Ribavirin treatment for chronic hepatitis D: a pilot study

To assess whether therapy with Ribavirin may affect the course of chronic delta hepatitis, nine Italian patients with this disease received the drug orally at a dosage of 15 mg/kg daily for 16 weeks. At the end of the therapy period, all patients were followed for 12 additional months. Seven patients completed the trial. Two patients were withdrawn: one developed hemolytic anemia, and the other intractable itching. At the end of treatment HD viremia was reduced in one patient, had cleared in another, and was unchanged in the remaining five patients. None of the patients decreased their alanine transferase (ALT) levels by more than 50%. At the doses given in this study. Ribarivin did not show significant antiviral effects in chronic hepatitis D, and was not effective in reducing the biochemical markers of liver inflammation and necrosis.     

The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis

BACKGROUND: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. METHODS: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. RESULTS: The DRB1*03,DQA1*0501, DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). CONCLUSION: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.     

A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy

Sixty-four heterosexual Italian carriers of HBsAg with chronic HBeAg and hepatitis B virus DNA-positive hepatitis were assigned randomly either to receive human lymphoblastoid interferon (injections of 5 million units per m2 three times per week for 6 months) or to serve as untreated controls. After 18 months of follow-up evaluation, 26 of the 33 treated patients (79%) had cleared hepatitis B virus DNA, 23 (70%) had lost HBeAg and 20 (61%) had seroconverted to anti-HBe. Fifteen of the 31 controls (48%) had cleared hepatitis B virus DNA (p = 0.01), 12 (39%) had lost HBeAg and nine (29%) had seroconverted to anti-HBe (p = 0.002). Eight treated patients but only one control had lost HBsAg and seroconverted to anti-HBs (24% vs. 3%, p = 0.01). Treated patients cleared hepatitis B virus markers after a mean interval of 4 months, compared with 8 months in the controls. All responders to interferon cleared intrahepatic HBcAg, and 50% showed histological improvement. The baseline hepatitis B virus DNA levels and the original histology were not predictive of a response to therapy; women appeared to respond better than men. Lymphoblastoid interferon provides an effective therapy in the heterosexual Italian patient with chronic hepatitis B.     

Serologic markers with fulminant hepatitis in persons positive for hepatitis B surface antigen. A worldwide epidemiologic and clinical survey

Of 377 cases of fulminant hepatitis in persons positive for hepatitis B surface antigen (HBsAg) in Greece, Italy, the United States, the United Kingdom, the Central African Republic, Taiwan, Egypt, and India, only 52% could be attributed to infection with hepatitis B virus, which was defined as the presence of the IgM antibody to the hepatitis B core antigen (IgM anti-HBc) and the absence of serum markers of infection by extraneous viruses. Thirty percent of cases were caused by coinfection with hepatitis B virus and hepatitis delta virus or by infection with hepatitis delta virus superimposed on carriers of chronic HBsAg. In 18.5% of the patients, the absence of IgM anti-HBc indicated that they were not known to carry HBsAg, but no obvious superimposed factor of hepatitis could be identified. The cause of fulminant hepatitis is complex, and major risk factors are a pre-existing HBsAg state and hepatitis delta virus infection. Superinfection of HBsAg carriers by non-A, non-B viruses seems to be the cause in a consistent proportion of cases.     

Loss of Tubuloglomerular Feedback in Decompensated Liver Cirrhosis: Physiopathological Implications

In healthy subjects, arterial pressure reduction or renal ischemia produces renal artery dilatation through autoregulation and tubuloglomerular feedback (TuGF). Patients with decompensated cirrhosis have reduced kidney perfusion pressure but show renal vasoconstriction instead of autoregulation-mediated vasodilation. This study investigates the consequences of kidney autoregulation loss on renal perfusion, glomerular filtration rate, and tubular handling of electrolytes in both compensated and ascitic nonazotemic cirrhotic patients. Forty-two consecutive patients with diuretic-free liver cirrhosis (32 with preascitic and 10 with ascitic disease) and 10 controls were submitted to the following determinations: (a) basal plasma renin activity and aldosterone levels; (b) endogenous dopaminergic activity measured as incremental aldosterone responses during metoclopramide administration; and (c) renal clearances of sodium, potassium, inulin, para-aminohippurate and lithium. Compared with the other groups, ascitic patients showed lower renal plasma flow (P < 0.01) and lithium clearance (P < 0.05), a higher filtration fraction (P < 0.01), and secondary aldosteronism. Controls and preascitic patients displayed tubuloglomerular feedback (the mechanism increasing the glomerular filtration rate when a reduced sodium load reaches the distal tubule), as demonstrated by negative correlations between fractional excretion of lithium (an expression of fractional delivery of sodium to the distal nephron) and glomerular filtration rate (respectively, r = –0.73, P < 0.03, and r = –0.48, P < 0.01). Conversely, patients with ascites showed a positive correlation between lithium fractional excretion and glomerular filtration rate (r = 0.64, P < 0.05). Reduction in renal perfusion, increased filtration fraction, and TuGF derangement, as found in decompensated patients, are indicative of prevalent postglomerular arteriolar vasoconstriction, with ensuing stimulation of proximal tubular sodium reabsorption.     

The obesity gene and colorectal cancer risk: a population study in Northern Italy

Background

Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity.

Aims

To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population.

Patients and methods

1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F = 197/144, mean age = 65.17 ± 11.16 years), colorectal adenoma (385 pts., M/F = 247/138, mean age = 62.49 ± 13.01 years), healthy controls (311 pts., M/F = 150/161, mean age = 57.31 ± 13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR.

Results

The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR = 1.106; CI 95% = 0.788-1.550; p = 0.561) or colorectal adenomas (OR = 0.830; CI 95% = 0.602-1.144; p = 0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI.

Conclusion

The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.     

Basic numerical processes in very preterm children: A critical transition from preschool to school age

Background

Serious difficulties in formal mathematical skills have been identified in preterm children. By contrast, basic-level numerical skills like magnitude judgments have not yet been tested in these children.

Aims

The aim of the present research was to investigate whether preterm birth also affects these basic numerical abilities, with particular attention to the transition from preschool to formal education.

Method

One hundred-forty very preterm children and 60 age-matched controls were recruited in a cross-sectional study at 6 and 8 years of age. Magnitude comparison tasks with non-symbolic dot displays or symbolic Arabic-number stimuli, measuring accuracy and reaction time, were administered to participants. We also investigated explicit number knowledge, as well as general cognitive developmental levels, to gain a broader picture of preterm abilities.

Results

Despite no general cognitive delay, the more simple approximate non-symbolic representation of numerical magnitude was affected by preterm birth, with slower reaction times at both ages compared to controls. Additionally, clear difficulties in the construction of the symbolic representation of numerical magnitude and in explicit number knowledge emerged in the 6-year-old preterm children, with a recovery from this serious delay finally by 8 years.

Conclusions

The serious delays identified here in basic numerical abilities in preterm children, despite normal IQ, point to the need for further studies in order to elucidate the relationship between basic numerical abilities and subsequent difficulties in formal mathematic achievement at school.     

Changing pattern of chronic hepatitis D in Southern Europe.

BACKGROUND & AIMS: The aim of this study was to assess changes in the clinical pattern of hepatitis D virus (HDV) infection in Italy, brought about by improved control of hepatitis B and D viruses, and to establish the natural history of chronic hepatitis D. METHODS: Histological diagnosis and clinical features of 122 patients with HDV recruited from 1987 to 1996 in three Italian tertiary referral centers (Torino, northern Italy; San Giovanni Rotondo and Castellana Grotte, southern Italy) were compared with those of 162 patients collected in the same centers in the previous decade. Patients from both groups with at least 6 months of follow-up were included in a new subgroup to assess the natural history of the disease. RESULTS: Among 162 patients referred from 1977 to 1986, 9 (6%) had mild hepatitis at histology vs. 9 (8%) of 122 patients referred in the second decade; 105 (65%) vs. 21 (17%) had severe hepatitis; 46 (28%) vs. 38 (31%) had histological asymptomatic cirrhosis; and 2 (1%) vs. 54 (44%) had clinically overt cirrhosis. For 159 patients (121 men and 38 women; mean age, 34 +/- 11), a follow-up of more than 6 months was documented, and they were included in the natural history subgroup. After 78 +/- 59 months of follow-up, 112 (70%) survived free of liver transplantation: 9 underwent transplantation, 32 died of liver failure, and 6 of acquired immunodeficiency syndrome. Estimated 5- and 10-year probability of survival free of orthotopic liver transplantation was 100% and 100% for patients with mild hepatitis, 90% and 90% for severe hepatitis, 81% and 58% for histological asymptomatic cirrhosis, and 49% and 40% for clinical cirrhosis (P < 0.01), respectively. CONCLUSIONS: Occurrence of fresh and severe forms of hepatitis D has diminished greatly in Italy. Contemporary patients represent cohorts infected years ago who survived the immediate medical impact of hepatitis D. The disease has been asymptomatic and nonprogressive in a minority; in the majority, it rapidly advanced to cirrhosis but thereafter subsided with stable clinical conditions for more than a decade.     

The HLA-DR3,DQ2 Heterozygous Genotype is Associated with an Accelerated Progression of Primary Sclerosing Cholangitis

Background: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. Methods: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. Results: The DRB1*03,DQA1*0501,DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). Conclusion: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.     

Cognitive Processing Variables in Breast Cancer: Worry and Distress at the End of Treatment

This study assessed the influence of cognitive processing variables on cancer worries and distress after breast cancer treatment. In multivariate analyses, while independent variables were intolerance of uncertainty and intrusive thoughts, constructs' variables were anxiety and depression symptoms and cancer-related worries. The intolerance to uncertainty had a tendency to influence on distress and concerns about cancer after the end of treatment (Wilks' λ = 0.687, p = 0.074). Whereas, thought intrusion had a significant influence on distress and cancer related worries (Wilks' λ = 0.228, p = 0.000). Cognitive variables could be addressed by the oncology nurse when considering the patients' concerns related to cancer and psychological distress.