Technetium-99m labelled red blood cells scintigraphy and not iminodiacetic acid cholescintigraphy facilitates the discrimination of hepatic cirrhosis from fibrosis.

OBJECTIVE: This pilot study was designed to investigate the efficacy of technetium-99m labelled red blood cells ((99m)Tc-RBC) compared with (99m)Tc-mebrofenin cholescintigraphy ((99m)Tc-MHS), in the diagnosis of hepatic dysfunction at early stages. SUBJECTS AND METHODS: Twenty four patients, 8 with hepatic fibrosis and 16 with cirrhosis, at Child-Pugh stage A to C and 20 age-matched controls were examined by (99m)Tc-RBC and by (99m)Tc-MHS. Dynamic acquisition and static images were semiquantitatively analused by studying the liver-to-heart (L/H) ratio estimated by both the (99m)Tc-RBC and (99m)Tc-MHS methods. The L/H ratios were compared between fibrosis, cirrhotic stages and controls, by Student's t test. Linear regression analysis of the L/H ratios for both methods has been applied in the whole study population. RESULTS: Labelled RBC could statistically differentiate fibrotic from normal liver parenchyma (P<0.001), whereas the (99m)Tc-MHS could not (P: 0.13). The L/H ratios of cirrhotic lesions using both methods were significantly lower than those in controls: (P<0.000001 for (99m)Tc-RBC and P<0.0001 for (99m)Tc-MHS). Statistically significant difference was demonstrated by both modalities between fibrotic and cirrhotic lesions ((99m)Tc-RBC: P: 0.003 and (99m)Tc-MHS: P: 0.024). CONCLUSION: Our study although in a limited number of patients suggested that as opposed to (99m)Tc-MHS, scintigraphic evaluation by (99m)Tc-RBC could be useful in the discrimination of patients with liver fibrosis, cirrhosis and normal controls.

Granulocyte colony stimulating factor in HCV genotype-1 patients who develop Peg-IFN-alpha2b related severe neutropenia: a preliminary report on treatment, safety and efficacy.

Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.

Natural history of chronic hepatitis B virus infection in children of different ethnic origins: a cohort study with up to 12 years' follow-up in northern Greece.

AIM: To investigate the mode of transmission and the natural history of chronic hepatitis B virus (HBV) infection in children of different ethnicities in Greece. This study was part of the Interreg I-II EC project. PATIENTS AND METHODS: One hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age 6.9 (5-12) y, were prospectively followed-up for a mean period of 5.3 (1-12) y for serological markers of HBV infection, serum alanine aminotransferase (ALT), HBV-DNA, alpha-fetoprotein levels and ultrasonography. RESULTS: Vertical transmission predominates (61.8%) in Moslem children and horizontal (44%) in those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55 of 173 (32%) had ALT > 2 x upper normal limit (UNL), ranging from 21% to 39%. Of 100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35 (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9 of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was significantly lower: in children with vertical transmission compared with horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children compared with both Christian children and those born in Russia (8.6% vs 12%, respectively, P < 0.001). No differences were found among the ethnic groups after adjusting for the mode of infection. Two of 173 children had progression of liver disease. CONCLUSIONS: The differences in HBeAg(+) status and seroconversion rate among the ethnic groups are related to the time/mode of HBV infection. The majority of children who developed anti-HBe immunity had biochemical remission, and a substantial number of the inactive carriers lost viremia during the observation period of up to 12 y.

Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C.

Daclatasvir (Daklinza™), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNα) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir-containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated.

Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population.

BACKGROUND: Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece. METHODS: Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ(2) test of independence. RESULTS: The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p=0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p<0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients. CONCLUSION: Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis.

The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study.

BACKGROUND/AIMS: To evaluate the fluctuating course of serum HBV-DNA levels during the natural history of chronic HBV infection in the general population of North-Eastern Greece, in association with liver disease progression. METHODS: Two hundred and sixty-three adults with chronic HBV, median 34 years of age, were randomly selected and prospectively followed-up for a maximum period of 12 years. Viral markers, liver biochemistry and physical examination were performed every 6 months, and liver biopsy/abdominal ultrasound every 2-4 years. RESULTS: At entry, 195/263 (76%) were HBeAg (-)/anti-HBe (+) inactive carriers: (a) almost all 195 individuals with undetectable or HBV-DNA levels <2000IU/ml had no liver disease at entry and at follow-up period by imaging or liver histology evaluation (b) only 4/195 (2%) showed HBV reactivation with HBV-DNA >2000IU/ml. At entry, 48/263 (18%) patients were chronic HBeAg(-); (a) 1/3 patients had intermittently HBV-DNA <2000IU/ml for at least one occasion and were misclassified as inactive carriers (b) 22/48 (46%) had moderate/severe histology at entry and 5/48 (10%) showed liver disease progression during follow-up. Logistic regression analysis was used to derive OR (95%CI) for factors associated with liver disease progression. CONCLUSIONS: Close monitoring of serum HBV-DNA levels is useful in the management of chronic HBeAg(-) patients, as associated with liver disease progression.

Liver involvement in acute vaso-occlusive crisis of sickle cell disease: prevalence and predisposing factors.

OBJECTIVE: To study the prevalence and predisposing factors of liver involvement in sickle cell disease (SCD) of patients with acute vaso-occlusive crisis. MATERIAL AND METHODS: We prospectively evaluated 41 consecutive patients (44% M, median age 39 years, range 16-56 years) with homozygous (HbSS; 12 cases) or sickle cell-beta thalassemia (HbSbeta-thal; 29 cases), admitted to our Medical Department in the period 2002 to 2004. Severity of crisis was graded by in-house-modified APACHE score; presence of asplenia or functional hyposplenism was also considered. Hematological and biochemical parameters including various relevant enzymes/isoenzymes were followed daily. RESULTS: Despite the fact that only 9 patients (22%) presented with acute painful hepatomegaly, liver involvement was evident in 16 (39%); hepatocellular-type injury was found in 1 patient, cholestatic in 8, and mixed in 7. Severity of crisis was not related to liver involvement (score 20.6 versus 18.2), but liver involvement occurred in the presence of normal spleen function (p<0.001) and platelet counts <500,000/mm(3) (p<0.001) were. Patients with liver involvement, compared with those without, had higher total and direct bilirubin levels (4.3 versus 2.9 mg/dL, p=0.050; 1.9 versus 0.8 mg/dL, p=0.010, respectively), lower hematocrit (19% versus 23%, p=0.030) and longer hospitalization (10 versus 6.3 days, p<0.001). CONCLUSIONS: In SCD, there is a 39% prevalence of acute veno-occlusive involvement of the liver, a figure that is much higher than previously reported. The type of injury is mostly mixed hepatocellular-cholestatic or purely cholestatic and its course is usually benign. Liver involvement occurs more often in patients with normal spleen function and is not associated with the overall severity of the acute episode, both observations being unreported previously.