Changes in the acute phase complement component and IL-6 levels in patients with chronic hepatitis C receiving interferon alpha-2b.

In order to study the effect of interferon alpha on the levels of acute phase complement proteins in vivo, serum concentrations of C9 and C1-inhibitor (C1-INH) were measured in patients with chronic hepatitis C before and 3 months after the beginning of interferon alpha2b therapy. Serum levels of the activation product of terminal complement pathway, C5b-9, HCV RNA and IL-6 were also determined. IFN alpha treatment significantly (P<0.0001) increased the serum concentrations of both complement proteins. C5b-9 levels were found to significantly decrease during the same period of time. When the patients were divided into responders or non-responders (more or less than 50% decrease in plasma HCV RNA concentrations) C9 and C1-INH levels were elevated only in the responder patients. There was no correlation between the changes of IL-6 levels or the amounts of IFN alpha administrated on one hand, and the changes in the complement protein levels on the other. These findings suggest that the marked increase in the serum concentrations of the acute phase complement proteins is a secondary phenomenon due to the IFN alpha-caused diminution of the viral load and the resulting immune complex-induced complement activation.

Therapy for chronic hepatitis C.

BACKGROUND/AIMS: in Hungary, over the past 5 years more than 900 patients with chronic hepatitis C have been examined for treatment with interferon at 16 major hepatology centres, using unified diagnostic and therapeutical criteria. Authors give an account of their experiences on the clinical features of patients with chronic hepatitis C and report the results of the interferon therapy. METHODS: a total of 993 patients--virtually the entire Hungarian hepatitis C patient population who had been referred for interferon treatment--were included in the program. Actually, the sustained efficacy of the therapy was evaluated in 724 cases. Treatment protocols (dose of interferon and duration of therapy) have changed with time from a weekly dose of 3x3 MU IFN for 6 months in the first period, to 3x3-5 MU for 12 months in the second period, and finally in the third period a combination therapy with ribavirin has also been introduced. RESULTS: in the first period, the end-of-treatment response (ETR) was 35%, sustained response (SR) 13%, the second phase schedule resulted in 42% ETR and 22% SR, while in the third period, ETR was 49% and SR 36%, respectively. Fibrosis in histology and baseline pretreatment HCV-RNA level appeared as predictors of response. The duration of treatment and the total dose of interferon exerted a moderate effect on therapeutic efficacy. Neither age nor gender influenced the outcome. CONCLUSIONS: our results-obtained in a Central East European country-are in accordance with findings of suboptimal efficacy of traditional interferon monotherapy for chronic hepatitis C reported in the West, and suggest the benefit of the combination treatment of interferon with ribavirin.

Prevalence, genotype distribution and outcome of hepatitis C infections among the employees of the Hungarian Central Hospital for infectious diseases.

Blood samples from 477 hospital workers (HWs) at the Central Hospital for Infectious Diseases, Budapest, Hungary were tested for hepatitis C virus (HCV) antibodies by enzyme immunoassay (EIA), and 13 (2.7%) of these were found to be HCV antibody positive. Ten (2.7%) were from nursing/housekeeping staff and three (2.9%) from medical staff. HCV antibody positive HWs were detected in 10 of 17 work places, and the prevalence rates in these departments or units varied between 1.2% and 6.5%. The prevalence increased gradually with increasing age, being 0% in these under 21 years of age and 9.5% in those above 50 years of age. Eleven (85%) of 13 HCV antibody positive HWs had HCV RNA in their sera, four of them intermittently during the follow-up period. HCV genotype 1 was present in two HWs, 1b in six HWs, 3a in one HW and 4 in two HWs. Chronic hepatitis C has developed in six (46%) HCV antibody positive HWs. Although the source of infection through needlestick could only be traced directly in one case, circumstantial evidence indicated that the majority of infections were occupationally acquired, originating from percutaneous or mucocutaneous exposure.

Preliminary report of a controlled trial of MTH-68/B virus vaccine treatment in acute B and C hepatitis: a phase II study.

Eighty four patients with viral hepatitis attributed to infection with hepatitis B virus (HBV) (n = 43) or hepatitis C virus (HCV) (n = 41) were included in this study employing the MTH-68/B vaccine, an attenuated variant of Bursal Disease Virus. Twenty of the 43 patients in the HBV group, and 22 of the 41 HCV patients were treated with MTH-68/B. The remaining patients received conventional therapy. Significantly more patients progressed into active chronic hepatitis on conventional therapy (13% of HBV and 26% of HCV cases respectively) than in the vaccine treated groups (0% and 9%). Relapses occurred less frequently in the vaccine treated groups (5% of HBV and 32% of HCV) than in the control groups (9% and 79%), while remissions within one month of treatment were observed more often in the vaccine treated groups (both 50% respectively) than in the control groups (26% of HBV and 21% of HCV patients respectively). The duration of hepatitis was also considerably shortened by MTH-68/B treatment in both HBV (from 7.5 +/- 3.7 to 5.9 +/- 3.0 weeks) and HCV patient groups (from 8.9 +/- 7.4 to 5.3 +/- 4.4 weeks). The data presented suggest that attenuated, non-pathogenic viruses may be of significant benefit for patients with viral hepatitis B and C infections.

Hepatocyte proliferation and cell cycle phase fractions in chronic viral hepatitis C by image analysis method.

OBJECTIVE: Chronic hepatitis is characterized by necrosis of liver cells, accompanied by an inflammatory reaction and compensatory cell proliferation. The interaction of the core and non-structural proteins of hepatitis C virus (HCV) with several cellular factors suggests that cell proliferation may be influenced by HCV. The aim of this study was to investigate hepatocyte proliferation and DNA ploidy patterns in patients with chronic viral hepatitis C (CH-C) compared with chronic non-viral hepatitis (CH-N), using a TV image analysis method. METHODS: The DNA index (DI) and cell phase fractions (G1, S, G2) were measured by means of digital picture analysis method on nuclear suspensions of Feulgen stained hepatocytes. Cells were taken from the liver biopsy specimens of 71 patients with CH-C and 24 patients with CH-N. Twenty-six normal liver samples were used as controls. RESULTS: Significantly higher G1 (94 +/- 4) and lower S (3.56 +/- 3.16) phase fractions were measured in CH-C compared with CH-N (G1, 90 +/- 6; S, 6.4 +/- 5.99). The DI of moderate (1.12 +/- 0.05) and severe (1.12 +/- 0.05) CH-C showed near-aneuploid DNA content, while diploidy (DI < 1.10) was detected in cases of CH-N. CONCLUSION: The higher G1 and lower S cell cycle phase fractions in CH-C reflect decreased hepatocyte proliferation compared with CH-N. The near-aneuploid DNA content of the HCV-infected liver samples may be a sign of increased genetic instability, which may contribute to the carcinogenic potential of HCV.

[Management of chronic hepatitis B]. / A krónikus B hepatitis kezelése.

The features of chronic hepatitis B virus (HBV) related liver diseases and the aim of their therapy have briefly discussed, then treatment modalities are listed. In Hungary, between 1994 and 1996, a total of 68 patients with chronic hepatitis B have been treated with interferon (IFN). IFN resulted in complete clinical-biochemical remission in 50% of the patients, and in 32% the HBV replication was also eliminated. There are various nucleoside analogues, among them mostly famciclovir and lamivudine have been intensively studied as potentially effective treatment for HBV infection, and controlled clinical trials are in progress with these drugs. Nucleoside analogues in combination with IFN possibly improve treatment results in this disease. Various immunomodulatory agents--such as levamisole, thymosine, interleukin-2, and other cytokines--as well as the prednisolon-withdrawal induced rebound phenomenon have also been tested in HBV infection, but with no generally established benefit. A recombinant HBsAg vaccine is under investigation for therapeutic use. For end-stage HBV liver cirrhosis, liver transplantation is the only treatment, but the problem of reinfection is not still solved for more reasons.

[Liver changes in HIV/AIDS]. / Májelváltozások HIV/AIDS-betegségben.

Loss of cellular immunity accompanying the progressive HIV/AIDS disease, results in altered clinical picture and outcome of traditional infections as well as severe and often lethal illness caused by facultative pathogens. Unusual infections may call the attention to the underlining HIV disease. Liver disease appears in the great majority of HIV/AIDS patients. The authors review the viral, bacterial, fungal and protozoal infections involving the liver in AIDS. Liver biopsy has a diagnostic value beside the serology and bacteriology and may give therapeutic consequences.

[Delta virus infection in hemodialyzed kidney patients and patients with chronic liver diseases]. / Haemodializált vesebetegek és krónikus májbetegek Delta vírus fertózése.

Sera of patients with chronic hepatitis and chronic haemodialysed uraemia were tested for both Hepatitis B virus and Hepatitis Delta virus markers from 1985. Hepatitis Delta virus seroconversion was found in 10 of 88 haemodialysed patients and anti-Delta-IgG sero-positivity in 11 of 108 chronic hepatitis patients. The clinical course of Delta superinfections in haemodialysed patients was as follows: 3 infections were symptomless, 7 patients had acute hepatitis, two of the latter group died because of fulminant hepatitis. Of the 11 HBsAg and anti-Delta-IgG positive chronic hepatitis patients 3 had primary hepatocellular cancer.

[Severe relapse of hepatitis C following liver transplantation. Successful treatment with a combination of interferon-alpha and ribavirin]. / Hepatitis C súlyos relapsusa májátültetés után. Sikeres kezelés interferon-alpha és ribavirin kombinációval.

A 38-year-old, male patient, with end-stage HCV cirrhosis, underwent liver transplantation (OLT). After a sufficient recovery a rapid elevation of ALT and profound jaundice developed 3 months after OLT, together with a 15-fold rise of pre-transplant HCV RNS level. Liver biopsy was carried out, histology excluded rejection and signs of acute hepatitis were observed. Interferon alpha 2b 3 MU TIW and ribavirin 800 mg/day resulted in normalization of ALT, se. bilirubin and decrease of viral load by 90 per cent at the 3rd month of treatment. Improvement of hepatitis and no rejection was shown by control histology. A 6-month combination therapy followed by continuous ribavirin monotherapy maintains a permanent good condition with normal ALT, no icterus, a continuously low HCV RNA level and a mild chronic hepatitis with fibrosis in the liver histology 18 months after OLT. Danger of HCV reactivation after OLT, difficulties of diagnosis, interactions of immunostimulant and immunosuppressive drugs, advantages of combination therapy are discussed.

[Interferon therapy of chronic viral hepatitis in Hungary: 5-year experience. A multicenter study]. / Krónikus vírushepatitisek interferon kezelése Magyarországon: 5 éves tapasztalatok. Multicentrikus tanulmány. Hepatológiai Centrumok Munkacsoportjai.

In Hungary over the past 5 years more than thousand patients with chronic viral hepatitis have been examined and included in a treatment program with interferon (IFN) at 16 major hepatology centers, using unified diagnostic and therapeutical criteria. Authors give an account of their experiences on the clinical features of patients with chronic viral hepatitis and report the results of the treatment with IFN. According to the rules and availability of IFN for patients with chronic viral hepatitis in the country, virtually the entire Hungarian population with this diseases who required IFN therapy have been included. A total of 94 patients suffered from hepatitis B virus (HBV) infection, in addition 11 HBV + hepatitis Delta virus (HDV), 24 HBV + Hepatitis C virus (HCV) related liver disease, and 993 had chronic hepatitis C. IFN therapy for chronic HBV hepatitis consisted of IFN 5 MU thrice weekly for 6 months, and resulted in 33% seroconversion and sustained remission with 14% HBsAg clearance. For chronic hepatitis C treatment protocols (dose of IFN and duration of therapy) have changed with the time (from a weekly dose of 3 x 3 MU IFN for 6 months, to 3 x 3 MU for 12 months), and even a combination with ribavirin has been introduced. Although the therapeutic results showed a gradual improvement form a 13% sustained response over 22% in the first and second periods, respectively, differences were most significant with the advent of the combination therapy, that resulted in 36% remission rate. Only fibrosis in histology and baseline pretreatment HCV-RNA level appeared as predictors of response in chronic hepatitis C. Neither age nor gender did influence the outcome, but longer duration of treatment and higher total dose of IFN resulted moderately higher sustained remission rates. The experiences are in accordance with findings of suboptimal efficacy of IFN monotherapy reported worldwide and emphasize the need of seeking for newer and combination therapeutic modalities for these chronic viral diseases.

[Screening for hepatitis C of hospital personnel at the Szent László Hospital of Budapest]. / Egészségügyi dolgozók C hepatitis szürövizsgálata a Szent László Kórházban.

UNLABELLED: The health-care workers are known to be at risk of occupational transmission of blood-borne viruses. The goal of the investigation was to determine the prevalence of hepatitis C virus (HCV) antibody and the occupational risk of HCV transmission among personnel at the Central. Hospital for Infectious Diseases, Budapest, Hungary. Serum samples of 409 health-care workers were tested for antibody to HCV with second and third generation ELISA-s and anti-HCV positive samples were confirmed with Western Blot Line EIA. A total of 10 (2.4%) of the health-care workers were confirmed to be anti-HCV positive. The prevalence of anti-HCV increased with advancing age: zero under 20 yr age group (N = 0/15), 0.9% in 21-30 yr age group (N = 1/112), 1.8% in 31-40 yr age group (N = 2/111), 3.1% in 41-50 yr age group (N = 3/96) and 4.0% in above 50 yr age group (N = 3/75). We found anti-HCV positive hospital worker in 9 out of 17 departments. The prevalence of hepatitis C antibody was 7.1-1.9% among the personnel of internal departments, pathology, intensive care unit and pediatric departments. No anti-HCV positive health-care worker was found in the surgery and laboratories. None of the physicians tested was seropositive for HCV. Eight of the nurses, one of the sanitary personnel and one pathological technician were seropositive for HCV. Two nurses developed a chronic C hepatitis after a needlestick accident. CONCLUSIONS: 1. The hospital personnel is at risk for HCV infection. 2. The occupational risk of HCV infection increases with age but the risk is considerable lower than that of hepatitis B infection. 3. The occupational risk is highest among the workers of the chronic internal department, pathology and intensive care unit. 4. The nurses are at higher risk of HCV infection than the physicians. 5. The needlestick injury is associated with an increased risk for acquiring HCV infection.

[Symptoms of fungal esophagitis in alcoholic liver disease]. / Túnetek alkoholos májbetegek gombás oesophagitisében.

Symptoms related to fungal esophagitis were studied in patients with alcoholic liver disease who underwent upper gastrointestinal endoscopy. Data of 517 patients were studied retrospectively (group I) and 100 alcoholic liver disease patients, that were successively admitted to hospital, were enrolled in the prospective part (group II). Out of the 41 cases with fungal esophagitis found in group I, data of 38 could be evaluated. In group II 13 of the 93 evaluable patients had fungal esophagitis; according to Kodsi's grading 10 patients had grade 1., one patient grade 2. and two patients grade 2-3. oesophagitis. There was no case with grade 4. esophagitis. The rate of symptoms among the 51 patients with fungal esophagitis was: anorexia 23 (45.0%), abdominal pain 22 (43.1%), vomiting 17 (33.3%), nausea 15 (29.4%), occult gastrointestinal bleeding 12 (23.5%), weight loss 9 (17.6%), melena 7 (13.7%), bloating 6 (11.7%), acidic regurgitation 3 (5.8%), haematemesis 2 (3.9%), thoracic pain 2 (3.9%), singultus 1 (1.9%), odynophagia 0 and dysphagia 0. In 7 patients (13.7%) none of the studied symptoms could be identified. Despite the relatively high frequency of symptom free fungal esophagitis reported in the literature, the total lack of odynophagia and dysphagia in our patient group was remarkable. In the lack of deglutition disorders the other symptoms do not raise the suspicion of esophagitis. The diagnosis in such cases can be established only by endoscopy.

[Clinical and histological findings in HCV-caused hepatitis]. / Klinikai és histologiai megfigyeléseink hepatitis C vírus okozta hepatitisben.

58 cases of acute HCV-hepatitis were studied from the debut of acute illness and were followed up over 1-12 years. A mean three week's delay of anti-HCV IgG (Ortho) positivity was observed after the first manifestation of hepatitis. 70.6% relapsed and a chronic hepatitis developed in 37.9%. Seven patients died in HCV-hepatitis. Clinical, chemical, morphological features of HCV-hepatitis different from other viral hepatitis are demonstrated. Persistence of morphological signs of lobular hepatitis after even several months of subacute and chronic outcome has been found characteristic in HCV-hepatitis. Difficulties in interpretation of liver morphology are discussed. Simultaneous evaluation of clinical picture, laboratory markers and morphology is necessary to select cases for therapeutic trials.

[Diagnostic and therapeutic experiences with purulent meningitis in adults]. / Diagnosztikus és terápiás tapasztalatok felnöttkori gennyes agyhártyalobban.

The authors reviewed data of 137 patients with purulent meningitis treated in the period of 10 years. Attention was paid to the frequency of predisposing and associated diseases, to the factors helping and delaying the diagnosis and to those altering the prognosis. The importance of effective supportive care, particulary covering pressure of the CNS as well as specific therapy was stressed. The circumstances and the conditions of management depending on the condition of the patient was emphasized. Thirty eight of patients (27%) has died.

[Adult-onset Kawasaki syndrome in the differential diagnosis of liver disease]. / Felnóttkori Kawasaki-szindróma a májbetegségek differenciáldiagnózisában.

The authors present a case of an adult with Kawasaki syndrome, who, due to jaundice, enlarged liver and abnormal liver function tests, was admitted the hospital with the suspicion of liver disease. The symptoms of Kawasaki syndrome appeared during the first nine days of the hospital stay. The authors emphasise, that liver function tests are frequently abnormal in adults presenting with this clinical entity, therefore Kawasaki syndrome should be taken into consideration in the differential diagnosis of liver diseases.

[Diagnostic value of abdominal ultrasonography and endoscopic retrograde cholangiopancreatography in obstructive jaundice]. / A hasi ultrahangvizsgálat és az endoscopos retrograd cholangiopancreatographia diagnosztikus értéke elzáródásos sárgaságban.

The diagnostic value of ultrasonography (US) and endoscopic retrograde cholangio-pancreatography (ERCP) was compared, in 66 patients with bile duct obstruction, who underwent subsequent biliary surgery. The level of the blockage was diagnosed by US with a 80%, by ERCP with a 95.4% sensitivity, while the cause of the obstruction was determined with a 50% and a 89% sensitivity, respectively. Predictive value of these examinations is over 90%. Based on the clinical results and on the high diagnostic value of the above mentioned examinations, it is essential to fill up the bile ducts with direct contrast material.

[Diagnostic value of the determination of serum alpha2-HS-glycoprotein]. / A szérum alpha 2-HS-glycoprotein meghatározások diagnosztikus értékéröl.

Opsonic glycoprotein, alpha 2-HS-glycoprotein concentration was studied in the serum of 753 patients with various hematological, malignant, immunological, metabolic, endocrine and liver diseases and 68 healthy controls. Decreased serum alpha 2-HS-glycoprotein levels were detected in patients with acute leukemias, chronic granulocyte and myelomonocyte leukemias, lymphomas, myelofibrosis, multiple myeloma, metastatizing solid tumors, systemic lupus erythematosus, rheumatoid arthritis, acute alcoholic hepatitis, fatty liver, chronic active hepatitis, liver cirrhosis, acute and chronic pancreatitis, and Crohn's disease. Elevated levels were measured in patients with B and NANB/C hepatitis. Further decreased levels were observed in some groups with secondary infections. Serum alpha 2-HS-glycoprotein levels are affected by many factors, influencing the synthesis and elimination of the protein. The detection of serum alpha 2-HS-glycoprotein concentration has no specific diagnostic value as a marker for tumors or other diseases, however, its determination can be useful for the assessment of a non-specific regulator of the host defence.

[Isoprinosine therapy in chronic hepatitis C (multicenter placebo-controlled double-blind prospective study)]. / Krónikus C hepatitis isoprinosin kezelése (Multicentrikus, prospektív, placebo-kontrollos kettös-vak vizsgálat).

A placebo controlled clinical trial. Thirty two patients with chronic C hepatitis have been enrolled in a double blinded study to assess the therapeutic effect on an orally given antiviral-immunomodulatory drug, Isoprinosine. Seventeen patients were given Isoprinosine (3 g/day) and fifteen were on placebo. The treatment has been lasted for four months, when patients examined monthly. Clinical signs, liver function tests and side effects were evaluated. At the end of the trial, side effects and elevated serum alanine aminotransferase (ALT/GPT) levels occurred with higher frequency in Isoprinosine-treated patients. The results show that this antiviral drug has no beneficial effect in chronic C hepatitis.

[Experience gained from the organization of the first group of patients who benefited from liver transplantation]. / Tapasztalatok a májátültetéssel gyógyítható betegek elsö csoportjának szervezésével.

The authors report in this ciency in the majority of the cases was alcohol abuse or article about their experiences, how could they select a small group of patients awaiting liver transplantation since September 1994. The cause of the liver insuffiHCV infection. During 37 weeks 3 liver transplantations were performed and 5 patients died on the waiting list. (15,6% of the patients on the waiting list.)