Histopathology of portal hypertension: a practical guideline.
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Humans↗
Biomedical subjects
F Callea
Publications and source records attributed to F Callea.
Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy.
OBJECTIVE: Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer (PLC) arising from intrahepatic bile ducts. We carried out a case-control study to assess the association between ICC and hepatitis B and C virus (HBV and HCV) infections, alcohol intake, and hepatolithiasis in Brescia, North Italy. METHODS: Among 370 subjects with histology-based diagnosis of PLC who were resident in the area and hospitalized in 1995-2000, 26 (7%) ICC cases were identified. A total of 824 subjects unaffected by hepatic diseases and frequency-matched with PLC cases by age, sex, date, and hospital of admission were recruited as controls. RESULTS: Among ICC cases the mean age was 65 years, 80.8% were males, and 38.5% had cirrhosis. Seropositivity for anti-HCV, HBsAg, alcohol intake >80 g/day and history of hepatolithiasis were found in 25%, 13%, 23.1%, and 26.9% of ICC cases and in 5.8%, 6.7%, 32.9%, and 10.6% of controls, respectively. The odds ratios adjusted for demographic factors by logistic regression (95% confidence interval; 95% CI) were 9.7 (1.6-58.9) for anti-HCV, 2.7 (0.4-18.4) for HBsAg, and 6.7 (1.3-33.4) for hepatolithiasis, whereas no association was found with alcohol drinking. CONCLUSIONS: HCV and hepatolithiasis may be risk factors for ICC in Western countries.
Aged↗
Genetic and immunological characterization of fibrinogen inclusion bodies in patients with hepatic fibrinogen storage and liver disease.
Fibrinogen storage in liver cells can occur under three different morphological inclusions. Type I contain all three fibrinogen chains (A alpha, B beta, and gamma) as well as D and E fragments, whereas type II and III lack B beta as well as D and E fragments. Patients with type I inclusions carry a point mutation (gamma 284 Gly-Arg). The mutation is not present in patients with type II and III inclusions. These results appear to suggest that the three various phenotypic expressions (i.e., morphological variants) reflect different genetical abnormalities of fibrinogen.
Fibrinogen↗
Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus.
A total of 204 patients with liver biopsy-proven hepatitis C virus (HCV) infection, 84 with and 120 without human immunodeficiency virus (HIV) coinfection, were studied, to evaluate variables possibly associated with the stage of liver fibrosis. All patients were injection drugs users, with a mean age of 32 years and an estimated duration of HCV infection of 12 years. Twenty-four patients (11%) had many fibrous septa with (5%) or without (6%) cirrhosis, 56 (27%) had few fibrous septa, and 124 (60%) had no fibrous septa. In all patients, an association was found between CD4 cell counts <500 cells/mm(3)and the presence of many fibrous septa (odds ratio, 3.2; P=.037), independent of HIV infection and other factors. These results suggest that HIV infection-induced CD4 depletion is independently associated with the severity of liver fibrosis in chronic HCV infection.
Adult↗
Fibrinogen brescia: hepatic endoplasmic reticulum storage and hypofibrinogenemia because of a gamma284 Gly-->Arg mutation.
The proposita suffered from liver cirrhosis and biopsy showed type 1 membrane-bound fiberglass inclusions. The hepatic inclusion bodies were weakly periodic acid-Schiff diastase-positive, and on immunoperoxidase staining reacted specifically with anti-fibrinogen antisera. Coagulation investigations revealed low functional and antigenic fibrinogen together with a prolonged thrombin time of 37 seconds (normal, 17 to 22 seconds) suggestive of a hypodysfibrinogenemia. DNA sequencing of all three fibrinogen genes showed a single heterozygous mutation of GGG (Gly)-->CGG (Arg) at codon 284 of the gamma-chain gene. However, examination of purified fibrinogen chains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reverse-phase high-performance liquid chromatography, ion-exchange high-performance liquid chromatography, and isoelectric focusing, failed to show any evidence of the mutant gamma(Br) chain in plasma fibrinogen. This finding was substantiated by electrospray ionization mass spectrometry, which showed only a normal gamma (and Bbeta) chain mass, but a large increase in the portion of their disialo isoforms. We speculate that misfolding of the variant protein causes hepatic retention and the subsequent hypofibrinogenemia, and that the functional defect (dysfibrinogenemia) results from hypersialylation of otherwise normal Bbeta and gamma chains consequent to the liver cirrhosis. These conclusions were supported by studies on six other family members with hypofibrinogenemia, and essentially normal clotting times, who were heterozygous for the gamma284 Gly-->Arg mutation.
Afibrinogenemia↗
Recurrent cholestasis and hypereosinophilia in a young female.
A 22-year-old female presented, in December 1998, with asthenia, itching and hypereosinophilia. In January 1997, due to the same clinical picture, the patient had inappropriately been diagnosed elsewhere to have an "idiopathic eosinophilic syndrome" and complete remission was obtained after short-term steroid treatment. Upon admission, physical examination was negative and blood tests revealed absolute eosinophilia [42%, i.e., 3,800 of 9,600 white blood cells], aspartate aminotransferase 4 x upper limits of normal, alanine aminotransferase 5 x upper limits of normal and alkaline phosphatase 2 x upper limits of normal. Both liver biopsy and endoscopic retrograde cholangiopancreatography findings were totally consistent with primary sclerosing cholangitis, while all known causes of hypereosinophilia and alteration in liver function tests were carefully excluded. The clinical course was characterized by complete clinical and biochemical normalization in absence of any treatment and further follow-up was completely negative.
Adult↗
Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis.
We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.
Aged↗
Inborn errors of metabolism and hepatocellular carcinoma (HCC).
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Carcinoma, Hepatocellular↗
Successful application of indirect in-situ polymerase chain reaction to tissues fixed in Bouin's solution.
AIMS: To evaluate the value of polymerase chain reaction-in situ hybridization (PCR-ISH) for the detection of human papillomaviruses (HPV) in paraffin sections of cervical biopsies fixed either in 10% formalin or in Bouin's solution. METHODS AND RESULTS: We analysed 40 biopsies from Italian women infected with the human immunodeficiency virus type 1 (HIV 1). In-situ hybridization techniques were performed with commercial biotinylated probes. The PCR-ISH was carried out by the 'hot start modification'. Cervical intraepithelial neoplasia (CIN) was found in 23 of 40 patients (57. 5%); eight cases showed condylomatous features. Human papillomavirus was detected in 42.5% by ISH and in 65% by PCR-ISH. Sixty-nine per cent of positive biopsies contained HPV 16, 18, 31 and 33. HPV 6 and 11 were found only in condylomata acuminata samples. CONCLUSIONS: The results point to a high incidence of HPV infection as well as of CIN in HIV-positive patients. Human papillomavirus type 16 appears to be most frequently associated with CIN. Polymerase chain reaction-ISH is more sensitive than ISH in the detection and typing of HPV DNA both in clinical and in 'latent' infections. The two techniques yielded the same results with either formalin- or Bouin's-fixed material.
Acetic Acid↗
Ultrasound evaluation of hepatic lymph nodes in patients with anti-hepatitis C virus antibody reactivity.
BACKGROUND: Portal lymphadenopathy is frequently found in inflammatory liver diseases. However, the mechanisms underlying portal lymphadenopathy are unknown. AIMS: To evaluate the prevalence of portal lymphadenopathy in patients with serum anti-hepatitis C Virus antibody reactivity and its relationship to clinical parameters. PATIENTS AND METHODS: The presence of portal lymphadenopathy was evaluated by upper abdominal Ultrasound by the same examiner in 114 patients with anti-hepatitis C Virus reactivity: 56 patients with normal liver enzyme activity and 58 randomly selected patients with increased liver enzyme activity undergoing liver biopsy. Laboratory tests were then performed in all patients the following day. RESULTS: Portal lymph nodes were found in a significantly higher percentage of patients with increased liver enzymes (74%) than in patients with persistently normal liver enzymes (29%: p < 0.01). Aminotransferases, gamma glutamyl transpeptidase levels and the percentage of patients with HCVRNA in serum and histological scores for piecemeal and lobular necrosis were significantly higher in patients showing hepatic lymph nodes. Multivariate analysis showed that only alanine aminotransferase and lobular necrosis were independently related to the presence of hepatic lymph nodes. A significant correlation was found between lymph node size, aminotransferase activity and lobular necrosis. CONCLUSION: Ultrasound-proven portal lymph node enlargement is an indirect sign of hepatocellular damage in patients with positive serum anti-hepatitis C Virus antibodies.
Adult↗
Iron chelation with oral deferiprone in patients with thalassemia.
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Biopsy↗
Variant liver estrogen receptor transcripts already occur at an early stage of chronic liver disease.
Variant estrogen receptors may be found in hepatocellular carcinoma and may influence its natural history. Because it is not known whether their occurrence is an early or a late event during the course of chronic liver disease or whether they cluster in some subgroups of patients, we investigated a series of patients in different stages of chronic liver disease. One hundred eleven consecutive patients were studied for variant estrogen receptor transcripts by reverse-transcription polymerase chain reaction of RNA extracted from liver biopsy specimens. In chronic active hepatitis, variant estrogen receptor transcripts were coexpressed with wild-type significantly more often in men than in women (P = .029) and in hepatitis B surface antigen (HBsAg)-positive subjects than in subjects positive for antibody to hepatitis C virus (P = .0006). In hepatocellular carcinoma, again in men (P = .004) and in HBsAg-positive patients (P = .0015), the variant estrogen receptor transcript was overexpressed or remained the only one expressed. Patients with liver cell dysplasia presented with the same estrogen receptor pattern than patients with hepatocellular carcinoma. This further reinforces the significance of liver cell dysplasia as a preneoplastic condition. The significantly higher occurrence of variant estrogen receptor in men (especially in HBsAg-positive men) already at an early stage of disease, like chronic active hepatitis, suggests that the alteration of estrogen receptors, favoring uncontrolled proliferation and development of hyperplasia, might constitute a prominent mechanism facilitating neoplastic transformation especially in men.
Adult↗
Adenomyomatosis of the gallbladder in childhood.
Adenomyomatosis of the gallbladder (ADMG) is defined as an acquired disease characterized by localized or diffuse hyperplastic extensions of the mucosa into, and often beyond, the thickened gallbladder muscular layer (Rokitansky-Aschoff's sinuses). In recent years, attention has been drawn to its malignant potential. The occurrence of ADMG has never been reported in children. The authors report the case of a 5-year-old boy with symptomatic ADMG, who was successfully treated by laparoscopic cholecystectomy.
Adenomyoma↗
Hepatitis C virus infection after renal transplantation: prevalence and course of morphologic lesions.
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Biopsy↗
Value of histochemical stains for copper in the diagnosis of Wilson's disease.
AIMS: The histochemical demonstration of hepatic copper is important in the diagnosis of Wilson's disease (WD). Conflicting results have been published with regard to the ability of different histochemical methods to demonstrate copper storage in the liver. Therefore, we evaluated the diagnostic value of three available histochemical methods in a large series of patients affected by WD. METHODS AND RESULTS: Seventy-nine consecutive liver needle biopsies, from 74 patients, 39 males and 35 females, aged 4-60 years (mean age 28.5 years) were stained with orcein, rhodanine and using Timm's method. On the basis of the histological picture, liver biopsies were subdivided into three groups: group A, steatosis; group B, interface hepatitis; group C, chronic hepatitis with bridging fibrosis and/or cirrhosis. In group A, 30.4% of the cases were positive using Timm's method, vs 13.2% using the rhodanine and 17.5% using the orcein method. In group B, Timm's method was positive in 40.1% while rhodanine and orcein showed positivity in 26.7%. In group C, the Timm's method stained 58.6%, rhodanine 36.6% and orcein 29.3% positively. CONCLUSIONS: Our data show that: (1) Timm's silver stain is the most sensitive method for the demonstration of copper in all cases of WD; (2) rhodanine and orcein have minor value in the diagnosis of WD, especially in the early stages of the disease; (3) to increase the diagnostic value of histochemistry for copper multiple histochemical stains in serial sections are required; and (4) although hepatic copper concentration is highest in the early stages of WD, the histochemical demonstration fails in a large number of cases.
Adolescent↗
[Multiple histochemical methods in the diagnosis of Wilson's disease. (Presentation of 74 cases and review of the literature)].
Conflicting results have been reported on the usefulness of histochemistry for copper in the diagnosis of Wilson's Disease (W.D.). In spite of the high number of methods proposed in the literature, no-one has shown to have the characteristics typical of a good histochemical method: high sensitivity associated with high specificity. On this basis, it seemed of interest to evaluate, in a large series of patients with W.D., the diagnostic value of the most commonly used histochemical methods for copper (rhodanine, orcein and Timm's method). To this end, 74 liver needle biopsies from patients affected by W.D., 39 males and 35 females, aged 4-60 years (mean age 28.5 years), were stained with rhodanine (R), orcein (O) and Timm's (T) methods. On the basis of the histological picture, liver biopsies were subdivided in four evolutive stages: stage I = steatosis; stage II = interface hepatitis; stage III = bridging fibrosis; stage IV = cirrhosis. In stage I, histochemistry for copper was positive in 11 out of 21 cases: 6 cases were T+; 1 case R+ and 2 cases O+; 2 cases were T+, R+, O+. In stage II, 11 out of 14 cases were positive for copper staining: 4 T+, 2 R+ and 2 O+; 3 cases were contemporary positives for T, R, O. In stage III, 22 out of 25 cases resulted positive: 8 T+, 3 R+ and 1 O+; 10 cases were positives, in the mean time, for more of one method. In stage IV, 12 of 14 cases were positives: 5 T+, 2 R+, 2 O+ and 3 cases were contemporaneously positives for multiple methods. Our data show that: 1) the percentage of positivity obtained using three histochemical methods for copper is higher than using only one method. From a practical point of view, it is mandatory to utilize, in clinical practice, multiple histochemical stains in order to increase the diagnostic utility of histochemistry for copper; 2) the Timm's method appears to be the most sensitive method for the demonstration of copper in all stages of W.D.; 3) even though hepatic copper already abounds in the early stages of W.D., this pool of intrahepatic copper is not yet demonstrable with any of the three histochemical techniques utilized.
Adolescent↗
Virological response to interferon treatment in hepatitis C virus carriers with normal aminotransferase levels and chronic hepatitis.
Hepatitis C virus (HCV) carriers with normal aminotransferase levels often show histological chronic hepatitis. This study was undertaken to determine the effect of interferon (IFN) in such patients. Nineteen HCV carriers with normal aminotransferase activities and chronic hepatitis were randomized to receive IFN-alpha2b (3 million units 3 times weekly for 12 months) or no treatment. Therapy was monitored by qualitative and quantitative determination of viral RNA. Patients who did not clear HCV RNA after 6 months discontinued therapy. In all, 9 patients constituted the control group, while 10 patients were treated. Five of these patients, still viremic after 6 months, stopped IFN. The remaining 5 patients, who cleared the viral RNA within 6 months, completed the 12-month course. Three of these patients relapsed off treatment, and 2 were still free of viremia 12 months after stopping therapy. A transient flare-up of aminotransferase activities was detected in 2 patients during treatment and in 3 patients after. None of the 9 control patients cleared the viral RNA during follow-up. A variable degree of sequence heterogeneity was detected in the hypervariable region before therapy, and IFN treatment decreased sequence diversity in all patients. These results indicate that IFN therapy can be effective in chronic HCV carriers with normal aminotransferase activities, inducing short-term virological response in 3 of 10 patients and sustained response in 2. The effects of treatment on viral load and quasispecies complexity were similar to those reported previously in patients with increased aminotransferase activities.
Adult↗
Chronic liver disease in the Alexandria governorate, Egypt: contribution of schistosomiasis and hepatitis virus infections.
BACKGROUND/AIMS: In Egypt chronic liver disease is customarily attributed to Schistosoma mansoni infection. Anti-HCV antibodies are highly prevalent among Egyptian blood donors, yet little is known about the risk factors, pathogenicity and virological features of HCV and its association with schistosomiasis. We studied 135 adult patients with chronic liver disease living in the Alexandria governorate, mostly in rural areas of the Nile Delta. METHODS: Evaluation included abdominal ultrasonography; detection of anti-HCV antibodies and markers of HBV and HDV infection; HCV-RNA assay by 5' untranslated region nested polymerase-chain-reaction and HCV genotyping by a line probe assay; serologic (anti-soluble egg antigen, anti-SEA) and parasitological examinations for Schistosoma mansoni infection; and liver biopsy, if not contraindicated. RESULTS: Ninety-one (67%) patients had anti-HCV and 107 (85%) anti-SEA, 32 (30%) of whom excreted schistosomal eggs in stools. In addition, 21 (16%) patients had HBsAg, 86 (64%) anti-HBc and four (3%) anti-delta. Thus, many patients had evidence of multiple infections, double in 66% (anti-HCV and anti-SEA), triple in 33% (anti-HCV HBsAg and anti-SEA). Based on our diagnostic criteria, 25 (19%) patients had schistosomal portal fibrosis (anti-HCV positive in eight), 24 (18%) chronic hepatitis (anti-HCV positive in 19), 76 (56%) cirrhosis (anti-HCV positive in 58) and 10 hepatic tumors (anti-HCV positive in six). At multivariate analysis, the presence of anti-HCV was independently associated with previous parenteral anti-schistosomal therapy, a history of hematemesis and seropositivity for anti-HBc. Fifty (55%) of 91 anti-HCV positive sera had HCV-RNA, in 41 cases classified as genotype 4a. Detection of HCV-RNA was associated with a more severe liver disease and occurred less frequently in patients with a history of schistosomiasis. CONCLUSIONS: HCV infection with genotype 4a is the main cause of severe chronic liver disease in Egypt, where it is highly associated with schistosomiasis.
Adult↗