Fast-track recovery after major liver and pancreatic resection from the nursing point of view.

Postoperative fast-track recovery protocols combine various methods to support immediate care of patients who undergo major surgery. These protocols include control of postoperative pain and early beginning of oral diet and mobilization. The combination of these approaches may reduce the rate of postoperative complications and facilitate hospital discharge. The aim of this study was to evaluate progress and parameters of fast-track recovery after major liver and pancreatic resection. A descriptive bibliographical review from 2001 to 2012 via electronic databases such as MEDLINE, PubMed, and Google Scholar was undertaken. Articles that focused on a fast-track protocol were studied. Reports focusing on the implementation of a fast-track protocol in the postoperative recovery of patients after major hepatectomy or pancreatectomy were selected. Fast-track protocols may be applicable to patients recovering after major liver or pancreatic resection. Future research should be focused on particular parameters of the fast-track protocol separately.

Liver function tests in viremic and nonviremic chronic hepatitis B virus-infected pregnant women: importance of alanine aminotransferase/sodium ratio.

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.

Presence of HBV-DNA in cord blood is associated with spontaneous preterm birth in pregnant women with HBeAg-negative chronic hepatitis B virus infection.

Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. In this study the spontaneous preterm birth rates in a group of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected pregnant women without known risk factors for preterm delivery as well as the role of maternal laboratory data and hepatitis B surface antigen/HBV deoxyribonucleic acid (HBV-DNA) in cord blood in respect to preterm labour were evaluated. 138 consecutive HBeAg-negative chronic HBV-infected pregnant women were evaluated during the perinatal period. Serum HBV-DNA was determined by using the Cobas Amplicor HBV Test in both maternal and cord blood samples. 102 women were finally evaluated (36 were excluded) and 15 of them (14.7%) had spontaneous preterm birth. A significant association between spontaneous preterm birth and HBV-DNA in cord blood was observed (p = 0.007). HBV-DNA positivity in cord blood was significantly associated with maternal HBV-DNA levels (p = 0.002). The relative risk of HBV-DNA in cord blood was 6.43 times higher among women with serum HBV-DNA ≥10,000 copies/ml and lymphocyte count <1,500 compared to those with all the other combinations of both parameters (p = 0.001). In conclusion, the presence of HBV-DNA in cord blood is significantly associated with spontaneous preterm birth in chronic HBV-infected pregnant women. Women with HBV-DNA ≥10,000 copies/ml and lymphocyte count <1,500 during the perinatal period have a higher probability of HBV-DNA in their cord blood.

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection?

UNLABELLED: The diagnosis of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA >or=2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg-negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score >or=7 and/or stage >or=2 in Ishak's classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA >or=200,000, 20,000-199,999, 2,000-19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. CONCLUSION: HBeAg-negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA >or=20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg-negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow-up.

Atypical autoimmune polyglandular syndrome type 3 overlapped by chronic HCV infection resulting in carcinogenesis and fatal infection.

The case of a woman with insulin-dependent diabetes mellitus, autoimmune thyroiditis, atrophic gastritis, pernicious anemia, and immunologic thrombocytopenic purpura consisting of autoimmune polyglandular syndrome type 3 associated with a history of gonadal failure is reported. Hepatitis C viral infection added xerophthalmia, lymphocytic sialadenitis, and exacerbation of idiopathic thrombocytopenic purpura. This unique disease constellation was complicated with splenic marginal zone lymphoma and gastric carcinoids. A lung infection, initially treated on an outpatient basis, proved fatal to the patient.

Case report: mixed cholestatic/hepatocellular liver injury induced by the herbicide quizalofop-p-ethyl.

CONTEXT: Quizalofop-p-ethyl is an often applied, slightly toxic herbicide for which no severe toxicity has been reported in humans. CASE PRESENTATION: We present the case of a farmer exposed to quizalofop-p-ethyl who presented with obstructive cholestasis. A complete workup disclosed no other cause of liver pathology, but liver biopsy established drug-induced hepatotoxicity. The patient was treated with ursodeoxycholic acid and prednisolone, and was recovered fully 70 days after his exposure to the herbicide. The patient was followed for the next 9 months. CONCLUSION: Quizalofop-p-ethyl can induce a mixed cholestatic/hepatocellular liver injury. We discuss possible mechanisms implicated in liver injury after exposure to quizalofop-p-ethyl. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: In patients presenting with mixed cholestatic/ hepatocellular liver injury, occupational exposure to quizalofop-p-ethyl in the course of agricultural use should be investigated.

Serological and virological profile of chronic HBV infected women at reproductive age in Greece. A two-year single center study.

OBJECTIVE: Seroprevalence of HBsAg in 26,746 women at reproductive age in Greece and evaluation of HBeAg/anti-HBe serological status as well as serum HBV-DNA levels in a subgroup of HBsAg(+) women at labor. STUDY DESIGN: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was calculated using a sensitive quantitative PCR assay, with a lower limit of quantification of 200 copies/ml. RESULTS: Overall, 1.53% of women were HBsAg(+) and the majority of them (64.96%) were Albanian. Among Albanian women the mean prevalence of HBsAg was 4.9%, 5.57% among Asian women, and 1.29% among women from Eastern European countries. The prevalence of HBsAg among African (0.29%) and Greek women (0.57%) was very low and significantly lower in comparison with the mean value of the studied population. Only 2.67% of HBsAg(+) women were HBeAg(+). Of a subgroup of women in labor with available serum samples 28.6% had undetectable levels of viremia (<200 copies/ml) and 15.9% had extremely low levels of viral replication (<400 copies/ml). Only 12.7% of pregnant women evaluated at labor exhibited extremely high serum HBV-DNA levels (>10,000,000 copies/ml) whereas 42.8% of them exhibited HBV-DNA levels between 1500 and 40,000 copies/ml. CONCLUSIONS: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher among specific ethnic populations (Asian, Albanian). The HBeAg(-)/antiHBe(+) serological status is a finding observed in the vast majority of HBsAg(+) women of our study population, and a significant percentage of them (approximately 44.5%) exhibit extremely low or even undetectable levels of viral replication at labor, suggesting possibly that only a proportion of HBsAg(+) women in Greece exhibit an extremely high risk of vertical transmission of the infection.

Impact of shorter duration of treatment on virological response rate in genotype 2 or 3 chronic hepatitis C virus infection.

OBJECTIVE: To evaluate the effect of shortened duration of pegylated interferon (PEG-IFN) and ribavirin (RIB) treatment on sustained virological response (SVR) rates in treatment-naomicronve patients with chronic hepatitis due to genotype 2 or 3 hepatitis C virus (HCV) infection and high pre-treatment viral load (>800,000 IU/mL). METHODS: Records of 142 patients with chronic hepatitis C (22 with cirrhosis) who had been treated with PEG-IFN and RIB for 24 weeks (Group A, n=88), both drugs for 12-16 weeks (Group B, n=39), or with PEG-IFN for 12-16 weeks and RIB for 24 weeks (Group C, n=15), were analyzed retrospectively. RESULTS: Overall, 81.7% of patients had SVR (Group A: 88.6%, Group B: 69.2% and Group C: 73.3%, p=0.02). Failure to achieve SVR was significantly related to treatment group (p=0.026 for Group B and p=0.002 for Group C, versus Group A), older age (p=0.023), higher liver biopsy stage (p=0.001) and presence of cirrhosis (p< 0.0001). In patients without cirrhosis, only the treatment group (p=0.018 for Group B and p=0.002 for Group C, compared to Group A) independently predicted failure to achieve SVR. CONCLUSION: Shorter duration of PEG-IFN treatment (12-16 weeks) adversely affected the SVR rate in patients with genotype 2 or 3 HCV infection. However, increasing the duration of RIB administration (12-16 weeks versus 24 weeks) in such patients did not have any beneficial effect on SVR in patients receiving short-duration PEG-IFN.

Serum procalcitonin levels in chronic hepatitis C patients under pegylated interferon-alpha plus ribavirin treatment.

OBJECTIVES: To evaluate the alterations of serum procalcitonin (PCT) levels in patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa) plus ribavirin (RIB) treatment and to correlate them with clinical and virological outcomes. STUDY DESIGN: Fifty-two consecutive patients (29 males, age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics) were evaluated for PCT levels at baseline and during the treatment course (at week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and again 6 months after completion of treatment. RESULTS: Two patients exhibited culture-proved bacterial infections during the treatment course. Thirty-six patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout the follow-up period except those two who exhibited bacterial infections during the treatment course. Virological responders exhibited significant decline of serum PCT levels over time compared to non-responders (p<0.001), even when adjusted for multiple baseline parameters (p=0.037). CONCLUSION: Serum PCT levels decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment, especially in the sustained virological responder group, while they elevate only when bacterial infections complicate the treatment course.

Changing serological status and low vaccination-induced protection rates against hepatitis B characterize chronic hepatitis C virus-infected injecting drug users in Greece: need for immunization policy.

OBJECTIVE: To evaluate the serological status of hepatitis B virus infection among Greek injecting drug users with chronic hepatitis C virus infection; to correlate hepatitis B virus infection status with the possible time of infection and the principal genotype of hepatitis C virus infection. METHODS: Two hundred and thirty consecutive injecting drug users with chronic hepatitis C virus infection were evaluated for serological markers of hepatitis B virus infection. One hundred and three of them (44.8%) reported intravenous drug use beginning before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical analysis of data was based on Student's t-test and chi analyses. RESULTS: Eighty-five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had serological markers of previous hepatitis B virus infection (P<0.001). Eleven patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients and 16.5% (21/127) of group B had vaccination-induced protective antibody levels (anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B, P=0.42). The percentages of patients infected with genotype-1 were also comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A significantly higher percentage of group A patients were infected with genotype-4 (19.7%) than those in group B (4.9%, P=0.02). CONCLUSION: The serological profile of hepatitis B virus infection among Greek hepatitis C virus-infected injecting drug users is changing. The proportion of successfully vaccinated hepatitis B virus injecting drug users, although significantly higher than the previous decades, is still relatively low. Vaccination policy in this high-risk group for viral hepatitis is urgently needed.

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease.

OBJECTIVE: To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. METHODS: One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05). RESULTS: Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. CONCLUSION: Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients: the effect of pegylated interferon plus ribavirin treatment.

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.

Relationship between serum b2-microglobulin levels and virological breakthrough in HBeAg-negative chronic hepatitis B patients, under long-term treatment schedules including lamivudine.

AIM: Predictive value of serum b2-microglobulin (b2m) levels for virological breakthrough (VB) in HBeAg-negative chronic hepatitis B (CHB) patients under long-term treatment schedules including lamivudine (LAM). METHODS: Serum b2m levels were calculated during treatment in 25 CHB patients under long-term LAM monotherapy (group A) and 12 patients under initial interferon plus LAM treatment followed by LAM monotherapy (group B), using the MEIA technology. We used Cox proportional hazard models in order to investigate the association between serum b2m levels and VB. RESULTS: Seven of 25 patients (28%), 9/25 (36%) and 14/25 (56%) from group A and 0/12, 2/12 (16.6%) and 3/12 (25%) from group B exhibited VB at months 12, 24 and 36 of treatment, respectively. All patients, from both groups, who did not show VB exhibited b2m elevation in mo 3. The duration of b2m elevation was significantly longer in the virological responder's subgroup from group A than the non-responder's one (7.3+/-2.6 vs 3.8+/-3.4 mo, P = 0.02). In comparison to group A patients whose b2m levels were increased at 3 mo, patients whose b2m levels were decreased had 4.6 times higher risk of experiencing VB (RR = 4.6, P = 0.024). When baseline variables were simultaneously included in the same Cox model, decreased b2m status was still associated with increased risk of VB (RR = 12.2, P = 0.03). CONCLUSION: In HBeAg-negative CHB patients under either long-term LAM monotherapy or initial combination treatment, serum b2m levels at 3 mo of treatment, compared to baseline ones, might be a predictor of risk for VB.

HBeAg negative serological status and low viral replication levels characterize chronic hepatitis B virus-infected women at reproductive age in Greece: a one-year prospective single center study.

AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13 581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe status as well as serum hepatitis B virus (HBV)-DNA levels in a subgroup of HBsAg(+) pregnant women at labor in Greece. METHODS: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive quantitative PCR assay. Statistical analysis of data was based on parametric methodology. RESULTS: Overall, 1.156% of women were HBsAg(+) and the majority of them (71.3%) were Albanian. The prevalence of HBsAg was 5.1% in Albanian women, 4.2% in Asian women and 1.14% in women from Eastern European countries. The prevalence of HBsAg in African (0.36%) and Greek women (0.29%) was very low. Only 4.45% of HBsAg(+) women were also HBeAg(+) whereas the vast majority of them were HBeAg(-)/anti-HBe(+). Undetectable levels of viremia (<200 copies/mL) were observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low levels of viral replication (<400 copies/mL). Only two pregnant women exhibited extremely high serum HBV-DNA levels (>10 000 000 copies/mL), whereas 32.26% exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher enough among specific populations. The HBeAg(-)/anti-HBe(+) serological status and the extremely low or even undetectable viral replicative status in the majority of HBsAg(+) women of our study population, suggest that only a small proportion of HBsAg(+) women in Greece exhibit a high risk for vertical transmission of the infection.

Serological profile of HBV infection and liver histopathology among injecting drug users with chronic HCV infection in Greece.

BACKGROUND: The aim of this study was to evaluate the serological status of HBV infection and liver histology in chronic HCV-infected injecting drug users (IDUs) and to correlate them with the possible time of infection and the principal HCV genotype. METHODS: Some 130 prior IDUs with chronic HCV infection were consecutively evaluated for the serological status of HBV infection. Fifty-eight (44.62%) reported intravenous drug use beginning before 1992 (group A) and 72 (55.38%) after 1992 (group B). HCV genotyping was available in 86 patients (PCR). Liver biopsy was performed in 48 patients (Ishak scoring system). There was no available data about alcohol consumption in the study population. Statistical analysis was based on the t-test and the chi(2) test (p<0.05). RESULTS: Some 82.8% of group A patients had previous HBV infection, whereas only 22.2% of group B patients did (p<0.001). Among group A patients, 10.3% were HBV-seronegative whereas 61.1% of group B patients were (p<0.001). Only 3.4% of group A patients were HBV-vaccinated compared to 16.7% in group B (p=0.016). HCV genotype was not associated with HBV serological status. No significant differences were detected in age, sex, possible time of infection, HBV serological status, or HCV genotype among those with higher vs. lower total grading scores. Seventy-five percent of patients had mild or no detectable fibrosis unrelated to the possible period of infection, the HBV serological status, and the HCV genotype. CONCLUSIONS: The serological profile of HBV infection is changing among Greek chronic HCV-infected IDUs, while the percentages of successfully HBV-vaccinated IDUs are relatively low. Severe liver disease is an uncommon finding in these patients, irrespective of the possible time of infection, the HBV serological status, and the HCV genotype.

Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis.

OBJECTIVE: To assess the presence of anticardiolipin antibodies (ACAs) in patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to associate this with the incidence of portal vein thrombosis (PVT) in HCC patients. PATIENTS AND METHODS: Sixty-five cirrhotic patients with HBV-related HCC, 28 naive patients with chronic HBV infection and 14 naive patients with chronic HDV infection were enrolled prospectively in the study. Thirty-two healthy blood donors were used as controls. The ACAs (immunoglobulin G and immunoglobulin M) were measured using an enzyme-linked immunosorbent assay system. Statistical analysis used non-parametric methodology (chi-squared test, Student t-test and Fisher exact test, P value<0.05). RESULTS: Eleven of the 65 patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In contrast, from the 43 patients without PVT, only three (11%) showed a positive titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six ACA positive HBV patients presented an extrahepatic manifestation of the disease. One out of 32 control patients (3%) had positive ACAs. CONCLUSION: Both chronic HBV and chronic HDV infections are potent stimulants for the production of ACAs. The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients with PVT suggests their possible participation in thrombotic mechanisms and in the hypercoagulable state that occurs in advanced liver disease and HCC.

Plasma pituitary adenylate cyclase activating polypeptide (PACAP) levels in chronic hepatitis B patients under lamivudine treatment.

OBJECTIVE: Lamivudine is a nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Plasma pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide that is produced within the lymphoid microenvironment and induces the production of Th2-type cytokines. The aim of our study was to investigate the possible alterations of plasma PACAP-38 levels in chronic hepatitis B (CHB) patients during lamivudine treatment and to compare them with biochemical, virological and histological data. METHODS: Plasma PACAP-38 levels were measured using competitive radio-immune analysis (RIA) in 25 CHB patients before and after completion of a 52-week lamivudine treatment period and in 22 healthy blood donors. Biochemical evaluation was done at baseline and every three months during treatment. Virological evaluation (HBV-DNA) was performed at baseline and at weeks 24 and 52 of treatment. Baseline liver histology was assessed for all patients at the beginning and at week 52 of the study for histological comparison with the pretreatment biopsy, according to the Ishak scoring system. Statistical evaluation of data was done using analysis of variance and Student's t-test. RESULTS: Virological breakthrough was observed in seven (28%) patients at week 52 of treatment. Histological improvement was observed in 21 (84%) CHB patients, despite the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) mutations. Plasma PACAP-38 levels were significantly lower in CHB patients at baseline than in healthy blood donors. Significant elevation of plasma peptide levels was observed in CHB patients after the completion of lamivudine treatment period, even in the subgroup of those who exhibited YMDD variants. CONCLUSION: The elevation of plasma PACAP-38 levels in treated CHB patients following lamivudine-induced elimination of viraemia suggests a possible alteration of T-cellular immune response, resulting in biochemical and histological remission of liver disease, even in patients who exhibited virological breakthrough.

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.

Serum beta2-microglobulin levels in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy: relationship with virological breakthrough.

OBJECTIVES: To evaluate the predictive value of serum beta2-microglobulin (beta2m) levels for virological breakthrough in hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy. METHODS: Serum beta2m levels were calculated at baseline and every three months during lamivudine monotherapy in 25 patients with chronic hepatitis B, using microparticle enzyme immunoassay technology to investigate their association with biochemical, virological and histological outcome data. Cox proportional hazard models were used to investigate the association between serum beta2m levels and virological breakthrough. RESULTS: Seven of 25 (28%), nine of 25 (36%) and 14 of 25 (56%) chronic hepatitis B patients exhibited virological breakthrough at months 12, 24 and 36 of treatment, respectively. All chronic hepatitis B patients who did not show virological breakthrough in the follow-up period exhibited beta2m elevation in month 3 of treatment. The duration (in months) of serum beta2m elevation was significantly higher in the responders group than the nonresponders group (7.3 +/- 2.6 versus 3.8 +/- 3.4, P=0.02). In contrast to patients whose serum beta2m levels were increased at three months, patients whose beta2m levels were decreased had a 4.6 times higher risk of experiencing virological breakthrough (hazards ratio 4.6, 95% CI 1.22 to 17.36). When age, pretreatment serum alanine aminotransferase and hepatitis B virus DNA levels, and grade of liver disease were simultaneously included in the same Cox model, decreased beta2m status was still associated with increased risk of virological breakthrough (hazards ratio 12.2, 95% CI 1.28 to 116.8). CONCLUSIONS: In hepatitis B e antigen-negative chronic hepatitis B patients under long term lamivudine monotherapy, serum b2m levels at three months of treatment, compared with baseline levels, are good predictors of risk for virological breakthrough.