Israel Medical Association Journal

Background: Hepatis C virus infection is presently an exclusion criterion to classify SjoÈ gren's syndrome; however, there are distinct clinicopathologic and biologic similarities between HCV-related and SS-related chronic inflammation of mucosa-associated lymphoid tissue and lymphoproliferation that suggest common pathogenetic pathways.

Objectives: To determine whether a subset of patients with sicca syndrome and HCV infection may present a true primary SS rather than a distinct clinicobiologic entity.

Methods: We extensively characterized 20 consecutive patients with positive anti-HCV antibodies and heavy subjective dry eye and/or dry mouth symptoms, plus positive unstimulated sialometry and/or Shirmer's test. We then compared these features with those in HCV-negative primary SS controls (classified according to the latest American-European Consensus Group Classification Criteria for SS).

Results: Of the 20 HCV-positive patients with sicca manifesta-tions, 12 (60%) had positive anti-SSA/SSB antibodies (3/12 by enzyme-linked immunosorbent assay and 6/12 by immunoblot) and/or positive salivary gland biopsy (at least 1 focus/4 mm2), which met the strict classification criteria for SS, as in the case of HCV-negative SS controls. Comparing the HCV-positive SS subset with HCV-negative SS controls showed similar female to male ratio (11/1 vs. 46/4), major salivary gland swelling (17% vs. 26%), positive antinuclear antibodies (75 vs. 94%) and positive rheumatoid factor (58 vs. 52%). Significant differences (P< 0.05) were seen in mean age (69 vs. 56 years), liver disease (50 vs. 2%), lung disease (25 vs. 0%), anti-SSA/SSB positivity (25 vs. 90%), and low C3 or C4 (83 vs. 36%). HCV-positive SS patients exhibited a trend for more frequent chronic gastritis (50 vs. 22%), fibromyalgia (33 vs. 14%), peripheral neuropathy (33 vs. 18%), purpura (33 vs. 19%) and cryoglobulinemia (33 vs. 6%).

Conclusions: A major subset of HCV-positive patients with definite subjective sicca symptoms and positive objective tests may indeed present a true, though peculiar, subset of SS. There are strict similarities with key clinical, pathologic and immunologic findings of definite HCV-negative SS. Other features appear more characteristic of HCV infection. When also considering that HCV is sialotropic and may be treated, HCV-related chronic sialadenitis represents a unique opportunity to clarify key pathogenetic events occurring in the large majority of HCV-negative SS; and similarities to typical primary SS, rather than differences, should be taken into account.
 

Background: Nitrofurantoin is a commonly prescribed urinary antiseptic. Hepatic injury has been associated with its use.

Objectives: To present three patients in whom long-term exposure to the drug resulted in chronic active hepatitis, and review the epidemiology, clinical immunology, histopathology, pathogenetic features and treatment of previously reported cases.

Findings: Withdrawing nitrofurantoin once the diagnosis was suspected did not lead to remission of the liver disease and glucocorticoids had to be administered. One patient died of liver failure.

Conclusions: Awareness of this unusual side effect of nitrofurantoin is important and caution should be exerted before prescribing it. Over the past years new insight into the immune nature of this drug has emerged.
 

Background: Epidemiological studies in different parts of the world have revealed controversial results on the association between hepatitis C virus infection and non-Hodgkin’s lymphoma. This discrepancy suggests that HCV[1] lymphotropism or its effect on host lymphocytes may be influenced by regional and racial factors, as well as by genomic variations.

Objective: To determine the prevalence of HCV infection in patients with lymphoproliferative disorders diagnosed and treated in our institute in Israel.

Methods: A total of 212 consecutive patients (95 males and 117 females) treated in our hematology outpatient clinic between August 1997 and September 1999 was screened for anti-HCV antibodies and hepatitis B surface antigen. HCV infection was confirmed by the presence of HCV RNA in the serum. The prevalence of HCV in patients with lymphoproliferative disorders was compared to a control group of patients with myeloproliferative disorders and myelodysplastic syndromes.

Results: HCV infection was more prevalent in the group of LPD[2] patients than in the control group, but this finding was not statistically significant. The prevalence of HCV among LPD patients was 7.8%, while that in the group with myeloproliferative and myelodysplastic disorders was 1.19% and in the general population 0.64%. Among the different classes of LPD, a significant association with HCV infection was established only in patients with diffuse large B cell lymphoma. Furthermore, HCV infection was significantly more prevalent than HBV infection in the LPD group, but not in the myeloproliferative and myelodysplastic disorders group.

Conclusions: Our finding of a significant association between HCV infection and diffuse large B cell lymphoma leads us to suggest that anti-HCV antibodies be performed routinely in such subjects.  

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 [1]LPD = lymphoproliferative disorders

[2] HCV = hepatitis C virus

Mixed cryoglobulinemia is a systemic vasculitis described as a triad characterized by purpura, weakness and arthralgias. Since the first description of the disease in 1964 by Meltzer and Franklin our understanding of its pathogenesis has increased considerably. The striking association of the disease with hepatitis C virus infection was initially noted in 1990. Since then, the disease has gained growing attention among investigators involved in the study of autoimmune systemic disorders because it represents one of the most intriguing models of autoimmunity triggered by a virus. Nonetheless, a number of answered questions still remain to be resolved and are reviewed in this article.

Background: Previous data showed that new recombi­nant hepatitis B virus vaccine, which contains the S-protein component of the HBV surface together with the Pre-S₁ and Pre-S₂, is considerably more immunogenic than a second-generation recombinant I-IBV vaccine.

Objectives:To compare the immunogenicity and safety of a novel recombinant HBV vaccine S1, Pre-S₁ and Pre-S₂ protein components of the hepatitis B surface antigen - Bio­TM

Hep^TM 10 לg dose, to a licensed vaccine containing only the S-protein component - Engerix-B, 20 לg dose.

Methods: A prospective randomized study included 524 adults - 260 in the Bio-Hep group and 264 in the Engerix-B group. Both vaccines were administered in a three-dose regimen given at 0, 1 and 6 months, and adverse events were recorded on a diary card 5 days after each vaccination. lmmunogenicity was tested by measuring anti-hepatitis B surface antibody.

Results: One month after the third injection, 98% of the BioHep^TM subjects were found to be seroprotected vs. 85.1% of the Engerix-B group. In addition, the geometric mean titers were 2,203 mlU/ml and 326 mlU/ml in the Bio-Hep-B and Engerix-B groups respectively. An immunogenic advantage of Bio-Hep-B was suggested by the rapid onset of antibody response - 66.5% were seroconverted one month after the first injection as compared to 19.3% in the Engerix-B group. No unexpected adverse events were observed, and the recorded events were mild in both groups.

Conclusions: BioHepTM, a novel recombinant HBV vaccine containing 5, Pre-S₁ and Pre-S₂ protein components. at a lower dose, is safe and more immunogenic than the conventional HBV vaccine that contains only S protein.

Background: Hepatitis B is a major problem worldwide. Israel has intermediate endemicity for hepatitis B virus, and an annual carrier rate of 1-3%.

Objective: To evaluate both the prevalence of HBV infection among family members of HBV carriers and the competence of family practitioners in performing a compre­hensive assessment.

Methods: A total of 152 HB surface antigen-positive blood donors were discovered in our subdistrict during the years 1993-97. Their family physicians were questioned regarding the patients' family members. Specific information on 85 spouses and 200 children was also obtained.

Results: Among the 85 married carriers, 5 of the spouses (5.9%) were found to be HBsAg positive. None of the 200 children was HB5Ag positive. We found that in a third (n=52) of the patients, the sexual partner had never been tested by a primary care physician. Patients were not routinely tested for HB e antigen or anti-HBe antibodies. Neither the parents nor the siblings had undergone any serological evaluation. How­ever, most family members of the carriers had received an HBV vaccine from their family physicians.

Conclusions: Our findings show that horizontal transmis­sion of HBV among spouses of HBV carriers still exists. We did not find any vertical transmission, probably due to male predominance and previous vaccination. Family physicians should be trained to perform an extensive serological evalua­tion of family members of patients with chronic HBV infection, including parents and siblings, and should vaccinate sero­negative family members.

Background: Between 1970 and 1979, there was an increase in the incidence of viral hepatitis in Israel with a shift of peak incidence to an older age in the Jewish population, followed by a declining trend during the early 1980s. In July 1999 universal immunization of infants against hepatitis A was introduced.

Objective: To evaluate the chan-ges in the epidemiology of viral hepatitis A in Israel during the past decade.

Methods: Viral hepatitis is a notifiable disease in Israel and cases are reported to the regional health offices, which in turn provide summary reports to the Ministry of Health's Department of Epidemiology. The data in this study were derived from the summary reports and from results of seroprevalence studies.

Results: Following the increase in the incidence of reported viral hepatitis (mainly due to type A) between 1970 and 1979, the rates then stabilized and around 1984 began to decline until 1992. Since then there has been a slight increase. Whereas until 1987 the rates were consistently higher in the Jewish population. since then they are higher in the Arab population. The shift in the peak age-specific incidence from the 1-4 to the 5-9 year age group observed in the Jewish population around 1970 occurred 20 years later in the Arab population. The previously described seasonality is no longer evident. Recent seroprevalence studies indicate that by age 18 years only about 30-40% of the Jewish population have anti-hepatitis A antibodies.

Conclusions: The decline in the incidence of hepatitis probably reflects the changing socioeconomic condition occurring at different times in the two major population groups. Since hepatitis A accounts for almost all the acute viral hepatitis in Israel, the universal vaccination of infants introduced in 1999 should substantially lower the morbidity within the next few years.

The hepatitis C virus is an enveloped positive-sense single-stranded RNA virus, which has been classified into 6 major genotypes and over 100 subtypes. HCV replicates mainly in the hepatocyte. Recently, infectious HCV cDNA clones have been generated. Despite evidence that innate and adaptative humoral and cellular immune responses are activated as part of an antiviral defense, HCV has a remarkable ability to establish persistent infection. The analysis of viral kinetics using mathematical modeling shows a relative steady state without treatment, while an immediate biphasic HCV decline occurs in blood during successful treatment, the latter being predictive of clearance of HCV by the end of treatment.

Background: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy.

Objectives: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population.

Methods: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay.

Results: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02).

Conclusions: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, lb being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.