Glomerulonephritis in autopsy cases with hepatitis C virus infection

1. The inducible isoform of nitric oxide synthase (iNOS) is expressed in human and experimental cardiac allografts and is localized to infiltrating macrophages, cardiac myocytes, endothelial cells and smooth muscle cells. A recent clinical report proposes a causal link between myocardial expression of iNOS and ventricular contractile dysfunction, a potentially graft- and life-threatening post-transplant complication. 2. Coronary blood flow is elevated in human graft recipients with biopsy proven cellular rejection, indicating that vasodilation accompanies graft rejection. In Lewis-to-F-344 coronary resistance vessels, which show intimal expression of iNOS, pressure-induced myogenic tone is significantly inhibited. Selective iNOS inhibition partially reverses the inhibition of myogenic tone, confirming that iNOS produces vasoactive nitric oxide (NO) and may mediate the rejection-induced vasodilation seen clinically. 3. Endothelial dysfunction, identified as loss of endothelium-dependent dilation, has tremendous prognostic significance in vascular diseases of multiple aetiologies. In transplantation, endothelial dysfunction predicts early cardiac allograft vasculopathy and poor clinical outcome. Lewis-to-F-344 coronary vessels develop endothelial dysfunction at 1 week post-transplantation, but this is preceded by a transient state of endothelial cell hyperfunction, with enhanced endothelial production of NO. 4. The normal interaction between endothelial and smooth muscle cells in coronary resistance vessels is critical for the regulation of coronary blood flow and the maintenance of fluid homeostasis. With allospecific expression of iNOS, the inhibition of vascular tone predicts greatly enhanced intravascular pressure in precapillary arterioles and capillaries; this would be expected to cause a net movement of fluid from the intravascular compartment into the myocardial interstitium, resulting in ventricular oedema, non-compliance and poor contractile performance.     

An autopsy case of ancient sarcoidosis associated with severe fibrosis in the liver and heart

The aim of the present trial was to study the effect of meticulous supragingival plaque control on (i) the subgingival microbiota, and (ii) the rate of progression of attachment loss in subjects with advanced periodontal disease. An intra-individual group of sites exposed to non-surgical periodontal therapy served as controls. 12 patients with advanced periodontal disease were subjected to a baseline examination (BL) including assessments of oral hygiene status, gingival condition (BoP), probing depth, clinical attachment level and subgingival microbiota from pooled samples from each quadrant. The assessments were repeated after 12, 24 and 36 months. Following BL, a split mouth study was initiated. The patients received oral hygiene instruction, supragingival scaling and case presentation. 2 quadrants in each patient were identified as "test" and the remaining 2 as "control" quadrants. Subgingival therapy was performed in all bleeding sites in the control quadrants. Oral hygiene instructions and plaque control exercises were repeated once every 2 weeks during the initial 3 months of the study. Thereafter the plaque control program was repeated once every 3 months for the duration of the 3 years. Sites demonstrating loss of clinical attachment > or =2 mm in the test quadrants were treated subgingivally. The results showed that in both test and control quadrants repeated oral hygiene instructions and supragingival plaque removal procedures resulted in low plaque scores throughout the study. The gingival bleeding scores and the frequency of periodontal pockets > or =4 mm was, however, significantly higher in the test quadrants than in the control quadrants. At the end of the 3 year study, the control quadrants showed significantly more reduced (> or =2 mm) pockets than the test quadrants, 265 versus 96. The number of sites in the test quadrants showing probing attachment loss > or =2 mm was more than 4x greater than in the control quadrants (59 versus 13). The microbiological findings indicate a more pronounced reduction only for P. gingivalis in the control quadrants. None of the other 4 marker bacteria consistently reflected or predicted the clinical parameters. The present study shows that only supragingival plaque control fails to prevent further periodontal tissue destruction in subjects with advanced periodontal disease.     

Polyarteritis nodosa associated with hepatitis C virus

BACKGROUND: To study the seroprevalence of hepatitis C virus in a cohort of six patients with a diagnosis of polyarteritis nodosa (PAN). METHODS: There have been included six patients with a diagnosis of PAN, carrying out a serodiagnosis of hepatitis B virus (VHB) and C (VHC) this last one by means of the following methods: ELISA, RIBA-II and PCR. RESULTS: These cases (50%) showed exclusive positivity to VHC by means of the three ways of diagnosis, two cases showed positivity to VHB (33.3%), one case (16.6%) showed positivity to both virus (VHB and (VHC) and one case didn't show positivity virus. CONCLUSIONS: It is probable a ethipatogenic relation between hepatitis C virus and polyarteritis nodosa, our sample doesn't show any difference from that written in the literature. The positive rheumatoid factors can give false positive for VHC by means of the technique ELISA because of this it is necessary to confirm the positive by means of the techniques RIBA-II and PCR.     

An unusual hyperplastic hepatocellular nodule in a patient with hepatitis C virus-related liver cirrhosis

Recent advances in diagnostic imaging techniques have increased the likelihood of detecting novel nodular lesions of the liver. We report here a case of unusual hyperplastic hepatocellular tumor found in a 70-yr-old woman with hepatitis C virus-related cirrhosis. A mass was incidentally detected in the right lobe by abdominal ultrasonography and confirmed by computed axial tomography (CT). Magnetic resonance imaging demonstrated that the tumor had hyperintense signal with a small hypointense region in the center and a thin, hypointense rim on T1-weighted image and a hypointense signal on T2-weighted image. CT during hepatic arteriography showed that the tumor was hypodense with a central hyperdense region, whereas CT during arterial portography revealed that the tumor was isodense and surrounded by a thin circular hypodense band with a central hypodense region. These radiographic findings suggested a diagnosis of dysplastic nodule with malignant foci of hepatocellular carcinoma. The patient underwent tumor resection. Macroscopically, the tumor, 45 x 45 x 30 mm in size, was encapsulated and had a central stellate-like scar with radiating septa. Histological examination showed a hyperplastic hepatocellular tumor without cellular, nuclear or structural atypia. The central fibrous scar contained abundant small, artery-like and vein-like vessels, whereas there were no normal portal triads but rather several portal tract-like structures lacking bile ducts in the parenchyma of the tumor. Some of the portal tract-like structures were composed of artery-like and vein-like vessels, and the others possessed vein-like vessels only. There were no bile ducts in the tumor. The nontumorous liver tissue had evidence of macronodular cirrhosis. Finally, this tumor was regarded as an unusual type of hyperplastic hepatocellular nodule encountered in cirrhotic liver, characterized by the presence of central stellate-like fibrosis and the lack of bile ducts. Although the pathogenesis of the hyperplastic lesion is unclear, it may represent a focal regenerative hepatocellular response to localized circulatory disorder.     

Epstein-Barr virus associated natural killer cell leukemia: report of an autopsy case

A 20-year-old female was admitted because of high fever, hepatosplenomegaly, severe hepatic dysfunction and coagulopathy. Peripheral blood showed pancytopenia and granular lymphocytes bearing the natural killer cell phenotype (CD2+CD3-CD16+CD56+CD57-TCR alpha beta-TCR gamma delta-) constituted 97% of leucocytes. Southern blot analysis of DNA obtained from peripheral blood mononuclear cells showed germ-line configuration of TCR beta, gamma and delta chain genes. EBV-DNA was detected in a single episomal form by using EBV-terminal repeat probe. Bone marrow findings were consistent with hemophagocytic syndrome and administration of VP-16 was effective transiently. After ten months she died from massive gastrointestinal bleeding. An in situ hybridization study identified EBV-RNA (EBER-1) in atypical lymphocytes infiltrating bone marrow, spleen and lymph nodes. Sections of liver showed steatosis and infiltration of T cells (CD3+ and EBER-1-negative) in the portal areas and few atypical lymphocytes in sinusoids. The patients developed an EBV-associated clonal proliferation of natural killer (NK) cells, but the clinical features were suggestive of chronic active EBV infection or virus-associated hemophagocytic syndrome (VAHS) rather than leukemia. Bone marrow transplantation for NK cell leukemia is an issue to be discussed.     

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P < 0.001), habitual heavy drinking (P < 0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc, P < 0.05), and age greater than 60 years (P < 0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80-9.78) in male patients, 3.27 (95% CI, 1.46-7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01-3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00-4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively, P < 0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4 +/- 4.4 years vs 28.4 +/- 3.9 years; P < 0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis.     

Dilated cardiomyopathy associated with hepatitis C virus infection

BACKGROUND: Myocarditis is thought to be commonly caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. In many cases, however, the evidence is only circumstantial, and direct conclusive proof is not available. Polymerase chain reaction (PCR) has been used to detect enterovirus RNA in myocardial tissue, but the wide discrepancy in results emphasizes the need for further study. METHODS AND RESULTS: We investigated hepatitis C virus infection in patients with dilated cardiomyopathy. The presence, type, and quantity of hepatitis C virus RNA were evaluated in the sera, and the presence of positive and negative strands of hepatitis C virus RNA in the heart was investigated with the PCR technique. Anti-hepatitis C virus antibody was present in the sera of 6 of 36 patients (16.7%) with dilated cardiomyopathy and in 1 of 40 patients (2.5%) with ischemic heart disease, showing a statistically significant (P < .05) difference. At an earlier time, acute myocarditis was suspected in 3 patients who had developed acute onset of heart failure, and the diagnosis was confirmed by endomyocardial biopsy in 1 patient. Hepatitis C virus RNA was present in the sera of 4 of the 6 patients, and all 4 had hepatitis C virus type II. The copy number of hepatitis C virus RNA in the serum was 8 x 10(2) to 2 x 10(3) genomes per 1 mL serum. Positive strands of hepatitis C virus were found in the hearts of 3 patients, and negative strands of hepatitis C virus were detected in the heart of 1 patient. CONCLUSIONS: The results suggest that hepatitis C virus infection is frequently found in patients with dilated cardiomyopathy and that hepatitis C virus is an important causal agent in the pathogenesis of the disease. Antiviral therapy against hepatitis C virus may be indicated in these patients.     

Posttransplant liver granulomatosis associated with hepatitis C?

BACKGROUND: Liver granulomatosis is an occasional finding in posttransplant liver biopsies. Its diagnosis is made more difficult by the variety of conditions that can lead to it. In the nontransplant setting, the association of liver granulomatosis and hepatitis C virus (HCV) infection has occasionally been described. METHODS: We describe the case of a patient with a liver transplantation for an HCV-associated cirrhosis who developed an alteration of liver tests. Granulomatosis was detected on the liver biopsy. RESULTS: Other causes of granulomatosis were satisfactorily excluded. The development of the lesions coincided with a viral flare-up. CONCLUSION: We think that HCV can be listed among the possible causes of liver granulomas in the posttransplant setting and that it must be considered in the differential diagnosis of this condition.     

A case of idiopathic iliopsoas hematoma associated with liver cirrhosis

We report a rare case of intratracheal thyroid ectopia in the setting of papillary thyroid carcinoma, resulting in the preoperative clinical impression of an aggressive, high-stage tumor. A 24-year-old opera singer presented with complaints of a gagging or choking sensation. The results of computed tomography revealed a mass in the left thyroid lobe with multiple small calcifications consistent with papillary thyroid carcinoma as well as a soft tissue mass in the adjacent left tracheal lumen thought to be direct invasion by the thyroid tumor. A total thyroidectomy was performed including excision of half of the first and second tracheal cartilages and the lower portion of the hemicricoid cartilage. The final histological findings revealed that the intratracheal component was composed of benign thyroid tissue and strands of benign thyrocytes coursed through the first tracheal membrane. Intratracheal thyroid ectopia is a rare symptomatic occurrence with a striking female predisposition. We have identified 23 cases of intratracheal thyroid ectopia from the literature. They occur most often at the level of the cricoid, usually posteriorly with a slight predisposition for the left side. Continuity between the intratracheal component and the thyroid lobe may be seen. Clinicians and pathologists must be aware of this entity to avoid mistaking it for evidence of thyroid invasion by a malignant neoplasm.     

Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma

In Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma-derived vaccine 5 micrograms i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non-vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7-year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti-hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post-transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti-HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.     

Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation

PURPOSE: To review the treatment of cirrhotic patients with hepatocellular carcinoma in the era of liver transplantation and to determine the most appropriate approach to the treatment of patients at different stages of disease. DATA SOURCES: A MEDLINE search of English-language articles published between 1981 and 1997 and the clinical experience of the Mount Sinai Liver Transplant Program. STUDY SELECTION: Selected studies were 1) original articles reporting results of resection and transplantation in the treatment of hepatocellular carcinoma in cirrhotic patients and 2) initial reports from major transplantation centers of multimethod therapies combining chemotherapy with transplantation. DATA EXTRACTION: Study designs were assessed with careful attention to methods and aims. Relevant data on patient population, tumor stage distribution, treatment, survival, and rate of recurrent disease were extracted and analyzed. DATA SYNTHESIS: Options for the treatment of hepatocellular carcinoma in cirrhotic patients vary according to tumor stage and severity of underlying liver disease. Resection remains an important method primarily in eastern countries, where the screening of high-risk populations has been associated with early detection of small asymptomatic lesions. Long-term survival after resection, however, is low. In western countries, liver transplantation is becoming the treatment of choice in patients with advanced cirrhosis and small, unresectable lesions; resection is reserved for cirrhotic patients with small, peripheral lesions and preserved hepatic function. Minimally invasive procedures (such as percutaneous ethanol injection and transarterial chemoembolization) have been developed to treat unresectable tumors. Transarterial chemoembolization may also be effective in patients with advanced cirrhosis and unresectable lesions who are awaiting transplantation. CONCLUSIONS: The efficacy of liver transplantation for hepatocellular carcinoma has been proven mainly in patients with advanced cirrhosis and small lesions. Future studies may clarify the role of approaches combining neoadjuvant chemotherapy with transplantation for large (stage III) tumors.     

Biological characteristics of esophageal squamous cell carcinoma associated with contiguous intraepithelial carcinoma

To evaluate the biological significance of esophageal squamous cell carcinoma that is associated with contiguous intraepithelial carcinoma, we analyzed 95 patients with operated esophageal carcinoma. Of these 95 patients, eight had in situ carcinoma. Among 87 cases in which the tumo had invaded more deeply than the lamina propria, there were 42 cases (48.3%) of contiguous intraepithelial carcinoma associated with the main tumor. The biological characteristics (proliferative activity of cells, as revealed by immunostaining with the Ki-67 monoclonal antibody) of 45 tumors without contiguous intraepithelial carcinoma (group A) were compared with those of 42 tumors with contiguous intraepithelial carcinoma (group B). The more advanced was the main lesion, the lower was the incidence of contiguous intraepithelial carcinoma. The mean Ki-67 score of the main tumors in group A was 51.6% and that of the main tumors in group B was 45.9%. The mean Ki-67 score of the main tumors in group B was very similar to that of the contiguous intraepithelial carcinomas that were associated with the main tumors (44.4%, P = 0.682). Furthermore, the mean Ki-67 score of contiguous intraepithelial carcinomas associated with main tumors was very similar to that of carcinomas in situ (41.2%, P = 0.529). From our results, it is suggested that tumors with high proliferative activity may be assumed to grow rapidly and, as a result, the region of intraepithelial carcinoma may develop into an invasive tumor. By contrast, tumors with low proliferative activity may grow slowly and, in such cases, the carcinoma may remain in the epithelium around the invasive tumor.     

Reproducibility of hepatitis C virus antibody detection with various confirmatory assays

Angiostrongylus costaricensis (classified under the more specific genus Parastrongylus by different authors) is a filiform intestinal nematode endemic to Central and South America, which afflicts primarily the pediatric population 1 to 13 years of age. Only three cases of adult infections have been previously documented outside the endemic region. To our knowledge, we report the first such case in the western United States, as well as the oldest patient yet recorded. Our patient is a 73-year-old woman living in Los Angeles who presented with an acute abdomen 4 weeks following a 5-month visit to El Salvador. Examination of the gross ileum removed at exploratory laparotomy revealed a perforation associated with a segmentally thickened intestinal wall. Microscopic examination showed eosinophilic ileitis, arterial lumens containing nematodes morphologically consistent with A costaricensis, eggs in the submucosa, and arteriolitis with thrombosis.     

GB virus C infection in patients with primary antibody deficiency

Sera from 77 patients with common variable immunodeficiency (CVID) were tested for GB virus C (GBV-C) RNA, because they are prone to unexplained chronic hepatitis, and from 28 patients with X-linked agammaglobulinemia (XLA) who have a similar primary antibody deficiency but are not prone to hepatitis. Eight CVID and 8 XLA patients were positive; 6 positive CVID and 3 XLA patients had abnormal liver enzymes, explained in 3 by either hepatitis B or C virus infection. Most patients tested had antibodies to the E2 antigen of GBV-C, apparently passively acquired from their immunoglobulin therapy. The high prevalence of GBV-C viremia in CVID and XLA patients is probably explained by their long-term exposure to blood products. Our data indicate that GBV-C does not cause chronic hepatitis in immunocompromised XLA patients and is not the cause of chronic non-B or -C hepatitis in the majority of CVID patients.