Introduction of Routine Hepatitis Immunization in Israel 

Emilia Anis, Alex Leventhal, Malvina Roitman, Paul E. Slater 

Notification of hepatitis A, which is endemic in Israel, has been compulsory since the establishment of the State. From 1992-98 an average of 2,600 cases were reported annually. Many infections are asymptomatic and mild, especially in children. In general, severity increases with age; in Western countries the case fatality rate is 1.5/1,000 among children less than 5 years old and 27/1,000 among those over 50. Until 1987 incidence in Israel was higher in Jews than in non-Jews, but since 1988 incidence has been about 50% higher in non-Jews.

Among Jews highest age specific rates shifted from children 1-4 years old to children 5-9 years old in 1970, and in non-Jews in 1989. Improved sanitary conditions and personal hygiene have reduced very early childhood exposure and hence increased the proportion of susceptible older children and adults, in whom symptomatic disease is more prevalent.

Israel is the first country in the world to include hepatitis A vaccine in its routine immunization schedule. The vaccine is given in 2 doses: at 18 months and 24-30 months of age, and there will be epidemiologic and serologic follow-up. A significant decrease in hepatitis A morbidity is expected in small children within 5 years. The percentage of reported cases in older children and in adults is expected to increase, although the absolute incidence among these groups will decrease.
 

Dept. of Epidemiology and Public Health Services, Israel Ministry of Health, Jerusalem

Does Incidence of Hepatitis AIncrease During Shmitah (The Sabbatical Year)?

Zvi Ackerman, Ita Goldstein, Elizabeth Ackerman

Depts. of Medicine, Hadassah University Hospital, Mount Scopus; Bikur Holim Hospital; Hebrew University-Hadassah Medical School; and Pediatrics Dept., Kupat Holim, Jerusalem

In Israel the biblical injunction of the sabbatical year (shmitah) prevails, whereby all Jewish-owned land should lie fallow during every seventh year. Consequently, it is customary for members of the orthodox Jewish community to eat only produce grown by non-Jews (Arabs). Many Arab farmers use sewage water for irrigation and since such water could be infected with hepatitis A virus (HAV), there is concern about the possibility of HAV epidemics during the sabbatical year.

We therefore we examined the data of the Israeli Center for Disease Control (ICDC). We found no obvious increase in incidence of viral hepatitis during, nor in the year immediately after, all sabbatical years since 1951. However, the data was not comprehensive as it included only partial information on morbidity from HAV in our Jewish inhabitants. Also, there was no data specific for the orthodox Jewish community, which is especially at risk for HAV from sewage-irrigated vegetables. Irrespective of shmitah, there should be constant effort to prevent HAV infection in Israel.

Acute and Chronic Hepatitis C in Hemodialysis Patients 

Nir Hilzenrat, Marcus Mostoslavsky, David Tovbin

Liver Disease Service - Division of Gastroenterology, Dialysis Unit, Dept. of Nephrology and Division of Internal Medicine, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba

Acquired infection with hepatitis C virus (HCV) in hemodialysis patients has been described lately. In dialysis units in Italy and France, the prevalence and incidence of HCV are 20-60% and 1-2%, respectively. Most infected patients develop chronic hepatitis. The clinical presentation of acute HCV in hemodialysis patients is very mild and therefore the diagnosis is often made only by laboratory tests. Acute infection is usually followed by mild elevation of liver enzymes and the presence of HCV-RNA and anti-HCV in serum.

We report a 48-year-old man on hemodialysis who developed acute hepatitis C. The diagnosis was made by finding mild elevation of liver enzymes and the presence of HCV-RNA in his serum. A few months later, he developed severe hepatitis which was followed by rapid deterioration in liver function. However, the virus was eradicated and liver function tests became normal. Surprisingly, serum anti-HCV antibodies were detected 5 months later.

Transarterial Oil Chemoembolization for Hepatocellular Carcinoma 

Izhar Levy, Anthony Verstandig, Talia Sasson, Dana Wolf, Ilia Krichon, Eugin Libson, Pinchas Levensart, Orit Papo, Oded Yurim, Ahmed Id, Daniel Shouval

Division of Medicine, Liver Unit and Invasive Radiology, Radiology, Pathology and Surgery Depts., Hadassah University Hospital, Ein Kerem, Jerusalem

Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis. Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver transplantation or hepatectomy are considered the only curative procedures, but can be applied in fewer than 10% of patients. In recent decades the most common treatments of HCC are transarterial chemoembolization with oil (TOCE) and percutaneous ethanol injection (PEI). We summarize our retrospective study of 100 patients (mean age 64) 3‏ treated by TE.

In 271 procedures between 1989-1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in 36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median survival for the 100 in the entire group was 19 months (10.9 months in those with conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in stages 2 or 3 was 30.1 months and 10.9 months, respectively (p<0.0001). Of the 57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated only by TOCE (median survival 15 and 26 months, respectively, p not significant).

Comparing Okuda 1 patients treated by TOCE only with the natural history of the disease and historical controls (Okuda 1 patients treated conservatively in 1984) median survival was 26 and 10 months respectively (p<0.001). The side effects of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and quality of life was maintained. Despite progress in the treatment of HCC by TOCE, PEI, and liver transplantation, long-term survival has remained unsatisfactory.

Low Prevalence of Hepatitis G Infection in Dialysis Patients

Doron Zamir, Shimon Shtorch, Chen Zamir, Zvi Fireman, Hilkiau Zonder

Internal Medicine Dept. A, Liver Clinic, Dialysis Unit and GI Unit, Hillel Yaffe Hospital and Hadera Subdistrict Health Office

Prevalence of hepatitis G virus (HGV) infection in the general western population ranges from 0.2-1.5%. In high-risk groups, such as patients with chronic liver disease, hematologic disorders and drug addicts, prevalence is as high as 10%-15%. Dialysis patients have increased rates of HGV infection (6%-50%).

We evaluated prevalence of HGV infection among dialysis patients, and the association between HGV infection and hepatitis C virus (HCV) infection. Serum samples were screened for HGV infection by RT-PCR. Screening for HCV infection was performed by an EIA test and confirmed by RIBA and RT-PCR for HCV. Sera were also tested for HBV markers.

The study group included all 78 hemodialysis patients and 7 of the 12 peritoneal dialysis patients in our unit during September to November 1997. 4 (5.2%) were HGV-positive but none were peritoneal dialysis patients. 1 of the 12 HCV-positives was also infected with HGV. HGV infection was not associated with duration of dialysis, number of blood transfusions or levels of transaminases.

Prevalence of HGV infection among our hemodialysis patients was low (5.2%), but higher than reported for the general population. Prevalence of HGV/HCV infection in hemodialysis patients was low and unrelated to duration of dialysis, number of blood transfusions and levels of transaminases.

EBV-Related Post-Transplantation Lymphoproliferative Disorder

D. Doron, O. Papo, O. Portnoy, E. Granot

Depts. of Pediatrics, Pathology, and Radiology, Hadassah University Hospital, Jerusalem

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Neurological Manifestations of Non A-G Viral Hepatitis

Rifaat Safadi, Yaron River, Yosef S. Haviv, Yaron Ilan

Liver Unit, Division of Medicine and Neurology Dept., Hadassah University Hospital, Jerusalem

Guillain-Barre and other neurologic syndromes rarely occur as complications of viral hepatitis (A, B and C). Other neurologic syndromes have also been reported in serologically defined viral hepatitis, including mononeuritis, auditory neuritis, and seizures. Chronic hepatitis B and mononeuritis multiplex are found together in 31-54% of patients with periarteritis nodosa. The mechanisms of these associations are unknown, but may include direct cytotoxicity of the virus or immune-mediated damage. Vasculitis of the vasa nervorum plays an intermediate role, at least in some cases. We describe a 36-year-old man with acute non A-G hepatitis complicated by Guillain-Barre syndrome. The neurological manifestation resolved completely without specific therapy within 6 days, as the hepatitis resolved.

Liver Surgery - Five Years of Experience

Franklin Greif, Moshe Rubin, Eitan Mor, Israel Nudelman, Arnold Sihon, Arie Figer, Alex Belinki, Shlomo Lelcuk

Hepatobiliary Unit and Depts. of Surgery B, Transplantation, Oncology and Radiology, Rabin Medical Center (Beilinson Campus) and Sackler School of Medicine, Tel Aviv University

Major hepatic resections have been associated with significant morbidity and mortality. In the past decade or so this has changed and such procedures are now done in increasing numbers. In the past 5 years we operated on 129 patients with benign or malignant hepatic lesions (75 females, 54 males; age-range 14-84). the reason for surgery was malignancy in 94 (72.9%) and benign lesions in 35 (27.1%). The most common indication for surgery was liver metastases secondary to colorectal cancer in 45% of all patients or 61.7% of those operated for malignancy. Primary liver cancer was the cause for liver resection in 13.2% of all patients or 18.1% for those with malignancy. Of the 35 patients with benign lesions the leading causes for surgery included: giant cavernous hemangioma, simple liver cysts, echinococcus cysts and focal nodular hyperplasia (11%, 22.8%, 20% and 14.3%, respectively).

76 patients underwent anatomical resection and 63 had either a nonanatomical resection or a different operation. Among the former the most common procedure was right hepatectomy (36) and among the later a nonanatomical resection equal to 1-3 Couinod segments (44). Operating time ranged from 55 min. to 8:41 hours with a mean of 3:31‏1:37. Mean hospital stay was 8.7‏5.8 days and 86.8% received between 0-2 units of blood. Overall mortality was 6.2% and 31.2% of the fatalities had cirrhosis. Overall mortality in noncirrhotic patients was 2.6%. The complication rate was 16.3% and only 7 patients (4.4%) were hospitalized in the intensive care unit. This indicates that major liver resections can be done safely, with morbidity and mortality similar to that of other major abdominal operations. 

Is Official Data on Reported Morbidity Valid? Hepatitis A in Israel as an Example

Yehuda Lerman, Gabriel Chodik, Hava Aloni, Shai Ashkenazi

Occupational Health and Rehabilitation Institute, Ra'anana, Schneider Children's Hospital, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University

Hepatitis A is one of the most frequently reported notifiable infectious diseases in Israel. The annual incidence as reported is around 70/100,000. The physician or the diagnostic laboratory notifies the district health office of the Ministry of Health.

The purpose of this research was to evaluate the sensitivity of passive surveillance of hepatitis A morbidity among adults, 18 years and over. Methods included study of notifications to the Ministry of Health or hospitalizations of cases of hepatitis A and of positive laboratory tests results (IgM) for hepatitis A. We estimated the extent of under-reporting by 2 different methods of extrapolation.

Data based on passive surveillance among the adult population, between 1.1.1993-31.12.1994, comprised less than 1/5 of the actual number of cases. Physicians notified about 6.2% of their hepatitis A patients. 5.1% of the notifications to the district health office were sent twice or more, usually both by the physicians and labs.

The official data on hepatitis A morbidity, based on passive surveillance, are considerably underestimated. Physicians and public health officials should be aware that such data may not accurately reflect the magnitude of the risk or the amount of disease that can be prevented. Efforts should be made to improve this situation.

Multisystem Disease Caused by BCG Imitating Miliary Tuberculosis

I. Tsikonov, D. Yeshurun, J.E. Naschitz

Dept. of Medicine A, Bnai Zion Medical Center and B. Rappaport Faculty of Medicine, The Technion, Haifa

As the prevalence of tuberculosis is on the rise in western countries, we present a 79-year-old man who developed a pulmonary tuberculosis-like syndrome following immunotherapy with BCG for carcinoma of the urinary bladder. The symptoms subsided following 3-drug antitubercular treatment, and the addition of steroids following negative cultures for Mycobacterium tuberculosis. The course of this disease, named BCG-osis, is much more favorable than miliary tuberculosis, even with milder treatment. It is important to keep in mind this phenomenon now that there is increasing treatment of cancers with BCG.

Brucellosis Presenting as Acute Abdomen

Nathan Kaufman, Noga Reichman, Edith Flatau

Dept. of Medicine B, HaEmek Medical Center, Afula

Usually symptoms of brucellosis are nonspecific and characterized by a wide range of complaints. Although the disease in Israel is almost exclusively food borne (caused by Brucella melitensis in unpasteurized goat milk products) so the main route of infection is the gastrointestinal tract, but gastrointestinal complications are rare, and only sporadic cases of ileitis or colitis have been described.

We present a 43-year-old woman with an acute abdomen, probably due to diverticulitis. It was diagnosed only after blood cultures were positive for Brucella melitensis. We believe that its protean manifestations should be consin addition to the other bizarre presentations of this disease, important in our region.

Extensive Liver Resection: a Series of 72 Cases

Moshe Hashmonai, Doron Kopelman, Ahmed Assalia, Yoram Klein, Hani Bahus, Alex Beny, Yaakov Baruch

Depts. of Surgery B, Oncology and Unit for Liver Diseases, Rambam Medical Center and Technion Faculty of Medicine, Haifa

Partial liver resection is the treatment of choice for various liver diseases, including primary and secondary (metastatic) malignancies, benign tumors, cysts, abscesses, trauma, etc. Improved knowledge of hepatic anatomy and physiology, improved diagnostic techniques and more developed peri-operative treatment have reduced postoperative morbidity and mortality to acceptable levels.

We present a series of 72 liver resections, the majority of which were liver lobectomies or more extensive procedures performed during 1982-1997. The percentage of postoperative complications, which ranged from 1.3% to 19.4%, and mortality (8.3%; 6/72) are comparable to those of other large series in the world literature. We believe that better appreciation of the surgical potential of Israel by our medical community will improve our therapeutic approach to various liver diseases.

Follicle-Stimulating Hormone in Azoospermia in Prediction of Spermatogenic Patterns

David B. Weiss, Shoshana Gottschalk-Sabag, Zvi Zukerman, Elchanan Bar-On, Zvi Kahana

Kupat Holim Me'uhedet; and Dept. of Pathology and Cytology and Male Infertility Unit, Shaare Zedek Medical Center, Jerusalem; Andrology Unit, Rabin Medical Center (Beilinson Campus), Petah Tikva; and Paper Research Consultant Institute, Jerusalem

Follicle-stimulating hormone (FSH) is considered to be the most important plasma hormone correlated with spermatogenesis. Elevated FSH plasma levels were shown to be associated with complete damage to testicular seminiferous tubule germinal epithelium. Recently, there have been conflicting reports with regard to the value of FSH plasma levels in predicting seminiferous tubule histology in the azoospermic patient and hence, as a guide for therapy in assisted reproduction using testicular sperm retrieval. The aim of this study was to evaluate whether FSH plasma levels can predict spermatogenic pattern in the testes of the azoospermic infertile patient. 69 infertile men with non-obstructive azoospermia and 18 with very severe oligospermia were studied. In all, plasma levels of testosterone, free testosterone, prolactin, luteinizing hormone and follicle-stimulating hormone were measured by enzyme immunoassay. In the azoospermic patients the seminiferous tubule spermatogenic pattern was determined in testicular aspirates obtained by multiple fine needle aspiration and categorized according to the most mature spermatogenic cell type in the aspirates: Sertoli cells only, spermatogenic maturation arrest or full spermatogenesis. There were no significant differences in plasma levels of any hormone measured except in very severely oligospermic and azoospermic patients. Both normal and elevated levels were detected in all, regardless of seminiferous tubule cytological pattern or plasma FSH in azoospermic patients. It is concluded that plasma levels of FSH can not be used as a predictive parameter, neither for the presence of spermatozoa nor for any other seminiferous tubule cytological pattern in azoospermic infertile men. They cannot serve as guides for selection of azoospermic men for trials of testicular sperm retrieval in assisted reproduction.

Abnormal Liver Function Tests in the Primary Care Setting

Shlomo Vinker, Sasson Nakar, Emanuel Nir, Eitan Hyam, Michael A. Weingarten

Dept. of Family Medicine, Rabin Medical Center, Sackler Faculty of Medicine; Tel Aviv University; and General Sick Fund, Central District

Results of laboratory tests ordered during a primary care encounter may reveal findings of abnormal liver function tests, including elevated liver enzymes, hyperbilirubinemia, hypoalbuminemia or abnormal coagulation tests. The object of this study was to describe the spectrum of these liver function test (LFT) abnormalities in primary care.

Results of all laboratory tests ordered during 10 months in an urban primary care clinic were retrospectively reviewed and the medical charts of patients with abnormal LFTs were studied. In 217/1088 (20%) of the tests at least 1 LFT abnormality was found in 156 patients. New diagnoses were made in 104 patients. The main diagnostic groups were: non-alcoholic fatty liver changes, Gilbert's disease, acute infectious hepatitis, alcoholic liver disease and cirrhosis and hepatotoxic drug injury. In 60 patients the physician classified the abnormality as negligible and not associated with significant disease. However, an abnormal test that had been ordered for evaluation of a specific complaint, was indeed likely to represent significant disease (X²=29.5, p<0.001). We conclude that finding abnormalities in liver function tests is common in the primary care clinic but does not often indicate significant liver disease.

Combined Treatment of Hepatic Tumors by Cryosurgery and Resection

Doron Kopelman, Alexander Beny, Ahmed Assalia, Diana Gaitini, Yoram Klein, Moshe Hashmonai

Depts. of Surgery B, Oncology and Radiology, Rambam Medical Center and Technion Faculty of Medicine, Haifa

Cryosurgery is an old technique which is being used for hepatic tumors as an adjuvant to hepatic resection. We recently treated 7 patients with multiple malignant liver tumors, 5 of whom had colorectal metastases, 1 carcinoid metastases, and 1 multiple hepatic lesions of hepatocellular carcinoma. 6 underwent combined liver resection and cryoablation of lesions in the remaining liver. In the 7th patient, only cryoablation was performed because hepatic resection was rejected and there was an extrahepatic metastasis. The advantages of this treatment are removal or destruction of all liver lesions found by any method, including intraoperative ultrasound examination, maximal preservation of normal liver parenchyma and that it is curative in patients inoperable by standard criteria.