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OBJECTIVE--To confirm the findings of pilot studies that interferon alfa is an effective treatment of Europid men with chronic hepatitis B virus infection. DESIGN--Randomised controlled trial of three months treatment with interferon alfa followed by 12 months of observation. SETTING--Outpatient clinic of a tertiary referral centre. PATIENTS--37 Treated men (six anti-HIV positive) and 34 untreated men (nine anti-HIV positive) who met the criteria for the trial. Four controls failed to complete follow up. INTERVENTIONS--The treated group received subcutaneous injections of 5-10 MU interferon alfa/m2 daily for five days, then 10 MU/m2 thrice weekly for 11 weeks. Follow up continued at monthly intervals for 12 months. Untreated controls were monitored over the same period. MAIN OUTCOME MEASURE--Hepatitis B e antigen and hepatitis B virus DNA state after 15 months of observation. RESULTS--12 Of the 37 treated patients cleared hepatitis B e antigen and hepatitis B virus DNA, whereas only one of 30 untreated controls seroconverted over the same period--an increased response rate of 29% (95% confidence interval 13% to 45%). The life table estimate of response at 15 months was 35% in treated patients, an increase of 32% above controls (95% confidence interval 16% to 48%). The response rates in groups by predictive pretreatment variables were 12 of 31 anti-HIV negative patients (excess response 34%; 95% confidence interval 14% to 54%), 12 of 26 with chronic active hepatitis before treatment (excess response 46%; 27% to 65%), and 12 of 21 with a pretreatment serum aspartate aminotransferase activity greater than 70 IU/l (excess response 46%; 16% to 76%). The combination of these factors predicted response with a sensitivity of 100% and a specificity of 80%. Four of the 12 responders, who had all been infected for less than two years, also lost hepatitis B surface antigen. Treatment was well tolerated. CONCLUSIONS--Interferon alfa is effective in the treatment of a proportion of Europid men with chronic hepatitis B virus infection, who might be identified before treatment. Additional strategies are required to improve the rate of response.

Summary Infections with the hepatotropic viruses non-A, non-B (NANB), hepatitis B (HBV) and delta agent (HDV) are described in two patients with haemophilia. The first patient illustrates the phenomenon of interference following a simultaneous exposure to NANB and HBV. The second patient, a carrier of hepatitis B surface antigen (HBsAg), acquired superinfection with HDV which resulted in acute hepatitis progressing to chronic hepatitis. Liver disease seen in multitransfused haemophiliacs may be significantly different to that seen in other patients. As a consequence of the infusion of blood clotting factor concentrates, these patients become the site of complex viral interactions.

The serologic and viral profiles of 24 patients who presented with acute hepatitis B virus (HBV) infection were studied. Although in rare cases, HBV-DNA was detectable before hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), in the majority the viral proteins appeared first. In acute hepatitis followed by recovery, as IgM anti-HBc (hepatitis B core antigen) titres rose, the level of HBV replication fell and serum transaminases became elevated. In patients progressing to chronic HBV infection, IgM anti-HBc titres rose early, viral replication was initially low but continued to rise as the serum transaminase levels became elevated. 7S IgM anti-HBc, although present in the phase of established chronic HBV infection, was not found in the early phase of the chronic infection. Thus this antibody appears to be a consequence of, rather than a causative factor in, chronic HBV infection.

Two reactive sequences of the pre-S regions of hepatitis B surface antigen were synthesized chemically and used in micro-ELISAs for the assay of pre-S1 and pre-S2 antigens in serum from patients with acute and chronic hepatitis B. Pre-S1 antigen correlated well with the presence of HBV-DNA and was no longer detectable on cessation of viral replication, after natural recovery and after successful treatment with alpha-interferon. Pre-S2 proteins were also lost after treatment with alpha-interferon. The results show that the assay of pre-S1 and pre-S2 proteins in serum provides additional useful markers for assessing patients with acute and chronic hepatitis B infection and for monitoring the response to treatment with interferon.

Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.

In Kenya hepatitis B virus (HBV) infection and its sequelae are common. We followed up 49 hepatitis B surface antigen (HBsAg)- positive mothers and their newborn infants for 9 months to determine the importance of perinatal transmission in the African and to relate this to the HBe and HBV-DNA status of the mother. Our study shows that perinatal transmission is relatively unimportant in Kenya and that this may be a consequence of the low levels of circulating HBV-DNA in the maternal plasma. These results imply that vaccination without hyperimmune globulin may be adequate to control HBV infection in Kenya.

Non-A, non-B (NANB) viral hepatitis was successfully transmitted to two colony-born Tamarins following inoculation with antihaemophilic factor VIII concentrate or the "H" inoculum. Both animals showed histological and ultrastructural evidence of viral hepatitis, with raised alanine aminotransferase (ALT) levels from the second week after inoculation through to the end of follow-up, 5 months later.

Summary This study set out to examine the relative effectiveness and tolerability of 12- versus 24-week courses of thrice weekly intramuscular lymphoblastoid interferon in the treatment of hepatitis B ‘e' antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, and to identify pretreatment factors predicting the outcome of therapy. Twenty patients were randomised to each treatment group. Treatment was associated with clearance of HBeAg and HBV-DNA in 59% of the 32 male patients, whereas none of the eight women responded (48% overall response rate). This response rate in males is at least three times the recorded spontaneous seroconversion rates in this population. Most of the women (5/8) were of Oriental origin and had minimal disease, factors that may have influenced response. The longer course was poorly tolerated and was therefore no more effective: eight of 20 patients withdrew because of side-effects. Variables associated with response included high AST (aspartate transaminase), short duration of disease and previous history of acute hepatitis. A response to antiviral therapy was accompanied by clinical and biochemical evidence of improvement in liver disease.

A high incidence of pharyngeal infection was found in babies with isolation-positive chlamydial conjunctivitis. Chlamydia trachomatis was isolated from the pharynx of 12 (52%) of 23 babies before treatment, and was reisolated from the eyes of 4 (12%) of 34 and from the pharynx of 14 (41%) of 34 after treatment. C trachomatis was reisolated significantly more often from babies treated only with topical tetracycline for 4 weeks (75%) than from those treated with both topical tetracycline and oral erythromycin for 2 weeks (32%). Reisolation from the eyes was associated with only minor clinical signs. Radiological signs of an inflammatory lesion in the chest were found in 2 of 8 babies examined because of persistent cough. These signs were not associated with high or rising titres of serum chlamydial antibody.

Some studies suggest that there is antigenic and nucleic acid homology of one type of non-A, non-B hepatitis virus with hepatitis B viral (HBV) proteins and DNA. Using molecular hybridization under high and low stringency conditions with high specific activity 32P-HBV DNA as a probe, serum and liver samples from patients and nonhuman primates infected with non-A, non-B hepatitis were examined. Our results provide no evidence of significant homology between the DNA extracted from serum and liver of patients and nonhuman primates infected with one type of non-A, non-B hepatitis and HBV DNA.

To test the effect of transplantation of T-cell-depleted bone marrow on recipient immune function the results of pre-transplantation immunisation with tetanus toxoid and hepatitis-B vaccine were studied in 38 donor-recipient pairs. Immunisation of the donor alone resulted in transfer of an antibody response to the recipient; immunisation of both donor and recipient resulted in potentiation of the antibody response in both magnitude and duration. These findings indicate that donor T-cell-depleted marrow can transfer humoral immunity to the recipient and that appropriate pre-transplant immunisation schedules may be of benefit to the recipient.

Liver biopsy specimens previously taken from 16 haemophilic patients with chronic non-A, non-B hepatitis were reviewed. The degree of fibrosis correlated with serum procollagen III peptide (sPIIIP) concentrations, measured both at the time of biopsy and 4.25 years later. Two patients with extremely high sPIIIP concentrations had collateral veins on computed tomography, suggesting portal hypertension. Twenty eight of 47 patients (60%) had splenomegaly on computed tomography, and of 28 patients in whom intravenous contrast medium was used, seven (25%) had collateral oesophageal veins. Serum procollagen III peptide estimations and computed tomography, both non-invasive investigations, indicated that hepatic fibrosis and portal hypertension had developed in a proportion of haemophilic patients with non-A, non-B hepatitis. Infection with the human immunodeficiency virus (HIV) may modify the course of this presumably cytopathic virus infection of the liver.

Highlights • GBV-B infection of tamarins is a valuable model for acute HCV infection. • We observed distinct expression patterns of PD-1, a marker of T-cell activation, on peripheral and hepatic lymphocytes. • Differential PD-1 expression is coincident with reduction in peripheral GBV-B. • Liver-associated viral RNA in the absence of peripheral viraemia indicates maintenance of occult infection., Flaviviruses related to hepatitis C virus (HCV) in suitable animal models may provide further insight into the role that cellular immunity contributes to spontaneous clearance of HCV. We characterised changes in lymphocyte populations in tamarins with an acute GBV-B infection, a hepatitis virus of the flaviviridae. Major immune cell populations were monitored in peripheral and intra-hepatic lymphocytes at high viraemia or following a period when peripheral virus was no longer detected. Limited changes in major lymphocyte populations were apparent during high viraemia; however, the proportions of CD3+ lymphocytes decreased and CD20+ lymphocytes increased once peripheral viraemia became undetectable. Intrahepatic lymphocyte populations increased at both time points post-infection. Distinct expression patterns of PD-1, a marker of T-cell activation, were observed on peripheral and hepatic lymphocytes; notably there was elevated PD-1 expression on hepatic CD4+ T-cells during high viraemia, suggesting an activated phenotype, which decreased following clearance of peripheral viraemia. At times when peripheral vRNA was not detected, suggesting viral clearance, we were able to readily detect GBV-B RNA in the liver, indicative of long-term virus replication. This study is the first description of changes in lymphocyte populations during GBV-B infection of tamarins and provides a foundation for more detailed investigations of the responses that contribute to the control of GBV-B infection.

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease.

Concentrated samples of saliva, urine, and seminal fluid from 23 men with chronic liver disease who were positive for hepatitis B e antigen were examined for the presence of hepatitis B virus deoxyribonucleic acid (HBV-DNA) by molecular hybridisation. HBV-DNA was detected in saliva from 15 of 17 men (88%), urine from 12 of 22 men (55%), and seminal fluid from 13 of 21 men (62%). The presence of hepatitis B virus in such secretions has important epidemiological implications for heterosexual and homosexual contact.

Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti-human immunodeficiency virus antibody status (p less than 0.001), chronic active hepatitis on liver biopsy (p less than 0.005), high AST level (p less than 0.001), low hepatitis B virus DNA level (p less than 0.001) and a history of acute hepatitis (p less than 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p less than 0.05). The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter, which predicted response in 77% with a specificity of 79% (p less than 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration (p less than 0.001).

A dot-blot hybridisation assay for serum HBV DNA is described using a non-radioactive (biotinylated) DNA probe. The assay is both sensitive (1 pg of HBV DNA) and reproducible, and shows several advantages over similar assays which use 32P-labelled probes for the routine detection of infectious virus particles both in blood and in other biological fluids.

Seventy-eight patients with congenital coagulation disorders were treated with hepatitis B vaccine either subcutaneously or intradermally. All the children (eight vaccinated subcutaneously and eight vaccinated intradermally) responded. Seventeen of 19 (90%) anti-HIV-negative adults vaccinated subcutaneously and 14/25 (56%) anti-HIV-negative adults vaccinated intradermally showed an immune response. At 24 months, the anti-HBs level was greater than 10 IU/l in all children vaccinated subcutaneously, 83% of children vaccinated intradermally, 77% of adults vaccinated subcutaneously, and 55% of adults vaccinated intradermally. Eight of 15 (53%) adult patients who were anti-HIV positive were also anti-HBc positive before vaccination and 6/8 (75%) failed to produce an amnestic response to vaccine. Subcutaneous vaccination with regular monitoring of anti-HBs levels and appropriate boosting is recommended.

Response to interferon therapy in chronic hepatitis B virus (HBV) carriers is preceded by the appearance of IgM class anti-HBc (antibody to hepatitis B core antigen). The temporal relationship and magnitude of the IgM anti-HBc response is variable suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins, induced by interferon. IgG 1, 2, 3, and 4 class anti-HBc did not change during therapy, but IgG 3 anti-HBc was significantly lower in responders than non-responders. IgG anti-HBc of all subclasses was absent in two Chinese HBV carriers. Lower than normal titres of anti-HBc (p less than 0.001) were detected in human immunodeficiency virus antibody positive (anti-HIV) HBV carriers. These data indicate the presence of altered immunity to the nucleocapsid antigens in these two types of chronic HBV carrier that are known to respond poorly to antiviral therapy.

The purpose of this study is to determine the effect of short-term social drinking on hepatitis B virus (HBV) replication as measured by serum levels of hepatitis B virus DNA (HBV-DNA). We studied five male carriers of hepatitis B e antigen who were social drinkers. Levels of HBV-DNA, blood alcohol, and aspartate aminotransferase (AST) were measured during abstinence from alcohol, before and during a test dose (29.8 g) of alcohol which followed one week of abstinence, and before and during the same test dose which followed social drinking for one week. We observed no significant changes in HBV-DNA or AST levels. These data suggest that a single one-week period of social drinking in patients with chronic HBV infection does not cause enhanced viral replication. The risks of repeated ingestion of moderate amounts of alcohol by such patients have not been established. Interpretation of our data is limited by the small number of subjects, and further studies are needed. Nevertheless, our results are consistent with published recommendations that social drinking by nonalcoholic HBV carriers should be restricted but need not be totally forbidden.

A randomised controlled trial was conducted in 29 HBV carriers who had been HBs and HBe antigen positive for more than six months. Fifteen patients were treated with ARA-AMP 10 mg/kg/day given as intramuscular injections 12 hours apart for five days followed by 5 mg/kg/day for 23 days. The 14 controls received no treatment. Serum HBV-DNA polymerase, and HBV-DNA decreased in all patients during therapy. Six treated patients lost serum HBV-DNA polymerase, HBV-DNA and HBeAg, HBsAg concentrations decreased, and five developed anti-HBe. One of these six patients lost HBsAg and developed anti-HBs. No such changes were observed in the control group over a similar 18 month period of observation. A four week course of ARA-AMP inhibits HBV replication and in a significant minority of patients this is long lasting and is associated with a reduced level of inflammatory activity in the liver.

Three tamarins (Saguinus labiatus), two of which had previously been infected with hepatitis A virus and parenteral non-A, non-B hepatitis, were inoculated intravenously with the agent of GB hepatitis. All three animals developed alanine aminotransferase abnormalities 2, weeks after inoculation. Peak alanine aminotransferase levels were recorded 4 weeks postinoculation. These declined thereafter but continued to fluctuate at abnormal levels for 32 weeks. Liver biopsies showed liver cell swelling and inflammation with focal necrosis. Portal tracts and areas around central veins were heavily infiltrated with mononuclear cells. A fourth animal (no previous exposure to hepatitis viruses) inoculated with GB was killed on Day 15 postinoculation. Serum and extracts of liver and feces from this day were used as inocula for three other animals. Only the serum and liver extract transmitted GB hepatitis. The fecal specimen did not transmit and a fecal extract taken at a later date from another animal was also noninfectious. GB hepatitis virus is distinct from the viruses causing Type A and blood-borne non-A, non-B-hepatitis. Although the virus is present in serum and has previously been transmitted per os, it is not shed in feces.

Ten patients with evidence of continuing HDV replication were treated with lymphoblastoid alpha-interferon and eight more were followed as a non-randomized control group. Four out of eight patients who completed one year of follow-up had cleared HIDV-RNA from the serum whilst none of the control group did so. In these four responding cases there was a transient Increase in transaminase levels during treatment and in two, this was followed by improvement. One patient also cleared HBV and seroconverted to anti-I-lBs (antibody to hepatitis B surface antigen - HBsAg). In one patient with sustained loss of HDV, recurrence of HDV infection was detected 18 months after completion of treatment. These data suggest that alpha-interferon can inhibit HDV replication in the short term but relapse after one to two years may occur. Inhibition of I-IDV-RNA is associated with improvement in the inflammatory liver disease and now larger studies are required to determine whether It influences survival.

Markers for acute hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis non-A, non-B (HNANB) infections were examined in the sera of 94 patients presenting with acute hepatitis in Kenya. Hepatitis B virus was responsible for 70% of cases, HNANB for 18%, and HAV for only 12%. The use of an IgM anti-HBc assay increased the rate of diagnosis of acute HBV infection, thereby reducing the proportion of cases designated as NANB.

The hepatitis D virus (HDV; previously called the "delta agent") is a defective organism which can replicate only in the presence of the hepatitis B virus (HBV). We tested the serum of 95 substance abusers, all of whom had sufficient evidence of chronic liver disease to warrant a liver biopsy, for hepatitis D virus antibody (anti-HDV). Anti-HDV was detected in five of eight hepatitis B surface antigen (HBsAg)-positive patients and 12 of 87 (14%) HBsAg-negative patients. Antibody to the hepatitis B core antigen (anti-HBc) was the sole hepatitis B marker in eight of the 12 (67%) anti-HDV-positive, HBsAg-negative patients but in only 14 of 75 (19%) anti-HDV-negative, HBsAg-negative patients (P less than 0.005). None of the anti-HDV-positive, HBsAg-negative patients had detectable IgM anti-HBc in the serum or hepatitis D antigen in liver tissue, and they had similar clinical features and liver biopsy diagnoses to HBsAg-negative patients without anti-HDV. We conclude that anti-HDV in HBsAg-negative substance abusers reflects infection with HDV and HBV in the distant past and does not indicate more severe liver disease than that seen in HBsAg-negative patients without anti-HDV.

The yield of infectious progeny of a genital strain of Chlamydia trachomatis in cycloheximide-treated McCoy cell cultures was 11-fold lower than that in untreated monolayers.

Exudate from Bartholin's ducts from 30 selected patients was investigated for Chlamydia trachomatis and Neisseria gonorrhoeae. N. gonorrhoeae was isolated from the duct exudate in 24 patients and C. trachomatis in nine. Concurrent infection of the ducts was present in seven (29.2%); the remaining two patients were sexual contacts of men with non-specific urethritis. The duct exudate was mucopus in seven patients, cloudy mucus in one, and clear mucus in the other. Although contamination of the vulva by C. trachomatis derived from cervical or urethral infection cannot be excluded, three cases are described which suggest that a true infection of the duct occurs and may persist after gonococcal infection has been cured.

Hepatitis A virus (HAV) shedding in the faeces, appearance of HAV-Ag (antigen) in the liver, and development of humoral immunity to HAV have been studied in experimentally infected tamarins. The appearance of liver damage measured by transaminase elevation and histology, in relation to the above variables, suggests that the virus is not cytopathic and the immune system contributes to the production of liver cell damage. Preliminary data suggest that HAV replication may occur in the mucosa of the small intestine and in the liver.

Chromatography with a solid-phase polyelectrolyte based on ethylene maleic anhydride polyelectrolyte (EMA PE) has been shown to remove a large proportion of hepatitis B surface antigen (HBsAg), including hepatitis B virus (HBV) particles, from contaminated cryoprecipitate. This process may reduce the risk of transmission of HBV infection when factor VIII concentrates are administered.

In 580 women with Chlamydia trachonmatis infection of the cervix, the degree of the infection was assessed by counting the number of chlamydial inclusions which developed in McCoy cell monolayers inoculated with cervical swab material under standardised conditions. In 34% of these women inclusion counts were

We have examined the relationship between hepatitis B virus infection and hepatocellular carcinoma in a series of 50 British patients with histologically-proven hepatocellular carcinoma. Serum HBsAg was detected in 10 patients (20 per cent), and of the remainder, 21 per cent of those tested had serological evidence of past hepatitis B virus exposure. None of nine tumour specimens from serum HBsAg negative patients had detectable HBV-DNA integration into the tumour cell genome. The presence or absence of serum HBsAg was of no prognostic significance in British patients with hepatocellular carcinoma. Liver cell dysplasia, a possible pre-malignant lesion, was noted in 53 per cent of patients who had had liver biopsies before the diagnosis of hepatocellular carcinoma, and in 79 per cent of biopsies taken at the time of diagnosis of hepatocellular carcinoma. The presence of liver cell dysplasia was not more common in serum HBsAg positive patients.

An immunoradiometric assay for hepatitis B surface antigen (HBsAg) that employs monoclonal antibodies directed against the common epitope(s) of HBsAg was used to analyse 3,694 samples of human serum. Further analysis of those sera identified as HBsAg-positive in this assay demonstrated that the findings with the monoclonal-antibody-based assay correlated with the presence of HBsAg as determined by Austria II. A small proportion of apparently false-positive reactions were observed, in that some sera, although reactive with the monoclonal antibodies, were not positive in conventional immunoassays using polyclonal antisera, nor were they neutralisable with polyclonal anti-HBs. The material purified by monoclonal immunoabsorbants from representative "true" and "false-positive" sera was run on polyacrylamide gels and examined under the electron microscope. The antigen in the apparently false-positive sera contained some polypeptides of similar size to those found in HBsAg, but no virus particles were seen by electron microscopy. The majority of patients with this monoclonal-antibody-reactive antigen gave either a history of hepatitis B virus (HBV) contact or had signs of liver disease.

Significant variation was found, between 46 isolates of hepatitis G virus (HGV), following direct sequencing of subgenomic PCR fragments from either or both the NS-3 and putative 'core' peptide. Nucleotide sequences of most HGV NS-3 fragments varied by 10-30% and of most putative 'core' peptide fragments by 2-20%. HGV was therefore shown to be much less variable than hepatitis C virus (HCV) and pairwise comparisons of HGV sequences demonstrated a single distinct distribution of evolutionary distances. Construction of phylogenetic trees, bootstrap analysis and calculation of mean distances between possible subtypes also indicated one level of variation between HGV NS-3 and putative 'core' peptide sequences, and the suggested degree of variation between isolates was similar to that between HCV subtypes. No evidence for clustering of sequences into multiple subtypes or genotypes was found. Although very small subgenomic fragments of HCV are indicative of the viral genotype it seems that the assignment of genetic groups is not possible for HGV using such small subgenomic fragments. The relatively limited genetic variation observed in HGV may reflect a relatively low level of host selection pressure stemming from the low level of host immunity stimulated by this virus.

This report describes a carrier of haemophilia A who developed fulminant non-A, non-B hepatitis after transfusion with cryoprecipitate. She survived, but developed chronic active hepatitis.

Summary. Hepatitis G virus (HGV) is a newly identified member of the Flaviviridae family. The positive-sense RNA genome of the virus contains a single open reading frame that encodes the viral polyprotein. Its genomic organization is similar to that of the hepatitis C virus (HCV) with which it has only 25% homology at the nucleotide level. Nucleotide sequences from the NS-3 helicase region of HCV varied by 10–30%. HGV is therefore much less variable than HCV. Construction of phylogenetic trees, and calculation of mean distances between possible subtypes, indicated one level of variation in NS-3 sequences: the degree of variation between isolates was similar to that observed between HCV subtypes. Thus no evidence for clustering of sequences into multiple genotypes was found. The virus is transmissible through blood transfusion and by exposure to blood products or intravenous drug use, and may result in acute or chronic hepatitis. A causative role of HGV in acute and chronic hepatitis is not yet established. Concurrent infection with hepatitis B virus (HBV) and HCV is common and persistent viraemia has been documented for many years, in many cases, in the absence of transaminase elevations.

Amino acid requirements of a Chlamydia trachomatis were defined in McCoy cell monolayer cultures, depleted of their nutrient reserves by maintenance in Earle balanced salt solution for at least 2 days, and then treated at infection with 1 microgram of cycloheximide per ml, an inhibitor of host cell protein and deoxyribonucleic acid synthesis. Serum-free Waymouth MB 752/1 medium lacking one amino acid or a group of related amino acids was added to depleted cultures before infection. Eight of the amino acids normally present in MB 752/1 were essential for chlamydial growth, six were advantageous for growth, and five were nonessential.

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.

SUMMARY: Chlamydia trachomatis is normally grown in McCoy monolayer coverslip cultures using partially defined media containing foetal calf serum at concentrations up to 10% (v/v). Omission of the serum decreased the number of inclusions produced by infecting the McCoy cells with a standard inoculum of a genital strain of C. trachomatis. Substitution of the foetal calf serum with a macromolecular fraction from the serum or with a mixture of sodium oleate, bovine serum albumin fraction V and fetuin maintained the inclusion count, but substitution with serum filtrate, containing the amino acids and other low molecular weight components, decreased the inclusion count of C. trachomatis. The role of calf serum and the need for a fully defined medium excluding serum for studying the growth of C. trachomatis in tissue culture are discussed.

Patients who are chronically infected with the hepatitis B virus are at an increased risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma. Therapeutic intervention offers the only means of interrupting this progression. Currently there are three licensed agents for the treatment of chronic hepatitis B virus infection. These are interferon-alpha, an immunomodulator, and two synthetic nucleos(t)ide analogs, namely lamivudine (Epivir, GlaxoSmithKline) and adefovir dipivoxil (Hepsera, Gilead Sciences). This review aims to summarize current experience with these drugs in the treatment and management of patients with chronic hepatitis B virus infection, their efficacy, and current problems of drug resistance. An outline of future treatment perspectives is also included.

The relationship between the histological diagnosis and serological and tissue markers of HBV replication in 41 Greek and 29 British patients with chronic HBV infection were studied. All the nine Greek and 13 British patients who were HBeAg positive had HBV-DNA in serum and HBcAg expression in the hepatocytes. The majority (73%) of these patients had active liver disease. Forty seven per cent of the Greek and 19% of the British patients who were anti-HBe positive continued to display HBcAg in the liver with or without HBV-DNA detected in serum. All but three of these patients had persistently active liver disease. Continuing inflammatory activity in the liver, however, was also found in 31% of anti-HBe positive patients who had no evidence of HBV replication. In these patients, other factors such as delta agent, NANB viruses, alcohol abuse or an autoimmune reaction initiated by HBV may be contributory.

The hepatitis viruses, named A-E, cause acute and chronic liver disease depending on the virus. Laboratory-based diagnosis relies on the detection of specific markers of infection for each virus, through the use of appropriate serological tests. In recent years, molecular tests that rely on the amplification of viral nucleic acids have also been employed, not only in confirming active viral replication but also in monitoring antiviral treatment efficacy. Some of these tests that are currently in use in routine diagnostic laboratories are outlined in this chapter.

An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.