against hepatitis A virus (HAV) infection for healthcare workers and the general population at risk in Ireland. METHODS: Four prevention strategies were compared: active immunization with Havrix Monodose (1440E.U); screening for anti-HAV antibody and then vaccinating; passive immunization; screening for anti-HAV antibody and then passive immunization. The cost-effective ratio was calculated for each prevention strategy. Threshold analysis, sensitivity analysis, and model extension to include indirect cost from work days lost and secondary attack rates through horizontal transmission were also derived. RESULTS: The medical costs were lowest and the infection rate highest when no preventive action was taken. Vaccination was most cost effective when the prevalence of immunity was 45% or less, reducing the infection rate by 98% when compared to nonprevention. Screening before vaccination was most cost effective when the prevalence of immunity was greater than 45%. Passive immunization and screening before passive immunization were not comparable to the other strategies in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio for vaccination was dependent on vaccine price, incidence of HAV, and prevalence of immunity in the target group. Extending the model to include indirect costs further increased the cost effectiveness of vaccination. CONCLUSION: The best cost-effective strategy relates to target group immunity. Where HAV immunity is 45% or less, vaccination is the strategy of choice and when immunity is greater than 45%, then screening followed by vaccination should be used. This study can be used to provide a framework within which choices can be made to achieve better health for less cost.

Chronic HCV histology is predictable from HCV RNA and IgM anti HCV results.

The aim of this study was to determine if knowledge of both the serum HCV RNA and serum anti core IgM antibody status enabled one to predict the histological severity in chronic hepatitis C. We studied 45 female patients with chronic hepatitis C infection. The presence or absence of IgM antibodies to HCV and HCV RNA by PCR in each patient's serum was determined. Liver biopsies performed were scored according to a modified Desmet's histological activity index. Negative HCV RNA patients had least histological change. HCV RNA positive patients who were also IgM antibody positive had lower scores than their IgM negative counterparts. The grade of histological severity is more accurately predictable from knowledge of both the HCV RNA and IgM anti HCV status of the patient.

Hepatitis A in urban Ireland.

AIMS: To determine the prevalence of immunity to hepatitis A virus (HAV) infection in urban Ireland and to categorize the region into low, intermediate or high HAV endemicity, and to analyse the significance of certain commonly associated risk factors. METHODS: Two hundred and thirty three volunteers were recruited from 6 general practices in Dublin, Ireland. There were 44 volunteers in the 10 to 19 yr age group, 40 in the 20 to 29, 42 in the 30 to 39, 43 in the 40 to 49 and 64 in the over 50 age groups. Each participant completed a detailed questionnaire and was tested for anti-HAV total antibody (primarily IgG) using a competitive ELISA assay. Urban Ireland was classified into the appropriate area of HAV endemicity according to the prevalence of immunity by age group. Risk factor differences were analysed for significance using the chi square test and Fisher's exact test. RESULTS: One hundred and fifty seven (67 per cent) volunteers were immune, of whom 20 (45 per cent) were in the 10 to 19 yr age group, 17 (43 per cent) in the 20 to 29, 30 (71 per cent) in the 30 to 39, 34 (79 per cent) in the 40 to 49 and 59 (92 per cent) in the over 50 age groups. Fifty-five per cent of the individuals studied below the age of 20 yr were non-immune. The immune rates over the age of 30 were significantly greater (p < 0.01) than those in the 10 to 29 age groups. Socioeconomic pattern in the total and 10 to 19 yr age group was a significant (p < 0.0002, p < 0.004 respectively) risk factor for infection. CONCLUSION: This study concludes that urban Ireland is an area of low HAV endemicity with age and socioeconomic status as the significant influences on seropositivity. This survey provides an insight into the changing epidemiology of HAV infection in Ireland and serves as a guide for immunisation of at risk population groups.

Autoimmune disease is not a feature of hepatitis C infection in Ireland.

To determine the prevalence of autoimmune disease, autoantibody positivity, or both in Irish persons with hepatitis C, we surveyed 98 such patients (55 recipients of anti-D, 25 intravenous drug abusers, and 18 blood transfusion recipients). We studied them clinically and tested for anti-nuclear, anti-smooth muscle, and anti-mitochondrial, liver-kidney microsomal, thyroid microsomal, thyroid globulin, and gastric parietal antibodies; and also for rheumatoid factor. In the anti-D antibody group (all female), two patients reported generalized musculoskeletal symptoms but had no demonstrable physical signs. We did not find cryoglobulins in any patient. We detected thyroid microsomal antibodies in only 6 of 55 (10.9%) patients. (In two of these, thyroid globulin antibodies were also positive). These patients were all clinically euthyroid, but two had borderline low-normal thyroid function tests. Titers for anti-nuclear antibodies were weakly positive in 5 of 55 (9.1%) patients, and gastric parietal antibodies were positive in 5 of 55 (9.1%) patients. In particular, we noted no antibodies to liver-kidney microsome. Rheumatoid factor was detected in eight patients. Forty-seven of 55 patients were genotype 1b, and 8 of 55 were genotype 3. In the intravenous drug abusers (8 women, 17 men), we detected no autoantibodies. Seven of the 25 genotypes were tested; three were genotype 3 and four were genotype 1b. In the transfusion group (10 women, 8 men), we detected no autoantibodies apart from weak anti-nuclear antibody Titers (1:10), which we found three patients. Five of 10 genotypes tested were of genotype 3 and the other five were of genotype 1b. These findings suggest that in Irish patients with hepatitis C, neither genotype nor source (and dose) of inoculum contributes to the development of autoimmune disease. How hepatitis C virus is associated with autoimmune disease in other studies remains unknown. The answer may, at least in part, be found in genetic; HLA typing studies should provide useful information.

Interferon-associated thyroid dysfunction in anti-D-related chronic hepatitis C.

To assess the frequency and nature of thyroid abnormality in association with interferon (IFN) therapy alone and in combination with ribavirin, 19 patients receiving IFN therapy for hepatitis C virus (HCV)-induced liver disease had thyroid function tests assessed on a monthly basis. Group I (n = 9) patients received 5 million U of IFN s.c. daily for 2 weeks, followed by 3 million U three times per week for 6 months. Group II (n = 10) patients received 3 million U IFN s.c. three times per week together with ribavirin 400 mg twice daily orally for 6 months. Five of 19 patients (26.3%) developed thyroid abnormalities, 3 (33.3%) in group I and 2 (20%) in group II. Three patients developed thyroid function tests consistent with hyperactivity, and 2 of these normalized on cessation of IFN therapy. One patient continued on IFN but remained clinically euthyroid with antithyroid treatment. Two patients developed thyroiditis and required thyroid supplementation. (One of the 2 had pretreatment antimicrosomal thyroid antibodies and a positive family history of thyroid disease.) Of the 3 patients with HCV type 1b, 1 had pretreatment thyroid antibodies, and all 3 had antibodies during IFN therapy. Neither of the 2 patients with genotype 3 had pre-IFN or post-IFN thyroid antibodies. Patients on IFN therapy need regular thyroid function testing. The frequency of abnormal thyroid tests may be dose related. HCV genotype may influence the development of thyroid antibodies.

Small cell carcinoma of the lung presenting as chylous ascites: a unique case.

A 67-year-old female presenting with a history of weight loss and abdominal distension was noted on examination to have ascites. Paracentesis revealed a chylous ascites and chest radiography showed a right hilar enlargement with mid-zone infiltration. Abdominal computed tomography demonstrated retroperitoneal lymphadenopathy and biopsy of this showed small cell undifferentiated carcinoma. This appears to be the first documented association between metastatic small cell carcinoma of the lung and chylous ascites.

Low rate of HCV transmission from women infected with contaminated anti-D immunoglobulin to their family contacts.

PURPOSE: To analyse the spread of HCV infection from women infected with batch number proven contaminated anti-D immunoglobulin to their family contacts. PATIENTS AND METHODS: Index cases. Sixty women who had been infected with hepatitis C after receiving HCV contaminated anti-D Immunoglobulin. All were positive for HCV antibodies by ELISA (Ortho & Murex, Abbott Laboratories) and RIBA3 (Chiron Corporation, Emerville, California) and were viraemic by PCR for HCV-RNA (Roche Diagnostic Systems, Basel, Switzerland). Liver biopsies were performed in 45 patients. All were in stable longterm relationships. CONTACTS: Fifty-five partners and 170 children were tested for HCV antibodies by ELISA (Ortho, Murex). Any positive contact was also tested for antibody by RIBA-3, HCV RNA by PCR, genotype determined and also had a liver biopsy performed. RESULTS: No male partners and only one child tested positive for HCV antibodies indicating low exposure over a combined time period of 862 years for partners and 2465 years for children. CONCLUSIONS: This study suggests a zero female to male sexual transmission rate of HCV and a low vertical transmission rate in anti-D associated HCV infection.

Jaundice at onset signifies a good prognosis in anti-D-associated HCV infection.

INTRODUCTION: Acute hepatitis presenting with jaundice occurs in less than a quarter of patients infected with the hepatitis C virus (HCV). These patients may be associated with a more benign clinical course than those who are asymptomatic. OBJECTIVE: To compare and contrast the polymerase chain reaction (PCR) and recombinant immunoblot assay (RIBA) status, serum alanine aminotransferase (ALT) levels and histological scores in age, disease duration and viral load matched HCV anti-D recipients with and without a history of jaundice. METHODS: HCV status was confirmed by detecting HCV-RNA by PCR and antibodies to HCV using enzyme-linked immunosorbent assay (ELISA) and RIBA-3. Serum ALT levels were measured in all patients and a liver biopsy was performed in 26/34 patients. All patients were genotyped. RESULTS: Fourteen out of 17 jaundiced patients were PCR negative and only 4/17 had RIBA scores greater than 9, whereas all non-jaundiced patients were PCR positive and all 17 had RIBA scores greater than 9. Thirteen out of 17 jaundiced patients had normal ALT values, 3/17 mildly elevated (41-100) and 1/17 greater than 100; 6/17 non-jaundiced patients had normal ALT levels, 9/17 mildly elevated (41-100) and 2/17 greater than 100; 7/9 jaundiced patients had mild histological scores, 0/9 moderate and 2/9 severe; 5/17 non-jaundiced patients had mild, 9/17 moderate and 3/17 severe histological scores. All 34 patients were of genotype 1b. CONCLUSION: Patients with jaundice had lower antibody scores, increased PCR negativity, normal serum ALT levels and low/normal histological scores. Jaundice at onset was an indicator of good prognosis.

The effect of light drinking on HCV liver disease: the jury is still out.

We carried out a study to determine if light drinking (1 unit alcohol/d) adversely affected liver histology in hepatitis C virus (HCV)-associated liver disease. Twenty-eight women who developed chronic hepatitis C (all genotype 1b) as a result of receiving contaminated anti-D immunoglobulin (Ig) had their alcohol intake assessed. Group I (n = 8) took no alcohol, Group II (n = 8) consumed less than one unit monthly and Group III (n = 12) took between two and 18 units (mean = 6.7 units) per week. All 28 subjects had a liver biopsy performed and their histology scored according to the global Knodell score (KI) and the international score for both inflammatory grading (II) and fibrotic staging (FI). The three scores were compared between the three groups and differences tested for significance. The median score for the three groups were Group I: KI = 2, II = 2 and FI = 0; Group II: KI = 4, II = 3.5 and FI = 0.5; Group III: KI = 5.5, II = 4 and FI = 1.5. Initial analysis showed that there was no difference between those who abstained from alcohol and those with a less than monthly consumption; these groups were united and compared with the light drinkers. On Mann-Whitney U test analysis, the P values for the differences between the light drinkers and the combined groups were 0.666 (KI), 0.159 (II) and 0.080 (FI) These results show a trend towards greater histological abnormality in people drinking one unit of alcohol per day, but larger groups will need to be assessed to determine if this is a true or chance finding.

Mild abnormalities in liver histology associated with chronic hepatitis: distinction from normal liver histology.

BACKGROUND: Chronic hepatitis C virus infection associated with contaminated anti-D immunoglobulin has become an issue of recent concern. The clinical course of chronic hepatitis C infection is unpredictable and histological assessment is felt to be the most reliable means of assessing disease status. Semiquantitative scoring systems have been devised, which assess degree of necroinflammatory disease activity (grade) and extent of disease progression with fibrosis (stage) in chronic hepatitis. Often, using these systems, biopsies of anti-D associated chronic hepatitis C cases show mild changes only, with low scores. The significance of these low scores is uncertain. AIMS: To evaluate the significance of low scores in chronic hepatitis. METHODS: Liver biopsies were assessed from two groups of patients in whom liver histology would be expected to be normal: 30 cases of Gilbert's syndrome and 13 necropsy cases of young people (< 45 years) with no history or risk factors for liver disease. These biopsies were scored using the histological activity index of Knodell et al and its recent modification (separation of scores for grade and stage) by Ishak et al. RESULTS: Twenty of 30 cases of Gilbert's syndrome and 11 of the 13 necropsy cases had chronic hepatitis scores of 1 or 2, whereas only eight cases of Gilbert's and two necropsy cases had scores of 0. The remaining two Gilbert's cases had scores of 3 and 5. Similar results were found using both the histological activity index of Knodell et al and the method of Ishak et al. CONCLUSION: The finding of low but positive scores using these systems in people with normal liver histology questions the reliability and significance of finding such scores in patients with chronic hepatitis and is of particular concern in the evaluation of chronic hepatitis C infection.

Two year old hepatitis A vaccine is as good as new.

This was a randomized, controlled, double-blind study assessing the reactogenicity and immunogenicity of newly produced vs 2 year old hepatitis A vaccine. Overall 215 non-immune volunteers, 18-39 years old were divided into four groups and administered vaccine at months 0, 1 and 6. Three groups each received a different vaccine lot which had been stored at 4 degrees C for 2 years, and one group received recently produced vaccine as control. The mean local and general adverse reaction rates were 59.1% and 17.4%, respectively, and all vaccinees had seroconverted by month 2. There were no significant differences in geometric mean anti-hepatitis A virus (HAV) antibody titres between the four groups. In conclusion 2 year old HAV vaccine is safe and equally immunogenic as newly produced vaccine.

Colonoscopic findings in Crohn's disease--reproducible, but of questionable benefit.

Colonoscopy, a useful diagnostic tool in inflammatory bowel disease, is very accurate in detecting disease and assessing disease extent in Crohn's disease. Despite their accuracy, colonoscopic findings have not been routinely used in the objective follow-up of patients with Crohn's disease. The GETAID (Groupe d'études theraputic des affections inflammatoire du tube digestif) group has shown that following an intensive training period, endoscopists can describe colonoscopic findings in a reproducible manner. However, these descriptions poorly correlate both with clinical or laboratory indexes, and with short or medium term prognosis following prednisolone therapy.

Who best assesses Crohn's disease?

UNLABELLED: Knowledge of the presence and the degree of inflammation in Crohn's disease would be useful in multicentre therapeutic trials. Objectives; The purpose of the present study was two fold, a) to determine the relationship between clinical assessment of activity by two clinicians with four previously published indices, the Crohn's disease activity index (CDAI), the Van Hees activity index (AI), the simple index of Harvey and Bradsaw (SI) and the Fielding index and b) for the first time, to study the internal correlation between these four indices. METHODS: A hundred and ninety-four assessments were performed on 56 patients with Crohn's disease. Following each clinical assessment, the aforementioned indices were calculated. RESULTS: Both clinicians gave the same rating of activity in 81% (157) of assessments. A good relationship was observed between the median indical values and the clinical gradings for all four indices. The best relationship was demonstrated with the AI with no overlap in 50% values with increasing grades of disease activity. All four indices demonstrated a good correlation with each other (p < 0.01). The best correlation was observed between more objective indices the AI and the Fielding index (r = 0.79) for first assessments only. Conclusion. The Van Hees AI is a reliable measure of inflammatory activity in Crohn's disease and would be useful in multicentre therapeutic trials.

Porphyrin metabolism in hepatitis C infection.

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.

Pancreatic vipomas: spectrum of presentation and evolution of diagnostic and therapeutic modalities.

Two patients are reported who presented with symptoms characteristic of a pancreatic vipoma. The necessity to measure more than one plasma VIP level for diagnosis, and the delay between the onset of illness and diagnosis is illustrated by both cases. Evidence suggests that vipomas are still under reported. The evolution of sophisticated diagnostic and therapeutic modalities over the twenty-five years separating both presentations is discussed.

Percutaneous endoscopic gastrostomy--results of an Irish single unit series.

The technique of percutaneous endoscopic gastrostomy (PEG) was first described in 1980, as an alternative to traditional surgical methods. The main indication for PEG is the need for longterm nutritional support. It is reported to have many advantages over surgical gastrostomy, being safer and cheaper. We reviewed our experience with the first 44 patients referred to our unit for PEG. The most common indications for referral were stroke, head injury and post brain surgery. There was a success rate of 97.6% and a complication rate of 13.8%. One patient (2.3%) suffered major complications as a result of early tube displacement. There were no procedure related deaths in our series and no deaths as a result of an underlying disease process within 30 days, reflecting appropriate patient selection. All patients benefited nutritionally from PEG placement. Two patients recovered sufficiently to no longer require a gastrostomy and the tube was easily removed in both cases.