Immunoglobulin G4 related chronic sclerosing sialadenitis.

BACKGROUND: ENT surgeons may be the first specialists to encounter and diagnose patients with salivary gland disease. A new entity involving the salivary glands has recently been described of which ENT surgeons need to be aware: immunoglobulin G4 related chronic sclerosing sialadenitis. METHOD: A literature search of Medline, Embase and Cochrane Library databases was performed, using the search terms 'IgG4', 'hyperIgG4 syndrome' and 'IgG4 related chronic sclerosing sialadenitis'. RESULTS: Knowledge concerning immunoglobulin G4 related chronic sclerosing sialadenitis is rapidly increasing. This new entity is part of a fibro-inflammatory corticosteroid-responsive systemic disease (immunoglobulin G4 related disease) and has been described in almost every organ. Biopsy of the submandibular gland can be diagnostic. However, the diagnosis can easily be overlooked if: clinical suspicion is not high, one is unaware of the classical morphology and/or immunoglobulin G4 staining is not performed. This paper presents a summary of the current understanding of the disease and its management. CONCLUSION: ENT surgeons should be aware of this new disease entity. Patients with systemic disease should be managed under a multidisciplinary team, with input from clinicians who have an interest in such diseases (such as gastroenterologists and rheumatologists), and input from histopathologists and radiologists.

Which patients with hepatitis C develop liver complications?

To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and alpha-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P <.001), advanced fibrosis (P =.004), and low albumin (P <.001). The corresponding independent risk factors for HCC were male gender (P =. 07), sporadic transmission (P <.001), and albumin (P <.001); bilirubin (P =.02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. Patients without definite risk factors for HCV (sporadic cases) are at higher risk of complications, possibly because of interaction between older age, duration of infection, country of birth, and HCV genotypes 1b and 4.

Molecular epidemiology of hepatitis C in Australia.

The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (< 1%). The most common genotypes were type 1 (52%) or type 3 (32%); type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 +/- 13 years, P< 0.001) and patients with genotype 3 were younger than the remaining patients (37 +/- 11 years vs 42 +/- 12 years, P< 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50% vs 13%, P< 0.001) whereas non-1b subtypes were more common among Australian-born patients. Likewise, 21 of 23 (91%) patients with type 4 were from Egypt and six of seven (86%) with type 6 were from Vietnam. The relative importance of parenteral risk factors for HCV also varied according to geographic origin. Thus, a definite risk factor for HCV acquisition was identified in > 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.

Effects of hepatitis G virus coinfection on severity of hepatitis C: relationship to risk factors and response to interferon treatment.

The aims of the present study were to identify characteristics that are more often associated with hepatitis G virus (HGV) coinfection in Australian patients infected with the hepatitis C virus (HCV) and to investigate the effects of HGV on the histological and functional severity of chronic hepatitis C. Serum samples from 209 patients with chronic hepatitis C were tested for HGV-RNA using single-round reverse transcriptase-polymerase chain reaction to primers directed at the NS5 region of the HGV genome. Hepatitis G virus RNA was detected in 40 cases (19%). Hepatitis G virus-coinfected patients tended to be younger and parenteral risks could be identified in all but six. Although country of birth did not differ significantly between the coinfected and HCV-alone groups, HGV-positive patients appeared to be less likely to have originated from Asia. On logistic regression analysis, HCV genotype 3a was found in a significantly higher proportion of patients with HGV coinfection than other genotypes (P < 0.01). Liver histology and response to interferon were similar in the HGV-coinfected and HCV-alone groups and liver-related complications appeared to occur less frequently in patients with both HGV and HCV. On univariate analysis, antipyrine clearance was found to be higher in the coinfected group (P < 0.05), implying better preservation of hepatic metabolic function, but this difference was lost when adjusted for HCV genotype. In conclusion, coinfection with HGV was more commonly associated with HCV genotype 3a, a genotype associated with injection drug use in younger patients. However, the presence of HGV coinfection did not adversely affect liver disease or the response to interferon treatment in patients with chronic hepatitis C.

Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment.

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Seroprevalence of hepatitis A antibodies among residents of a centre for people with developmental disabilities.

BACKGROUND: In February 1993, 11 cases of hepatitis A virus (HAV) were identified in permanent residents of a centre for young people with developmental disabilities. AIMS: To define the extent of the outbreak in the centre, to determine the seroprevalence of hepatitis A antibodies (anti-HAV) in permanent residents, and to ascertain risk factors for serological evidence of HAV infection. METHODS: A cross-sectional serological survey of 270 permanent residents, aged eight to 40 years, in a centre for people with developmental disabilities, was conducted in western Sydney. Using a radioimmunoassay technique, sera were tested for anti-HAV (IgM and total antibody). We used logistic regression to determine risk factors for presence of anti-HAV. RESULTS: Blood samples were collected from 259 permanent residents (96%). Serological testing revealed anti-HAV in 128 residents tested (49%). Presence of anti-HAV was associated with living in specific residential units, and with residents' age and length of stay at the centre, but was not associated with reported behavioural factors. CONCLUSIONS: More than half of the residents of the centre were susceptible to HAV infection. Behavioural characteristics of the residents and their close contact with each other make HAV transmission difficult to control. HAV vaccine should be promoted in communities at risk, such as those with developmental disabilities.

Hepatitis C virus infection in haemodialysis patients.

Antibody to hepatitis C has been variously detected in 1-20% of haemodialysis patients in recent studies from overseas. To determine the frequency of antibodies to the C100-3 protein of the hepatitis C virus (anti-HCV) a cross-sectional study was performed in 60 patients on maintenance haemodialysis in Western Sydney. Six patients (10%) were anti-HCV seropositive. Four of the six anti-HCV positive patients were also hepatitis B core antibody positive, compared with nine of 54 anti-HCV negative patients (p less than 0.05). All anti-HCV positive patients had received multiple blood transfusions. Serum alanine aminotransferase (ALT) was not useful as a screening test. Recent evidence suggests that anti-HCV seropositivity underestimates infectivity.

Does hepatitis C virus play a role in "non-viral" chronic liver disease?

It has recently been suggested that the hepatitis C virus may play a significant role in chronic liver diseases, such as autoimmune chronic active hepatitis, which are usually attributed to non-viral causes. We tested for antibodies to hepatitis C virus (anti-HCV) in sera from 140 patients with well characterised "non-viral" chronic liver diseases as well as sera from 51 patients thought to have chronic non-A, non-B (NANB) hepatitis (acting as positive controls) and 25 patients with non-hepatic autoimmune disorders. As expected, 45 of 51 patients (88%) diagnosed as having chronic NANB hepatitis were anti-HCV seropositive. Among 26 patients with cryptogenic cirrhosis, 8 were anti-HCV seropositive; in 5 patients (22%) there was no apparent risk factor for parenteral transmission. In the remaining 114 patients with chronic liver disease, 10 patients (9%) were seropositive for anti-HCV. However, 5 of these patients had a significant risk factor for parenteral transmission of hepatitis C virus, leaving only 5 of 106 (4.7%) with unexplained positive anti-HCV test results. Among patients with high titres of circulating autoantibodies but no liver disease, no positive results occurred. It is concluded that hepatitis C virus infection may account for some cases of cryptogenic cirrhosis. Although anti-HCV occurs more commonly in patients with other "non-viral" chronic liver diseases than has been reported in the community (0.5%-1.2%), the low prevalence of the antibodies indicates that hepatitis C virus infection is unlikely to be important in the aetiology or pathogenesis of autoimmune chronic active hepatitis and other poorly understood chronic liver diseases.

Hepatitis C virus in intravenous drug users.

Sera from 172 intravenous drug users were tested for the presence of antibodies to hepatitis C virus (anti-HCV). The results were analysed in relation to aspects of the history of drug use and evidence of liver disease. The presence of anti-HCV was strongly associated with duration of intravenous drug use. Two-thirds of patients were anti-HCV seropositive within two years of commencing regular intravenous drug use, and there was 100% seropositivity among people injecting drugs for more than eight years. Seropositivity for hepatitis C virus closely paralleled exposure to hepatitis B virus, which was also endemic in this population. In contrast, only one patient tested positive for antibodies to the human immunodeficiency virus. The presence of anti-HCV correlated poorly with biochemical markers of hepatitis. About half the patients with anti-HCV had normal serum levels of alanine aminotransferase, whereas an abnormal liver biochemistry was frequently observed in anti-HCV seronegative subjects. Previous studies of non-A, non-B hepatitis that have used abnormal liver biochemistry as a marker have underestimated the prevalence of chronic hepatitis among intravenous drug users; the use of a specific screening test reveals that infection with hepatitis C virus is very common in this population.

Should all pregnant women be screened for hepatitis B surface antigen?

One thousand, one hundred and ninety-three pregnant women were screened for hepatitis B surface antigen (HBsAg) carriage after their histories had been reviewed to assess their risk status. In this prospective study, carrier rates were examined according to conventional risk criteria and also according to extended criteria that included the country of birth of the patient's parents. Twenty-six (2.2%) patients were found to be HBsAg seropositive, and one of these patients showed no identifiable risk factors. In four hepatitis B virus carriers, the only risk factor was that the patients' parents had been born in a country that was classified as high risk. Thus, five (19%) of 26 patients would not have been identified by means of previously-accepted screening procedures. Four hundred and forty-two (37%) patients showed at least one conventional risk factor and 558 (47%) patients showed at least one risk factor by our extended criteria. Given the high costs to the community of chronic hepatitis B virus carriage, it was concluded that the screening of all antenatal clinic patients for the presence of HBsAg is cost effective.

Hepatitis B infection among STD clinic patients in Sydney.

Evidence of current or past infection with hepatitis B has been studied in 809 patients attending clinics for sexually transmitted diseases in Sydney by assaying serological markers. Prevalence rates were 13.9% among male heterosexuals; 13.5% among female heterosexuals; 30.7% among female prostitutes; 64.3% among male homosexuals and 47.1% among male bisexuals. The prevalence was 80% for male homosexuals aged 36 years or more. Vaccination should be considered for persons at high risk of sexual transmission of hepatitis B, and it is the immunization of this group that is likely to have a major impact on this disease.

Further studies on neonatal rotavirus infections.

Forty newborn babies who were shown to be excreting rotaviruses within a few days of birth were tested daily for one month. Most were found to excrete virus for only a short period of time. In 48% of babies, virus was found on one day only, in 25% it was present for two days, and in 10% for three days. Most of these infections did not appear to confer lasting immunity. Only 21% of young children who excreted virus as neonates had detectable circulating complement-fixing antibodies when eight to eighteen months old. A survey of newborn babies showed that 89% of babies possessed the antibody, but, by the age of four to six months, the antibody was present only in 7%. This supports the view that infected neonates fail to develop circulating complement-fixing antibodies. Infection rates did not differ significantly between breast-fed and bottle-fed babies. Likewise, maternal antibody levels could not be shown to have any effect on infection. No rotavirus particles were found in breast milk.

Rotavirus infections of neonates.

Faecal specimens from 628 newborn babies in the nurseries of six metropolitan hospitals were examined by electron microscopy for rotaviruses. 304 babies (49%) were found to be excreting virus. All those infected were in five nurseries; viruses were not detected in specimens from the sixth nursery. Two nurseries were studied for 9 mo and another for 11 mo and rotaviruses were found consistently in 40-50% of stools examined. There was no seasonal variation. None of the neonates under the age of one day were infected but by the age of three to four days approximately 50% were excreting virus. Most of those shedding virus were symptom-free but 84 (28%) had diarrhoea. Persisting endemic rotavirus infection is apparently common in hospital nurseries in Sydney. The virus is probably transmitted by environmental spread from neonate to neonate.