Hepatitis RSS : Gourt

Hepatitis: HBV infection increases risk of pancreatic cancer

A large, case–control study conducted in China has shown that HBV infection increases the risk of pancreatic ductal adenocarcinoma (PDAC). Qiwen et al. assessed hepatitis B status in 943 patients with confirmed PDAC and 1,128 matched controls. Individuals with chronic HBV infection (positive

Screening for tuberculosis and hepatitis B prior to the initiation of anti-tumor necrosis therapy

Background:Since the introduction of infliximab, anti-tumor necrosis factor alpha (anti-TNF-α) agents have been used with increasing frequency for the treatment of inflammatory bowel disease (IBD). Reactivation of latent Mycobacterium tuberculosis (TB) soon became recognized as a complication of therapy. More recently, reactivation of hepatitis B while on anti-TNF therapy has been documented. The aim of this study was to assess the adherence to screening for latent TB and hepatitis B by gastroenterologists prior to initiation of an anti-TNF.Methods:This is a retrospective analysis of all patients with IBD treated with an anti-TNF at a large urban academic hospital. In our population, 65% of patients were screened for latent TB prior to the initiation of anti-TNF therapy, while 25% of patients were screened for hepatitis B.Results:Failure to screen for latent TB was strongly correlated with prior exposure to an anti-TNF (odds ratio [OR]: 5.3; P < 0.0001) and initiation of treatment prior to 2006 (OR: 5.8; P < 0.0001). Failure to screen for hepatitis B was associated with lack of an abnormal alanine aminotransferase (OR: 2.6; P = 0.005) and treatment prior to 2010 (OR: 3.3; P = 0.02). Providers who had been in practice longer were less likely screen for TB or hepatitis B.Conclusions:The rate of screening for both latent TB and hepatitis B in this study was inadequate. While the rate of screening is increasing, further systems improvements and physician education is needed. (Inflamm Bowel Dis 2011;)

Level of α-fetoprotein predicts mortality among patients with hepatitis C-related hepatocellular carcinoma.

Level of α-fetoprotein predicts mortality among patients with hepatitis C-related hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2011 Nov;9(11):989-94 Authors: Tyson GL, Duan Z, Kramer JR, Davila JA, Richardson PA, El-Serag HB Abstract BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC. METHODS: In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment. RESULTS: The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively. CONCLUSIONS: Serum AFP level at the time of diagnosis with HCV-related HCC is an independent predictor of mortality. PMID: 21820396 [PubMed - indexed for MEDLINE]

Effects of a sustained virologic response on outcomes of patients with chronic hepatitis C.

Effects of a sustained virologic response on outcomes of patients with chronic hepatitis C. Clin Gastroenterol Hepatol. 2011 Nov;9(11):923-30 Authors: Ng V, Saab S Abstract For patients with chronic hepatitis C virus infection, the goal of antiviral therapy is to achieve a sustained virologic response (SVR). We review the durability of the SVR and its effects on liver-related mortality, hepatic decompensation, and the development of hepatocellular carcinoma. We performed a systematic review of the effects of the SVR on liver-related hepatic outcomes and found the SVR to be durable (range, 98.4%-100%). An SVR reduced liver-related mortality among patients with chronic hepatitis C (3.3- to 25-fold), the incidence of hepatocellular carcinoma (1.7- to 4.2-fold), and hepatic decompensation (2.7- to 17.4-fold). An SVR can lead to regression of fibrosis and cirrhosis, and has been associated with a reduced rate of hepatic decompensation, a reduced risk for hepatocellular carcinoma, and reduced liver-related mortality. PMID: 21699815 [PubMed - indexed for MEDLINE]

Full-dose peginterferon Alfa-2a and low-dose ribavirin treatment of genotypes 1 and 4 chronic hepatitis C patients with end-stage renal disease.

Full-dose peginterferon Alfa-2a and low-dose ribavirin treatment of genotypes 1 and 4 chronic hepatitis C patients with end-stage renal disease. Clin Gastroenterol Hepatol. 2011 Nov;9(11):1004; author reply 1005 Authors: Abdulhadi-Ali MM, Alsaudi D, Agha A, Ibraheem-Alqahtani N, Furnari M, Savarino V, Giannini EG PMID: 21699813 [PubMed - indexed for MEDLINE]

Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B.

Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B. World J Gastroenterol. 2011 Nov 21;17(43):4825-30 Authors: Xiang XX, Zhou XQ, Wang JX, Xie Q, Cai X, Yu H, Zhou HJ Abstract AIM: To study the effects of synthetic nonmethylated CpG-containing oligodeoxynucleotides (CpG-ODNs), either alone or combined with recombinant Hepatitis B surface antigen (HBsAg) polypeptide, on the phenotype, function, and intracellular signaling pathways of monocyte-derived dendritic cells (DCs) in patients with chronic hepatitis B (CHB). METHODS: Peripheral blood monocytes isolated from CHB patients and healthy volunteers were induced to be dendritic cells by recombinant human granulocyte-monocyte colony stimulating factor and interleukin-4. The DCs were then treated with CpG-ODNs, CpG-ODNs/HBsAg, or tumor necrosis factor (TNF)-α for 18 h. The expression of surface molecules including HLA-DR, CD86, and CD1a in DCs were detected by flow cytometry, and the expression of signal transducers and activators of transcription (STAT1, 3, 4, 5, 6) and suppressors of cell signaling (SOCS1, 3) were determined by Western blotting assay. In addition, the capacity of DCs to stimulate allogeneic T lymphocytes and the amount of IL-12p70 released from DCs were measured. RESULTS: In the DCs derived from patients with CHB, treatment with TNF-α, CpG-ODNs, or CpG-ODNs/HBsAg, as compared to the vector control, significantly increased the expression of HLA-DR, stimulated the release of IL-12p70, and enhanced the capacity of DCs to stimulate allogenic T lymphocytes. The expressions of STAT1/4/6 and SOCS1/3, but not STAT3/5, were upregulated by TNF-α, CpG-ODNs, and CpG-ODNs/HBsAg. In addition, the expression of CD1a was upregulated only in the presence of both CpG-ODNs and HBsAg. CONCLUSION: The treatment with CpG-ODNs, either alone or combined with HBsAg, has a remarkable stimulatory effect on the impaired phenotype and function of DCs in CHB, possibly by regulating the expression of STAT1, 4, 6 and SOCS1, 3. PMID: 22147985 [PubMed - indexed for MEDLINE]

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients.

De novo combination therapy with lamivudine and adefovir dipivoxil in chronic hepatitis B patients. World J Gastroenterol. 2011 Nov 21;17(43):4804-9 Authors: Fan XH, Geng JZ, Wang LF, Zheng YY, Lu HY, Li J, Xu XY Abstract AIM: To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B (CHB) patients with decompensated cirrhosis. METHODS: Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study. All of the patients were given 48 wk combination therapy with lamivudine (LAM) and adefovir dipivoxil (ADV). Briefly, 10 patients were given the de novo combination therapy with LAM and ADV, whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus (HBV) genetic mutation. RESULTS: Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4, 12, 24 and 48 wk after treatment. Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups. The serum HBV DNA level was still detectable in every patient in the two groups at 4 and 12 wk after combination treatment. However, in the de novo combination group, serum HBV DNA levels in 4 (40%) and 9 (90%) patients was decreased to below 1×10(3) copies/mL at 24 and 48 wk after the combination treatment, respectively. In parallel, serum HBV DNA levels in 2 (20%) and 8 (40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment, respectively. Furthermore, 6 (60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment, whereas only 4 (20%) patients in the add-on combination group achieved seroconversion. Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment. Moreover, patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts. CONCLUSION: De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score, virus inhibition and renal function. PMID: 22147982 [PubMed - indexed for MEDLINE]

"Liverscore" is predictive of both liver fibrosis and activity in chronic hepatitis C.

"Liverscore" is predictive of both liver fibrosis and activity in chronic hepatitis C. World J Gastroenterol. 2011 Nov 7;17(41):4607-13 Authors: Arain SA, Jamal Q, Omair A Abstract AIM: To formulate a noninvasive index predictive of severity of liver fibrosis and activity in chronic hepatitis C. METHODS: This cross sectional study was conducted on polymerase chain reaction positive, treatment naïve patients. Fibrosis was staged on a five point scale from F0-F4 and activity was graded on a four point scale from A0-A3, according to the METAVIR system. Patients were divided into two overall severity groups, minimal disease (< F2 and < A2) and significant disease (≥ F2 or ≥ A2). Eleven markers were measured in blood. Statistically, the primary outcome variable was identification of minimal and significant overall disease. Indices were formulated using β regression values of different combinations of nine statistically significant factors. Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis. RESULTS: A total of 98 patients were included and of these 46 had an overall clinically significant disease. Our final six marker index, Liverscore for Hepatitis C, consisted of age, alanine transaminase, gamma-glutamyl transpeptidase, apolipoprotein A-1, alpha-2 macroglobulin and hyaluronic acid. The area under the curve was found to be 0.813. On a 0-1 scale, negative predictive value at a cutoff level of ≤ 0.40 was 83%, while positive predictive value at ≥ 0.80 remained 89%. Altogether, 61% of the patients had these discriminative scores. CONCLUSION: This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical decision making. PMID: 22147967 [PubMed - indexed for MEDLINE]

FibroSURE and FibroScan in relation to treatment response in chronic hepatitis C virus.

FibroSURE and FibroScan in relation to treatment response in chronic hepatitis C virus. World J Gastroenterol. 2011 Nov 7;17(41):4581-9 Authors: Patel K, Friedrich-Rust M, Lurie Y, Grigorescu M, Stanciu C, Lee CM, Schiff ER, Häussinger D, Manns MP, Gerken G, Colle I, Torbenson M, Pulkstenis E, Subramanian GM, McHutchison JG, Zeuzem S Abstract AIM: To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus (HCV) cohort. METHODS: Patients with chronic HCV were randomized to receive interferon-based therapy for 24 (genotypes 2/3) or 48 (genotype 1) wk. FibroSURE™ (FS) was assessed at baseline and at week-12 post-treatment follow-up. Baseline biopsy for METAVIR was assessed by a single pathologist. FibroScan(®) transient elastography (TE) was performed during treatment in a patient subset. RESULTS: Two thousand and sixty patients (n = 253 in Asia) were classified as METAVIR F0-1 (n = 1682) or F2-4 (n = 378). For F2-4, FS (n = 2055) had sensitivity and specificity of 0.87 and 0.61, respectively, with area under the receiver-operating curve of 0.82; corresponding values for TE (n = 214) and combined FS/TE (n = 209) were 0.77, 0.88 and 0.88, and 0.93, 0.68 and 0.88. Overall FS/TE agreement for F2-4 was 71% (κ = 0.41) and higher in Asians vs non-Asians (κ = 0.86 vs 0.35; P < 0.001). Combined FS/TE had 97% accuracy in Asians (n = 33). Baseline FS (0.38 vs 0.51, P < 0.001) and TE (8.0 kPa vs 11.9 kPa, P = 0.006) scores were lower in patients with sustained virological response than in nonresponders, and were maintained through follow-up. CONCLUSION: FS and TE may reliably differentiate mild from moderate-advanced disease, with a potential for high diagnostic accuracy in Asians with chronic HCV. PMID: 22147963 [PubMed - indexed for MEDLINE]

Physical activity and nutrition attitudes in obese Hispanic children with non-alcoholic steatohepatitis.

Physical activity and nutrition attitudes in obese Hispanic children with non-alcoholic steatohepatitis. World J Gastroenterol. 2011 Oct 21;17(39):4396-403 Authors: Hattar LN, Wilson TA, Tabotabo LA, Smith EO, Abrams SH Abstract AIM: To assess nutrition, physical activity and healthful knowledge in obese children with biopsy-proven non-alcoholic steatohepatitis (NASH or NA) compared to children without liver disease. METHODS: Children with biopsy-proven NASH comprised the NASH group. Age, sex and ethnicity matched control groups consisted of obese (OB) and lean (CO) children with no liver disease. Subjects were administered the School Physical Activity and Nutrition Survey and one blood draw was obtained. RESULTS: Fifty-seven patients were enrolled with a mean age of 12.1 ± 2.1 years, and all were Hispanic. Even though the OB and NA had a similar increased body mass index (%), 35% of the NA group always read nutrition labels compared to none in the OB (P < 0.05), and more NA children felt their diet is "less healthy". NA consumed the least amount of fruits with only 25% having ≥ 1 fruit/d vs 45% in OB and 64.7% in CO (P < 0.05 NA vs CO). Only 15% of NA subjects performed light exercise vs 35% and 59% of OB and CO groups, respectively (P = 0.02). The mean physical activity score was lowest in the NA group (P < 0.05). Amongst the subjects with NASH, we found that 100% of patients with grade 2 or 3 fibrosis had a sedentary score > 2 compared to only 63.6% of those with grade 1 or no fibrosis (P < 0.05). CONCLUSION: Children with NASH had increased se-dentary behavior, decreased activity, and fruit intake. Larger studies may determine the benefit of changing these behaviors as treatment for NASH. PMID: 22110265 [PubMed - indexed for MEDLINE]

Redistribution of regulatory T-cells across the evolving stages of chronic hepatitis C.

Redistribution of regulatory T-cells across the evolving stages of chronic hepatitis C. Dig Liver Dis. 2011 Oct;43(10):807-13 Authors: Ferri S, Lalanne C, Lanzoni G, Bassi M, Asioli S, Cipriano V, Pappas G, Muratori P, Lenzi M, Muratori L Abstract BACKGROUND: Hepatitis C virus infection frequently leads to chronic hepatitis, possibly evolving to end-stage liver disease and hepatocellular carcinoma. Regulatory T cells can affect antiviral immune response thus influencing the outcome of the disease. AIM: To determine numeric and functional distribution of regulatory T cells expressing CD4+CD25hiFoxp3+ (T-regs) during the different stages of hepatitis C virus-related liver disease. METHODS: 90 hepatitis C viraemic patients and 50 healthy controls were included. Surface and intracellular (Foxp3) T-reg markers were evaluated by flow cytometry. Target cell proliferation and interferon-gamma production were evaluated in 37 HCV patients. In 16 cases intrahepatic distribution of Foxp3 by immuno-histochemistry was assessed. RESULTS: T-regs were increased in hepatitis C virus infected patients and correlated inversely with aminotransferases and directly with MELD score and disease duration. A preserved inhibitory ability of interferon-gamma production was distinctive of patients with normal aminotransferases. Circulating T-regs did not correlate with intrahepatic distribution of Foxp3. CONCLUSIONS: In chronic hepatitis C, selective expansion of peripheral T-regs in patients with normal aminotransferases and advanced disease suggests that, though a continual low level inflammation does not prevent liver disease progression, once cirrhosis has developed it may represent an attempt to prevent immuno-mediated decompensation. PMID: 21684822 [PubMed - indexed for MEDLINE]