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The purpose of our study was to verify the correlation between biochemical and histological inflammatory activity in chronic hepatitis C. The histological activity index (HAI) of 42 patients with chronic hepatitis C was correlated with their transaminase activity. There was indeed a significant correlation between histological activity and the AST (r = 0.54, p = 0.0002) and ALT level (r = 0.36, p = 0.018) respectively. Due to considerable scatter of the results, transaminase activity did not allow reliable assessment of inflammatory activity in individual cases. In the majority, markedly elevated transaminase activity was associated with marked histological inflammatory activity, whereas normal or slightly elevated transaminase activity was found in all stages of inflammatory activity. To assess inflammatory activity in chronic hepatitis C, a liberal indication for liver biopsy should therefore be adopted.

The aim of the study was to determine the frequency and course of hepatitis C viremia in clinically healthy, anti-HCV positive test subjects, and to ascertain whether the HCV antibodies of the IgM type differed between viremia and immunity. In 21 anti-HCV positive blood donors (test subjects) with normal transaminase activity, two serum samples, taken at an interval of 25 +/- 10 months, have been investigated for HCV-RNA and HCV-IgM antibodies. In a total of 16 test subjects (76%) HCV-RNA was found during the first test and/or the follow-up: 14 of them were positive on both occasions, and one test subject each was HCV-RNA positive exclusively at the first test and the follow-up respectively. At the time of the follow-up the serum transaminase level was elevated in 4 test subjects. 3 of these 4 were HCV-RNA positive also. On the other hand, the results of the HCV-PCR were nonuniform in HCV-IgM antibody negative test subjects. The above results demonstrate that in the majority of clinically healthy, anti-HCV positive test subjects with normal transaminase activity, a viremia exists which persists and the course of which may include inflammatory phases. The proof of HCV-IgM antibodies correlates with a viremia. On the other hand, the lack of HCV-IgM antibodies does not exclude viremia.

The purpose of this study was to evaluate the frequency, nature and significance of the complications of endoscopic sphincterotomy. Between 1989 and 1993 endoscopic sphincterotomy was performed in 973 patients with benign affections of the bileducts. 398 patients were our own and 575 were admitted from other hospitals. The complications were recorded retrospectively on the basis of the discharge reports, which were available for each of our own patients (group A) and for 85% of the admitted patients (group B). Complications in all group A patients mentioned in the discharge reports were recorded and their clinical relevance was evaluated based on the patient records. Complications were mentioned in the reports of 82 (9.2%) of 887 cases and were more frequent in patients of group B (52 of 489: 10.6%) than in patients of group A (30 of 398: 7.6%). Pancreatitis was mentioned significantly more frequent in group B (2.5% vs 5.7%, p < 0.02). Reviewing the patient records of group A showed that clinically significant complications occurred in only 8 (2%) of 398 cases. The other complications mentioned in the discharge reports could not be confirmed or were without clinical significance. Hospitalization was short for these patients (5.3 +/- 2.2 days), which points to the fact that the findings were insignificant. 2 (0.2%) of 887 patients underwent surgery and 2 (0.2%) of 887 patients died due to a complication. These results clearly show that the complication rate determined on the basis of the discharge reports alone overestimates the true morbidity of the procedure. Often, an elevated amylase after ERCP/endoscopic sphincterotomy was erroneously interpreted as a pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary complications are more frequent in laparoscopic than in open cholecystectomy. The aim of the study was to evaluate the diagnostic and therapeutic value of endoscopic retrograde cholangiopancreatography (ERCP) in the management of complications of laparoscopic cholecystectomy. We therefore report on the result of 49 ERCP after laparoscopic cholecystectomy done at our department between January 1991 and March 1993. Patients were referred from 16 different surgical institutions. In 29 cases endoscopic sphincterotomy was performed without complications. Indications for ERCP were "persistent biliary pain" (n = 27), bile leakage (n = 7), pancreatitis (n = 5), abscess (n = 5), painless jaundice (n = 3) and asymptomatic bile duct stone in routine cholangiography (n = 2). In the group of patients with "persistent biliary pain" we found bile duct stones in 12 (80%) of 15 cases with cholestasis and in 3 (30%) of 10 without cholestasis. The stones were endoscopically removed after sphincterotomy. In 2 patients without cholestasis, cannulation of the bile duct failed. 7 patients showed biliary leakage, 4 from inadequate clipping of the cystic stump (2 in combination with a common bile duct stone), 2 from the hepatic duct and 1 from insufficient anastomosis after reconstruction of a common bile duct. After endoscopic sphincterotomy and, if necessary, stone extraction by Dormia basket, leakage from the cystic stump and hepatic duct healed. The insufficient common bile duct anastomosis required reconstruction by hepaticojejunostomy. Three of 5 patients with postoperative pancreatitis had common bile duct stones, while one with chronic pancreatitis had a concrement in the pancreatic duct which was endoscopically removed.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of our study was to compare the sensitivity of hepatitis C virus polymerase chain reaction (HCV-PCR) by use of two different primer sets which amplify PCR products of different length. Serum samples of 70 patients with chronic hepatitis C were tested by "nested primer" PCR, using either "NCR primers" that amplify cDNA-fragments of 340 basepairs (bp), or by "PT primers" which amplify fragments of 59 bp only. HCV-RNA was detected in 40 patients (57%) by "NCR primers" and in 69 patients (90%) by "PT primers" (p < 0.001). 23 of 70 patients (33%), which were HCV-RNA negative by "NCR primers", were positive by "PT primers", but no patient negative by "PT primers" was found to be positive by "NCR primers". 20 healthy controls tested by both primer sets were all HCV-RNA negative. We conclude that the sensitivity of HCV-PCR is significantly improved by use of primers that amplify "short" PCR products and recommend the use of "PT primers" for HCV-PCR.

Parenteral transmission of hepatitis C virus (HCV) through blood transfusions and intravenous drug misuse is well established. Since 50% of patients with hepatitis C have no history of parenteral exposure, other ways of transmission must exist. The purpose of this study was to examine the epidemiological importance of heterosexual intercourse for transmission of HCV infection. 29 heterosexual contacts (13 men, 16 women, mean age 47 years) of 29 index patients (16 men, 13 women, mean age 49 years) with histologically und serologically documented chronic hepatitis C were questioned about parenteral exposure and sexual behaviour. Their serum samples were examined for ALT activity and anti-HCV antibodies (first-generation Ortho-HCV-ELISA). Five contacts were using condoms to prevent infection. Five of 24 contacts (21%) practising unprotected sexual intercourse, but none of 5 contacts using condoms, showed evidence of heterosexual HCV transmission: 4 were anti-HCV positive (one with elevated ALT activity) and another showed elevated ALT activity with a negative anti-HCV test. None of these contacts had a history of parenteral exposure. Our results indicate that heterosexual transmission of HCV is epidemiologically important. The true rate of infection may be even higher, for two reasons: (1) not every HCV infection is detected by the anti-HCV test, and (2) the anti-HCV test may turn negative again in uncomplicated infection.

The aim of our study was to evaluate whether a negative HCV test of the first generation (HCV-ELISA 1) using the antigen C100-3 excludes chronic HCV infection, or whether patients exist who are negative for antibodies to C100-3 in spite of chronic hepatitis C. 27 patients with histologically proven chronic non-A, non-B hepatitis, all of whom were HCV-ELISA 1 negative, were tested by the HCV test systems of the second generation (Ortho-HCV-ELISA 2 and Chiron-HCV-RIBA 2) based on the distinct HCV antigens 5-1-1, C100-3, C33c and C22-3. To determine the presence of viremia, serum samples were also tested for HCV-RNA with "nested" PCR. 10 of 27 patients proved to be persistently negative when tested with the second generation assays. One patient showed low grade reactivity by HCV-ELISA 2, but non-reactivity by HCV-RIBA 2. In none of these 11 patients was HCV-RNA detected. 16 (60%) of 27 patients negative with HCV-ELISA 1 were positive with HCV-ELISA 2. HCV-RIBA 2 detected antibodies to the structural core antigen C22-3 in all of these 16 patients and antibodies to the non-structural antigen C33c in 14 of them, while antibodies to 5-1-1 or C100-3 were not found in any of these cases. 10 (63%) of the 16 HCV-ELISA 1 negative, but HCV-ELISA 2 and HCV-RIBA 2 positive patients were positive for HCV-RNA by "nested" PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify the relationship between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC), frozen serum samples from 213 patients with histologically proven liver cirrhosis alone (96 alcoholics, 59 HBsAg positive, 29 non-A, non-B hepatitis, 29 cryptogenic) and 40 patients with liver cirrhosis and HCC (12 alcoholics, 7 HBsAg positive, 7 non-A, non-B hepatitis, 14 cryptogenic) were analyzed for antibodies to hepatitis C virus (anti-HCV) with the ortho-HCV-ELISA. The results were as follows. 50 of 253 (20%) patients were anti-HCV positive. The prevalence of anti-HCV was significantly higher in patients with HCC than in patients without HCC (14 of 40 [35%] vs 36 of 213 [17%]; p less than 0.001). In anti-HCV-positive patients HCC were significantly more frequent than in anti-HCV-negative patients (14 of 50 [28%] vs 26 of 203 [13%]; p less than 0.001). The significantly higher occurrence of HCC in anti-HCV-positive patients was not related to other known risk factors such as alcoholism or chronic hepatitis B virus (HBV) infection. Patients with HCV infection as the only risk factor also had a significantly higher occurrence of HCC (12 of 38 [32%] vs 26 of 203 [13%]; p less than 0.001). Our data suggest that chronic HCV infection plays an important role in the pathogenesis of HCC, in particular in patients with cirrhosis unrelated to alcohol or HBV infection.

Our study was designed to evaluate the clinical significance of the ELISA-anti-HCV test. 90 patients with histologically proven chronic non-A, non-B hepatitis (NANBH) and a control group consisting of 36 patients with primary biliary cirrhosis (PBC) were analyzed for antibodies to hepatitis C virus (anti-HCV). Frozen serum samples were tested with the ortho-HCV-ELISA. 67 of 90 (74%) patients with chronic NANBH showed antibodies to the hepatitis C virus. The prevalence of anti-HCV in patients with parenterally transmitted and sporadic chronic NANBH was 70% (23 of 33) and 77% (44 of 57) and in patients with chronic active and chronic persistent NANBH 73% (27 of 37) and 76% (40 of 53) respectively. No significant difference in the prevalence of anti-HCV in the 4 subgroups of patients with chronic NANBH was found. 2 of 36 patients (6%) with PBC were anti-HCV positive without evidence of previous HCV infection. Our results bear out the experience of other authors, that HCV is the commonest pathogen of chronic NANBH. The low prevalence of anti-HCV in patients with PBC suggests good specificity. There have been reports in the literature of "false positive results", particularly in autoimmune hepatitis, and it has been shown that borderline positive test results are often unspecific and therefore to be interpreted with care.

Stored serum samples of 20 patients with clinically and bioptically proven non-A, non-B hepatitis (NANBH) in the acute stage were tested for the presence of antibodies to hepatitis C virus (anti-HCV) by means of the Ortho ELISA system. After a mean period of 8 weeks from onset of the disease, 8 of 20 patients (40%) had anti-HCV. Our follow-up study included 14 patients. Of 9 primarily anti-HCV-negative patients, 2 became positive after 2 and 7 months respectively, whereas 7 patients remained anti-HCV-negative up to 52 months (range 1-128) after the onset of hepatitis. The prevalence of anti-HCV was 71% in 7 patients with parenteral hepatitis related to transfusions (n = 2) or drug abuse (n = 5), and 38% in 13 patients with sporadic NANBH. Of the 8 anti-HCV-negative patients with sporadic NANBH, 5 had stayed in one of the countries where enterically transmitted NANBH is endemic 3 to 6 weeks before the onset of their disease. Our results show that at present the anti-HCV-test supplies an etiologic basis for approximately half of all cases of NANBH in acute stage. Nevertheless, in most cases the acute NANBH remains a diagnosis of exclusion.