Pregnancy and liver transplantation.
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Biomedical subjects
Publications and source records attributed to Y Ashur.
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A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.
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A 54-yr-old man underwent orthotopic liver transplantation for cirrhosis caused by hepatitis C virus and associated with cryoglobulinemia and proteinuria. Four months after transplantation, the patient was reinfected with hepatitis C virus and cryoglobulinemia recurred, accompanied by increasing proteinuria, ascites, and pleural and pericardial effusion. Serum cryoglobulins and pleural and pericardial effusion disappeared rapidly following treatment with ribavirin, whereas proteinuria remain unchanged. We believe that pericardial effusion is an unusual presentation of hepatitis C virus-associated cryoglobulinemia.
Hepatitis C virus (HCV) has nucleotide sequence diversity distributed throughout the viral genome, with variants showing even less than 70% homology. There is some evidence that sequence variation of HCV genotypes partly determines the course of infection and response to treatment with interferon. We studied the sera of 29 Israeli HCV patients, all suffering from chronic liver disease, and 34 patients with renal failure necessitating hemodialysis. HCV genotypes were detected using a reverse hybridization assay (LiPA), after reverse transcription polymerase chain reaction, using primers spanning the 5' UTR of the HCV genome. In this preliminary report the predominant HCV type detected was type 1, found in 65% of the chronic hepatitis patients and in 88% of the hemodialysis patients. Subtype 1b was the most prevalent and was detected in >40% of the chronic hepatitis patients and in >70%of the dialysis patients. Other types detected were 2a and 3, and in only two patients was type 4 found. More than 50% of patients with type 1 (1a or 1b) among patients with chronic hepatitis had received blood transfusion in the past, but only 16.6% of patients bearing subtype 2a HCV had such a history. Our preliminary evaluation revealed that patients bearing subtype 1b seemed to have a better response to interferon treatment, as compared with patients infected with subtypes 1a, 2a, who displayed a low response rate.
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Mixed cryoglobulinemia is a well-known complication after hepatitis C virus (HCV) infection. We report five cases in which cryoglobulinemia appeared or grossly exacerbated following orthotopic liver transplantation (OLT). Cryoglobulinemia and the associated clinical symptoms resolved or improved in two patients treated with ribavirin after liver transplantation, while plasmapheresis was ineffective in another patient. The mechanism involved in induction of cryoglobulinemia after liver transplantation is unknown. However, the effect of antiviral therapy observed in these patients suggests a correlation between cryoglobulinemia, HCV replication, and possibly hepatocellular disease activity. A larger-scale study is warranted to test the effect of ribavirin on post-OLT HCV-associated cryoglobulinemia.
Orthotopic liver transplantation (OLT) is widely practised in developed countries. The procedure is costly, the supply of donor organs limited, and it is not known how many patients need transplantation. A community-wide estimate of the needs for OLT was performed over two years in all general hospitals in Israel. Records of 1851 patients with liver disease were screened to identify those who might eventually need OLT. The annual estimate of transplantation needs in the country was 10-15.5 per million population, with equal numbers of males and females. The addition of patients with nonreformed alcoholism and end-stage liver disease, originally set as an exclusion criteria, would have added 20% to this estimate. 37% of potential candidates were under 40 years of age at diagnosis, and about 50% were 55-64 years old. Almost 80% of patients had cirrhosis of the liver and 13.6% had fulminant hepatitis. These findings provide a basis for a national plan of OLT in Israel, and similar studies might be useful in other countries.
The prevalence of hepatitis C virus (HCV) infection in patients with chronic liver disease (CLD) in Israel has not yet been reported. A retrospective analysis was performed on the first 92 consecutive patients referred to our Liver Unit with serologically confirmed antibodies to hepatitis C virus (anti-HCV) who had evidence for chronic hepatitis, cirrhosis, and hepatocellular carcinoma. We compared 31 patients who were anti-HCV positive with 61 patients who had evidence for both previous or present infection with hepatitis B virus (HBV) as well as HCV. Dual infection was significantly more prevalent in Jewish patients of non-Ashkenazi origin, who were also characterized by higher rates of portal hypertension manifested by ascites, bleeding esophageal varices as well as hepatic encephalopathy and spontaneous bacterial peritonitis. We conclude that dual infection of HBV and HCV was found in 66% of patients with anti-HCV positive liver disease in Jerusalem, and that these patients develop more serious complications than CLD patients with anti-HCV alone.
OBJECTIVE: To evaluate the role of IgA in hepatitis C virus (HCV) infection. We have tested serum IgA levels in patients with antibodies to HCV. DESIGN: A retrospective study. PATIENTS: The IgA levels were tested in serum samples from 94 patients with antibodies to HCV examined during 1989-1990. RESULTS: Low IgA levels were found in 16/94 (17%) patients. In three of these 16 patients (3.2% of the original 94), no IgA was detected by radial immunodiffusion. In nine of 16 patients, previous pre-HCV infection serum samples with undetectable anti-HCV antibodies were available. In four of these nine patients, IgA deficiency was found in the preinfection serum, while in the remaining five patients, previous IgA levels were normal and the occurrence of anti-HCV was associated with the recent development of IgA deficiency. CONCLUSIONS: The results of this study indicate that IgA deficiency is a risk factor for HCV infection in some patients, whereas in others it might be caused by the viral disease.
Pre- and postexposure prophylaxis against hepatitis A virus (HAV) infection with immune serum globulin (Ig) is only effective for 4-6 months. We compared the safety, tolerability and immunogenicity of a single i.m. injection of Ig with a single and booster dose of an inactivated hepatitis A virus vaccine (iHAV) in adults. Healthy volunteers (18-50 years) received a single Ig i.m. injection (n = 30), or iHAV i.m. (n = 15) at 0 and 24 weeks, or placebo (n = 4) at the same intervals. Anti-HAV seroconversion was measured by radioimmunoassay (RIA) and neutralizing antibodies by an antigen reduction assay. After Ig injection (0.06 ml/kg), anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12 and 0% by week 20. In contrast, after a single 25 ng dose, RIA seropositivity in iHAV vaccinees was 80% by week 2, reaching 100% by week 5 and persisted up to week 24, at which time anti-HAV geometric mean titres (GMT) were two fold higher than those seen at week 1 after Ig. Postbooster anti-HAV titres in iHAV recipients rose within 4 weeks to 73-fold greater than the peak GMT seen one week after Ig, and 400-fold higher than GMT at 12 weeks after Ig. Neutralizing antibody titres after iHAV followed a similar pattern, as observed for anti-HAV. iHAV was well tolerated; placebo and vaccine tolerability were indistinguishable, with no serious adverse experiences observed. In conclusion, active vaccination with a single iHAV dose may eventually replace Ig for pre-exposure prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerability, and immunogenicity of a single i.m. injection of IG with single and booster doses of an inactivated hepatitis A virus vaccine (iHAV) in adults. A total of 75 healthy volunteers (aged 18-50 years) were evaluated in two separate studies. The first included 15 volunteers who received 25 units iHAV i.m. at 0 and 24 weeks. The second, a randomly controlled study, consisted of three groups receiving 25 units iHAV i.m. at 0, 1, and 6 months, or at 0, 2, and 6 months, or 0.06 ml/kg IG i.m. given once. Anti-HAV seroconversion was measured by radioimmunoassay (RIA). After IG injection, anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12, and 0% by week 20. In contrast, after a single 25-unit dose, RIA seropositivity in iHAV vaccines was 73% by week 2, reaching 100% by week 5, and persisted in all up to week 24, at which time anti-HAV geometric mean titers (GMT) were 2-fold higher than those seen at week 1 after IG. Administration of a booster dose given 1 or 2 months after primary immunization did not significantly improve the quantitative anti-HAV response at 6 months as compared to the effect of the primary dose.(ABSTRACT TRUNCATED AT 250 WORDS)