[Chronic osteomyelitis: a new therapeutical idea] / Osteomielite cronica: una nuova idea terapeutica.

We studied the case of a male patient aged 43 affected by post-traumatic chronic osteomyelitis with frequent relapses. Having supposed an insufficiency of the arterial and venous microcirculation in perilesional bone and soft tissue we decided for a therapy with iloprost and antibacterial drugs. After 15 months of treatment the patient hasn't showed any clinically evident relapsing episodes and we have not reported any side effects related to the therapy.

Are there any sex differences in fatty liver? A study of glucose metabolism and body fat distribution.

BACKGROUND AND AIMS: Fatty liver is a common condition found more often in males. Whether sex differences affect its development is presently unknown. The hypothesis that glucose metabolism alterations or central body fat distribution are gender-related in fatty liver was investigated. METHODS: Overall 199 consecutive subjects seen in the Division of Internal Medicine and Gastroenterology, Modena City Hospital, were enrolled. In the main arm of the present study, 44 men with sonographic fatty liver and 47 controls without, and 18 women with and 19 without fatty liver had their body mass index (an index of overall adiposity), hepatobiliary serum enzymes, serum cholesterol and triglycerides determined. All underwent oral glucose tolerance tests (estimated through the glucose area under the curve with the trapezoidal method). In the ancillary arm study, 17 other men with and 14 without, and 11 other women with and 29 without fatty liver had anthropometric measurements of body fat distribution (waist/hip, waist/height and skinfold thickness). RESULTS: Following statistical evaluation including univariate and multivariate analyses (main study), elevated body mass index was found to be an independent predictor of fatty liver in either sex. Glucose area under the curve and a central-type body fat distribution (ancillary study) predicted FL only in women. CONCLUSIONS: Fatty liver could be gender-related in the present series.

Alpha but not beta interferon is useful in chronic active hepatitis due to hepatitis C virus. A prospective, double-blind, randomized study.

Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.

Identification of subjects at risk for colorectal carcinoma through a test based on K-ras determination in the stool.

BACKGROUND & AIMS: The gold standard for screening for colorectal carcinoma is colonoscopy. The aim of this study was to compare endoscopic results with those obtained using the noninvasive screening test of K-ras determination in the stool in a large population of patients undergoing colonoscopy. METHODS: Two hundred thirty consecutive patients were studied by K-ras amplification on stool-derived DNA using polymerase chain reaction and oligomer-specific hybridization. RESULTS: Wild-type K-ras was amplified in 103 of 230 patients (44.8%), the rate of amplification being directly proportional to the presence of an organic disease of the intestine characterized by hyperproliferating mucosa. In 30 of these 103 patients (29.1%), a K-ras mutation was found. Four of 5 with early colorectal carcinoma, all who had K-ras mutations in the tumor, were identified. In first-degree relatives of patients with colorectal carcinoma, all subjects either carrying adenomas > 1 cm in diameter or multiple smaller adenomas were identified. In patients with inflammatory bowel disease, the test identified the only patient with neoplastic transformation. CONCLUSIONS: The sensitivity and specificity of K-ras determination on stool-derived DNA in patients with colorectal carcinoma, in first-degree relatives of patients with colorectal carcinoma, and in patients with inflammatory bowel disease support the opportunity of a large-scale trial to validate its use as a screening test.

Long-term follow-up of hepatitis C virus (HCV) infection in liver transplant patients.

Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT). To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long-term outcome of 22 patients with end-stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post-OLT liver disease. For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme-linked immuno-assays and by recombinant immuno-blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers). Of the 16 pre-OLT antiHCV-positive patients, 14 (87.5%) had recurrence of HCV infection while 2 cleared HCV. Pre-OLT genotype recurred in 11 of these 14 patients (2 genotype I) 8 genotype II - in 1 case associated with genotype III - and 1 genotype IV). Of the 6 pre-OLT antiHCV-negative patients, only 1 (16.6%) became persistently HCV-infected, with genotypes I and II. The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared.

Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients.

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76 +/- 18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were short-term responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the short-term responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II +/- I and 1 gt II +/- III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genotype, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P < 0.01 vs. untreated patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for hepatitis B virus infection in patients with chronic hepatitis C with and without serological markers of hepatitis B.

To assess the influence of HBV infection on anti-HCV-positive chronic liver disease, we performed a prospective case-control study comparing 19 HBsAg-positive, anti-HCV-positive patients with 38 HBsAg-negative, anti-HCV-positive patients, pair-matched for age, sex, and ALT levels. HBV and HCV infections were investigated by standard serology and polymerase chain reaction. HCV RNA was found in all patients with CAH and in 90.0% with cirrhosis (33% HBsAg-positive). HBV DNA sequences were found, in the HBsAg-positive subjects, in 71.4% of CAH and in 83.3% of cirrhotics; in the HBsAg-negative ones, only 10% of CAH but 77.7% of cirrhotics had demonstrable HBV DNA sequences. Consequently, 80.0% of cirrhotics had evidence of both HBV and HCV infection. Conventional serology gives partial information on the true occurrence of HBV infection in HBsAg-negative patients, while PCR defines more accurately the HBV status. When the rate of double infection is defined in this way, it correlates with the presence of cirrhosis.

Hepatitis C virus infection, HBsAg carrier state and hepatocellular carcinoma: relative risk and population attributable risk from a case-control study in Italy.

In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8-51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5-32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9-72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1-41.4), whereas no association (RR 1.5; 95% CI = 0.6-3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocellular carcinoma: risk factors other than HBV.

The putative risk factors for hepatocellular carcinoma (HCC) are several, even in countries endemic for hepatitis B virus (HBV) infection. Cirrhosis characterizes more than 90% of HCC cases. The phases of inflammation, necrosis and regeneration, present for long periods in cirrhosis, might be most relevant in hepatocarcinogenesis. It is not clear what role is played by sex hormones while alcohol probably has a promoter role. Aflatoxins are known carcinogenins in the experimental animal: however it is difficult to evaluate the impact in human carcinogenesis due to the lack of reliable methods of measuring aflatoxin exposure in population studies. In conclusion, the aetiology of HCC is multifactorial and the main risk factor resides in the presence of underlying chronic liver disease.

PIP: Experimental and epidemiological studies of risk factors for hepatocellular carcinoma (HCC): cirrhosis, male sex, oral contraceptives, alcohol, smoking, and aflatoxins, are evaluated, with meta-analysis for oral contraceptives, alcohol, and smoking. It is likely that an initiating event and one or more promoting events interact, probably with prolonged inflammation, necrosis and regeneration, to cause cancer in several types of cirrhosis. Over 90% of HCC patients have cirrhosis, usually from hepatitis B virus. The viral post-necrotic liver is often chronically dysplastic, but other types of cirrhosis are associated with HCC if they endure long enough. The proportion of men with HCC increases as hepatitis progressors to cirrhosis and then to HCC. Meta-analyses of 3 oral contraceptive studies resulted in a risk of 2.8 for 8 years of use, but 9.9 for 8 years. Population studies do not show any concentration of HCC in countries with high pill use, so the rarity of this cancer may have biased the results. Large epidemiologic studies are needed to refine risk estimates for oral contraceptives and HCC. Alcohol abuse of 80 g/day gives a risk of about 1.65 in pooled studies, compared to a risk of 1.1 for 80 g/day. Smoking gives a risk of 1.9, but there is no evidence for a secular trend by country in proportion to dose, as is evident for lung cancer. There is good experimental evidence that aflatoxin acts as an initiator for liver cancer, but there is not practical way to judge exposure for clinical studies.

HCV RNA in serum of asymptomatic blood donors involved in post-transfusion hepatitis (PTH).

A group of blood donors involved in post-transfusion hepatitis was investigated for the presence of the anti-HCV antibody and of HCV RNA as a more direct infection marker. RNA was extracted from serum, reverse transcribed and amplified using primers which belonged to the non structural region. The amplified product of the PCR reaction was 582 base pairs. Seven (25.9%) of the 27 blood donors examined were found anti-HCV-positive by ELISA; five (71.4%) of these were HCV RNA positive. Among the 20 anti-HCV-negative blood donors, four (20.0%) were HCV RNA positive. ALT levels were below 45 UI/l in 18 donors, while the other nine had ALTs over the limit accepted for transfusion. The anti-HCV-negative HCV RNA-positive blood donors had normal ALTs. Our study offers a direct explanation for the substantial proportion of residual cases of anti-HCV-positive post-transfusion hepatitis and suggests the necessity of creating a register of blood donors who have at some time presented blood enzyme abnormalities and for whom second level investigations such as HCV RNA should be used.