Histopathology of the liver in children with chronic hepatitis C viral infection

Although the epidemiology, natural history, and pathological aspects of chronic hepatitis C are well-defined in the adult population, little is known about the characteristics of chronic hepatitis C infection in children. Reports on the histological features and progression of hepatitis C in children are scarce, and consist primarily of multicenter studies in Japanese and European children. Given the geographic variations in viral genotype and the association of pathology with genotype, whether the Japanese and European studies can be extended to the North American populations is unclear. We report the histopathology of the liver in 40 children with chronic hepatitis C infection treated in a single North American institution. The children included 19 males and 21 females ranging in age from 2.0 to 18.6 years at the time of liver biopsy (mean +/- SD: 11.4 +/- 4.3 years). Our findings indicate that the characteristic histopathological lesions of chronic hepatitis C infection, including sinusoidal lymphocytosis, steatosis, portal lymphoid aggregates/follicles, and bile duct epithelial damage, occur with approximately the same frequencies in children as have been reported in adults. Necroinflammatory activity was generally mild. Portal fibrosis was present in 78% of the specimens, including fibrous portal expansion (26%), bridging fibrosis (22%), bridging fibrosis with architectural distortion (22%), and cirrhosis (8%). Centrilobular pericellular fibrosis, which has not been previously reported in the context of chronic hepatitis C infection in adults or children, was also a prominent feature in our series, occurring with a similar frequency as steatosis or portal lymphoid aggregates/follicles. Our data suggest that in spite of mild histological necroinflammatory activity in general, the stage of fibrosis in children can be severe in spite of relatively short duration of infection.     

Arthritis in patients with chronic hepatitis C virus infection

OBJECTIVE: To describe the clinical picture of arthritis in patients with chronic infection by hepatitis C virus (HCV). METHODS: Two patient populations were studied. Patients with arthritis and evidence of serum elevation of alanine aminotransferase (ALT) at the consultation were checked for HCV infection. A second group of 303 consecutive patients with rheumatoid arthritis (RA) were also checked for the presence of HCV antibodies. All patients attended the outpatient rheumatology unit of a tertiary care teaching hospital. Chronic HCV infection was determined by the presence of viral RNA in serum. A group of 315 first-time blood donors served as controls. RESULTS: Twenty-eight patients with arthritis and chronic HCV infection were identified. Seven fulfilled criteria for RA, psoriatic arthritis was found in one patient, systemic lupus erythematosus in one, gout in 2, chondrocalcinosis in 2, osteoarthritis in 7, and tenosynovitis in one. In 7 patients with a clinical picture of intermittent arthritis, a definitive diagnosis could not be made. In these patients, mixed cryoglobulinemia was present in 6/7 (86%), whereas mixed cryoglobulinemia was found in 6/21 (28%) of the other patients. Among patients with RA, 23 (7.6%) had HCV antibodies, and active infection by HCV was found in 7 (2.3%) patients. The prevalence of HCV antibodies in a blood donor population was 0.95%, significantly different (p<0.001; 95% CI 0.03, 0.10) compared to patients with RA. The distribution of antibodies determined by recombinant immunoblot analysis was similar (p = NS) between RA patients and blood donors with HCV antibodies. CONCLUSION: There is not a single clinical picture of arthritis in patients with chronic HCV infection. There is a well defined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent, mono or oligoarticular, nondestructive arthritis affecting large and medium size joints. Although a high prevalence of HCV antibodies is suspected in patients with RA, its occurrence may be coincidental and its interpretation is difficult to determine from the data in this study.     

Superoxide dismutase in patients with chronic hepatitis C virus infection

It has been reported that hepatitis C virus (HCV) may cause oxidative stress in infected cells. Patients with chronic hepatitis C exhibit an increased production of tumor necrosis factor-alpha (TNF alpha), a cytokine that can produce oxidative stress by stimulating the generation of reactive oxygen species (ROS). Cell defense against ROS includes overexpression of Mn-superoxide dismutase (SOD), an inducible mitochondrial enzyme. To investigate cell defense against oxidative stress in HCV infection, we analyzed Mn-SOD mRNA in liver and in peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis C. Mn-SOD expression in PBMC was significantly increased in patients with HCV infection. Patients with sustained virological and biochemical response after therapy showed significantly lower Mn-SOD than patients with positive viremia. By contrast, Mn-SOD expression was not enhanced in the liver of patients with chronic hepatitis C. The values of Mn-SOD mRNA did not correlate with TNF alpha mRNA expression, viral load, or liver disease activity. Our results indicate that in HCV infection an induction of Mn-SOD was present in PBMC but absent in the liver, suggesting that this organ could be less protected against oxidative damage. Oxidative stress could participate in the pathogenesis of HCV infection.     

Jaw and leg claudication in a patient with temporal arteritis, chronic sialoadenitis and previous hepatitis C virus infection

OBJECTIVES: Poisoning by organophosphate insecticides causes cholinergic toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathy which usually occurs after ingestion of large doses of certain organophosphate insecticides and has so far only been reported in patients with preceding cholinergic toxicity. Surprisingly, it was recently reported by other authors that an exclusively sensory neuropathy developed in eight patients after repeated unquantified exposures to chlorpyrifos, which did not cause clear-cut cholinergic toxicity. The objective was to assess whether an exclusively sensory neuropathy develops in patients severely poisoned by various OPs. METHODS: Toxicological studies and electrophysiological measurements were performed in peripheral motor and sensory nerves in 11 patients after acute organophosphate poisoning among which two subjects were poisoned with chlorpyrifos. RESULTS: Three patients developed OPIDP, including one poisoned by chlorpyrifos. Exclusively sensory neuropathy was never seen after either single or repeated acute organophosphate poisoning. A mild sensory component was associated with a severe motor component in two of the three cases of OPIDP, the other was an exclusively motor polyneuropathy. CONCLUSION: A sensory-motor polyneuropathy caused by organophosphate insecticides might occur after a severe poisoning and the sensory component, if present, is milder than the motor one. Bearing in mind the toxicological characteristics of these organophosphate insecticides, other causes should be sought for sensory peripheral neuropathies in patients who did not display severe cholinergic toxicity a few weeks before the onset of symptoms and signs.     

Antibody-negative chronic hepatitis C virus infection in immunocompetent children

Two new pyrrolidine alkaloids, broussonetines G and H, were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines G and H were formulated as 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 6:10;10:13-diepoxytridecyl)-pyrrolidine (1) and 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 5:9;9:13-diepoxytridecyl)-pyrrolidine (2), respectively, by spectroscopic methods. 1 and 2 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Serum hepatitis G virus RNA in patients with chronic viral hepatitis

OBJECTIVES: The hepatitis G virus (HGV) is a newly described flavivirus that affects a high proportion of patients with chronic viral hepatitis: our objective was to determine what role HGV might play in the course of disease. METHODS: We evaluated stored serum samples from 108 patients with chronic hepatitis B and 99 patients with chronic hepatitis C who participated in trials of alpha-interferon or ribavirin for the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by branched DNA and for the presence of HGV RNA by polymerase chain reaction (PCR), using primers from the NS5 region of the genome. RESULTS: Initially, 20 (19%) patients with hepatitis B and 11 (11%) with hepatitis C had HGV RNA in their serum. Patients with and without HGV infection were similar with regard to clinical features, laboratory tests, and hepatic histology. HGV RNA levels fell during interferon therapy and became undetectable in those receiving the highest doses; however, HGV RNA levels returned to pretreatment values when therapy was stopped. With ribavirin therapy, HGV RNA levels did not change. Two- to 12-yr follow-up serum samples were available from 17 initially HGV RNA-positive patients, of whom only 10 (59%) were still positive. CONCLUSIONS: HGV infection is common among patients with chronic hepatitis B and C but has little effect on the short-term course of disease or response to therapy. HGV RNA levels are suppressed but not eradicated by alpha-interferon and are unaffected by ribavirin treatment. Spontaneous loss of HGV RNA occurs over time in a proportion of patients.     

Pulmonary Nocardia otitidiscaviarum infection in a patient with chronic respiratory infection

We report a case of pulmonary Nocardia (N.) otitidiscaviarum infection in a 76-year-old man with chronic respiratory infection. The patient responded poorly to intravenous imipenem and oral minocycline, but later improved after treatment with trimethoprim-sulfamethoxazole. Pulmonary infection with N. otitidiscaviarum should be considered in the differential diagnosis of chronic respiratory infections. Further studies are needed to evaluate the correlation between species and drug susceptibility.     

Autoimmune hepatitis and autoimmune manifestations in patients with chronic viral hepatitis

Mucosal adherence and germ tube formation have been considered as important virulence factors of Candida albicans. We investigated 11 clinical isolates (among them six isolates from oesophageal thrush) for quantification of adherence to buccal epithelial cells and germ tube formation in the continuous flow culture in vitro, and correlated the results with the clinical data of the patients. Adherence varied considerably between the different C. albicans strains. Strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells. Isolates from cases with heavy colonisation but clinically without candidosis were less adherent. Only after 30 min germ tube formation was observed in the continuous flow culture. Strains with stronger adherence also showed significantly faster and increased germ tube formation. The patients with oesophageal thrush did not suffer any particular immunosuppression such as HIV infection, although in most cases chronic alcoholism was apparent. We conclude, that in cases with minor immunosuppression the expression of the virulence factors adherence and germ tube formation plays an important role in the pathogenesis of candidosis, whereas it may be of less importance in cases with severe immunosuppression. In the latter they may, however, influence outcome.     

Primary hepatic lymphoma in a patient with chronic hepatitis B

Primary hepatic lymphoma is a rare disorder and the clinical behavior remains unknown. We report a patient with primary hepatic lymphoma who had chronic hepatitis B. She was asymptomatic; however, a solitary tumor in the left lobe was incidentally detected. After left hepatic lobectomy was performed, a diagnosis of non-Hodgkin's lymphoma was made. No tumor was found except in the liver. Immunohistochemical stains for hepatitis B surface and core antigens were positive in hepatocytes; however, both were negative in the tumor tissue. The patient received no chemotherapy and the tumor relapsed. After chemotherapy, the tumor disappeared. However, exacerbation of hepatitis occurred after the fourth chemotherapy. The patient was followed up without chemotherapy, and she remains in apparent remission. Chemotherapy is effective against primary hepatic lymphoma and, if possible, patients with this disorder should be treated with chemotherapy postoperatively.     

Histopathological characteristics of chronic hepatitis C virus infection in Turkey

Pseudoangiomatous hyperplasia of the mammary stroma is a benign mesenchymal proliferative lesion. It is rarely observed as a tumor mass that has to be differentiated from angiosarcoma. We give a review of the literature and report a case unusual in that it occurred in a clinical setting of HIV infection, was rapidly growing, and has been the largest described so far.