Detection of hepatitis B virus markers in sera of asymptomatic hepatitis B surface antigen carriers with special emphasis to pre-S-encoded proteins.

Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.

HBsAg clearance in patients with long-standing chronic active hepatitis B and hepatitis B virus-induced liver cirrhosis.

During a period of 3 years we observed 5 patients with chronic active hepatitis B and 2 with hepatitis B virus-induced liver cirrhosis who cleared HBsAg from their sera after 2-14 years of HBsAg carriership. 4 of them developed anti-HBs. After HBsAg clearance there was no evidence of persisting inflammatory activity within their livers. 5 of the 7 patients had been treated for 1-39 months with prednisolone, sometimes in combination with azathioprine. This therapy, however, had been stopped more than 3 years before these patients terminated their HBsAg carriership. Our observations indicate that even after long-standing chronic active hepatitis B or hepatitis B virus-induced liver cirrhosis HBsAg may be eliminated in a considerable number of patients.

Endoscopic removal of common bile duct stones through the intact papilla after medical sphincter dilation.

Recently, glyceryl trinitrate was shown to effectively dilate the smooth muscle of the sphincter of Oddi. This information was applied to endoscopic therapy of bile duct stones. In 21 patients a total of 32 common bile duct stones, 6-12 mm (means = 8.7 mm) in diameter, were removed through the intact sphincter after its medical dilation by administration of 1.2-3.6 mg glyceryl trinitrate. Thirty of 32 stones could be extracted without difficulty. The remaining two concrements had to be crushed by endoscopic mechanical lithotripsy before removal. No complications were observed during or after the procedure. Follow-up manometric examinations showed the papillary function to be well preserved. We therefore consider this new, safe, and easy method to be the treatment of choice for the removal of small- and medium-sized bile duct stones.

[Oral zinc in Wilson disease--an alternative to D-penicillamine]. / Orale Zink-Therapie bei Morbus Wilson--eine Alternative zu D-Penicillamin.

Recently Brewer et al. reported the possibility of an oral zinc therapy in Wilson's Disease. We treated a 19 years old patient with decompensated liver cirrhosis due to Wilson's disease with zinc-sulphate. D-Penicillamine had to be withdrawn since proteinuria occurred under treatment. After the discontinuation of D-Penicillamine an increase of serum copper almost up to normal range was observed; concomitantly urinary copper elimination decreased. Under oral zinc sulphate therapy (145 mg/day) a drop of serum copper level was achieved and liver function improved: serum albumin, gamma globulins and prothrombin time reached normal values. The patient did not complain any side effects during oral zinc sulphate therapy. Oral zinc therapy in Wilson's Disease may be regarded as an alternative to D-Penicillamine treatment when this drug has to be discontinued because of side effects.

[Retroperitoneal cyst: a little known internal medicine problem]. / Retroperitoneale Zyste: Ein wenig bekanntes internistisches Problem.

Retroperitoneal cysts are often a differential diagnostic problem. The diagnosis is not infrequently made only by laparotomy. Our experience with a 33 year old patient with pain localized in the left upper part of the abdomen and "cyst of the spleen" confirms this rule. The diagnosis of a lymphatic cyst of the retroperitoneum was made after the surgical enucleation.

[Diagnosis of cavernomatous transformation of the portal vein]. / Diagnostik der kavernomatösen Pfortadertransformation.

In 10 patients at the age of 17 to 59 years the diagnosis of a cavernomatous transformation of the portal vein primarily was made by sonography and was confirmed by computer tomography and angiography, respectively. These findings were seen by chance when an abdominal ultrasound was performed in order to clarify splenomegaly or esophageal varices. The characteristics of the disease are the positive proof of a convoluted agglomeration of racemose venous structures that have replaced the normal single portal vein and signs of portal hypertension. The sonographic figures are so typical that ultrasound is the decisive procedure in its diagnosis and that direct or indirect splenoportography is not necessary. The present results show that clinical manifestations of cavernomatous transformation of the portal vein are delayed sometimes in to adolescence and that invasive diagnostic methods are only necessary when shunt operation is planned.

Active hepatitis B vaccination of dialysis patients and medical staff.

One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 micrograms vaccine (V) i.m. Uremic patients, who were just about to start chronic dialysis treatment (N = 7), were given 40 micrograms V, and at the first vaccination 3 ml hyperimmune globulin (HBIG) in addition. The medical personnel was alternately vaccinated with 20 micrograms V (N = 8), 40 micrograms (N = 11), 40 micrograms V, and 3 ml HBIG at the first vaccination (N = 10). After 12 months, 50% of the male dialysis patients, 66% of the female dialysis patients, and 95% of the medical staff developed anti-HBs antibodies. The anti-HBs titer of the dialysis patients was ten times lower than in the medical staff. The simultaneous passive immunization did not lead to any impairment of the anti-HBs titer in the dialysis patients and staff. The type of renal disease, length of time on dialysis, hematocrit, and immunoglobulin concentration did not influence the rate of immunization. After 12 months, 43 patients without antibody response were vaccinated a fourth time. Sixteen of these patients then developed anti-HBs, improving the immunization rate from 56.5 to 71.7%. A fifth vaccination only led to seroconversion, when brief or borderline anti-HBs could already be demonstrated previously. In dialysis patients who fail to develop anti-HBs after three doses of vaccine, a fourth vaccination is recommended after 12 months.

[Chronic active hepatitis: recurrence after long-term immunosuppressive therapy in spite of normal liver histology]. / Chronisch aktive Hepatitis: Rezidiv nach langjähriger immunsuppressiver Therapie trotz normaler Leberhistologie.

We report the case of a patient with liver-kidney microsomal antibody (LKM) positive chronic active hepatitis (CAH) which was followed-up for 12 years. Besides LKM the patient's serum was positive for thyroid microsomal antibodies, but negative for antinuclear, liver membrane and smooth muscle antibodies as well as hepatitis B virus markers. The patient was HLA B 8 negative. The disease of the 23 year old female patient began as an acute hepatitis which progressed to CAH. Immuno-suppressive therapy with a combination of prednisone and azathioprine led to a long lasting normalization of transaminases, gammaglobulin levels, and finally liver histology. Despite a normal liver histology after more than six years of continuous treatment the discontinuation of therapy was followed by a relapse. The presented case with LKM-positive CAH demonstrates that discontinuation of immuno-suppressive therapy may be followed by a relapse even if normal liver histology has been achieved under treatment.

Diagnosis and therapy of liver abscess by ultrasonographic imaging, puncture and drainage.

Liver abscesses in 19 patients were primarily diagnosed by real-time ultrasound. Characteristic features and changes in the course of disease are described. Fine needle puncture under ultrasonographic guidance confirmed the diagnosis and permitted bacteriologic examination. Ultrasonographically guided abscess drainage dramatically improved the clinical condition, and can be recommended as an alternative to surgical drainage.

Changes in gallbladder motor function during the female cycle--a risk factor leading to gallstone formation?

The gallbladder volume of eight women with stable cycles was determined by sonography. Furthermore, gallbladder contraction--following an orally administered fatty meal and the spontaneous refilling of the empty gallbladder--was quantitatively examined. The formula of a rotation ellipsoid, which has been proven to be adequately accurate in in vitro studies, was used for calculating the gallbladder volume. In the gestagen phase (21st or 22nd day) the intraindividual studies showed greater fasting volumes, higher residual volumes after contraction, slower gallbladder emptying, and retarded refilling of the empty gallbladder as compared to the estrogen phase (12th or 13th day). The hormonally modified contraction behavior and the differing course of gallbladder filling may play a major role in the pathogenesis of gallstone formation.

The significance of serologic, histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen.

Eighty-eight asymptomatic carriers of hepatitis B surface antigen (HBsAg) were followed with biochemical, serologic, histologic, and immunohistologic studies over a period of four years. None of the 78 HBsAg carriers with normal or minimally changed liver tissue, antibody to hepatitis B e antigen (HBeAg) in serum, and no intranuclear hepatitis B core antigen (HBcAg) developed a chronic inflammatory liver disease. Four individuals lost circulatory HBsAg, and at least two individuals terminated their HBsAg carrier state. Seven asymptomatic HBsAg carriers with chronic hepatitis were characterized by HBeAg in serum and intranuclear HBcAg. However, three HBsAg carriers with chronic hepatitis and an absence of intrahepatocellular HBcAg were positive for antibody to HBeAg over the observation period. The mechanism that leads to chronic hepatitis in these patients remains to be determined.

Ultrasonically guided fine needle aspiration biopsy of hepatic and pancreatic space-occupying lesions and percutaneous abscess drainage.

Ultrasonically guided fine needle aspiration biopsy as a safe, easy and uncomplicated procedure permitted cytological diagnosis in 54 out of 57 patients (94.7%) with confirmed tumor infiltrations of the liver and in 25 out of 30 patients (83.3%) with sonographically localized space -- occupying tumor-suspect lesions of the pancreas, 22 of which were verified as pancreatic cancer by laparatomy or autopsy, 3 patients suffered from malignant lymphoma. False negative results were obtained in 1.8% and 6.7%, respectively. There was no false positive diagnosis of neoplasm. Ultrasonically guided aspiration biopsy thus appears to be an excellent method for verification of clinically or sonographically suspected hepatic or pancreatic tumors or such suspected by other procedures. 42 cysts or abscesses in pancreas and liver were punctured and drained in 8 cases, using a flexible catheter. The therapeutical management of cysts or abscesses under ultrasonic guidance may shorten hospitalization or avoid intraabdominal operation.

Follow-up of anti-HBc titers in healthy HBsAg carriers and patients with chronic inflammatory liver diseases.

Sera of 85 asymptomatic HBsAg carriers found among blood donors were tested for anti-HBc titers and were retested 4 years later. The results were correlated with the histological findings of first and final biopsy. None of 75 HBsAg carriers with normal or minimally changed liver tissue, 71 of them anti-HBe positive, developed chronic inflammatory liver disease. 4 HBsAg carriers eliminated HBsAg from the serum after a 1-to 3-year HBsAg-carrier state and 2 developed antibody against HBsAg in the sequel. In 65 of 75 cases we found unchanged anti-HBc titers. The geometrical mean titer (GMT) was 1:7,800 in the first and 1:7,000 in the final examination with a range of 1:400 and 1:25,600 in the group of HBsAg carriers with normal liver, and was 1:14,200 and 1:10,300, respectively, with a range of 1:800 and 1:51,200 in HBsAg carriers with minimal changes. In both groups the decrease of anti-HBc concentration within 4 years was not significant. The group of 10 HBsAg carriers with chronic hepatitis did not differ from healthy HBsAg carriers in respect to anti-HBc titers. Anti-HBc titers varied between 1:6,400 and 1:25,600, the GMT was 1:13,700 and 1:12,800, respectively. It is speculated that in healthy HBsAg carriers shedding of serologically undetectable quantities of complete and/or defective HBcAg from liver cell nuclei which contain HBcAg not detectable by immunofluorescence maintain the production of anti-HBc.

Failure to detect naturally occurring serum inhibitors of hepatitis B virus deoxyribonucleic acid polymerase.

Sera of patients with past or ongoing hepatitis -B virus infection were tested for the presence of inhibitors of hepatitis -B virus-specific deoxyribonucleic acid (DNA) polymerase activity. None of the sera tested, which included those from anti-hepatitis B surface- and anti-hepatitis B core antigen-positive hemophiliacs, anti-hepatitis Bc antigen-positive hepatitis B surface antigen carriers, patients with hepatitis B surface antigen-positive chronic active hepatitis, hepatitis B surface antigen-positive hemodialysis patients, tumor patients with minimal hepatitis, patients with acute type B, type A, and type non-A, non-B hepatitis and individuals with autoimmune phenomena, contained inhibitors of DNA polymerase activity. This implies that the DNA polymerase test is not affected when utilized to quantitate DNA-containing Dane particles. In addition, there is no evidence that inhibitors of DNA polymerase activity play some pathogenic role in the course of hepatitis B virus infection.

[Spread of hepatitis B virus infection among family contacts of asymptomatic HBsAg carriers (author's transl)]. / Die Ausbreitung von Hepatitis-B-Infektionen in Familien HBsAg-positiver Träger.

Family members of 34 asymptomatic HBsAg carriers were tested for different hepatitis B virus (HBV) markers. Among 67 family members tested 24 (36%) presented signs of a past or ongoing HBV-infection. Spread of HBV-infection was particularly high in those families in which the HBsAg carrier was positive for HBeAg and Dane particle-associated DNA polymerase activity. Non-parenteral "horizontal" transmission of HBV among spouses and brothers and sisters and probably parenteral vertical transmission of HBV from carrier mothers to their infants occurred in approximately the same frequency. Fathers transmitted HBV unfrequently to their offsprings. The results show that the risk to acquire a HBV-infection from an asymptomatic HBsAg carrier is closely linked to the serological findings in the HBe/anti-HBe-system of the index HBsAg carrier and not to the family relationship to the HBsAg carrier.

[Long-term results after operative treatment of acute haemorrhagic necrotising pancreatitis (author's transl)]. / Langzeitergebnisse nach operativer Therapie der akuten hämorrhagisch-nekrotisierenden Pankreatitis. Unter besonderer Berücksichtigung der endokrinen und exokrinen Pankreasfunktion.

A follow-up investigation of 20 patients, surgically treated for acute haemorrhagic necrotising pancreatitis, was performed in an average of 2 3/4 years after the operation. Twelve patients showed manifest diabetes mellitus, four further cases had a suspicious oral glucose tolerance test. Only one patient was insulin dependent. A secretin-pancreozymin test performed in 15 patients showed a dissociated or global pancreatic insufficiency in 13 cases. The extent of the endocrine and exocrine functional disturbance did not correlate with the extent of surgery. Postoperative functional defects were readily improved therapeutically in most cases. Only in patients who continued to consume alcohol were there digestive disturbances. The results indicate that the functional state of the remaining pancreas does not only depend on the extent of surgery but also on the extent of already existing or persisting toxic inflammatory damage and on the regenerative capacity of the remaining parenchyma.

[Radioimmunological determination of HBeAg/anti-HBe in HBsAg-positive liver diseases and in "healthy" HBsAg carriers]. / Radioimmunologischer Nachweis von HBeAg/anti-HBe bei HBsAg-positiven Leberekrankungen und "gesunden" HBsAg-Trägern.

This paper describes a "solid-phase"-radioimmunoassay for the demonstration of HBeAg and anti-HBe. The investigations revealed the following results: 1. HBeAg is positive in all patients with acute type B-hepatitis during the acute phase of illness. During the normal course of the disease HBeAg turns to negative followed by an anti-HBe lasting for several months. 2. Cases with a persistent virus B-replication as HBsAg-positive CPH, CAH or patients on hemodialysis are positive for HBeAg in their serum. By means of the fluorescent antibody technique these patients have demonstrable HBcAg and HBeAg in their liver biopsies. 3. Healthy HBsAg carriers are anti-HBe-positive in their serum. In their liver biopsies there are no signs of an on-going virus B-replication (HBsAg and HBeAg negative). 4. The radioimmunological determination of HBeAg and anti-HBe enables us to differentiate between the groups with HBsAg positive acute or chronic hepatitis and the group of healthy HBsAg-carriers.