Josep Costa

PREVALENCE OF ANTIBODIES TO HEPATITIS C VIRUS IN SPANISH PATIENTS WITH HEPATOCELLULAR CARCINOMA AND HEPATIC CIRRHOSIS

The prevalence of antibodies against hepatitis C virus (HCV) was investigated in 96 patients with hepatocellular carcinoma, 106 patients with liver cirrhosis without evidence of cancer, and 177 controls without liver disease. 75% of patients with hepatocellular carcinoma had HCV antibodies (anti-HCV), a significantly higher proportion than that observed in patients with cirrhosis (55.6%), or controls (7.3%). The prevalence of anti-HCV was significantly higher in patients with alcoholic cirrhosis and hepatocellular carcinoma (76%) than in patients with alcoholic cirrhosis alone (38.7%) whereas in patients with cryptogenic cirrhosis there was no significant difference between those with and without primary liver cell cancer (81.4% and 77.5%, respectively). These results indicate that HCV infection may have a role in the pathogenesis of hepatocellular carcinoma, even in patients with chronic liver disease apparently related to other agents such as alcohol, and that this recently identified hepatitis virus may be found in a large proportion of patients with cryptogenic cirrhosis.

Hepatitis C Virus Infection in Patients with Nonalcoholic Chronic Liver Disease

STUDY OBJECTIVE To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN Cross-sectional study. SETTING The liver unit of a referral-based university hospital. PATIENTS Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.

Prevalence and mother‐to‐infant transmission of hepatitis viruses B, C, and E in Southern Tanzania

Hepatitis B and C markers were tested in 980 pregnant women, in the infants born to infected mothers, and in a random sample of 42 and 50, respectively, children born to uninfected mothers in Tanzania. Sixty‐two women (6.3%) were positive for HBsAg and 15 (24%) were HBeAg‐seropositive. Anti‐HCV was detected in 49 women (5%), 15 (31%) of whom had detectable viremia. HCV RNA serum levels were low and only genotype 4 was identified. Sixty‐six women (6.7%) were positive for anti‐HIV, six of whom were coinfected with HBV and one with HCV. Anti‐HEV was negative in the 180 women tested. At 8 months of age, HBsAg was detected in 8% and 2% of children born to HBV‐infected and noninfected mothers, respectively (P = 0.2). Corresponding figures at 18 months of age were 31% and 21% (P = 0.3). When tested at 2 months of age, HCV RNA was not detected in any of the 43 children born to anti‐HCV–positive mothers nor in any of 50 children born to anti‐HCV–negative mothers. At 18 months, only one child, born to an anti‐HCV–positive mother, had detectable HCV RNA. None of the infants born to women with HIV coinfection were infected with hepatitis viruses. This study suggests that exposure to HEV does not occur in southern Tanzania. The prevalence of current HBV infection in pregnant women from rural Tanzania is lower than in other sub‐Saharan areas. In early childhood, HBV infection appears to occur by horizontal rather than maternofilial mechanisms of transmission. The prevalence of HCV infection is similar to that in other African countries. The results of this study show for the first time in Africa that mother‐to‐infant transmission does not play a significant role in the acquisition of HCV infection. J. Med. Virol. 58:215–220, 1999.

Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.

Surgicale studied the immunogenicity of the standard schedule of recombinant hepatitis B vaccine (20 μmUg per dose at months 0, 1, and 6) in 21 anti-human immunodeficiency virus (HIV)-positive persons. Relatively low titers of anti-HBs developed in only five subjects (23.8%) 1 month after the third dose; all five had T4 cell counts greater than 700 cells/mm and none of the 11 subjects with a T4 cell count below this value responded. Five of the 16 nonresponders to the vaccine later had acquired immunodeficiency syndrome (AIDS)-related complex (two) and AIDS (three), while none of the responders did. Our results show that anti-HIV–positive persons are poor responders to the recombinant hepatitis B vaccine, and that the absence of a response is an indicator of a more severe immune deficiency and of a poor prognosis. An optimal regimen of hepatitis B vaccination in HIV-infected persons is still to be established.

Large Outbreak of Measles in a Community with High Vaccination Coverage: Implications for the Vaccination Schedule

BACKGROUND Attempts to eliminate measles from a country or region may be disrupted by an imported case that affects indigenous persons. The objective of this study was to analyze epidemiological and clinical characteristics of a measles outbreak in Catalonia, Spain, in 2006. METHODS Data on cases of measles reported to the Department of Health, Generalitat of Catalonia, during the period 28 August 2006 through 8 July 2007 were collected. Suspected cases were confirmed by determination of measles-specific immunoglobulin M antibodies and/or detection of virus genome. Incidences were calculated using the estimated population of Catalonia for 2006, and 95% confidence intervals were determined assuming a Poisson distribution. The association between proportions was determined using the chi(2) test and Fishers exact test. The level of statistical significance was set at alpha = .05. RESULTS A total of 381 cases were confirmed, for an incidence of 6.6 cases per 100,000 persons. A total of 89.5% of cases occurred in nonvaccinated persons, mainly those aged < or =15 months (incidence, 278.2 cases per 100,000 persons; mean age of patients, 12 months). Indigenous subjects accounted for 89.8% of cases, and laboratory confirmation of results was obtained for 87.1%. Measles genotype D4 was identified in all sequenced samples. CONCLUSIONS The age distribution of cases of measles among children aged <15 months suggests that the first dose of vaccine should be routinely administered at the age of 12 months.

Hepatitis G virus infection in chronic hepatitis C: frequency, features and response to interferon therapy

BACKGROUND/AIMS The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the response to interferon therapy in this disease. METHODS HGV-RNA was investigated by reverse transcription-polymerase chain reaction in serum from 143 consecutive patients who received interferon alpha-2b (3 MU t.i.w.) for 24 weeks. Baseline features and response to therapy in HGV-infected and non-infected patients were compared. To assess the antiviral effect of interferon, serial quantitative measurement of HCV-RNA and HGV-RNA in serum was performed in patients co-infected with HCV and HGV. RESULTS Eight patients (5.6%) presented HGV-RNA sequences in serum. No significant differences were found between HGV-infected and non-infected patients in relation to age, sex, source of infection, liver function tests, liver histology and HCV genotype, nor in the biochemical response to interferon, which was sustained in 12% and 15%, transient in 37% and 30% and absent in 50% and 55% of HGV-infected and non-infected patients, respectively. HGV-RNA became negative in all treated patients, but sustained viral inhibition was observed only in those with low viral load. CONCLUSIONS The prevalence of HGV infection in HCV-infected patients is relatively low in our geographical area. HGV co-infection does not appear to modify the clinical presentation nor the response to interferon in chronic hepatitis C. HGV is sensitive to interferon, particularly if pre-treatment viral load is low.

Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of maternal pertussis antibodies to the newborn

BACKGROUND AND OBJECTIVES Pertussis is currently an emerging public health concern in some countries with high vaccination coverage. It is expected that maternal pertussis immunization could provide newborn protection. We compared pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and post-vaccination) with respect to levels in the newborn at delivery in women vaccinated during pregnancy. We also estimated anti-PT titers at primary infant vaccination. METHODS Observational study of pregnant women vaccinated with Tdap (≥20 weeks gestation) and their newborns between May 2012 and August 2013. Anti-PT levels were determined by ELISA in maternal (pre- and post-vaccination) and newborn blood. RESULTS Pre-vaccination, post-vaccination maternal and newborn samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3) years. Median weeks of gestation at vaccination were 27.2 (Q1-Q3 21.7-30.8). Anti-PT (≥10 IU/ml) levels were found in 37.1% of maternal pre-vaccination samples (geometric mean titer (GMT) 7.9 IU/ml (95% CI 6.8-9.2)), 90.2% of post-vaccination samples (GMT 31.1 IU/ml (95% CI 26.6-36.3)) and 94.7% of newborns (GMT 37.8 IU/ml (95% CI 32.3-44.1)). The Lin concordance index between post-vaccination maternal and newborn samples was 0.8 (95% CI 0.8-0.9). Transplacental transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated anti-PT levels ≥10 IU/ml. CONCLUSIONS There was a high correlation between anti-PT levels in mothers and newborns, with higher levels in newborns, which should be sufficient to provide protection against pertussis during the first months of life. Vaccination of pregnant women seems to be an immunogenic strategy to protect newborns until primary infant immunization.

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

BACKGROUND/AIMS Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment. METHODS ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). RESULTS After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p = 0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this time was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum. CONCLUSIONS A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.

Incidence of Non-A, Non-B Hepatitis after Screening Blood Donors for Antibodies to Hepatitis C Virus and Surrogate Markers

Abstract ▪Objective:To compare the effect of screening blood donors for antibodies to hepatitis C virus (anti-HCV) on the incidence of non-A, non-B hepatitis in recipients with that of screening bl...

Recombinant α2c-interferon therapy in fulminant viral hepatitis

Summary Recombinant α 2c -interferon was administered to 12 consecutive patients with fulminant viral hepatitis. The disease was caused by coinfection by HBV and HDV in seven patients, by HDV superinfection of a chronic HBV carrier in two, by HBV alone in two and by HAV in one. Eight patients were drug addicts. Interferon administration was initiated shortly after the onset of hepatic encephalopathy and no patient was in grade IV coma at the beginning of therapy. Ten patients died and only two survived. One of the survivors was an asymptomatic HBV carrier superinfected by HDV in whom treatment with interferon for 3 months did not prevent the development of chronic delta infection and liver cirrhosis. These results show that α 2c -interferon does not have significant therapeutic value in fulminant viral hepatitis, particularly if it is caused by HDV.