Evaluation of HBV and HCV antigens expression in correlation with HBV DNA and HCV RNA occurrence in liver biopsy specimens of patients with chronic hepatitis type B and chronic hepatitis type C, respectively.

MATERIAL AND METHODS: The material studied consisted of single liver biopsy specimens and serum samples from 97 patients diagnosed by clinical and serological criteria as having chronic hepatitis of either type B (38 patients seropositive for HBsAg) or type C (59 patients seropositive for anti-HCV). Diagnosis of chronic hepatitis, including grading and staging of the process, was established by histopathological examination of routinely stained serial paraffin sections. The expression of HBV and HCV antigens was detected in frozen sections by amplified immunoperoxidase method (EnVision, DAKO) with the use of monoclonal anti-HBs antibodies (DAKO), polyclonal anti-HBc antibodies (Biogenex) and FITC-labeled human antibodies to HCV antigens. HBV DNA and HCV RNA were searched for in tissue homogenates with PCR (In Gen; Terpol, Sieradz) and RT PCR (Cobas Amplicor HCV RNA, Roche), respectively. RESULTS: HBsAg was detected in all and HBcAg in 26 of the 38 biopsy specimens with chronic hepatitis type B from patients who were seropositive for HBsAg and anti-HBc, and for either HBeAg (25 cases) or anti-HBe (13 cases). HBV DNA was identified in 32 out of 38 liver biopsy specimens. Out of the 32 HBV DNA positive specimens, 6 that had been obtained from patients seropositive for anti-HBe, lacked HBcAg expression. HCV antigens were found in 27 (50%) out of 54 specimens which showed the presence of HCV RNA. CONCLUSIONS: These results are indicative for a strong positive correlation between the expression of HBV antigens and that of HBV DNA in liver biopsy specimens. The detection of HCV antigens has proved to positively correlate with that of HCV RNA in 50% of the specimens examined. It appears, therefore, that testing of liver biopsy specimens for HBV and HCV antigens may, in a significant proportion of cases, extend the histopathological diagnosis as to include identification of the etiologic factor.

Comparative analysis of plasma lipoprotein components assessed by ultracentrifugation in primary biliary cirrhosis and chronic hepatitis.

UNLABELLED: The evaluation of lipid and lipoprotein profiles in liver diseases has important cognitive aspects and provides practical information contributing to the diagnosis of liver pathology. There are few studies of this problem using the ultracentrifugation method. AIM OF THE STUDY: A comparison of lipid profile (obtained by plasma ultracentrifugation) in patients with primary biliary cirrhosis (PBC) and chronic hepatitis (CH). MATERIAL AND METHODS: 103 percutaneous liver biopsies were routinely performed from 1994 to 1997. Blood samples were taken from all the patients at the time of biopsy for further evaluation of lipid profile. 15 patients with PBC and 15 patients with CH (of HBV or/and HCV etiology) were studied. RESULTS: In patients with CH mean total, esterified and free cholesterol levels (166 mg%, 117.6 mg% and 48.1 mg%, respectively) were significantly lower (p < 0.002; p < 0.004; p < 0.006, respectively) than in patients with PBC (237.5 mg%, 165.7 mg% and 71.8 mg%, respectively). The phospholipid concentration in sera of patients with PBC were significantly higher (271.1 mg%, p < 0.0004) than in patients with CH (187.6 mg%), whereas apolipoprotein B and apoAII were significantly lower. Total, esterified and free cholesterol levels in LDL fraction were significantly higher in patients with PBC (175.3 mg%, p < 0.007; 117.9 mg%, p < 0.02; 57.6 mg%, p < 0.01, respectively) than in patients with CH (113.7 mg%, 78.7 mg% and 35 mg%, respectively). The concentration of phospholipids in LDL fraction in patients with PBC was significantly higher (166.8 mg%; p < 0.003) in comparison with patients with CH (96.3 mg%). The differences in other lipoprotein fractions (VLDL and HDL) were not statistically significant. CONCLUSIONS: High levels of total, free and esterified cholesterol as well as phospholipids, apolipoprotein B and AII were observed by us in patients with PBC in comparison with patients suffering from CH. The increase of cholesterol (total, esterified and free) and the phospholipid concentration in serum, are a manifestation of their higher concentration in LDL fraction.

Incidence and treatment of hepatitis C virus infection in children with haemophilia in Poland.

In 80% of children with haemophilia treated in our department, screening tests showed the presence of antibodies against the hepatitis C virus (HCV). HCV RNA was detected in serum in 41% of cases. In 20% of cases there were periodic increases in the level of alanine aminotransferase (ALT) activity, and in these cases liver biopsy was performed after factor concentrate replacement. No haemorrhagic complications or pain complaints were reported either during the biopsy or immediately afterwards. In all cases histopathological examination revealed chronic hepatitis type C - chronic mild hepatitis and chronic minimal hepatitis. Eight boys were treated with interferon (INF) alpha. In two cases this therapy was successful. No HCV RNA was detected in serum and transaminase activity was normal during the year following interferon treatment.

Wilson's disease coexisting with viral hepatitis type C: a case report with histological and ultrastructural studies of the liver.

Histopathological and ultrastructural findings in the liver of a female patient who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are reported. Light and electron microscopy examinations demonstrated a variety of morphological alterations--many of them frequently seen in livers of patients with WD and others that can be found in cases presenting HCV infection. The influence of coexistence of these two diseases on morphological changes is discussed.

Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients.

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

Hepatitis G virus coinfection in chronic hepatitis B and C patients in Poland.

This study evaluated the epidemiology and impact of hepatitis G virus (HGV) infection in patients with chronic hepatitis B and C. Serum samples were obtained from 128 consecutive untreated patients with chronic hepatitis B (72 cases) or C (56 cases). The presence of HGV RNA was determined by PCR amplification of the 5'untranslated region; the sensitivity of the assays was ten template copy equivalents. The prevalence of HGV RNA in hepatitis B and C was found to be 25% and 34%, respectively. HGV-positive and HGV-negative patients did not differ with respect to risk factors for infection, age, sex, or alanine aminotransferase activity. Similarly, there was no difference in the severity of liver disease, as assessed with HAI score. In conclusion, we found a very high prevalence of HGV infection in chronic hepatitis B and C patients in Poland. Nevertheless, no evidence was found that HGV coinfection has any impact on the severity of the underlying disease.

Clinical course of concomitant Hbv and Hcv infection in renal allograft recipients.

We evaluated the impact of concomitant infection with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) on the clinical course after renal transplantation (Tx). In 335 patients (pts) transplanted between 1991 and 1993 we found 30 (9%) recipients who were positive for Hepatitis B surface antigen (HBsAg) (ELISA, Organon) and anti-HCV antibodies (immunoblot assay Lia Tek) preTx. Chronic liver disease (CLD) (two-fold or greater increase in serum ALT and AST levels for at least six months) developed in 40.7% coinfected pts as compared to 24.4% and 25.7% pts infected only with HCV or HBV, respectively. Maintenance immunosuppression consisted of P + Aza + CsA, mean follow-up time was 28 +/- 15 months. The mean time of the onset of CLD was 3.0 months (range: 1-18 months) after Tx. Percutaneous liver biopsy performed in 5 CLD pts revealed chronic active hepatitis (CAH) in 4 and chronic persistent hepatitis (CPH) in 1 pt. Four pts who had CAH and were positive for HCV RNA (RT PCR) in serum and for HBcAg in liver tissue, received interferon-alpha therapy for 6 months. Clinical improvement of liver function was observed in all of them, but none cleared HBsAg or HCV RNA. One pt lost his graft due to acute rejection. Concomitant infection with HBV and HCV is associated with the high risk of development of CLD early after Tx. We recommend that pretransplant evaluation of both anti-HCV and HBsAg positive pts should include liver biopsy to exclude potential recipients with CAH.

AIDS pathology: infections and neoplasms in 55 fatal AIDS cases. A postmortem study.

The study evaluated the incidence of infections and neoplasms in 55 out of 104 patients with AIDS who died in Poland from January 1986 to April 1994 (the estimated autopsy rate-52.8%). Histopathological examination revealed 103 infections and 11 neoplasms. In 40 persons (73%) either multiple infections or a neoplasm and an infection were diagnosed. Cytomegalovirus infection was most common. (65.5% of cases) followed by Pneumocystis carinii (24% of cases). These infections were the leading cause of death in 20% and 16% of cases, respectively. The results of this study showed a significantly lower incidence of Pneumocystis carinii, Kaposi's sarcoma and non-Hodgkin's lymphoma in comparison with the results of similar studies in countries with a large number of AIDS cases.

[Etiology of chronic hepatitis as evaluated by liver biopsy and serum samples submitted to the Department of Immunopathology of the National Institute of Hygiene in 1993-1995]. / Etiologia przewleklych zapalen watroby na podstawie badan biopsji watroby i surowic nadeslanych do Zakladu Immunopatologii Panstwowego Zakladu Higieny w Latach 1993-1995.

The purpose of this study was to assess the relative incidence of chronic hepatitis in a population of patients with chronic liver disease and to determine the etiological spectrum of this syndrome with special reference to its defined histopathological forms. Histopathology aided by immunohistochemistry, and serology aided by the PCR method were employed in studies of liver biopsy specimens and serum samples, respectively. Out of 1150 patients with chronic liver disease examined, chronic hepatitis was diagnosed in 685 (60% of all cases examined). In this group, there were 308 males aged 18-74 yrs (mean 32 yrs), 153 females aged 18-71 yrs (mean 43 yrs), and 213 children aged 1-17 yrs (mean 8 yrs). Viral infections documented in these patients included HBV (50.4%), HCV (36.2%), HBV/HCV (7.2%) and HBV/HDV (0.7%); cryptogenic and autoimmune hepatitis (AIH) accounted for 2.9% and 2.6% all cases, respectively. In the group of minimal hepatitis (16.1%), HBV infection was documented in 66.4% of cases, HCV-in 29.1%, HBV/HCV-in 3.6% (one case of AIH was included into this group). In the group of mild hepatitis (44.2%), HBV infection accounted for 47.3% of cases, HCV-for 41.9%, HBV/HCV-for 9.9%, and 0.9% was diagnosed as cryptogenic. In the group of moderate hepatitis (19.6%), HBV infection accounted for 50% of cases, HCV-for 37.3%, and HBV/HCV-for 4.5%; cases of cryptogenic and AIH accounted for 3.7% and 4.5%, respectively. In the group of severe hepatitis (20.1%), HBV etiology was found in 44.9% of cases, HCV-in 28.3%, HBV/HCV-in 6.5% and HBV/HDV-in 3.6%; cryptogenic and AIH accounted for 6.5% and 8.0% of cases, respectively. There was a high incidence of low-titer autoantibodies (SMA, ANA and LKM) ranging from 75% in cryptogenic hepatitis and 51% in each HBV and HBV/HCV hepatitis to 46.3% in HCV hepatitis.

[Correlation of clinical and morphological diagnoses in 55 fatal AIDS cases]. / Korelacje rozpoznan klinicznych i morfologicznych w 55 przypadkach zgonów w przebiegu AIDS.

Pathomorphological studies were performed in 60 HIV-infected patients and the accuracy of clinical diagnoses of infections and neoplasms was evaluated. In 5 cases clinical diagnosis of AIDS was not confirmed at autopsy. 114 infections and neoplasms were found in 55 AIDS-patients, of these 80 (70%) were not diagnosed clinically. Clinical diagnosis of the cause of death was consistent with morphological findings in 24 AIDS cases (45.5%). The results justify a plea for a close co-operation of clinicians, microbiologists and pathologists to improve the accuracy of clinical diagnoses in AIDS patients. In a fatal case of AIDS a post-mortem study should always be performed.

HIV lymphadenopathy--a histopathological and immunomorphological study of 65 cases.

Lymph nodes from 65 HIV-infected persons were studied by morphological and immunomorphological methods. Early stages of HIV lymphadenopathy (follicular hyperplasia without fragmentation or follicular hyperplasia with severe fragmentation) were revealed in 92% of patients with PGL and the most advanced stadium of HIV-related lymphadenopathy (diffuse pattern) in 92% of AIDS patients. Striking B-cell activation and polyclonal proliferation, found in 19 lymph nodes (35% of advanced lymphadenopathy cases--follicular atrophy or diffuse pattern) justified separation of these cases as a particular subgroup of HIV lymphadenopathy.

[Fatty liver assessed by histologic examination in patients with hyperlipoproteinemia]. / Stluszczenie watroby oceniane badaniem histologicznym u osób z hiperlipoproteinemia.

Out of 665 patients after liver biopsy performed during 14 years of the work of the Clinic, 35 cases of patients with non-alcoholic liver steatosis and hyperlipoproteinaemia were selected and analysed retrospectively. The cases of patients with the presence of HBV or HCV infection markers were excluded. The histological material was divided according to the intensity of steatosis expressed as the per cent of hepatocytes with the features of fatty degeneration and also according to the following classification: I--steatosis, II--steatosis with hepatitis, III--steatosis with portal fibrosis, IV--steatotic cirrhosis. In the patients in whom the per cent of hepatocytes with fatty degeneration in biopsy examination exceeded 60%, the mean serum triglyceride concentration was 5.53 mmol/l and was over twice higher than that in the group with steatosis not exceeding 30% of hepatocytes. Similarly, in the patients with steatosis and accompanying hepatitis (steatohepatitis), the mean triglyceride concentration was 5.28 mmol/l and was over twice higher than that in the patients with steatosis with accompanying portal fibrosis. The patients with steatohepatitis had significantly lower HDL concentrations than those with the remaining types of histological changes.

Hepatocellular-cholestatic liver injury due to amoxycillin-clavulanic acid combination.

Two cases (first cases from Poland and Eastern Europe) with liver injury due to amoxycillin-clavulanic acid (augmentin) are reported. Pruritus and jaundice were the main symptoms. Liver biopsy revealed mixed hepatocellular-cholestatic liver injury in both cases. In addition, in one case the microgranulomalike aggregate of inflammatory cells was found. Clinical and laboratory abnormalities returned to normal within 13 weeks.

[Hepatitis due to HDV infections]. / Zapalenie watroby wywolane zakazeniem HDV.

From May 1985 to the end of February 1988 the Department of Immunopathology carried out serological studies of 518 samples of the blood serum and made an immunomorphological analysis of 518 hepatic specimens taken by needle biopsy from chronic HBsAg carries. In four cases we found the presence of antigen delta (HDV Ag) in the nuclei of the hepatocytes. These are the first fully documented by immunomorphological and serological methods cases of HDV infection in Poland. We also discussed the epidemiology and biology of viral infection in delta hepatitis.