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We present the retrospective analysis of clinical manifestations and laboratory findings observed in 30 patients (M/F 13/17; age range 9-66 yrs) affected by acute rheumatic fever observed within the Infectious Disease Department along a period of 18 years (1986-2004). Diagnosis of carditis was stated on clinical and echocardiographical bases and occurred in 50% of patients. Such patients presented mild to moderate heart disease (30%) and severe carditis (20%). Therefore, our data stand to confirm that rheumatic cardiac disease could determine permanent and/or severe heart damage. All patients were observed during a 48-month period of follow-up without exitus.

Fibrosis and nodular regeneration are the hallmarks of liver cirrhosis. To assess the degree of fibrosis and the severity of the structural changes affecting parenchymal and extraparenchymal components in liver cirrhosis, a computerized morphometric model has been applied to liver specimens from patients undergoing liver transplantation for primary biliary cirrhosis, posthepatitic and alcoholic cirrhosis. Fifty-eight hepatectomy specimens from patients undergoing liver transplantation for cirrhosis were analyzed: 17 alcoholic, 28 posthepatitic (HBV-related and HCV-related cirrhosis), and 13 primary biliary cirrhoses. Liver specimens were fixed in 10% neutral-buffered formalin and embedded in paraffin. Sections were stained with chromotrope-aniline blue method and monoclonal antibodies against cytokeratin 7 and CD31. Volume fractions of parenchymal compartment and fibrosis were stereologically determined on the specimens stained with chromotrope-aniline blue method. Volume fractions of portal bile ducts, proliferated bile ductules, and hepatocytes with biliary metaplasia were measured on cytokeratin 7 stains, while volume fractions of capillary units have been evaluated on CD31 staining. Volume fraction of fibrosis was higher in primary biliary cirrhosis than in the other disease-induced cirrhosis. The main differences were related to immunohistochemical staining. Volume fraction of hepatocytes with biliary metaplasia was higher in HCV-related cirrhosis, whereas volume fractions of biliary structures were more prominent in HBV-related cirrhosis. Primary biliary cirrhosis was characterized by a reduced number of bile ducts and by a wider expression of cytokeratin 7 into periportal hepatocytes. Capillary units were more prominent in primary biliary cirrhosis than alcoholic and posthepatitic cirrhosis. Our computerized morphometric model well describes and quantifies the morphological alterations of the liver and it could represent an adjunctive tool to evaluate the degree of dysplastic phenomena involving parenchymal and extraparenchymal compartments., (2004 Wiley-Liss, Inc.)

A 43 year-old woman presented with fever, abdominal pain, epato-splenomegaly, ascites, cholestasis, anemia, thrombocytopenia and previous diagnosis of sclerosing cholangitis based on liver biopsy and endoscopic retrograde cholangiopancreatography(ERCP). The bone marrow biopsy and the revision of liver biopsy using antitryptase stain diagnosed systemic mastocytosis. Because of the aggressive course of the disease the patient was treated with an acute myeloid leukaemia chemotherapy regimen without success.

A 27 year old man with hereditary haemorrhagic telangiectasia who developed progressive liver dysfunction underwent living related right lobe transplantation. Pulmonary arteriography did not reveal arteriovenous malformation or abnormal intrapulmonary venous channels. The postoperative course was characterised by persistent hypoxaemia and respiratory failure developed. On day 6, a massive haemoptysis developed and the patient died shortly thereafter. The native liver showed a nodular pseudocirrhotic transformation, with highly dilated and irregularly interconnected vein-like or arterial-like structures in the fibrous septa. Pathological examination of both lungs showed irregular thickening of the wall of the arteries, secondary to eccentric and/or concentric myointimal hyperplasia. This case suggests that massive haemoptysis can develop even when arteriovenous malformations are undetectable by pulmonary arteriography, and it questions the role and the appropriateness of living donor liver transplantation in high risk patients.

Background/aims: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of chronic hepatitis C., Methods: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or 18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin for 48 weeks., Results: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40% and 36% for group C and D (P=0.63). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels., Conclusions: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.

summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.

To assess the degree of fibrosis and the structural changes affecting parenchymal and extraparenchymal components in liver cirrhosis, a computerized morphometric model has been applied to liver specimens from patients with posthepatitic and alcoholic cirrhosis. All specimens have been stained with chromotrope-aniline blue method and monoclonal antibodies against cytokeratin 7, CD31, and VIII factor. Volume fractions of parenchymal compartment and fibrosis have been determined stereologically on CAB slices; moreover, volume fractions of portal bile ducts and proliferated bile ductules, hepatocytes with biliary metaplasia, capillary units, and vascular structures have been measured. Volume fraction of fibrosis was higher in alcoholic cirrhosis when compared with the case of posthepatitic cirrhosis. Volume fractions describing parenchymal compartment showed a similar trend in both viral groups. The main differences were related to immunohistochemical stainings. Volume fraction of hepatocytes with biliary metaplasia was higher in hepatitis C virus-related cirrhosis, whereas volume fractions of biliary structures were more prominent in hepatitis B virus-related cirrhosis. Capillary units were more prominent in posthepatitic cirrhosis than in alcoholic cirrhosis. Interestingly, both forms of posthepatitic cirrhosis show similar features when compared with alcoholic cirrhosis. Our computerized morphometric model well describes and quantifies the morphological alterations of the liver, and it could represent an adjunctive tool to evaluate the degree of dysplastic phenomena involving parenchymal and extraparenchymal components.

Background/aims: To evaluate demographic characteristics, liver histology and virological features of hepatitis C virus (HCV) carriers with normal alanine transaminase (ALT) levels., Methods: A nationwide prospective study was started in 1997. Four Italian centres have participated in this study., Results: Eight hundred and eighty subjects entered the study. One hundred and eighty-nine (21.5%) were excluded during the follow-up because of ALT increase. Among the 691 patients with persistent ALT normality, 72% were females. An overall prevalence of genotype 2 was found (52%). Normal liver was found in 17% of the patients; 34% had minimal chronic hepatitis, 44% mild hepatitis, 4% moderate to severe hepatitis, and 1% had cirrhosis. Clinical and virological features did not differ between subjects with ALT flares and those with persistently normal ALT. Baseline ALT levels have no effects on liver histology and clinical outcome., Conclusions: Many HCV carriers have significant chronic liver damage, although in the majority of them liver lesions are minimal or mild. Up to 60% of HCV carriers in Italy harbour non-1 HCV types. Current definition of HCV carriers with persistently normal ALT levels, based upon three normal ALT values over a 6-month period, is not adequate to discriminate between carriers with persistent ALT normality and those with transient biochemical remission. Longer follow-ups are needed.

Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV- and HCV-RNA-positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.

Data from experimental hepatocarcinogenesis and recent studies in humans have suggested that the emergence of hepatocellular carcinoma (HCC) is a stepwise process. However, despite abundant experimental data, the precise molecular mechanisms and genetic alterations involved in human liver carcinogenesis are still unclear. Comparative genomic hybridization was used to analyze 26 hepatocellular nodules obtained from patients undergoing liver transplantation or surgical resection for HCC. According to the criteria proposed by the International Working Party, 16 nodules were classified as multiacinar regenerative nodules (MRN), 4 as low-grade dysplastic nodules (LG-DN), and 6 as high-grade dysplastic nodules (HG-DN). Our aim was to investigate the possible genetic differences between MRN, LG-DN, and HG-DN. The whole group of nodules showed only a few aberrations (mean 1.1/case), without any significant pattern. This finding is comparable to what happens in non-neoplastic tissue. On the contrary, in three of six HG-DN, we found deletions of 8p and gains of 1q. LG-DN and MRN did not show these chromosomal imbalances. These results confirm the important role of allelic losses on 8p as well as of gains of 1q in HCC. We conclude that the genes that are important in early stages of hepatocarcinogenesis are probably located on these chromosomal arms.

Wound infection and secondary meningitis represent important complications for patients undergoing acoustic neuroma surgery. The aim of this paper is to evaluate the efficacy of a short-term protocol with vancomycin and netilmicin. We studied 434 patients submitted to acoustic neuroma surgery in the Otorhinolaryngology Division, A.O. Ospedali Riuniti di Bergamo, during the years 1987-1997. The utility of this protocol was evaluated on the basis of the occurrence of infective episodes during the first ten-day follow-up.

Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combination treatment with interferon (IFN) and ribavirin have been promising, but long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monotherapy in 18 patients with moderate to severe recurrent hepatitis C and a median follow-up of 32 months after the completion of combined therapy. All patients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), and 8 patients were also hepatitis C virus RNA negative in serum (virological ETR, 44%) at the end of combined treatment. At last follow-up after the completion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained response [LT-SR], 72%), and 5 patients also maintained viral clearance (virological LT-SR, 27%). Comparison of liver biopsy specimens before and after 12 months of combined therapy showed improvement in grading scores of at least two points in the majority of the patients (73%). Notably, a trend toward fibrotic progression was only noted in nonresponders. Regarding side effects, despite the low dose of ribavirn, almost half the patients developed hemolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that combined therapy with low-dose ribavirin followed by long-term ribavirin monotherapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.

The clinical course and outcome of 5 adult patients who underwent orthotopic liver transplantation (OLT) and developed Kaposi's sarcoma (KS) is reported. From October 1986 to July 2000, a total of 459 patients underwent 499 OLTs at our hospital. The immunosuppressive regimen consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Tacrolimus was administered only in selected patients. Five patients developed KS, and the pathological diagnosis was established months 9 to 23 after OLT. Four of 5 patients died of KS, surviving 0 to 6 months after pathological diagnosis. The fifth patient, with KS confined to the skin, is disease free 6 months after diagnosis. All patients were treated with reduction of immunosuppressive therapy and/or chemotherapy. Retrospective molecular investigation by polymerase chain reaction for human herpesvirus type 8 DNA detected specific viral sequences in histological specimens of tissues involved by KS. In our experience with adult liver transplant recipients, we registered a slightly lower prevalence of KS compared with other reported data, but observed a high rate of graft involvement and mortality.

As far as concerns chronic hepatitis C virus infection in pregnant women, different points remain to be elucidated, such as the clinical course, the rate of mother-to-child hepatitis C virus transmission and, in particular, its route and the possible risk factors. This review aimed to analyse current data on the prevalence of chronic hepatitis C virus infection in pregnant women and its relationship with risk factors, the rate of mother-to-child hepatitis C virus transmission and the factors possibly involved, particularly the maternal hepatitis C virus viral load and the human immunodeficiency virus coinfection, and the type of delivery and feeding. Finally, the appropriate timing for HCV-RNA testing in newborns has been reviewed.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Well-established risk factors include infections with two very different viruses: the DNA virus causing hepatitis B (HBV) and the RNA virus inducing hepatitis C (HCV). In order to determine whether genetic differences exist between HBV- and HCV-induced HCC, 41 HCC samples of known vival status were examined by comparative genomic hybridization (CGH). The analysis revealed frequent deletions of 1p (24%), 4q (39%), 6q (41%), 8p (44%), 9p (24%), 11q (24%), 12q (22%), and 13q (39%), as well as common gains of 1q (46%), 6p+ (20%), 8q+ (41%), 11q (27%), and 17q+ (37%). There was no significant difference in the number and type of chromosomal imbalances between 25 HCV- and 16 HBV-infected tumours. This is consistent with models suggesting that HBV and HCV cause cancer through non-specific inflammatory and regenerative processes, rather than through virus-specific interactions with defined target genes. Chromosomal imbalances were also unrelated to the grade and stage of HCC. This may suggest that most gross genomic alterations occur early during HCC development and that further progression of these tumours may be associated with other types of genetic changes, not detectable by CGH. In summary, these data show that characteristic gross genomic changes occur in HCC, but these alterations at present do not appear to have diagnostic or prognostic applications., (Copyright 2000 John Wiley & Sons, Ltd.)

The prevalence and natural course of chronic hepatitis C virus (HCV) infection was evaluated in 15,250 consecutive pregnant women. The rate of HCV vertical and perinatal transmission was also assessed. The presence of anti-HCV was tested by means of EIA III and confirmed by recombinant immunoblot assay III. Alanine transaminase (ALT), anti-human immunodeficiency virus (HIV), and HCV-RNA were tested during the first month and third trimester of pregnancy, and 6 months after delivery; the same tests were made in all of the newborns of anti-HCV-positive mothers at birth (on cord blood samples) and then at 4-month intervals. Anti-HCV positivity was found in 370 cases (2.4%), 72% of whom were also HCV-RNA-positive. The proportion of women with hypertransaminases decreased from 56.4% at the first examination during the first month of pregnancy to 7.4% in the last trimester, and then increased again after delivery (54. 5%), without any concomitant changes in the proportion of those with viremia. The proportion of anti-HCV- and HCV-RNA-positive newborns was 5.1% after 1 year (8 of 155), all of whom had the same genotype as their mother. The rate of HCV transmission was not affected by the type of delivery or feeding, or the HIV status of the mother. The results of this large-scale study confirm previous data in smaller series concerning the prevalence of HCV infection in pregnant women, and strongly support the hypothesis of a favorable (possibly immunomediated) effect of pregnancy on liver cell necrosis in anti-HCV-positive women.

Objectives Our aim was to analyze the evolution of HCV infection in children infected at birth. Methods Between September 1994 and December 1998 we analyzed in a prospective study 8 children born of anti-HCV and HCV RNA positive women. Each baby was controlled at birth, every 3 months during the first year of life, and then every 6 months searching for anti-HCV antibodies (ELISA 3, RIBA 2-3), HCV RNA (RT PCR), ALT and viral genotype. Results Viral RNA was detectable in the first 3 months of life in all babies (100%) and remained positive during the follow-up. Viral genotypes were the same for mothers and their children. In 6 babies (75%) ALT remained pathologic during follow-up. Conclusions HCV infection in children usually has an asymptomatic outcome; the infection has chronic features in the majority of cases.

Background A new hepatitis-associated RNA virus, belonging to the Flaviviridae, has been recently discovered and called HGV (GBV-C). This virus has been shown to be transmitted parenterally. In this study we examined a group of children born to HCV infected women. Methods Between September 1994 and December 1998, we studied a cohort of 53 pregnant women, aged between 20 and 43 years. They were all HCV Ab and HCV RNA positive, with a diagnosis of chronic hepatitis. One patient was HbsAg positive and 4 patients (pts.) (7.5%) were HIV Ab positive. Anamnestic information revealed that: 28 pts. (52.8%) were IVDUs, 11 pts. (20.8%) had been haemotransfused and 14 pts. (26.4%) had no risk factors. We examined HGV RNA by RT nested PCR, using primers from the 5'UTR of HGV. Anti-HGV antibodies (anti-E2) were detected with an ELISA test using recombinant E2 protein. Ten of the 53 pregnant women (18.9%) were HGV RNA positive (32 other pts., 60.4%, were positive for anti-E2 antibodies). We monitored their children for 18-24 months (with clinicai and haematological controls), looking for HGV RNA, anti-E2 antibodies, HCV RNA and for ALT serum levels. Results Seven (70%) new-bom children proved HGV RNA positive at follow-up; all babies were HCV RNA negative at controls. Four of them were born vaginally; none of them was breast-fed. HGV RNA was first detectable at the 3rd month of life in 3 babies, and all babies were HGV RNA positive at the 6th month of life. Six babies (85.7%) remained positive during the observation period. One baby (14.3%) seroconverted at 10 months, developing anti E-2 antibodies and becoming HGV RNA negative. Four babies (57.1%) maintained normal ALT serum levels during the whole follow-up period, while 3 patients showed a low increase in ALT serum levels. The ALT values normalised at later controls. Conclusions HGV infection shows a very high (70%) rate of vertical transmission but a low and doubtful pathogenicity with asymptomatic evolution in babies. Patients who did not develop anti-E2 antibodies at the 12th month of life remained infected without persistent signs of hepatic failure.

We investigated the angiogenic phenotype of regenerative and dysplastic hepatocellular nodules to assess whether these lesions have distinct vascular profiles compared with the adjacent nonneoplastic or malignant liver. Forty-three liver nodules surgically removed from 18 patients were classified into regenerative and dysplastic categories. Serial sections of each nodule, adjacent cirrhotic liver (16 patients), and associated hepatocellular carcinoma (HCC) (6 patients), have been immunostained against CD31 and alpha-smooth muscle actin (alphaSMA) to detect capillary and muscular vessels. The study included 20 large regenerative nodules (LRNs), 13 low-grade dysplastic nodules (LGDNs), and 10 high-grade dysplastic nodules (HGDNs). The number of both capillary units and unpaired arteries was significantly increased in HGDNs and malignant lesions over LGDNs, regenerative, and cirrhotic nodules (P <.01), which showed an overlapping vascular profile. In addition, the number of capillary units, but not that of unpaired arteries, was significantly increased in HCC compared with HGDNs (P <.01). These results show that certain angiogenic features segregate HGDNs from other nonmalignant nodules such as LRNs and LGDNs. The former group of lesions is similar to HCC whereas the latter group is undistinguishable from the adjacent cirrhosis as far as their vascular profile is concerned. The adopted investigative approach does not support the morphological distinction between LRNs and LGDNs although it suggests that HGDNs are likely advanced precursors of HCC. An abnormal number of capillary units and/or unpaired arteries in a nonmalignant hepatocellular nodule can be diagnostically helpful to identify a precancerous lesion.

Controversial results have been reported concerning the correlation between serum levels of IgM antibodies to hepatitis B core antigen (IgM HBcAb) and the histological activity of chronic hepatitis B. In this study, paired serum samples and liver biopsies were collected from 200 consecutive chronic hepatitis B patients (mean age 39.2 +/- 0.8 years; M:F 154:46; 41 hepatitis B e antigen (HBeAg) positive) and tested for IgM HBcAb using a semiquantitative highly sensitive assay (IMx CORE-M(R)). The severity of liver disease was assessed by the Ishak score, grading the necroinflammatory activity (by using the histology activity index, HAI) and staging the fibrosis. The index values of IgM HBcAb were significantly different among patients with mild (HAI < or = 6), moderate (HAI 7-12) and severe (HAI > or = 13) necroinflammatory activity but the stage of fibrosis was unrelated to the IgM HBcAb. According to the index value of IgM HBcAb, we selected three groups of patients: Group A included 36 patients with an index value below 0.200; Group B, 99 patients with an index value between 0.200 and 0.500; and Group C, 65 patients with an index value over 0.500. The mean HAI grading in Group A was 5.3 +/- 0.4, in Group B it was 7.4 +/- 0.3 and in Group C it was 8.9 +/- 0.4 (f = 16.5, P < 0.0001). A mild HAI grading was observed in 77.8% of Group A, in 47.5% of Group B and in 23.1% of Group C patients; conversely, severe grading was detected in 0% of Group A, in 11.1% of Group B and in 18.5% of Group C patients (P < 0.0001). An index value of IgM HBcAb below 0.200 was 75% predictive of a mild necroinflammatory activity (29% sensitivity and 91.6% specificity) and ruled out a severe activity. Therefore, the quantitative assessment of IgM HBcAb appears to be a useful clinical tool in the prediction of the necroinflammatory activity of chronic hepatitis B. A serum index value of IgM HBcAb consistently below 0.200 could be considered a surrogate marker of remission of hepatitis B virus-induced liver disease.

Background: There is no uniformity of opinions about the possibility of sexual transmission of hepatitis-C-virus infection. Moreover the infection during pregnancy is often underestimated., Methods: One hundred and seventy-eight anti-HCV-positive pregnant women were investigated to evaluate the incidence of HCV infection and the possibility of sexual transmission of the disease to the partners., Results: 126 patients out of 178 (70.8%) were positive for viral infection at PCR. In 96 patients (53.9%) HCV-positivity was detected for the first time in the actual pregnancy. 147 male partners out of 178 were checked for HCV-positivity and in 31 of them (21.1%) HCV antibodies were found., Conclusions: The results underline the importance of a screening for HCV-positivity in every pregnant, searching for anti-HCV antibodies also in patients not reporting risk factors. ALT values seem to be of little importance in the monitoring of the pathology. Sexual transmission of HCV virus from woman to man seems to occur rarely.

In a subset of patients attending liver units, a chronic increase in serum transaminases may remain of undetermined cause despite thorough investigations. On the other hand, elevated levels of serum transaminases have been reported in about 40% of adult celiac patients. To evaluate the prevalence of subclinical celiac disease in patients with chronic unexplained hypertransaminasemia in comparison with that in the general population (0.5%), 140 consecutive patients with chronic increases of serum transaminases levels of unknown cause were tested for antigliadin and antiendomysium IgA antibodies. All patients with positive antibody tests were offered upper gastrointestinal endoscopy with distal duodenal biopsy. Thirteen patients (9.3%, 95% confidence interval 5. 0-15.4) had positive antigliadin and antiendomysium antibodies. The prevalence of antibodies was 17% in women and 5.4% in men (8/47 vs. 5/93 respectively; relative risk 3.2, 95% confidence interval 1.1-9. 1). Distal duodenal biopsy performed in all but one of the patients showed mild villous atrophy with increased intraepithelial lymphocytes in three cases, subtotal villous atrophy in six, and total villous atrophy in three. The prevalence of celiac disease in the patient group was significantly higher than that in the general population (P <.001) with a relative risk of 18.6 (95% confidence interval 11.1-31.2). On the basis of the present findings, screening for celiac disease is an important tool in the initial diagnostic work-up of patients with chronic unexplained hypertransaminasemia.

Evidence indicates that the GBV-C or hepatitis G virus can cause persistent infection in humans, but little is known on the importance of vertical transmission. To assess the risk of mother-to-infant transmission and the clinical outcome of infected babies, we investigated 175 anti-HCV positive mothers and followed-up their children for 3-33 months. GBV-C RNA was detected by RT-PCR and anti-E2 antibody was assayed by EIA. Thirty-four (19.4%) women were GBV-C RNA positive and transmission occurred to 21 (61.8%) babies; 20 (95.2%) acquired GBV-C alone, and one (4.8%) GBV-C and HCV. Maternal factors such as intravenous drug use, HIV coinfection, HCV-RNA positivity, and type of feeding were not correlated with GBV-C transmission. GBV-C RNA remained persistently positive in all infected babies but one baby who seroconverted to anti-E2. Seven (35%) babies with GBV-C alone developed marginally elevated ALT; the baby with HCV and GBV-C co-infection had the highest ALT peak value (664 IU/l). Seven of the 141 (5%) babies born to the GBV-C RNA negative mothers acquired HCV and six (85.7%) had abnormal ALT. The mean ALT peak value was significantly higher (P < 0.05) for babies with HCV than for those with GBV-C. None of the children with GBV-C or with HCV became icteric. GBV-C is frequently present in anti-HCV positive women. The infection is transmitted efficiently from mother to baby and rate of transmission is much higher than that for HCV. GBV-C can cause persistent infection in babies but usually without clear evidence of liver disease.

To assess the rate of mother-to-infant transmission of hepatitis C virus (HCV) and to identify potential risk factors for transmission, we followed up (mean 22.4 months, range 1-7.5 years) a cohort of 291 babies born to anti-HCV-positive mothers, 40 of whom were also HIV coinfected. Seventeen (5.8%) babies acquired HCV infection, but none became icteric. All babies developed chronic HCV infection with 16 babies showing elevated levels of ALT. The rate of transmission was higher in babies born to mothers coinfected with HIV than in those born to mothers with HCV alone (22.5 vs. 3.2%, p < 0.0001). No association was seen between a specific maternal HCV genotype and an increased risk of neonatal infection. The median level of HCV-RNA was higher in mothers who transmitted infection than in those who did not, although the ranges overlapped. In this study, maternal history of chronic liver disease, mode of delivery and type of feeding were not predictive of HCV infection.

Several genotypes of hepatitis C virus (HCV) have been recently identified by phylogenetic analysis, but their clinical relevance in the liver transplant setting is unknown. We evaluated the incidence and course of recurrent hepatitis C after transplantation in 50 patients who underwent transplantation for HCV-related liver disease. Liver biopsy specimens were obtained when clinically indicated and at yearly intervals; hepatitis was histologically graded and staged according to standard criteria. HCV-RNA was detected by nested reverse-transcription polymerase chain reaction (RT-PCR). HCV genotyping was performed by primer specific PCR. Follow-up was 6 to 62 months. HCV genotype distribution after transplantation of our 50 patients was as follows: 31 type 1b, 13 type 2a, 3 type 1a, 1 type 3a, 1 type 1b/2a, and 1, undetermined. Actuarial rates of recurrent hepatitis and of severe fibrosis or cirrhosis 5 years after transplantation were 56% and 20%, respectively, in patients infected by type 1b and 33% (P = .18) and 8% (P = .16) in those infected by 2a. In conclusion, this study provides evidence that in patients infected by HCV type 1b there is a trend for a more aggressive recurrent liver disease.

Inflammatory pseudotumour is a rare pathologic lesion, of unknown aetiology, rarely involving the liver. Resection seems to be the treatment of choice and it is generally associated with a good prognosis. Histologically, these processes appear to be benign, nevertheless, aggressive courses or recurrences of inflammatory pseudotumour with tumor-like deaths have been reported. The cases of two patients are described who underwent hepatic lobectomy for a liver mass that was diagnosed as liver inflammatory pseudotumour at the initial histopathological assessment: albeit a malignant course followed and both the patients died cachectic. One patient, a 39-year-old man, had an unusually aggressive clinical course and recurrence of the disease with multiple hepatic masses and extension into the thorax six years later. In the other case, in a 28-year-old woman, the hepatic lesion was identified as a low-grade hepatic sarcoma only seven years after surgery.

Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoembolization was performed on 25 patients. The perioperative mortality rate was 27% (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94%, 76%, 76%, and 83%, 75%, 75%, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for unresectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.

A case of end-stage renal failure caused by renal amyloidosis of the AA type is reported. No chronic disease responsible for the deposition of reactive amyloid was detected until giant lymph node hyperplasia of the angiofollicular type was identified in a mediastinal mass. Amyloid was found within the tumour mass and was characterized by immunochemistry with monoclonal antibodies to be of the AA type. Castleman's disease should be added to the list of chronic diseases endangering renal function by inducing the production and tissue deposition of secondary (AA) amyloid.

Ehlers-Danlos syndrome derives from some defect collagen synthesis or structure. It collects several disorders, clinically and genetically different. The young woman history with silent disease until lethal spontaneous arterial rupture is presented. Post-mortem examination shows type IV syndrome aspects: arterial fragility and right vertebral aneurisma rupture into pleural cavity with consequent fatal emothorax. Moreover there are mitral valve myxomatous degeneration, ascending aorta dilatation, lungs emphysema and meningioma.

In the interstitial cell infiltrates associated with primary glomerulonephritis, approximately the same cellular composition has been found, T cells being predominant, monocytes fewer, and B cells least. Cell composition did not seem to be related to the cell density; the lowest percentages of monocytes have been observed with either very high (FSGS) or very low (MGN) cell densities; and the highest percentages of T cells, with either the highest (FSGS) or the lowest (MGN) cell densities. On the other hand, some relationship seemed to exist with the cell distribution in the interstitium. The cell composition was nearly the same in diffuse and disseminated patterns, but was markedly different in nodular (focal) cell infiltrates; T cells were always in first place, but B cells instead of monocytes were in second place. Furthermore, IL2-receptor-presenting cells have been more often observed in nodular (focal) than in both diffuse and disseminated patterns, and more markedly in nonjuxtaglomerular than in juxtaglomerular noduli (foci). In conclusion, cell composition of interstitial infiltrates seems to reflect a cell-mediated immune reaction, leading to all interstitial cell infiltrates associated with primary glomerulonephritis. It is conceivable that the nodular (focal) pattern of distribution might correspond to a discrete mechanism and have a different meaning.

Two cases of tuberculosis peritonitis are here reported. Two young black males, who had recently immigrated from Senegal to Italy, were admitted to the Hospital because of aspecific, acute abdominal pain and underwent exploratory laparotomy. In both cases a flare-up of quiescent, post-primary chronic intestinal tuberculous infection was found at surgery. Extra-European immigrants often live in poor hygienic conditions in our country and are exposed to infectious ailments, which are unusual for the Italian population. In the differential diagnosis of acute abdominal pain in African immigrants, tuberculosis peritonitis should be always considered.

Three cases of visceral toxocariasis in adult patients are here described. Toxocariasis is a not uncommon, probably underestimated infection and the diagnosis should be considered also in adults who present clinical signs and it must be confirmed by serological tests.

Benign recurrent cholestasis. Report of three cases. 3 cases of benign intrahepatic recurrent cholestasis are reported. The disease is very rare and both clinical and pathological features are necessary for the right diagnosis. The value of liver biopsy in excluding other icteric diseases is stressed; clinical and serological findings are also important for the diagnosis and for the management of the patient.

We report a case of cystadenocarcinoma occurring in a pregnant woman. After child birth, a subtotal pancreatectomy was performed, without rupture of the cyst. The patient is asymptomatic, 24 months after surgery. The presentation of cystadenocarcinoma in pregnancy has been reported in another single case. The possibility of hormonal dependence is discussed.

The authors describe a case of intraspinal extradural ganglionic cyst. This is a rare condition which has not previously been reported in the literature. The differential diagnosis is discussed.

The AA describe a case of neonatal sepsis caused by Listeria monocytogenes observed in their Intensive Care Unit. The preterm neonate, born at the 30th week of gestational age, died after three days, showing clinical signs of sepsis and severe respiratory distress. Although the anamnesis of the mother revealed an episode of fever one month before delivery, the origin of which was not identified, it was not possible to isolate the Listeria in the mother. The AA discuss some clinical and therapeutical aspects of listeriosis; this infection is not very frequent in Italy, nevertheless it should not be underestimated either in the mother or in the neonate.

The authors report a case of massive left hemothorax in a 15-day-old baby girl, caused by the rupture of a thoracic neuroblastoma.

Parathyroid glands from 50 cases of primary hyperparathyroidism were examined by light and electron microscopy in an attempt to elucidate the diagnostic role of electron microscopy in this disease. In the cases in which only one gland was removed at surgery, a final diagnosis by light microscopy was not possible. The electron microscopic findings for some of these single glands (e.g., ribosomal-lamellar complexes and groups of centrioles) suggested that they were adenomas. In cases in which two or more enlarged glands were removed, a correct final diagnosis could be made on the basis of the light microscopic findings alone, and electron microscopy provided no further significant information. Where one enlarged gland and one normally sized gland were removed, electron microscopy disclosed important findings in the normally sized glands. Specifically, light microscopic examination of normally sized glands suggested endocrine suppression, while electron microscopy showed chief cell activity, thereby changing the final diagnosis from adenoma to hyperplasia. The clinical follow-up assessment in some of these patients confirmed the electron microscopic findings. Therefore, the incidence of adenoma in patients with primary hyperparathyroidism should be critically re-evaluated by ultrastructural studies of the normal glands that should be removed with the enlarged ones.