Phenprocoumon-induced hepatitis mimicking non-A, non-B hepatitis

A 58-year-old man presented with jaundice 6 months after aortic valve replacement. Although non-A, non-B hepatitis was initially suspected, the final diagnosis of phenprocoumon (Marcoumar)-induced hepatitis progressing to cirrhosis was based on recurrence of jaundice after re-exposure to the drug, improvement after withdrawal and centrilobular necrosis with eosinophilic infiltration in the liver biopsy. Antibodies to hepatitis C virus were absent. The aortic valve was replaced by a bioprosthesis to eliminate the need for life-long anticoagulation.     

Autoantibody pattern in non-A,non-B hepatitis

Summary Acute 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.

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Autoantikörper-Muster bei non-A, non-B-Hepatitis

Zusammenfassung Von 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.

     

Serologic determination of non-A, non-B hepatitis

As to the antigens of hepatitis non-A non-B there are controversial opinions concerning existence and demonstrability. Up to now they were not successful neither in standardizing nor in unifying their test systems. On the basis of own investigations of 1,600 sera of patients with hepatitis non-A non-B and of several control groups, no doubt, a high incidence of precipitations among the sera of hepatitis non-A non-B could be established, but we did not succeed in standardizing the material which was uniform also with regard to the causing virus. Since real antigen-antibody reactions are causative for the heterogeneous phenomena, there nature is to establish by means of suitable methods (methods of the 3rd generation, monoclonal antibodies).     

Aplastic anemia and non-A, non-B hepatitis

Severe aplastic anemia is a rare but important complication of hepatitis. The agent(s) responsible for the hepatitis in these cases have not been well defined. Sixteen patient with hepatitis-associated aplastic anemia were studied for evidence of recent infection with hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and Toxoplasma. Results were compared with data from 10 randomly selected patients with aplastic anemia unassociated with hepatitis. Of the 16 patients, recent acute hepatitis A infection could be excluded in at least 14 patients. Hepatitis B surface antigen (HBsAg) was present in only one patient. A diagnosis of recent hepatitis B infection could not be excluded with confidence in two others. Tests for cytomegalovirus, Epstein-Barr virus, and Toxoplasma gave negative results. No patient with aplasia unassociated with hepatitis had evidence of recent hepatitis A infection, and the frequency of hepatitis B antibodies in this group was indistinguishable from that in patients with hepatitis. These data indicate that most cases of hepatitis that preceded aplastic anemia were not caused by hepatitis A virus or hepatitis B virus; non-A, non-B agents were probably involved in at least 13 of the 16 cases studied.     

Transmission of non-A, non-B hepatitis.

In studies conducted in the early 1950s, sera from six asymptomatic blood donors, implicated in the transmission of viral hepatitis, were inoculated into 10 to 20 volunteers each. Five of these "implicated" donor sera transmitted clinically apparent hepatitis to the recipients. The stored serum samples from these studies have been reanalyzed using serologic markers for hepatitis B virus and hepatitis A virus infection. Two of the donor sera were hepatitis B surface antigen (HBsAg)-positive, and both transmitted hepatitis B virus infection to all susceptible recipients, half of whom showing clinical symptoms. The remaining three infectious donors were HBs-Ag-negative, yet were icterogenic to 10% to 47% of recipients. Testing of serum samples from these recipients with hepatitis showed no evidence of hepatitis B virus or hepatitis A virus infection. This study and other recent evidence suggest that there is a third type of human viral hepatitis--non-A, non-B hepatitis--which is due to a transmissible agent and may well be associated with a chronic carrier state.     

Cutaneous papulo-vesicular eruptions in non-A, non-B hepatitis

A relapsing papulo-vesicular rash with or without pruritus was observed in 54 out of 148 patients (36%) with posttransfusion or sporadic, acute or chronic, non-A, non-B (NANB) hepatitis. The predominant location was the trunk and the anterior surfaces of the upper extremities. The face was affected less often. The eruptive phase was accompanied by general symptoms and increases in aminotransferases and gamma-GT values. The nature of the eruption was consistent with cutaneous reactions as frequently seen in enterovirus infections. No predominance was found for special groups of patients when the skin lesions were correlated to either sex, mode of infection or pattern of transaminase elevation (i.e. monophasic or bi-, and multi-phasic).     

Acute viral hepatitis in Lebanon: evidence for a HAV-like non-A non-B hepatitis

Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.     

Acute viral hepatitis in Lebanon: evidence for an HAV-like non-A non-B hepatitis

ABSTRACT— Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (<1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (>14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.     

Acute sporadic non-A,non-B hepatitis in a pediatric population living in Cairo,Egypt

Summary One-hundred and four cases of acute viral hepatitis and 100 controls 13 years of age and less were entered into a study of acute hepatitis in children in Cairo, Egypt. Study subjects, who were mainly from a lower socioeconomic level, were selected from a public pediatric clinic. Acute non-A, non-B hepatitis was diagnosed in 51 (49%) patients, hepatitis A in 46 (44%), possible hepatitis B in three (3%), and EBV hepatitis in four (4%) patients. Contact with a family member with jaundice was found to be significantly associated with hepatitis A. A history of a blood transfusion, a medical injection, and knowledge of an individual outside of the household with jaundice during the prior six months were significantly associated with non-A, non-B hepatitis. A significant association was not found between the type of hepatitis and the age and gender of study subjects and the extent of household crowding. In this pediatric population living in an urban area of a developing country, non-A, non-B hepatitis was found to be a major cause of acute sporadic hepatitis.

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Akute, sporadisch auftretende Non-A, Non-B-Hepatitis bei ägyptischen Kindern in Kairo

Zusammenfassung In einer Studie zur akuten Hepatitis bei ägyptischen Kindern in Kairo wurden 104 Fälle mit akuter Virushepatitis und 100 Kontrollfälle im Alter von bis zu 13 Jahren analysiert. Die Untersuchung erfolgte an Patienten eines pädiatrischen Allgemeinkrankenhauses, die Kinder kamen vorwiegend aus der unteren sozioökonomischen Schicht. Bei 51 der Kinder (49%) wurde eine akute Non-A, Non-B-Hepatitis diagnostiziert, bei 46 (44%) eine A-Hepatitis, bei drei (3%) eine mögliche B-Hepatitis und bei vier (4%) eine EBV-Hepatitis. Die Hepatitis A war eindeutig assoziiert mit Kontakt zu einem Familienmitglied mit ikterischer Erkrankung. Die Non-A, Non-B-Hepatitis wies eine signifikante Assoziation mit vorausgegangener Bluttransfusion, therapeutischer Injektion und mit Fällen ikterischer Erkrankung, die bei Personen außerhalb des Haushalts sechs Monate vor Erkrankung des Kindes aufgetreten waren, auf. Der Hepatitistyp korrelierte nicht mit dem Alter und Geschlecht des untersuchten Patienten und der Enge der Wohnverhältnisse. Bei pädiatrischen Patienten aus dem städtischen Wohnbereich eines Entwicklungslandes erwies sich die Non-A, Non-B-Hepatitis als eine der Hauptursachen der akuten, sporadisch auftretenden Hepatitis.

     

Epidemic non-A, non-B hepatitis in patients from Pakistan

Epidemic non-A, non-B hepatitis was diagnosed in three young Pakistani men during a 10-month period at the Los Angeles County-University of Southern California Medical Center. All three patients had recently visited or lived in Karachi, Pakistan. None had serologic markers of hepatitis B virus infection or IgM antibody (acute-phase) to hepatitis A virus. A liver biopsy from one patient showed marked cholestasis and cholangiolar transformation of hepatocytes, a pattern previously described in patients with epidemic non-A, non-B hepatitis. Immune electron microscopy of a stool specimen obtained from this patient 10 days after the onset of symptoms showed virus-like particles, 27 nm in diameter, that were specifically aggregated by antibody contained in acute-phase sera from the three Pakistani patients, from patients with non-A, non-B hepatitis in Burma and Nepal, and from an experimentally infected marmoset. Recognition of three separate cases of probable epidemic-type non-A, non-B hepatitis in patients at one institution during such a short time suggests that Pakistan is endemic for this infection and that the disease may be more commonly spread to the United States than is now presumed.     

Virus hepatitis B, A, non-A, non-B

Hepatitis B vaccine is safe and effective. Its impact on the prevention of the disease, however, has been limited. In high risk areas, such as the Far East, mass vaccination of all babies is recommended. Even in low risk areas, such as Northern Europe and the United States, vaccination as part of a routine childhood immunisation programme might be effective so that protection is given before the adult becomes at risk of drug abuse or becoming a promiscuous homosexual or has joined the Health Care Service. A booster injection is probably necessary 5-7 years after primary vaccination. Hepatitis A still causes enormous epidemics. In Western Europe, large numbers of adults are at risk and the economic consequences are considerable. Vaccines which will replace serum immune globulin prophylaxis are under development. Epidemic non-A, non-B hepatitis is caused by a 27-34 nm virus, enterically transmitted. An antibody can be detected in the serum of sufferers from the epidemic but not the sporadic disease. Parenteral non-A, non-B hepatitis is associated with a viral genomic clone, isolated from infected chimpanzee liver and plasma. An antibody to it has been shown in serum of infectious blood donors and in haemophiliac patients previously exposed to blood products.     

Transient agranulocytosis associated with non-A, non-B hepatitis

A 44-yr-old woman with non-A, non-B hepatitis developed agranulocytosis and absence of marrow granulocyte precursor cells with only mild involvement of other blood elements. The agranulocytosis was complicated by gram-negative septicemia, successfully treated with antibiotic therapy. Marrow recovery followed 2 wk of supportive therapy. Before reversal of the agranulocytosis, a future bone marrow transplant was a consideration, making the use of therapeutic granulocyte transfusions, with their ability to sensitize the recipient, potentially harmful. Experience in this case indicates that agranulocytosis associated with non-A, non-B hepatitis may be reversible, and supports the use of supportive care including appropriate antibiotics, and if necessary, granulocyte transfusions, pending marrow recovery.     

Interferon therapy for non-A, non-B chronic hepatitis

We report the results of our study on 8-week consecutive interferon (IFN) treatment for chronic non-A, non-B hepatitis. In the 6 MIU/day group, most cases had continuously normalized alanineaminotransferase (ALT) levels even after IFN treatment was discontinued. In responders whose ALT levels remained normal, not only the degree of inflammation, as seen from HAI scores, but also liver histopathological features were improved. Moreover, antibody to hepatitis C virus (anti-HCV) titer in responders was continuously decreased. Antiviral effects of IFN were observed by detection of HCV-RNA using the PCR technique. HCV-RNA became negative with IFN treatment, however, in some patients who relapsed after discontinuation of IFN treatment, reelevation of ALT levels was usually preceded by re-appearance of HCV-RNA.