Virus-related Chronic Hepatitis Research Articles

Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis.

The aim of this study was to find novel biomarkers and develop a non-invasive, effective diagnostic model for hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to assess the expression of differentially expressed genes (AGRN, JAG1, CCL5, ID3, CCND1, and CAPN2) in peripheral blood mononuclear cells (PBMCs) from healthy subjects, chronic hepatitis B (CHB), and liver fibrosis/cirrhosis (LF/LC) patients. The molecular mechanisms underlying AGRN-regulated CHB were further explored and verified in LX2 cells, in which small interfering RNA (siRNA) was used to block AGRN gene expression. Finally, enzyme-linked Immunosorbent Assay (ELISA) was used to measure AGRN protein expression in 100 healthy volunteers, 100 CHB patients, and 100 LF/LC patients, and the efficacy of the diagnostic model was assessed by the Area Under the Curve (AUC). AGRN mRNA displayed a steady rise in the PBMCs of normal, CHB, and LF/LC patients. Besides, AGRN expression was markedly elevated in activated LX2 cells, whereas the expression of COL1 and α-SMA decreased when AGRN was inhibited using siRNA. In addition, downregulation of AGRN can reduce the gene expression of β-catenin and c-MYC while upregulating the expression of GSK-3β. Furthermore, PLT and AGRN were used to develop a non-invasive diagnostic model (PA). To identify CHB patients from healthy subjects, the AUC of the PA model was 0.951, with a sensitivity of 87.0% and a specificity of 91.0%. The AUC of the PA model was 0.922 with a sensitivity of 82.0% and a specificity of 90.0% when differentiating between LF/LC and CHB patients. The current study indicated that AGRN could be a potential plasma biomarker and the established PA model could improve the diagnostic accuracy for HBV-related liver diseases.

Особенности иммунологического статуса и углеводного обмена на разных стадиях фиброза печени у больных хроническим гепатитом, ассоциированным с вирусом С

Актуальность. В статье рассматриваются вопросы взаимосвязей структурных изменений печени с показателями иммунологического статуса у больных с хроническим вирус­ным гепатитом С (ХГС). Цель: определить особенности изменений иммунологического статуса и углеводного обмена у больных ХГС в зависимости от стадии фиброза. Материалы и методы. Обследованы 94 пациента с хроническим гепатитом С, средний возраст которых составил (49,91 ± 11,23) года. Выполнили морфологическое исследование у 42 больных, сдвиговолновую эластографию печени (СВЭ) и оценку коэффициента затухания ультразвука. Для изучения ассоциа­ций иммунологического статуса и углеводного обмена со структурными изменениями печени всех больных разделили на группы: с умеренным (FI + FII) и выраженным фиброзом (FIII + FIV) по шкале METAVIR. Определяли субпопуляционный состав лимфоцитов, циркулирующих иммунных комплексов, проводили оценку иммунного статуса. Осуществили оценку инсулинорезистентности с помощью индекса HOMA-IR. Статистическую обработку полученных результатов проводили с помощью пакета прикладных программ Statistica 6.1 (серийный номер AGAR909 E415822FA). Результаты. У 73,4 % больных ХГС снижено относительное содержание СD3+-лимфоцитов. Медиана относительного содержания СD4+-лимфоцитов была ниже в 1,4 раза (р < 0,05) по сравнению с контролем. У больных ХГС СD4+-клетки стимулируют продукцию антител В-лимфоцитами (r = 0,56, р < 0,01) и активируют СD8+ Т-клетки (r = 0,59, р < 0,01), специфические для вирусинфицированных клеток. Нарушение (снижение) индекса иммунорегуляции установлено у 79,8 % больных. Определены отрицательные корреляционные связи между содержанием Т-хелперов и СВЭ печени (r = –0,26, р < 0,05). Определено увеличение содержания инсулина у больных ХГС с выраженным фиброзом относительно его уровня в группе контроля в 2,3 раза (р < 0,05) и больных с умеренным фиброзом в 1,3 раза (р < 0,05), установлена связь этого показателя с жесткостью печени по данным СВЭ (r = 0,43, р < 0,05). Выявлена связь между уровнем ИЛ-6 и СВЭ печени (r = 0,68, р < 0,01), степенью фиброза (по METAVIR) (r = 0,57, р < 0,01). Отдельные иммунологические показатели (содержание В-лимфоцитов, Т-хелперов, TNF-α, ИЛ-6 и инсулина) могут быть использованы для разработки неинвазивной диагностики умеренного и выраженного фиброза печени у больных с ХГС. Выводы. У больных с ХГС прогрессирование фиброза печени сопровождается истощением клеточного звена иммунитета, повышением уровня провоспалительных цитокинов и нарушением углеводного обмена в зависимости от выраженности фиброзной трансформации.

P53 and rb Promoter Methylation in Hepatitis C virus-related Chronic Hepatitis and Hepatocellular Carcinoma

Aim: To identify methylation in p53 and rb during hepatitis C virus (HCV) infection in individuals in Pakistan. Materials & methods: Methylation-specific PCR was used on liver biopsies from hepatocellular carcinoma and chronic hepatitis C patients and on blood samples from healthy individuals. Real-time PCR was used to assess changes in the expression of p53 and rb in Huh-7 cells transfected with HCV-3a. Results: The p53 and rb promoters were methylated in hepatocellular carcinoma patients. The presence of HCV-3a- Core (p = 0.03), HCV-3a- NS-3 (p = 0.01) and HCV-3a- NS-5a (p = 0.02) downregulated p53 expression. Exposure to HCV-3a- Core (p = 0.04) downregulated rb expression. Conclusion: It can be hypothesized that HCV-induced epigenetic modifications may lead to the development of hepatic cancer that in turn inactivates p53 and rb.

Dynamic thiol-disulfide homeostasis is disturbed in hepatitis B virus-related chronic hepatitis and liver cirrhosis

Background/aim: Thiol-disulfide homeostasis is an important antioxidant defense mechanism. This study was conducted to investigate dynamic thiol-disulfide homeostasis in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis. Materials and methods: Seventy-one treatment-naive patients with chronic hepatitis B (CHB), 50 patients with hepatitis B virusassociated liver cirrhosis, and 45 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentrations were measured using an automated method. Results: Mean serum total thiol concentrations in the control, CHB, and cirrhosis groups were 481.64 ± 37.87 µmol/L, 438.50 ± 71.35 µmol/L, and 358.07 ± 80.47 µmol/L, respectively (P < 0.001), and mean serum native thiol concentrations in the control, CHB, and cirrhosis groups were 452.92 ± 36.43 µmol/L, 400.16 ± 65.92 µmol/L, and 328.15 ± 74.91 µmol/L, respectively (P < 0.001). Mean serum disulfide concentrations in the control, CHB, and cirrhosis groups were 14.38 ± 3.38 µmol/L, 19.19 ± 6.16 µmol/L, and 14.98 ± 5.53 µmol/L, respectively (P < 0.001). There was a progressive decrease in both mean serum native and total thiol concentrations parallel to the liver fibrosis stage. Conclusion: : Thiol-disulfide homeostasis is disturbed in patients with hepatitis B virus-related chronic hepatitis and liver cirrhosis.

Direct-acting antiviral drugs for chronic hepatitis C and risk of major vascular events: a systematic review.

Direct-acting antiviral drugs (DAAs) were recently approved for treating hepatitis C virus-related chronic hepatitis. As advanced chronic liver disease may predispose patients to thrombotic events, it is still uncertain whether DAAs may influence the actual risk of major arterial and venous thrombotic events. We performed a systematic review to assess the incidence of major vascular events in patients receiving DAAs for HCV chronic hepatitis during phase-III randomized controlled trials (RCTs). Two reviewers identified studies through Pubmed database until October 2015. Reporting and incidence of any vascular events were compared with reporting and incidence of major bleeding, anemia (a prespecified safety outcome) and headache (a common non-prespecified safety outcome). 33 RCTs, encompassing 14,764 patients, were included. Only 13 (39%) and 4 (12%) RCTs provide data on any arterial or venous events, respectively. Occurrence of anemia and headache is reported in all studies. Crude unweighted rate of major arterial events is 0.16% (95% CI 0.10-0.24) of the total included population and 0.47% in those 13 RCTs reporting data. Crude unweighted rate of major venous events is 0.03% of the total included population (95% CI 0.01-0.08) and 0.22% in those four RCTs reporting data. Crude unweighted rate of major bleeding is 0.07% (95% CI 0.03-0.1). Incidence of thrombotic events in HCV patients receiving DAAs may be low, but an incorrect estimation cannot be excluded.

THU-224 - Liver stiffness evaluated by means of ARFI is related not only to fibrosis in patients with hepatitis C virus-related chronic hepatitis

THU-224 - Liver stiffness evaluated by means of ARFI is related not only to fibrosis in patients with hepatitis C virus-related chronic hepatitis

Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.

Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.

The reliability of digital image analysis and immunohistochemistry in the estimation of liver fibrosis in hepatitis C virus-related chronic hepatitis

The reliability of digital image analysis and immunohistochemistry in the estimation of liver fibrosis in hepatitis C virus-related chronic hepatitis

Thrombocytopenia in patients with hepatitis B virus-related chronic hepatitis: Evaluation of the immature platelet fraction

The immature platelet fraction (IPF) measures the number of reticulated platelets in peripheral blood, and can be used to help determine if thrombocytopenia is secondary to low-platelet production or increased platelet turnover. The aim of this study was to determine whether abnormalities in the IPF were associated with thrombocytopenia in patients with hepatitis B virus-related chronic hepatitis (CHB). One hundred fifty-six patients with chronic hepatitis B, including 80 thrombocytopenia, 76 without thrombocytopenia, and 48 healthy controls were enrolled in the study. The IPF percentages (IPF%) were measured using a XE-2100 multiparameter automatic hematology analyzer. We demonstrated that in the thrombocytopenic group, the IPF% was significantly increased compared with that in healthy controls and the non-thrombocytopenic group (both p < 0.001). Multivariate analysis demonstrated that IPF%, splenomegaly, and the model for end-stage liver disease score were independent predictors for thrombocytopenia (both p < 0.001). High IPF% during the course of thrombocytopenia suggests that platelet destruction/sequestration due to hypersplenism is a major factor contributing to thrombocytopenia in patients with CHB.

Selenium levels in patients with hepatitis C virus-related chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma: A pilot study

Selenium levels in patients with hepatitis C virus-related chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma: A pilot study

Participation of natural killer cells in the pathogenesis of bile duct lesions in biliary atresia

AimsImmunological disturbances including innate immunity after a suspected viral infection are considered important to the pathogenesis of bile duct lesions in cases of biliary atresia (BA). In this study, we...

Coeliac disease and C virus-related chronic hepatitis: a non association

BackgroundA higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C.Materials and methodsTwo hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent.Results1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological.Conclusions1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Potential usefulness of DNA methylation as a risk marker for digestive cancer associated with inflammation

DNA methylation has been deeply involved in the development and progression of digestive cancer, while aberrant DNA methylation has also often been observed in aged and inflammatory digestive tissues. Helicobacter pylori-related chronic gastritis, ulcerative colitis, and hepatitis B virus- and hepatitis C virus-related chronic hepatitis, are significant risk factors for developing cancer. A number of studies have revealed the specific methylation patterns for specific tissue types. DNA methylation status is stably transmitted to daughter cells. Also, unlike genetic mutations, it is possible to detect very tiny amounts of methylated DNA among tissues. Therefore, the use of aberrant methylation as a marker could be applicable to risk estimation of cancer development. We discuss the potential usefulness of DNA methylation as a risk marker for inflammation-associated digestive cancer, especially with attempts on gastric cancer, ulcerative colitis-associated cancer, and hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma.

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

AbstractChelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus– or hepatitis C virus–related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical management of chronic liver disease in thalassemia patients is a team management issue requiring a multidisciplinary approach. The purposes of this paper are to summarize the knowledge on the epidemiology and the risks of transmission of viral infections, to analyze invasive and noninvasive methods for the diagnosis of chronic liver disease, to report the knowledge on clinical course of chronic viral hepatitis, and to suggest the management of antiviral therapy in thalassemia patients with chronic hepatitis B or C virus or cirrhosis.

Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis: Differences and similarities

To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C (CHC) or chronic hepatitis B (CHB). We retrospectively evaluated 852 consecutive patients (726 CHC and 126 CHB) who had undergone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome (MS), body mass index (BMI), and apparent disease duration (ADD). Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biopsies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis (>30%) and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis >30% in CHC, whereas only age and BMI were related to steatosis in CHB. These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.

Hepatocyte membrane-bound IgG and circulating liver-specific autoantibodies in chronic liver disease: relation to hepatitis B virus serum markers and liver histology.

Hepatocytes isolated from 101 biopsies were examined for membrane-bound IgG. The sera of the patients were tested for anti-liver-specific lipoprotein by radioimmunoassay and for liver membrane autoantibody (by indirect immunofluorescence on isolated rabbit hepatocytes. The seven patients with normal liver or minor nonspecific alterations were negative for membrane IgG and serum antibodies. Membrane IgG with granular distribution was found in 41 patients [21 hepatitis B virus-related chronic active hepatitis (CAH), 3 cryptogenic CAH, 3 chronic persistent hepatitis, 6 prolonged viral hepatitis, 1 alcoholic cirrhosis, and 6 primary biliary cirrhosis]. Membrane IgG with linear fluorescence pattern was detected in 12 cases (4 autoimmune CAH, 3 HBsAg-positive CAH, 2 alcoholic cirrhosis, 1 anti-HBc positive CAH, 1 cryptogenic CAH, and 1 prolonged viral hepatitis). A strong association between granular IgG and serum HBsAg was found. Nuclear localization of IgG was found in 34 patients and correlated with the positivity of granular membrane IgG. The highest prevalence of anti-liver-specific lipoprotein was found in primary biliary cirrhosis and autoimmune CAH cases which were also positive for liver membrane autoantibody. No relationship was found between the presence of membrane IgG and circulating liver-specific autoantibodies. Membrane IgG and anti-liver-specific lipoprotein correlated with the presence of moderate and severe portal inflammatory infiltration but not with piecemeal necrosis or transaminase levels. Eleven of the twelve patients with linear membrane IgG presented chronic active liver disease with moderate to severe signs of liver damage. Therefore, it is suggested that, while granular membrane IgGs are related to hepatitis B virus, antigenic expression on the hepatocyte surface and/or the presence of immune complexes, linear membrane IgG could play a role in the immunopathogenesis of liver cell damage particularly in "autoimmune" cases which present high percentages of positive cells liver-specific autoantibodies.

Perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis with hepatocellular carcinoma

Liver cirrhosis is reportedly one of the conditions preceding peripheral-type intrahepatic cholangiocarcinoma but not hilar/perihilar cholangiocarcinoma. Herein, we report a case of perihilar cholangiocarcinoma arising in a hepatitis C virus-related cirrhotic liver. The patient was a 69-year-old man. He was diagnosed with hepatitis C virus-related chronic hepatitis at the age of 56 years, and 9 years later, multiple hepatocellular carcinomas were detected by imaging modalities. Despite treatments, including chemotherapy, he died of hepatic failure at the age of 69 years. At autopsy, in addition to multiple nodules of hepatocellular carcinoma, we found a white mucinous and fibrous tumor spreading from the hepatic hilum to the periphery along the left lateral segmental bile ducts in the advanced cirrhotic liver. This tumor was histologically a cholangiocarcinoma that involved mainly the peribiliary glands and showed variable cystic dilation, suggesting that it might have been derived from these peribiliary glands. Immunohistochemically, the cholangiocarcinoma cells were positive for cytokeratin 7 and mucin core protein 1, and negative for cytokeratin 20 and mucin core protein 2. Hilar/perihilar cholangiocarcinoma arising in hepatitis C virus-related liver cirrhosis has rarely been reported. This case warrants further studies to clarify the possible involvement of hepatitis C virus in tumorigenesis of hilar/perihilar cholangiocarcinoma.

A prospective study of acute drug‐induced liver injury in patients suffering from non‐alcoholic fatty liver disease

Liver damage due to facultative hepatotoxins is scarcely foreseeable. We evaluated the prevalence of acute drug-induced liver injury (DILI) in a specific setting, assessing eventual interactions with pre-existing hepatic illnesses. The research was carried out in an Italian tertiary care hospital, by analyzing 248 patients with non-advanced liver disease, divided into two well-matched groups: 174 patients (median age 53, 94 females) with hepatitis C virus-related chronic hepatitis; and 74 (median age 55, 39 females) with non-alcoholic fatty liver disease (NAFLD). Six patients (2.4% of the whole population) belonging to the NAFLD group (chi(2)-test, P = 0.004) suffered from acute hepatoxicity related to the following drugs, that is antihypertensive, acting on platelet aggregation, antimicrobial, non-steroidal anti-inflammatory and proton pump inhibitor. The NAFLD presence was an independent risk factor in determining drug-related acute hepatitis, with an odds ratio of 3.95 (95% confidence intervals: 11.48-1.35). Central obesity was relevant in every patient with acute toxicity. Alcohol consumption and drug association did not influence the acute drug-induced liver damage. NAFLD conveys a nearly fourfold increase of DILI risk in obese middle-aged patients. NAFLD, characterized by mitochondrial dysfunction, could predispose to drug-induced hepatotoxicity that probably shares the same pathophysiological mechanism.

Thyroid Cancer in HCV-Related Chronic Hepatitis Patients: A Case-Control Study

The present study prospectively investigated prevalence and features of thyroid cancer in patients with hepatitis C virus-related chronic hepatitis (HCV+) in comparison to two samples from the general population with different iodine intake. We studied the prevalence of thyroid cancer in 308 unselected HCV+ patients in comparison to two population-based, gender- and age-matched control groups: 1) 616 subjects from an iodine deficient area; 2) 616 subjects from an iodine-sufficient area. Thyroid status was assessed by measurement of circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and when indicated, fine-needle aspiration cytology. Circulating thyrotropin, anti-thyroglobulin, and anti-thyroperoxidase antibodies levels, and the prevalence of hypothyroidism were significantly higher in HCV+ patients (p < 0.001 for all). Six patients with papillary thyroid cancer were detected among HCV+ patients, whereas no case was observed in control 1 (p = 0.001), and only one case was observed in control 2 (p = 0.003). In HCV+ patients 83% with thyroid cancer had evidence of thyroid autoimmunity vs 31% of the other HCV+ patients (p = 0.02). These data suggest a high prevalence of thyroid papillary cancer in HCV+ patients, overall in presence of thyroid autoimmunity; careful thyroid monitoring is indicated during the follow-up of these patients.