Hepatocellular Carcinoma 11 and a Half Years after the Resolution of Chronic Hepatitis C Virus Infection Successfully Treated with Interferon

A 41-year-old Japanese man had received successful interferon (IFN) therapy against chronic hepatitis C in 1994. Since then, serum hepatitis C virus (HCV) RNA had been negative, and aminotransferase levels had been continuously normal. He had abstained from alcohol. However, his serum aminotransferase levels showed slight elevation as his body weight increased gradually. He was diagnosed as having fatty liver and diabetes mellitus. In January 2006, 11 and a half years after the resolution of HCV infection, he was found to have a hepatic nodule 4.0 cm in diameter at liver S4/8 region by plain abdominal CT at an annual follow-up examination. He was diagnosed as having hepatocellular carcinoma (HCC) by angiography. The tumor was curatively resected and its histological diagnosis was moderately differentiated HCC. Noncancerous lesion of the liver revealed fibrosis of stage F2 and mild inflammation of grade A1 with mild steatosis. This case suggests that all patients with chronic HCV infection should be followed as long as possible for the potential development of HCC even after clearance of the virus

The Hypervariable Region 1 Protein of Hepatitis C Virus Broadly Reactive with Sera of Patients with Chronic Hepatitis C Has a Similar Amino Acid Sequence with the Consensus Sequence

AbstractHypervariable region 1 (HVR1) proteins of hepatitis C virus (HCV) have been reported to react broadly with sera of patients with HCV infection. However, the variability of the broad reactivity of individual HVR1 proteins has not been elucidated. We assessed the reactivity of 25 different HVR1 proteins (genotype 1b) with sera of 81 patients with HCV infection (genotype 1b) by Western blot. HVR1 proteins reacted with 2–60 sera. The number of sera reactive with each HVR1 protein significantly correlated with the number of amino acid residues identical to the consensus sequence defined by Puntoriero et al. (G. Puntoriero, A. Lahm, S. Zucchelli, B. B. Ercole, R. Tafi, M. Penzzanera, M. U. Mondelli, R. Cortese, A. Tramontano, G. Galfre', and A. Nicosia. 1998. EMBO J. 17, 3521–3533.) (r = 0.561, P < 0.005). The most widely reactive HVR1 protein, 12-22, had a sequence similar to the consensus sequence. The peptide with C-terminal 13-amino-acids sequence of HVR1 protein 12-22 (NH2-CSFTSLFTPGPSQK) was injected into rabbits as an immunogen. The rabbit immune sera reacted with 9 of 25 HVR1 proteins of genotype 1b including HVR1 protein 12-22 and with 3 of 12 proteins of genotype 2a. These results indicate that the HVR1 protein broadly reactive with patients' sera has a sequence similar to the consensus sequence, can induce broadly reactive sera, and could be one of the candidate immunogens in a prophylactic vaccine against HCV

Functional impairment of circulating FcεRI+ monocytes and myeloid dendritic cells in hepatocellular carcinoma and cholangiocarcinoma patients

Background Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. Methods In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI+ monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI+ monocyte subpopulation. Results A significant decrease in the frequency of TNFα producing FcεRI+ monocytes and mDCs in HCC and CCA patients when compared to the group of healthy individuals was observed, and a close association between FcεRI+ monocytes and mDCs dysfunction was identified. In addition, the phenotypic characteristics of FcεRI+ monocytes from healthy individuals strongly suggest that this population drives to mDCs, which matches with the fact that both populations are functionally affected. Conclusions The frequency and the function of circulating mDCs and FcεRI+ monocytes are affected in both HCC and CCA patients, and FcεRI+ monocytes could represent those fated to become mDCs.publishe

Surgery information reduces anxiety in the pre-operative period

PURPOSE: Patients preparing to undergo surgery should not suffer needless anxiety. This study aimed to evaluate anxiety levels on the day before surgery as related to the information known by the patient regarding the diagnosis, surgical procedure, or anesthesia. METHOD: Patients reported their knowledge of diagnosis, surgery, and anesthesia. The Spielberger State-Trait Anxiety Inventory (STAI) was used to measure patient anxiety levels. RESULTS: One hundred and forty-nine patients were selected, and 82 females and 38 males were interviewed. Twenty-nine patients were excluded due to illiteracy. The state-anxiety levels were alike for males and females (36.10 ± 11.94 vs. 37.61 ± 8.76) (mean ± SD). Trait-anxiety levels were higher for women (42.55 ± 10.39 vs. 38.08 ± 12.25, P = 0.041). Patient education level did not influence the state-anxiety level but was inversely related to the trait-anxiety level. Knowledge of the diagnosis was clear for 91.7% of patients, of the surgery for 75.0%, and of anesthesia for 37.5%. Unfamiliarity with the surgical procedure raised state-anxiety levels (P = 0.021). A lower state-anxiety level was found among patients who did not know the diagnosis but knew about the surgery (P = 0.038). CONCLUSIONS: Increased knowledge of patients regarding the surgery they are about to undergo may reduce their state-anxiety levels.PROPÓSITO: Pacientes que vão ser operados não devem sofrer ansiedade. Este estudo tem por objetivo comparar o grau de ansiedade no dia anterior à cirurgia entre pacientes que têm informação sobre seu diagnóstico, cirurgia e anestesia. MÉTODOS: Pacientes referiram seu conhecimento sobre o diagnóstico, a cirurgia e a anestesia. O inventário de Spielberger, State-Trait Anxiety Inventory (STAI), mediu a ansiedade. RESULTADOS: Cento e quarenta e nove pacientes foram selecionados, 82 mulheres e 38 homens foram entrevistados. Vinte e nove pacientes foram excluídos do estudo por analfabetismo. A ansiedade-estado foi semelhante para homens e mulheres, (36,10 ± 11,94 vs. 37,61 ± 8,76) (mean ± SD). A ansiedade-traço foi maior entre mulheres (42,55 ± 10,39 vs. 38,08 ± 12,25, P = 0,041). O nível de educação não influenciou a ansiedade-estado mas mostrou-se inversamente relacionado à ansiedade-traço. O diagnóstico fora claro para 91,7% dos pacientes entrevistados, cirurgia para 75% e anestesia para 37,5%. O desconhecimento da cirurgia elevou a ansiedade-estado (P = 0,021) cujo menor índice foi encontrado entre pacientes que não conheciam seu diagnóstico, mas sabiam sobre a cirurgia (P = 0,038). CONCLUSÕES: O conhecimento sobre a cirurgia a ser realizada pode reduzir o estado de ansiedade

ORIGINAL RESEARCH SURGERY INFORMATION REDUCES ANXIETY IN THE PRE-OPERATIVE PERIOD

PURPOSE: Patients preparing to undergo surgery should not suffer needless anxiety. This study aimed to evaluate anxiety levels on the day before surgery as related to the information known by the patient regarding the diagnosis, surgical procedure, or anesthesia. METHOD: Patients reported their knowledge of diagnosis, surgery, and anesthesia. The Spielberger State-Trait Anxiety Inventory (STAI) was used to measure patient anxiety levels. RESULTS: One hundred and forty-nine patients were selected, and 82 females and 38 males were interviewed. Twentynine patients were excluded due to illiteracy. The state-anxiety levels were alike for males and females (36.10 ± 11.94 vs. 37.61 ± 8.76) (mean ± SD). Trait-anxiety levels were higher for women (42.55 ± 10.39 vs. 38.08 ± 12.25, P = 0.041). Patient education level did not influence the state-anxiety level but was inversely related to the trait-anxiety level. Knowledge of the diagnosis was clear for 91.7% of patients, of the surgery for 75.0%, and of anesthesia for 37.5%. Unfamiliarity with the surgical procedure raised state-anxiety levels (P = 0.021). A lower state-anxiety level was found among patients who did not know the diagnosis but knew about the surgery (P = 0.038). CONCLUSIONS: Increased knowledge of patients regarding the surgery they are about to undergo may reduce their state-anxiety levels

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-β

Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4 + regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4 + T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4 + T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV + hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function. Conclusions/Significance: These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses