Francesco Caredda

INFLUENCE OF DELTA INFECTION ON SEVERITY OF HEPATITIS B

The prevalence of serum markers of primary delta infection was determined in 532 patients with acute benign hepatitis B seen in Italy, and in 111 patients with fulminant hepatitis B seen in Italy, France and England. Patients with fulminant hepatitis had significantly higher prevalence of delta markers (43/111, 39%) than did those with benign hepatitis (101/532, 19%). In 25 of the 43 patients with delta-positive fulminant hepatitis, serum markers indicated a primary hepatitis B infection while in the remaining 18, IgM antibody to hepatitis B core antigen was absent, indicating that hepatitis B preceded superinfection with the delta agent. The increased morbidity of HBsAg hepatitis with delta infection may result from the cumulative simultaneous exposure to hepatitis B virus and delta, or from superinfection of HBsAg carriers with delta.

Serological response to the hepatitis delta virus in hepatitis D.

Sera from 74 hepatitis B surface antigen-positive individuals, who presented with acute hepatitis delta virus (HDV) infection which ran a self-limited course in 58 and progressed to chronicity in 16, were tested over time for HDV markers. In self-limited disease the serum pattern varied from early HD-antigenaemia followed by IgM and IgG anti-HD seroconversion, to the appearance of IgM and IgG anti-HD without antigenaemia, or the isolated expression of either the IgM or the IgG antibody. The typical case of IgM anti-HD was transient and appeared with a mean delay of 10-15 days from admission in the different serological subgroups. The IgG antibody usually developed several weeks later during convalescence. In contrast, patients with disease destined to become chronic had a brisk IgM antibody response and IgG anti-HD was detectable with a mean delay of 15 days; generally, the IgM and the IgG antibody persisted over the follow-up time. IgM antibody to HDV is often the only serological test positive in the clinical stage of hepatitis D and repeated testing for this marker is necessary to diagnose acute HDV co-infection. The serological follow-up provides important prognostic information: waning of IgM confirms resolution of HDV infection, persistence predicts chronicity.

CLINICAL SIGNIFICANCE OF ANTIBODY TO THE HEPATITIS DELTA VIRUS IN SYMPTOMLESS HBsAg CARRIERS

Antibody to the hepatitis delta virus (anti-delta) was detected in 112 out of 2487 (5%) individuals fortuitously found to have the hepatitis B surface antigen (HBsAg) in the blood. Liver function was impaired in 38% (43 of 112) of the anti-delta-positive carriers but in only 9% (215 of 2375) of the anti-delta-negative subjects (p less than 0.001). Liver biopsy specimens were obtained from 31 antibody-positive and 97 antibody-negative subjects with impaired liver function. Important histological changes were observed in 61% of the 31 antibody-positive carriers (7 chronic active hepatitis, 4 active cirrhosis, 8 inactive cirrhosis) but in only 19% of the 97 antibody-negative carriers (p less than 0.001). The presence of anti-delta in serum identifies a subpopulation of apparently healthy HBsAg carriers whose risk of underlying liver disease is four times higher than that in the ordinary carrier. The identification of anti-delta in a symptom-free HBsAg carrier with abnormal liver function is thus an indication for a diagnostic liver biopsy.

Attempted treatment of fulminant viral hepatitis with human fibroblast interferon

Summaryβ-interferon was administered by intravenous infusion to 16 patients affected with fulminant hepatitis B virus infection in third or fourth-grade coma. Ten patients presented a superinfection or a co-infection due to the delta (δ)-agent. None had detectable interferon (IFN) activity before therapy was begun. Besides fever, no significant side-effects were observed during treatment. Both the IFN-treated group as well as the “historical” control group, made up of 70 cases of fulminant virus hepatitis, not treated with IFN and observed during a previous ten year-period, received supportive therapy; survival rates were similar in both groups. Furthermore, the presence or absence of the δ-agent did not appear to affect survival rates significantly.Zusammenfassungβ-Interferon wurde 16 Patienten i.v. infundiert, die an einem Leberkoma dritten oder vierten Grades infolge fulminanter Hepatitis-B-Virus-Infektion litten. Zehn von ihnen wiesen eine durch δ-Agens bedingte Super- oder Koinfektion auf. Bei keinem Patienten konnte eine meßbare Interferon (IFN)-Aktivität vor Therapie-Beginn nachgewiesen werden. Außer Fieber wurden während der Behandlung keine nennenswerten Nebenwirkungen beobachtet. Die Überlebensraten waren nahezu gleich bei den mit Interferon behandelten Patienten und bei einer aus 70 Fällen von fulminanter Virus-B-Hepatitis gebildeten „historischen“ Kontrollgruppe, welche in den vorherigen zehn Jahren lediglich mit unterstützenden Maßnahmen behandelt worden war. Außerdem konnten keine statistisch signifikanten Unterschiede in der Überlebenstrate δ-positiver und δ-negativer Patienten festgestellt werden.

The aetiology of acute hepatitis in Zimbabwe

The cause of acute viral hepatitis in 141 patients admitted to both Infectious Diseases Hospitals in Harare (Zimbabwe) was hepatitis A in 44, hepatitis B in 86 and hepatitis Non-A Non-B in 11. The wide distribution of hepatitis A and B viruses and early exposure to both in Zimbabwe are shown by the high positivity rate for anti-HAV antibody in patients under 10 years old (87.5%) and for anti-HBs antibody in patients over 20 (60%). Among the 86 hepatitis B cases, e and delta systems were also investigated: 66 patients (76.5%) were HBeAg positive, six (7%) anti-HBe positive and 14 (16.5%) negative for both; only one was anti-delta positive. Two cases of fulminant liver failure (both occurring in HBsAg and anti-HBc IgM positive, but delta-markers negative patients) and five cases of hepatoma (only one of whom was negative for all HBV markers) are described.

Detection and Further Characterization of a Newly Described Microsomal Autoantibody Associated with Chronic Delta Infection

Sera from 162 patients with acute or chronic hepatitis and from patients with autoimmune diseases have been investigated for autoantibodies by indirect immunofluorescence on human and animal tissues. A small proportion (14.2%) of young patients with chronic delta hepatitis has been found positive for cytoplasmic staining which was maximal in hepatocytes and renal proximal tubules. This autoantibody has been found to react with microsomal antigenic determinant different from the classic liver-kidney microsomal LKM antigen as demonstrated by fluorescence absorption experiments with purified subcellular organelles and by fluorescence-blocking tests. The microsomal autoantibody displayed also organ and species-specificity different from those shown by the LKM-positive sera. The positive patients showed persistence of the microsomal autoantibody during the follow-up without other serological markers of autoimmunity. There was no evidence of a particular course of chronic delta hepatitis in patients positive for the microsomal autoantibody.

Cryoglobulins and infectious diseases

SummaryThe relationship between infectious diseases due to various pathogenetic factors and cryoglobulin production mechanisms has been investigated. Cryoglobulins have been evidenced in infections caused by very heterogeneous pathogens, i.e. leptospirosis, psittacosis, Mediterranean tick typhus, brucellosis, gram-negative bacterial septicemias, in which they had never been previously reported. In type A hepatitis a high cryoglobulin prevalence (91%) has been confirmed during the acute phase, with a rapid decrease both in prevalence and concentration in the subsequent stages of the disease. Cryoglobulins were all of type III and were mainly represented by IgM; anti-HAV-IgM antibodies have been evidenced in all but one cryoprecipitates. In non-A, non-B hepatitis a lower cryoglobulin prevalence (44.7%) was shown during the acute phase and the same fast decrease has been noted in the subsequent stages. Cryoglobulins were all of type III and in some cases polyclonal IgG was the only Ig class present in cryoprecipitates. The cryoglobulin prevalence in the acute phase of HBsAg-positive hepatitis amounted to 73.4%; all the cryoprecipitates were of type III. No correlation between the presence of cryoglobulins and HBeAg positivity or between cryoglobulins and delta agent infections was found. In all the cases studied the presence of cryoglobulins was related to the persistence of liver damage. Cryoglobulins were not found in HBsAg chronic carriers, while they have been evidenced, by a preliminary study, in 41.6% of HTLV-III antibody-positive subjects complaining of a persistent generalized lymphadenopathy without clinical or laboratory signs of liver impairment. No HTLV-III antibodies were found by ELISA method in the type III cryoprecipitates.

Autoantibody Pattern in Non-A, Non-B Hepatitis

SummaryAcute and convalescent sera from 44 patients with non-A, non-B hepatitis were tested for organ and non-organ specific autoantibodies by indirect immunofluorescence. In the acute-phase sera, 36.4% of the patients were positive for smooth muscle antibodies. Brush border antibodies and anti-reticulin antibodies were detected in 13.6% of the patients. Only two patients (4.5%) were positive for anti-nuclear anti-bodies. The autoantibody pattern did not relate to the different epidemiology, sex, a previous hepatitis B virus infection or to the biochemical liver function tests. The autoantibody pattern did not differ statistically in patients who recovered (23 cases) and in patients who progressed to chronic liver disease (21 cases), even if a higher frequency of smooth muscle antibodies was detected in the latter group. Convalescent sera screening showed that the clinical course of the disease did not relate to the behaviour of smooth muscle antibodies, brush border antibodies and anti-reticulin antibodies. However, an increase (28.6%) in anti-nuclear antibodies in patients who progressed to chronic liver disease was observed. The clinical significance of the presence of serological markers of autoimmunity in patients with chronic sequelae following acute non-A, non-B hepatitis is discussed.ZusammenfassungVon 44 Patienten mit non-A, non-B-Hepatitis wurden die Seren aus der akuten Phase und Rekonvaleszenz auf organspezifische und nicht-organ-spezifische Autoantikörper im indirekten Immunfluoreszenztest geprüft. Im akuten Krankheitsstadium waren 36,4% der Seren positiv für Antikörper gegen glatte Muskulatur. Antikörper gegen Bürstensaum und gegen Retikulin wurden bei 13,6% der Patienten entdeckt. Nur bei zwei Patienten (4,5%) waren antinukleäre Antikörper nachzuweisen. Das Autoantikörper-Muster stand nicht in Beziehung zu unterschiedlichen epidemiologischen Gegebenheiten, Geschlecht, vorhergehender Hepatitis B Virus-Infektion oder biochemischen Leberfunktionsparametern. Zwischen dem Autoantikörper-Muster der geheilten Patienten (23 Fälle) und der Patienten, die eine chronische Leberkrankheit entwickelten (21 Fälle), bestand kein statistischer Unterschied, auch wenn in der letztgenannten Gruppe Antikörper gegen glatte Muskulatur häufiger vorkamen. Die Untersuchung der Rekonvaleszentenseren zeigte, daß der klinische Verlauf nicht mit dem Verhalten der Antikörper gegen glatte Muskulatur, Bürstensaum und Retikulin korrelierte. Hingegen ließen sich vermehrt antinukleäre Antikörper bei Patienten mit chronischem Krankheitsverlauf nachweisen (28,6%). Die klinische Bedeutung von serologischen Markern für auto-immunologische Vorgänge bei Patienten mit chronischen Folgeerscheinungen nach akuter non-A, non-B-Hepatitis wird diskutiert.

Simultaneously acquired hepatitis B and hepatitis D virus infections.

Points Infective endocarditis: a preventable disease? (P Lyn); Sutures or adhesive tapes for primary closure of pretibial lacerations (F Dudley Hart); Ovariectomy and breast cancer: did Schinzinger beat Beatson? (H Vorherr); Accidental digitalis poisoning due to drinking herbal tea (G P Spickett); Chest physiotherapy in primary pneumonia (J Sim and others); Is peritoneal dialysis a good long term treatment? (D G Oreopoulos); Acute appendicitis and dietary fibre (R G Benians); Fenclofenac induced interstitial nephritis (L Sellars and others); Review body proposes 6-3% rise (A J Macdonald) ..... ....... 57