• H2A monoubiquitination
• HCV
• PA28γ/REGγ/PMSE3/Ki
• RNF2

• Humans
• Proteasome Endopeptidase Complex/metabolism
• Proteasome Endopeptidase Complex/genetics
• Acetylation
• Polycomb Repressive Complex 1/metabolism
• Polycomb Repressive Complex 1/genetics
• Hepacivirus/genetics
• Hepacivirus/drug effects
• Hepacivirus/physiology
• Autoantigens/metabolism
• Autoantigens/genetics
• Hepatitis C/virology
• Hepatitis C/metabolism
• Hepatitis C/genetics
• Ubiquitination
• Proteolysis
• HEK293 Cells
• Histones/metabolism
• Histones/genetics

• 24fk0210109 Japan Agency for Medical Research and Development (AMED)
• Moonshot R&D JPMJMS2025 MEXT | Japan Science and Technology Agency (JST)
• Scholarship donation Teijin Pharma
• Scholarship donation Yakult Honsha (Yakult)

• Hepatogenous diabetes
• Hyperinsulinemia
• Impaired glucose tolerance
• Insulin resistance
• Liver cirrhosis
• Non-alcoholic fatty liver disease

• Humans
• Liver Cirrhosis/metabolism
• Insulin Resistance/physiology
• Diabetes Mellitus, Type 2/metabolism
• Animals
• Signal Transduction
• Insulin/metabolism

• HCC
• HCV
• Hepatitis C virus
• Hepatocellular carcinoma
• metabolic dysfunction
• senescence
• steatosis

• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Disease Progression
• Hepacivirus
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/pathology
• Humans
• Liver Neoplasms/pathology
• Obesity/drug therapy
• Sustained Virologic Response

• MR/R023026/1 Medical Research Council
• MR/K0019494/1 Medical Research Council
• 23390 Cancer Research UK
• C9380/A26813 Cancer Research UK
• C18342/A23390 Cancer Research UK

• Diabetes/insulin resistance
• Hepatitis C virus
• Islet beta-cell
• microRNA

• Animals
• Diabetes Mellitus/etiology
• Diabetes Mellitus/metabolism
• Diabetes Mellitus/virology
• Hepacivirus/physiology
• Hepatitis C/complications
• Hepatitis C/metabolism
• Hepatitis C/pathology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/metabolism
• Hepatitis C, Chronic/pathology
• Humans
• Insulin/metabolism
• Insulin Resistance/physiology
• Signal Transduction/physiology

The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.

• Chronic hepatitis C
• Sustained virologic response
• Hepatic steatosis
• Diabetes mellitus
• Cardiovascular disease

• Antiviral Agents/therapeutic use
• Genotype
• Hepacivirus
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/drug therapy
• Humans
• Interferons/therapeutic use
• Sustained Virologic Response

• Cardiovascular diseases
• Chronic hepatitis C infection
• Diabetes mellitus
• Fatty liver
• Insulin resistance
• Metabolic syndrome

• Hepacivirus
• Hepatitis C/complications
• Hepatitis C/epidemiology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/epidemiology
• Humans
• Liver Cirrhosis/epidemiology
• Liver Neoplasms/epidemiology

• 19S regulator
• 20S proteasome
• Inhibitor
• PA200
• PA28
• Proteasome activator

• Animals
• Antineoplastic Agents/pharmacology
• Humans
• Molecular Targeted Therapy
• Neoplasms/drug therapy
• Neoplasms/enzymology
• Proteasome Endopeptidase Complex/drug effects
• Proteasome Endopeptidase Complex/metabolism
• Proteasome Inhibitors/pharmacology
• Proteolysis

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.

• AMPK
• GLP-1
• diabetes mellitus
• hepatitis C virus
• liraglutide

• HBV
• HCV
• cirrhosis
• hepatocellular carcinoma

• HBV
• HCV
• cirrhosis
• hepatocellular carcinoma

• DAAs
• chronic hepatitis C
• insulin resistance
• type 2 diabetes mellitus

• direct-acting antivirals
• hepatitis C virus
• insulin resistance
• liver fibrosis

Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors.

This article is part of the themed issue ‘Human oncogenic viruses’.

• chronic viral hepatitis
• hepatitis B
• hepatitis C
• hepatocarcinogenesis
• hepatocellular carcinoma
• virus-induced cancer

• Hepatitis C
• Hypobetalipoproteinemia
• Insulin resistance
• Microsomal triglyceride transfer protein
• Steatosis
• Tumor necrosis factor

• Animals
• Cytokines/metabolism
• Diabetes Mellitus, Type 2/epidemiology
• Dyslipidemias/metabolism
• Fatty Liver/epidemiology
• Hepacivirus
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/epidemiology
• Hepatitis C, Chronic/metabolism
• Humans
• Incretins/metabolism
• Insulin Resistance
• Insulin-Secreting Cells/virology
• Lipid Metabolism
• Mice
• Prevalence
• Risk Factors
• Signal Transduction

• cirrhosis
• hepatogenous diabetes
• insulin resistance
• orthotopic liver transplant
• β-cell dysfunction

• glucose metabolism
• hepatitis C virus (HCV)
• insulin resistance
• transgenic mice
• type 2 diabetes

To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control.

This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis.

Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI (P = 0.684).

Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy.

• Hepatitis C
• Sofosbuvir
• Hyperlipidemia
• Hemoglobin A1c
• Low-density lipoprotein

• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/physiopathology
• Hepatitis C, Chronic/complications
• Humans
• Liver Cirrhosis/complications
• Models, Biological

• 671231 European Research Council
• R01 DK099558 NIDDK NIH HHS

Hepatitis C virus (HCV) is closely associated with insulin resistance (IS), acting primarily by interfering with insulin signaling pathways, increasing cytokine-mediated (tumor necrosis factor α, interleukin 6) inflammatory responses and enhancing oxidative stress. In the insulin signaling pathways, the insulin receptor substrate (IRS) is one of the key regulatory factors. The present study constructed gene regulatory sub-networks specific for IRS1 and IRS2 in Huh7 cells and HCV-infected Huh7 (HCV-Huh7) cells using linear programming and a decomposition algorithm, and investigated the possible mechanisms underlying the function of IRS1/2 in HCV-induced IS in Huh7 cells. All data were obtained from GSE20948 of the Gene Expression Omnibus database from the National Center for Biotechnology Information. Genes which were significantly differentially expressed between Huh7 and HCV-Huh7 cells were analyzed using the significance analysis of microarray algorithm. The top 50 genes, including IRS1/2, were used as target genes to determine the gene regulatory networks and next the sub-networks of IRS1 and IRS2 in HCV-Huh7 and Huh7 cells using Gene Regulatory Network Inference Tool, an algorithm based on linear programming and the decomposition process. The IRS1/2 sub-networks were divided into upstream/downstream groups and activation/suppression clusters, and were further analyzed using Molecule Annotation System 3.0 and Database for Annotation, Visualization, and Integrated Discovery software, two online platforms for enrichment and clustering analysis and visualization. The results indicated that in Huh7 cells, the downstream network of IRS2 is more complex than that of IRS1, indicating that the insulin metabolism in Huh7 cells may be primarily mediated by IRS2. In HCV-Huh7 cells, the downstream pathway of IRS2 is blocked, suggesting that this may be the underlying mechanism in HCV infection that leads to insulin resistance. The present findings add a further dimension to the understanding of the pathological mechanisms of HCV infection-associated insulin resistance, and provide novel concepts for insulin resistance and glucose metabolism research.

AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis C virus (HCV) nonstructural protein 5A (NS5A).

METHODS: The human hepatoma cell lines, Huh7 and Huh7.5, were infected with HCV or transiently-transfected with a vector expressing HCV NS5A. The effect of HCV NS5A on the status of the critical players involved in insulin signaling was analyzed using real-time quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version 5.0.

RESULTS: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway, we analyzed the status of insulin receptor substrate-1 (IRS-1) phosphorylation in HCV infected cells or Huh7.5 cells transfected with an HCV NS5A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1 (Ser³⁰⁷) in HCV infected or NS5A transfected Huh7.5 cells compared to their respective controls. Furthermore, an increased phosphorylation of Akt (Ser⁴⁷³) was observed in HCV infected and NS5A transfected cells compared to their mock infected cells. In contrast, we observed decreased phosphorylation of Akt Thr308 phosphorylation in HCV NS5A transfected cells. These results suggest that Huh7.5 cells either infected with HCV or ectopically expressing HCV NS5A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue (Ser³⁰⁷) followed by decreased phosphorylation of Akt Thr³⁰⁸, Fox01 Ser²⁵⁶ and GSK3β Ser⁹, the downstream players of the insulin signaling pathway. Furthermore, increased expression of PECK and glucose-6-phosphatase, the molecules involved in gluconeogenesis, in HCV NS5A transfected cells was observed.

CONCLUSION: Taken together, our results suggest the role of HCV NS5A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.

• Hepatitis C virus nonstructural protein 5A
• Insulin resistance
• Forkhead box protein 01
• Glycogen synthase kinase-beta
• Gluconeogenesis

• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/virology
• Cell Line, Tumor
• Forkhead Box Protein O1
• Forkhead Transcription Factors/metabolism
• Gluconeogenesis
• Glycogen Synthase Kinase 3/metabolism
• Glycogen Synthase Kinase 3 beta
• Hepacivirus/genetics
• Hepacivirus/metabolism
• Host-Pathogen Interactions
• Humans
• Insulin Receptor Substrate Proteins/metabolism
• Insulin Resistance
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/virology
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Serine
• Signal Transduction
• Transfection
• Viral Nonstructural Proteins/genetics
• Viral Nonstructural Proteins/metabolism

• hepatocellular carcinoma
• insulin resistance
• insulin signalling

• adipokine
• chronic hepatitis C
• fibrosis
• insulin resistance
• liver
• steatosis

Genetic and cellular studies have shown that the host’s innate and adaptive immune responses are an important correlate of viral infection outcome. The features of the host’s immune response (host resistance) reflect the coevolution between hosts and pathogens that has occurred over millennia, and that has also resulted in a number of strategies developed by viruses to improve fitness and survival within the host (viral adaptation). In this review, we discuss viral adaptation to host immune pressure via protein–protein interactions and sequence-specific mutations. Specifically, we will present the “state of play” on viral escape mutations to host T-cell responses in the context of the hepatitis C virus, and their influence on infection outcome.

• adaptive immune response
• hepatitis C virus
• immune escape
• viral adaptation

Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4⁺ and CD8⁺ T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of “elite controllers,” or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8⁺ T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human leukocyte antigen (HLA)-restricted T cell immunity in natural infection, and the challenges these pose for designing effective preventative or therapeutic vaccines.

• HCV
• HIV
• anti-viral immune responses
• preventative vaccine
• viral immune escape

• Animals
• Carcinoma, Hepatocellular/etiology
• Cell Transformation, Neoplastic/pathology
• Hepacivirus/pathogenicity
• Hepatitis C/complications
• Humans
• Liver Neoplasms/etiology
• Mice

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a “viral” steatosis which is frequently superimposed to a “metabolic” one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.

• Hepatitis C virus
• Metabolism
• Insulin resistance
• Diabetes mellitus
• Steatosis
• Fibrosis
• Atherosclerosis
• Cardiovascular risk

• Animals
• Atherosclerosis/etiology
• Fatty Liver/etiology
• Hepatitis C/complications
• Hepatitis C/metabolism
• Humans
• Insulin Resistance
• Liver Cirrhosis/etiology

Hepatitis C virus (HCV) infection disrupts the normal metabolism processes, but is also influenced by several of the host’s metabolic factors. An obvious and significantly detrimental pathophysiological feature of HCV infection is insulin resistance in hepatic and peripheral tissues. Substantial research efforts have been put forth recently to elucidate the molecular mechanism of HCV-induced insulin resistance, and several cytokines, such as tumor necrosis factor-α, have been identified as important contributors to the development of insulin resistance in the distant peripheral tissues of HCV-infected patients and animal models. The demonstrated etiologies of HCV-induced whole-body insulin resistance include oxidative stress, lipid metabolism abnormalities, hepatic steatosis and iron overload. In addition, myriad effects of this condition have been characterized, including glucose intolerance, resistance to antiviral therapy, progression of hepatic fibrosis, development of hepatocellular carcinoma, and general decrease in quality of life. Metabolic-related conditions and disorders, such as visceral obesity and diabetes mellitus, have been shown to synergistically enhance HCV-induced metabolic disturbance, and are associated with worse prognosis. Yet, the molecular interactions between HCV-induced metabolic disturbance and host-associated metabolic factors remain largely unknown. The diet and lifestyle recommendations for chronic hepatitis C are basically the same as those for obesity, diabetes, and metabolic syndrome. Specifically, patients are suggested to restrict their dietary iron intake, abstain from alcohol and tobacco, and increase their intake of green tea and coffee (to attain the beneficial effects of caffeine and polyphenols). While successful clinical management of HCV-infected patients with metabolic disorders has also been achieved with some anti-diabetic (i.e., metformin) and anti-lipid (i.e., statins) medications, it is recommended that sulfonylurea and insulin be avoided.

• Hepatitis C virus
• Insulin resistance
• Diabetes
• Lipid metabolism abnormality
• Hepatic steatosis
• Iron overload
• Oxidative stress
• Visceral obesity

• Animals
• Diet Therapy
• Fatty Liver/metabolism
• Glucose/metabolism
• Hepatitis C/metabolism
• Hepatitis C/therapy
• Humans
• Hypoglycemic Agents/therapeutic use
• Hypolipidemic Agents/therapeutic use
• Insulin Resistance
• Iron/metabolism
• Lipid Metabolism
• Oxidative Stress

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Hepatitis B or hepatitis C virus infection has been considered the most important etiologic factor for human HCC. Recently, it has been suggested that diabetes mellitus is a risk factor for HCC, and that insulin resistance as a critical component of diabetes mellitus pathogenesis may be involved in the occurrence of hepatitis virus-related HCC. Since IRS-1-Ser312 is a molecule that is involved in the pathogenesis of both hepatitis C virus and diabetes mellitus, IRS-1 or ROS may play a role in the development of HCC associated with diabetes mellitus and hepatitis B virus. Hence, diabetes mellitus and hepatitis virus not only are independent risk factors for HCC but also interact with each other to contribute to the development of this malignancy.

• Hepatocellular carcinoma
• Diabetes mellitus
• Hepatitis B virus
• Hepatitis C virus

• hepatocellular carcinoma
• hepatitis c virus

• Asia/epidemiology
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/therapy
• Hepatitis C, Chronic/complications
• Humans
• Liver Neoplasms/etiology
• Liver Neoplasms/prevention & control

Diabetes and cancer represent two complex, diverse, chronic, and potentially fatal diseases. Cancer is the second leading cause of death, while diabetes is the seventh leading cause of death with the latter still likely underreported. There is a growing body of evidence published in recent years that suggest substantial increase in cancer incidence in diabetic patients. The worldwide prevalence of diabetes was estimated to rise from 171 million in 2000 to 366 million in 2030. About 26.9% of all people over 65 have diabetes and 60% have cancer. Overall, 8–18% of cancer patients have diabetes. In the context of epidemiology, the burden of both diseases, small association between diabetes and cancer will be clinically relevant and should translate into significant consequences for future health care solutions. This paper summarizes most of the epidemiological association studies between diabetes and cancer including studies relating to the general all-site increase of malignancies in diabetes and elevated organ-specific cancer rate in diabetes as comorbidity. Additionally, we have discussed the possible pathophysiological mechanisms that likely may be involved in promoting carcinogenesis in diabetes and the potential of different antidiabetic therapies to influence cancer incidence.

Hepatitis C virus (HCV), a hepatotropic virus, is a single stranded-positive RNA virus of ~9,600 nt. length belonging to the Flaviviridae family. HCV infection causes acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). It has been reported that HCV-coding proteins interact with host-cell factors that are involved in cell cycle regulation, transcriptional regulation, cell proliferation and apoptosis. Severe inflammation and advanced liver fibrosis in the liver background are also associated with the incidence of HCV-related HCC. In this review, we discuss the mechanism of hepatocarcinogenesis in HCV-related liver diseases.

• Carcinogenesis
• Cirrhosis
• Fibrosis
• Hepatitis C virus
• Hepatocellular carcinoma
• Inflammation

Background. Chronic hepatitis C virus (HCV) has become the global “epidemic” with an estimated 123 million people currently infected worldwide. As the same time diabetes is also rapidly emerging as a global health care problem that threatens to reach pandemic levels by 2030. Objective. To investigate the magnitude of HCV infection in type II diabetes as compared to controls. Methodology. A case control study design was conducted at Jimma University Specialized Hospital from May to June 2010. A total of 604 study subjects were included in this study. Sociodemographic and risk factor data were collected by questionnaire. From serum sample, HCVAb screening was done by rapid antibody screening test. Liver functioning tests and total cholesterol tests were done by Dr. Lange LP 800 spectrophotometer. Results. The prevalence of HCV in type II diabetes and nondiabetic controls was 9.9% and 3.3%, respectively. In multivariate analysis, HCV seropositives have high risk of developing diabetes as compared with seronegatives (AOR = 2.997, 95% CI: (1.08, 8.315)). Conclusion. In this study, we found a positive association between past HCV infection and type II diabetes. As we did not perform HCV RNA test, we could not assess the association with HCV viremia.