Emanuel Sikuler

Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome.

Objective: To examine the impact of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on pregnancy outcomes.

Hepatitis B and C viruses serology in patients with SLE.

Sera of 95 patients with SLE were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibodies. The results show that HBsAg was not detected in the sera of all of the SLE patients. Only one patient was confirmed to have anti-HCV antibodies, suggesting that chronic infection with hepatitis B and C is not increased in patients with SLE compared with the general population.

Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies

The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti‐HCV and HCV‐RNA. In addition, HCV genotype and HCV viral load were determined in HCV‐RNA‐positive sera. Anti‐HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV‐RNA‐positive. Among the 267 HCV‐seronegative dialysis patients, 25 (9%) were found to be HCV‐RNA‐positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV‐seropositives. In contrast, in the Liver Clinic patients, HCV‐RNA was found exclusively in HCV‐seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference.  Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.

HCV antibodies in saliva and urine

Infection with hepatitis C virus (HCV) is usually established by detection of serum antibodies (anti‐HCV). This study was conducted in order to evaluate whether saliva and urine may substitute serum for anti‐HCV detection. Serum, saliva, and urine were obtained simultaneously from 141 patients with a variety of liver diseases and from 52 patients with autoimmune diseases (systemic lupus erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of saliva and urine samples was tested for anti‐HCV using a modification of a serum anti‐HCV kit. Western blot analysis was used as a confirmation method. Of the patients with liver diseases, 73 were anti‐HCV‐seropositive. Salivary and urinary anti‐HCV could be detected in 66 (90%) and 36 (49%) of the anti‐HCV‐serpositive patients, respectively. The presence of anti‐HCV in saliva or urine was not related to the severity of liver disease. All the anti‐HCV‐seronegative liver patients were negative for salivary anti‐HCV and 22 (32%) had urinary anti‐HCV. The patients with autoimmune diseases were all anti‐HCV‐seronegative. None had detectable salivary anti‐HCV while 33 (63%) were positive for urinary anti‐HCV. Western Blot analysis confirmed the presence of anti‐HCV in all serum and saliva samples tested but only in 2/12 urine samples. The results suggest that saliva, but not urine, may serve as a substitute for serum for the determination of anti‐HCV positivity. J. Med. Virol. 55:24–27, 1998.

Hepatitis C virus infection and genotypes in Southern Israel and the Gaza strip

The Gaza Strip borders the southern part of Israel and Egypt. There is a remarkable difference in the prevalence of antibodies to hepatitis C virus (HCV) between Israel (0.5%) and Egypt (10%). A few thousand inhabitants cross the borders daily from the Gaza Strip to both countries. The objectives of this study were to investigate the prevalence of HCV infection in the Gaza Strip, an area that was not studied before, and to study HCV transmission in the Gaza Strip by characterizing the genotypes of HCV in Southern Israel and the Gaza Strip and comparing them with those found in Egypt. HCV prevalence in the Gaza Strip was found to be 2.2%, relatively higher than in Israel but lower than in Egypt. The most common genotypes found were type 1b in Southern Israel and type 4 in the Gaza Strip, corresponding to the most prevalent genotype in Egypt. Similarity between type 4 isolates from the Gaza Strip and Egypt was illustrated further by sequence analysis of the HCV 5′ noncoding region (NCR). J. Med. Virol. 56:230–233, 1998.

Hemodynamic effects of hypothyroidism induced by methimazole in normal and portal hypertensive rats.

Portal hypertension is accompanied by a hyperdynamic circulatory state that shares some similarities with thyrotoxicosis. This study was conducted in order to investigate the hemodynamic effects of hypothyroidism in a rat model with portal hypertension induced by partial portal vein ligation (PVL). Four groups of 10 rats each were studied: normal control and hypothyroid rats, and PVL control and hypothyroid rats. Hypothyroidism was induced by methimazole 0.04% in drinking water. Hemodynamic measurements were performed using the radioactive microsphere technique. Induction of hypothyroidism was confirmed by elevated TSH levels. In the PVL groups, hypothyroidism ameliorated the hyperdynamic circulation. Portal venous inflow and portal pressure dropped significantly: 7.1±0.2 vs 4.8±0.3 ml/min/100 g body wt (P<0.01) and 13.4±0.9 vs 10.9±0.8 mm Hg; (P<0.01), respectively. In normal rats, hypothyroidism was manifested by a hypodynamic circulatory state. These results demonstrate that hypothyroidism induced by methimazole is followed by amelioration of the hyperdynamic circulation, normalization of portal venous inflow, and reduction of portal pressure.

The Effects of Hypothyroidism on Liver Status of Cirrhotic Patients

We have shown, in animal models as well as in retrospective human study, that some degree of decreased thyroid function is beneficial for subjects with liver damage of various etiologies. Therefore, we herein present the results of a cohort population study. Between 1991 and 1994, 18 patients (12 women and 6 men; mean age, 59 ± 24 years) with both biopsy-proven active cirrhosis (5 hepatitis C virus, 4 hepatitis B virus, 1 immunocompromised host, 2 primary biliary cirrhosis, 1 alcoholic, and 5 cryptogenic; Childs-Pugh criteria: A-8, B-8, C-2) and primary or induced (by either drug or surgery) thyroxine-treated hypothyroidism were prospectively followed. Each patient was examined at least twice yearly and served as their own control. The thyroid of the profiled patients ranged between euthyroidism and subclinical hypothyroidism. Liver function tests were evaluated and compared in states of normal versus increased thyroid-stimulating hormone (TSH) blood levels. A significant improvement in alanine aminotransferase (p < 0.001), alkaline phosphatase (p < 0.0001), albumin (p < 0.001), and bilirubin (p < 0.01) was found in the increased TSH group. Prothrombin time was also found to be significantly better (p < 0.001). We conclude that euthyroid patients with liver cirrhosis might benefit from a controlled hypothyroidism.

Autoimmune Hepatitis in a Genetically Susceptible Patient (Is It Triggered by Acute Viral Hepatitis A

The pathogenic mechanisms for autoimmune hepatitis (AIH) are not completely known. Susceptibility to AIH is associated with the human leukocyte antigens (HLA) class II: DR3 and DR4. Nevertheless, AIH does not have a strong genetic predisposition, suggesting that other factors are involved. Perhaps the strongest evidence of a viral cause for AIH exists for hepatitis C virus. AIH has been reported to develop rarely after acute infection with hepatitis A virus. We report on a 55-year-old woman in whom AIH developed during the convalescence period of serologically proven acute viral hepatitis type A. HLA class II DRB1*0401, which was reported to be associated with AIH with a moderate coarse and late appearance in life, was found in this patient. Steroid therapy was followed by a complete clinical remission. Our case supports the possibility that acute hepatitis A may trigger the development of AIH in a genetically susceptible subject.

Hepatitis C virus infection and extrahepatic malignancies

An association between chronic hepatitis C (HCV) infection and non-Hodgkins lymphoma has been reported. We carried out this study to evaluate the possibility of an association between HCV infection and other extrahepatic malignancies. The medical records of 103 unselected, consecutively chosen, anti HCV-positive and 105 hepatitis B surface antigen (HBsAg)-positive patients attending the liver clinic or hospitalized in the Department of Medicine were reviewed. Patients in whom anti-HCV positivity was detected after the malignancy was diagnosed were excluded. Malignancy rates in the general Israeli population were obtained from the Israeli cancer registry. The ages of anti-HCV-positive and HBsAg-positive patients were 54 +/- 16 (+/-SD) (range, 15-84) and 45 +/- 12 (range, 20-78) years, respectively; the male/female ratios were 50/53 and 73/32, respectively. Extrahepatic malignancies were found in 15 (14.6%) of the anti-HCV and in three (2.9%) of the HBsAg-positive patients. Thirteen of the malignancies were found among the 60 anti-HCV-positive patients aged > or =55 years old. Only one malignancy was found among the 28 HBsAg-positive patients of the same age group (p < 0.01). The rate of extrahepatic malignancies in these HCV-infected patients was significantly higher (p < 0.01) than expected in the general population. An association between HCV infection and extrahepatic malignancy may exist, but further prospective studies, including a large number of patients with HCV infection, will be necessary to define this observation.

Iatrogenic Transmission of Hepatitis C Virus (HCV) by an Anesthesiologist: Comparative Molecular Analysis of the HCV-E1 and HCV-E2 Hypervariable Regions

BACKGROUND Transmission of hepatitis C virus (HCV) from infected health care workers to patients rarely occurs. In 2003, a cluster of patients with HCV infection was identified at a medical center in Israel. All patients had a common history of various surgical procedures performed during the period 2001-2003. All patients had been anesthetized by an anesthesiologist who was an injection drug user and was infected with genotype 2a HCV. Screening was initiated by the hospital to identify newly infected patients with HCV infection and to determine the source of the iatrogenic HCV infection outbreak using comparative molecular analysis of the HCV E1 and HCV E2 hypervariable regions (HVR1 and HVR2). METHODS A total of 1200 patients who were anesthetized by the anesthesiologist (the related group) and 873 hospital personnel and patients anesthetized by other anesthetists (the unrelated group) were examined. Serum samples were screened for anti-HCV antibodies, HCV RNA, and genotype. Sequence analysis of HVR1 and HVR2 was performed after reverse-transcriptase polymerase chain reaction. RESULTS HCV type 2a was found in 33 patients in the related group but in only 1 patient in the unrelated group. The differences between the sequences isolated from the related group serum samples and the sequences isolated from genotype 2a control group serum samples (obtained from 15 patients) were highly statistically significant. The genetic distances from the anesthesiologist sequence were 1.4%-4.4% in the HVR1 and 0%-3% in the HVR2 in the related group serum samples, whereas in the HCV genotype 2a control group serum samples, the genetic distances were 22%-45% and 10%-35%, respectively. CONCLUSIONS Molecular analysis revealed sequence similarity of HVR1 and HVR2 in the related group, suggesting that the anesthesiologist with chronic HCV infection may have transmitted HCV to 33 patients.