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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.

Hepatitis B virus (HBV) reinfection is a major threat to HBV-infected patients undergoing orthotopic liver transplantation. Eleven HBsAg-positive patients with end-stage liver disease underwent liver transplantation. All were treated with high doses of anti-HBs antibodies, initiated first during the anhepatic stage of the operation and continued every 2-8 weeks thereafter according to anti-HBs levels in the serum. Attempts were made to keep anti-HBs levels above 400 IU/ml. Patients were followed for 8-42 months and only one of them had any evidence for recurrence of HBV infection 40 months post-transplantation. We conclude that continuous administration of anti-HBs and maintenance of high levels of anti-HBs in the serum prevent recurrence of HBV infection.

In order to study the asymptomatic hepatitis C virus (HCV)-positive blood donors in Israel we analyzed their sera for HCV-RNA using the polymerase chain reaction technique. We found that 0.44% of blood donors were anti-HCV positive. Of those who had repeatedly positive anti-HCV, 82% had evidence of HCV-RNA. One-third of them had elevated liver enzymes, but no detectable cryoglobulins were found in their sera. Although HCV-RNA was detected in the majority of the patients, we were unable to demonstrate vertical or horizontal transmission among the family members of our carrier population.

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.

A total of 471 Israel Defense Forces (IDF) blood donors identified as hepatitis B virus (HBV) carriers were examined a few months after blood donation. When compared to the general population of IDF blood donors the HBV carriers were older, belonged to certain ethnic groups and were predominantly males. Physical examination revealed minimal findings: 1 (0.3%) had splenomegaly and 5 (1.6%) had hepatomegaly. Fifty-two individuals (11.1%) had elevated liver enzymes. E antigen was present in 3.2% of HBV carriers, 94% had anti-e antibodies and 1.9% had anti-delta antibodies. Of 258 carriers tested for HBV DNA, 29 (11.2%) were positive. Abnormal liver enzymes were significantly associated with the presence of e antigen as well as with the presence of HBV DNA.

Chlorpromazine-induced liver damage is usually manifested by intrahepatic cholestasis. Hypoplastic bone marrow associated with agranulocytosis is a well-known side effect of chlorpromazine treatment. A 35-year-old woman with liver and bone marrow granulomas associated with agranulocytosis induced by chlorpromazine treatment is described.

An analysis of the etiology of acute viral hepatitis in 172 hospitalized patients showed that 70.9% suffered from hepatitis A (HA), 12.2% from hepatitis B (HB), 1.7% from infectious mononucleosis and 15.1% (26 cases) from non-A, non-B hepatitis. Patients who had received blood transfusions during the 6 mo preceding the onset of the disease were not included in the present survey. The male:female ratio in the patients with non-A, non-B hepatitis was 1:88; 73% were Ashkenazic and 27% non-Ashkenazic Jews. The ethnic distribution of patients with non-A, non-B hepatitis was similar to that of patients with HA but differed from that of HB patients (only 41% Ashkenazic). Thirty-eight percent of the non-A, non-B group had had contact with jaundiced patients during the 6 mo preceding the onset of the disease, and 46% were students or soldiers. The clinical course of the disease was, on the whole, milder than that of HB and similar to that of HA. Since many cases of non-A, non-B hepatitis are anicteric, it is concluded that the disease is a significant problem in Israel.

Two patients with sublingual thyroid glands and hypothyroidism since childhood are described. Because of enlargement of the sella turcica both were erroneously diagnosed as having primary pituitary tumors resulting in secondary hypothyroidism. One of the patients was even treated with pituitary gland irradiation. Following substitution thyroid therapy, thyroid-stimulating hormone (TSH) levels promptly returned to normal. Ectopic thyroid glands, which are often incapable of adequate hormonogenesis, may cause secondary pituitary enlargement and lead to the suspicion of a pituitary adenoma. The correct diagnosis can easily be established by measuring serum TSH levels, which are elevated in the former condition.

Left ventricular (LV) size and function were studied by echocardiography and measurement of systolic time intervals in 14 patients with liver cirrhosis. There was a small increase in LV end-diastolic dimension, and an increase in systolic ventricular performance, calculated stroke dimension and stroke and cardiac indices. Mean blood pressure was low normal. Preejection period was shortened and the preejection period/LV ejection time ratio, decreased. The data indicate that patients with liver cirrhosis have mild LV enlargment, reduced peripheral resistance and an increase in mesurements of systolic LV performance.

A study of 90 asymptomatic hepatitis B surface antigen (HBsAg) carriers in Jerusalem showed a predominance of males over females (4:1) and of North African Jews over Jews of European or American Origin. The predominance of males remained apparent, but was not significant, when origin was controlled. Possible sources of infection were contact with jaundiced patients (29%), dental treatment (58%) and drug addiction (8%). Fifty-one percent had hepatitis B core antibody (anti-HBc) of the IgM class, 2% had hepatitis B e-antigen (HBeAg), 94% hepatitis B e-antibody (anti-HBe) and 93% had hepatitis A antibody (anti-HAV). Fourty-two percent had donated blood at least once prior to the detection of the carrier state. Fifty-five percent of 128 asymptomatic family contacts had evidence of hepatitis B virus infection. Minor abnormalities in liver function tests were found in 22% of the carriers and splenomegaly in 11%. Of ten liver biopsies performed in these cases, one had chronic active hepatitis, five had minimal histological changes, and four were normal.