High serum resistin in chronic viral hepatitis is not a marker of metabolic disorder.

BACKGROUND/AIMS: The role of resistin, an adipocyte-secreted hormone, in insulin resistance and in inflammation is controversial. In chronic hepatitis C, insulin resistance, type 2 diabetes and liver steatosis are frequent and inconsistently correlated to circulating resistin levels. In this study we assessed if viral aetiology and host metabolic parameters influence serum resistin in patients with HCV- and HBV- related chronic hepatitis. METHODOLOGY: Serum resistin was measured by ELISA and correlated to viral aetiology, age, gender, BMI, HOMA-IR, liver steatosis, hepatitis staging and grading, blood glucose, triglycerides and cholesterol in 43 patients with chronic hepatitis C, in 16 with chronic hepatitis B and in 29 healthy controls. RESULTS: In both groups of patients resistin was significantly higher than in controls, with higher values in HBV- than in HCV-patients (p = 0.0007). Resistin levels were correlated to aetiology and, inversely, to age (p = 0.026), diabetes (p = 0.036) and steatosis (p = 0.029). Multiple regression analysis showed that resistin concentration was dependent only on the aetiology of liver disease (p = 0.001). CONCLUSIONS: In chronic viral hepatitis serum resistin levels are high and not associated with altered metabolic parameters or with the histological activity of the disease. The meaning of higher resistin in HBV- than in HCV- chronic hepatitis is unclear.

Prognostic factors of survival in complicated viral and alcoholic cirrhosis without hepatocellular carcinoma. A retrospective study.

AIM: In several studies, attention is needed to one specific complication, in particularly to hepatocellular carcinoma, which modifies the natural history of liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify which complications, alone or in combination, are predictive factors of mortality in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma. METHODS: Case records of 255 patients with decompensated viral or alcoholic cirrhosis between January 1990 and December 2000 were retrospectively analyzed. Relevant clinical and laboratory parameters, and their relationship to mortality, were studied. RESULTS: The mean duration of follow-up period was 29 months in which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients underwent liver transplantation. The cumulative mortality rate of patients with complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3 years and 65.1% after 8 years. A multivariate Cox's model identified the following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)-ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001), alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000). CONCLUSION: The mortality in a group of patients with alcoholic cirrhosis is longer than in those with viral cirrhosis . Moreover, ascites in combination with other complications, HRS and hemorrage-SBP association are independent predictors of mortality in patients with complicated liver cirrhosis.

Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC).

BACKGROUND: Using data from a case-control study carried out in Italy 1989-1992, we estimated the odds ratios (OR) and the population attributable risks (AR) for inflammatory bowel diseases (IBD) in relation to smoking, oral contraception and breastfeeding in infancy. METHODS: The study focused on 819 cases of IBD (594 ulcerative colitis: UC; 225 Crohn's disease: CD) originating from populations resident in 10 Italian areas, and age-sex matched paired controls. RESULTS: Compared with non-smokers, former smokers were at increased risk of UC (OR = 3.0; 95% confidence interval [CI]: 2.1-4.3), whereas current smokers were at increased risk of CD (OR = 1.7; 95% CI: 1.1-2.6). Females who reported use of oral contraceptives for at least one month before onset of symptoms had a higher risk of CD (OR = 3.4; 95% CI: 1.0-11.9), whereas no significant risk was observed for UC. Lack of breastfeeding was associated with an increased risk of UC (OR = 1.5; 95% CI: 1.1-2.1) and CD (OR = 1.9; 95% CI: 1.1-3.3). Being a 'former smoker' was the factor with the highest attributable risk of UC both in males (AR = 28%; 95% CI: 20-35 %) and in females (AR = 12%; 95% CI: 5-18%). Smoking was the factor with the highest attributable risk for CD in males (AR = 31%; 95% CI: 11-50%). Lack of breastfeeding accounted for the highest proportion of CD in females (AR = 11%; 95% CI: 1-22%). Oral contraceptive use accounted for 7% of cases of UC and for 11% of cases of CD. CONCLUSIONS: Taken together, the considered factors were responsible for a proportion of IBD ranging from 26% (CD females) to 36% (CD males). It is concluded that other environmental and genetic factors may be involved in the aetiology of IBD.

Interferon retreatment of patients with chronic hepatitis C. A long-term follow-up.

BACKGROUND/AIMS: We retrospectively evaluated the long-term efficacy of interferon retreatment in patients with chronic hepatitis C, who did not have a sustained response to a 1st cycle of treatment. METHODOLOGY: Sixty-six patients, 43 non-responder and 23 relapser to alpha interferon treatment, were retreated with alpha interferon, 6 MU thrice weekly for 12 months. Response was defined as negative HCV viremia. Responders underwent long-term follow-up (27-43 months). RESULTS: The response rates were 14% and 35% at the end of retreatment, 7% and 22% at 6 months, and 2% and 13% at long-term follow-up in non-responders and relapsers respectively. The outcome of retreatment was not statistically influenced by age, cirrhosis, viral genotype, dose and duration of previous treatment. CONCLUSIONS: Interferon retreatment, for sustained viral eradication, is not effective in non-responders and useful in few relapsers. Whereas, retreatment could prove effective in slowing down the activity of the disease and reducing the incidence of hepatocarcinoma, since some relapses occur late during the follow-up. Therefore, retreatment should be confined to relapsers with contraindications to new more efficient therapeutic strategies.

Lymphocyte populations in peripheral blood and in liver biopsy specimens from patients with acute and chronic hepatitis.

Lymphocyte subpopulations, both in peripheral blood and in liver specimens obtained with the Menghini needle, were evaluated by E and EA rosette technique in 30 patients with chronic active hepatitis (CAH), 8 patients with chronic persistent hepatitis (CPH), 11 patients with acute viral hepatitis (AVH) and 11 patients with normal histology or minimal non-specific changes. Circulating E-RCF concentration and percentage were significantly decreased in CAH and CPH patients. Only one patient with acute hepatitis had a decreased number of circulating E-RFC. The ratio of peripheral blood E-RFC to liver tissue E-RFC was decreased in the patient with chronic disease. In all the groups studied, the percentage of liver tissue and peripheral EA-RFC was similar to that found in the blood from controls. Significant differences were not found between patients with and without evidence for HB viral infection.

Class I HLA antigens hepatic display and beta-2-microglobulin serum values in chronic hepatitis C: effect of treatment with recombinant alpha interferon.

BACKGROUND/AIMS: Enhanced hepatocellular display of class I HLA antigens together with rising serum beta-2-microglobulin (a subunit of class I HLA molecule) and transaminases is reported in patients with chronic hepatitis B during treatment with interferon as an index of immune lysis of virus infected cells. METHODOLOGY: We studied class I HLA antigens and beta-2-microglobulin display in the livers of 23 patients with chronic hepatitis C before and after a 12 month treatment with recombinant alpha interferon. Beta-2-microglobulin serum values were monitored. In all the patients before treatment, class I HLA antigens and beta-2-microglobulin were diffusely displayed in the bile duct epithelium, in the sinusoidal lining cells, in approximately 50% of the inflammatory cells and in the hepatocyte membrane with marked staining in the areas of periportal and lobular necrosis. RESULTS: At the end of the treatment, class I HLA antigens and beta-2-microglobulin were no longer or only faintly detectable in the hepatocytes of 12 patients who showed clinical and histological improvement. The immunohistochemical pattern was unchanged in the 11 patients who did not respond to the therapy. Baseline serum beta-2-microglobulin values were high in all the patients and decreased significantly only in the group of responders. No peaks of transaminases were registered. CONCLUSIONS: The disappearance or reduction of HLA hepatocellular display without acute increase of serum beta-2-microglobulin values and transaminases during successful treatment with interferon in chronic hepatitis C suggests a clearance of the virus due to direct antiviral rather than immunologically mediated mechanism.

Ten year follow-up of patients with chronic hepatitis C treated with interferon.

BACKGROUND/AIMS: The impact of the treatment with interferon (IFN) on the natural history of chronic hepatitis C is not defined. The aim of this study was to evaluate the long term effect of the treatment in patients with chronic hepatitis C. METHODOLOGY: In 31 patients with chronic hepatitis C (9 with cirrhosis) consecutively treated with recombinant alpha 2a interferon (r alpha 2a IFN), the evolution of the disease at 10 years from the therapy was evaluated by means of upper endoscopy, liver ultrasonography (US), liver function tests and hepatitis C virus (HCV) viremia. RESULTS: Among 10/31 patients previously classified as responders, only 1 has signs of evolution to cirrhosis; HCV-RNA is still present in 2. Among 21 non-responder patients, 5 developed hepatocarcinoma (HCC) and 4 died during the follow-up; HCV-RNA is present in all the patients still alive. The 6 patients already cirrhotic when treated have clinical signs of progression to Child class B and C. The biochemical, ultrasonographical and endoscopical evaluation shows onset of cirrhosis in 7 of the others. CONCLUSIONS: Patients with chronic hepatitis C who respond to treatment with interferon have good outcome and rare evolution to cirrhosis. The treatment does not seem to influence the natural history of the disease in non-responders.

[Assessment of portal hypertension in hepatic cirrhosis in relation to etiologic factors]. / Valutazione dell'ipertensione portale nella cirrosi epatica in rapporto ai fattori etiologici.

Hundred-forty-one patients, 78 affected by alcoholic liver cirrhosis and 63 by posthepatitic cirrhosis were studied in order to assess the degree of portal hypertension in liver cirrhosis of different etiology taking into account the developing stages of the disease. Etiological assessment was based on anamnesis, laboratory data, needle liver biopsy and patients of each group were divided into 3 subgroups (grade A, B, C) according to Child-Turcotte classification. A > 1.3 cm diameter of portal vein and a > 13 cm spleen size evaluated by means of real-time ultrasonography together with the occurrence of esophageal varices at endoscopy were considered as signs of portal hypertension. Our study shows that such signs are more frequent in patients affected by posthepatitic cirrhosis in comparison with those affected by alcoholic cirrhosis. If the severity of the disease was considered, at the early stage (grade A) no significant difference was reported in portal diameters while splenomegaly and esophageal varices appeared more frequent in posthepatitic cirrhosis. In grade B patients the increase of portal and spleen size proved significantly greater in posthepatitic cirrhosis whereas prevalence of esophageal varices was similar in the two groups. The lack of differences in the three considered parameters at the end stage of the disease may be due to severe changes in liver morphology actually similar in the 2 groups apart from etiological factors.

[Behavior of anti-HBc IgM in acute and chronic hepatitis]. / Comportamento degli anti-HBc IgM nelle epatiti acute e croniche.

Anti-HBV core IgM antibodies (anti-HBc IgM) were tested by RIA in the sera from 269 patients with acute viral hepatitis (AVH), from 39 patients with chronic HBSAg+ hepatitis (CH) at various stage of evolution, in 41 asymptomatic HBsAg carriers and in 30 healthy volunteers. Anti-HBc IgM were found in 100/108 HBsAg+ AVH, in 6/161 HBsAg--AVH, in 9/39 with CH and only 1 asymptomatic HBsAg carrier. Among the chronic patients with anti-HBc IgM, 3 were HBeAg+ and 6 were anti-HBe+. The test of anti-HBc IgM results useful in the early aetiological diagnosis of acute hepatitis since it is always positive in HBV acute hepatitis even in the subjects who early seroconvert to anti-HBs; the absence of anti-HBc IgM in the HBsAg+ acute hepatitis suggests other overinfecting agents. The presence of anti-HBc IgM in CH seems not to be related to an active viral replication.

[Prevalence of non A - non B hepatitis in childhood (author's transl)]. / Incidenza di epatiti non A - non B in soggetti dell'età evolutiva.

Little is known from the literature about the epidemiology of non A - non B hepatitis (NANB/H) in childhood. Aim of this study was to assess the prevalence of NANB/H in a consecutive series of children with acute viral hepatitis hospitalized over an one year's period. Thirty children, 9 females, aged 3-12 years, were studied. Serial blood samples were tested for HBsAg, anti-HBs, anti-HBc, anti-HAV (Abbott RIA), anti-HAV-IgM (Absorption Staph. aureus protein A), anti-EBV (Immunofluorescence), anti-CMV, anti-Herpes s. virus (complement fixation). The diagnosis of NANB/H was based on the absence of these markers. Nineteen patients (63,3%) had type A, and 5 (16,6%), had type B hepatitis. One child showed antibodies anti-Herpes with rising titer and 5 (16.6%), 2 females, were considered suffering from NANB/H. None of these patients had been injected or haemotransfuded; all but one came from rural ambient and two from the same family. Two children had an anicteric course. The illness lasted less than 30 days in all but one, who showed three peaks of transaminases and recovered after 70 days. These data show a prevalence of NANB/H in childhood greater than that elsewhere reported, while the absence of injections suggests a way of infection other than parenteral.

Insulin-like growth factor-II is a useful marker to detect hepatocellular carcinoma?

BACKGROUND: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC. METHODS: Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data. RESULTS: The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels (r=0.427, p=0.0001) and with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP. CONCLUSION: Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment.

[e/Anti-e system in liver disease]. / Sistema e/anti e in patologia epatica.

HBeAg and anti-HBe were tested by RIA (Abbott Kits) in 53 patients (38 HBsAg +) with acute viral hepatitis (AVH), in 27 patients (5 HBsAg +) with chronic active hepatitis (CAH), in 54 (8 HBsAg +) with cirrhosis, in 32 (17 HBsAg +) undergoing haemodialysis, in 6 HBsAg carriers and in 45 controls. Most of the patients with HBsAg + AVH were HBeAg + in the first week and showed seroconversion to anti-HBe within the fourth week of the illness. Two from the four patients still HBeAg + in the fourth week seroconverted later on and clinically recovered, one is still HBsAg +/HBeAg + in the seventh week and one developed CAH HBsAg +/HBeAg +. High prevalence of HBeAg was found in the haemodialysed (94%) and in the patients with CAH (80%) while anti-HBe was more frequent in the HBsAg carriers (100%) and in the cirrhotics (62,5%). Among the patients HBsAg-, none was HBeAg + while 18% with CAH, 21,7% with cirrhosis, 26,6% of the haemodialysed and 4% of the controls were anti-HBe +. Our data, relating to AVH, are similar to those referred in the literature, but show conversely high prevalence of anti-HBe in CAH and in cirrhosis.

[Anti-HBc antibodies in chronic liver diseases]. / Gli anticorpi anti-HBC nelle epatopatie croniche.

The prevalence of the anti-HBc antibodies was studied in 54 patients with chronic liver disease and in a group of controls pair-matches. The meaning of the anti-HBc antibodies titer in the patients HBsAg negative is discussed. From our data, obtained by Radioimmunoassay, anti-HBc titers I:I000 seem to indicate an ongoing or recent viral replication, being probative, even in the absence of the HBsAg marker, for the viral etiology.

HCV infection, hepatic HLA display and composition of the mononuclear cell inflammatory infiltrate in chronic alcoholic liver disease.

Viral infection may play a role in alcoholic liver disease with histological features of chronic active hepatitis (CAH). Human leucocyte antigen (HLA) hepatocellular display is supposed to allow HLA-restricted T-lymphocyte cytotoxicity in chronic viral hepatitis. We studied the presence of serum anti-hepatitis C virus (HCV) antibodies, the hepatic HLA display and the composition of the mononuclear cell infiltrate in 16 patients with alcoholic liver disease and histological features of CAH and in 11 patients with alcohol-related degenerative changes. All patients were negative for hepatitis B virus (HBV) markers. Anti-HCV were tested by microplate ELISA. Class I HLA A, B, class II HLA DR, lymphocytes pan T, T helper/inducer, T suppressor/cytotoxic, B, and K NK cells were stained on liver cryostat sections by monoclonal antibodies and double indirect immunoperoxidase. Anti-HCV were present in all the patients with features of CAH and absent in those with only degenerative changes. In livers with features of CAH the mononuclear cell infiltrate consisted largely of T lymphocytes with marked prevalence of suppressor/cytotoxic cells in periportal and lobular areas. K NK cells were rare. Class I HLA, diffusely displayed on bile duct epithelium and on sinusoidal cells, also appeared on liver cells in the areas of periportal and lobular necrosis, namely on the hepatocytes in close contact with suppressor/cytotoxic T cells. In livers with only degenerative changes class I HLA were diffusely displayed on bile duct epithelium and on sinusoidal cells but absent on the hepatocytes. In all the specimens HLA DR antigens were expressed on sinusoidal and inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)