Hepatocellular Carcinoma In HCV-infected Patients Research Articles

Serum α-fetoprotein level at treatment completion is a useful predictor of hepatocellular carcinoma occurrence more than one year after hepatitis C virus eradication by direct-acting antiviral treatment.

Direct-acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved liver function of HCV patients. The risk of hepatocellular carcinoma (HCC) occurrence following HCV eradication has been previously reported, but HCC may have been missed following imaging diagnosis before DAA administration in previous studies. Therefore, the present study aimed to identify definite predictors of HCC occurrence ≥1year after DAA treatment. Among 956 patients receiving DAAs for HCV infection, 567 patients who achieved sustained virologic response with no history of HCC treatment were enrolled in this study between September 2014 and July 2021. The incidence of HCC in HCV-infected patients ≥1year following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinical characteristics and blood test results. In the present study, 25 patients developed HCC. The incidence of HCC was 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5years, respectively, from the end of treatment with DAAs. Multivariate logistic analysis revealed serum α-fetoprotein level at end of treatment (EOT-AFP) >3.8ng/ml ≥1year following treatment with DAAs (HR, 9.7; p<.0001) as an independent factor that may contribute to HCC occurrence following DAA treatment. In conclusion, serum EOT-AFP level may serve an important role in determining the risk of HCC occurrence ≥1year after DAA treatment. Regular examinations are required even if serum EOT-AFP level is low at treatment completion.

Evaluation of Transforming Growth Factor- β 1 Gene Expression and Polymorphism in Diagnosis of Hepatocellular Carcinoma in HCV-Infected Patients

Background: Transforming growth factor-beta1 (TGF-β1), a member of transforming growth factor beta family, functions as a multi-functional cytokine and plays a key role in cellular growth, proliferation and differentiation. Aim of the work: To evaluate the role of TGF-β1 polymorphisms 509 C>T and TGF-β1 Gene expression in diagnosis of hepatocellular carcinoma (HCC) in cirrhotic Egyptian patients due to hepatitis C virus (HCV). Subjects and methods: Thirty five cirrhotic with HCC patients, thirty cirrhotic without HCC patients and 20 healthy volunteers were enrolled in this study. TGF-β1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction and molecular study of TGF-β1 509 C>T (rs1800469) polymorphism by Taqman allele discrimination was done for all subjects. Results: Showed that TGF-β1 -509 CT genotype was the most frequent genotype in HCC patients and the most frequent allele was T allele in HCC patients, without significant difference of TGF-β1 -509 polymorphism in the studied groups. TGF-β1 gene expression was significantly higher in HCC patients (mean 3.19±1.8) than in cirrhotic without HCC patients (mean 1.76±0.95) (p T was not associated with the risk of HCC in HCV-cirrhotic patients.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

HMGB1 and SEPP1 as predictors of hepatocellular carcinoma in patients with viral C hepatitis: Effect of DAAs

BackgroundHepatitis C viral infection (HCV) and hepatocellular carcinoma (HCC) are potential health problems. New directly acting antivirals (DAAs) changed HCV treatment strategies. Selenoprotein P1 (SEPP1) is a hepatokine implicated in HCC pathogenesis. High mobility group box1 (HMGB1), a nuclear DNA-binding protein, involved in immune and inflammatory responses in HCV and HCC. Therefore, the aim of current study was to investigate HMGB1 and SEPP1 levels in HCV and HCV + HCC patients and exploring DAAs effect on them. Methods15 healthy volunteers, 25 HCV and 25 HCV + HCC patients were included. Liver function tests, alpha fetoprotein (AFP), SEPP1 and HMGB1 serum levels were evaluated. For HCV group blood samples before and after treatment with sofosbuvir/daclatasvir combination were collected. ResultsHMGB1 was significantly higher in HCV + HCC group than in control and HCV groups (p < .05). SEPP1 decreased significantly in HCV and HCV + HCC groups compared to control group (p < .001). SEPP1 significantly elevated after treatment with DAAs (p = .001). HMGB1 and SEPP1 were negatively correlated with each other in HCV group (p = .047). Logistic regression analysis showed that HMGB1 and SEPP1 could be used as predictors for HCC in HCV infected patients (p = .02,p = .002) respectively. Receiver operating characteristic curve (ROC) revealed HMGB1 had 32% sensitivity and 100% specificity in differentiating HCV from HCV + HCC patients, both SEPP1 and HMGB1 had high sensitivity (92%,60%) and 93% specificity in differentiating healthy from HCV + HCC group. ConclusionHMGB1 and SEPP1 are involved in pathogenesis of HCV and HCV induced HCC. Both of them could serve as predictive biomarkers for HCC in HCV patients.

The development of hepatocellular carcinoma in HCV-infected patients treated with DAA: A comprehensive analysis.

It has been proven that hepatitis C virus (HCV) eradication after interferon-based treatment can reduce the risk of hepatocarcinogenesis. However, there were some arguments about whether the treatment of direct-acting antivirals (DAAs) boosts the development of hepatocellular carcinoma (HCC). We systematically review this crucial topic by combining all the relevant articles to calculate the pooled HCC density after DAA treatment. Studies reporting the recurrence or occurrence in chronic hepatitis C patients who received DAA regimen were selected from three retrieval library screening. Data on baseline and outcomes were extracted independently by three observers. Primary outcomes were incidence density of HCC. Pooled estimates of HCC occurrence and recurrence rate per 100 person-years (py) were undertaken by random-effects meta-analysis. Sixteen studies with 61334 patients, embracing 20 cohorts, were enrolled in this study and divided into two groups (HCC occurrence and HCC recurrence). In the pooled analysis, HCC developed at a rate of 3.5/100 py [95% confidence interval (CI): 2.4, 5.3] among patients without a history of HCC compared with 17.4/100 py (95% CI: 7.8, 39.0) among patients existed. Furthermore, HCC occurrence rate following DAA-induced sustained virological response (SVR) was 2.1/100 py (95% CI: 1.4, 3.4); however, the rate in patients without SVR was 9.1/100 py (95% CI: 5.4, 15.3). HCV cured after DAA therapy could induce a reduction of 78% in the risk of HCC occurrence compared with non-responders. There is no strong evidence for an increased risk of HCC occurrence or recurrence in patients treated by DAA. There was a significant decline in the incidence of HCC occurrence after SVR.

De novo Occurrence and Recurrence of HCC in HCV Infected Patients Treated With DAAʼs: A Single Center 2-Year Experience

Introduction: Multiple studies have shown the efficacy of new direct-acting antivirals (DAA) with cure rate of over 90% in HCV infected patients. Recently published studies have suggested increased incidence of de novo and recurrent HCC(Hepatocellular carcinoma) in cirrhotic patients in SVR(sustained virological response) after completing therapy. A possible mechanism is breakdown of immune surveillance after starting DAA. We report a small case series in a population of chronic HCV infected patients, with and without prior history of HCC, who developed HCC after receiving direct acting antivirals (DAAs) with the aim of adding to existing literature.Table: Table. Clinical Variables Related To HCV and HCCTable. DAA: therapy associated variablesMethods: We retrospectively reviewed 16 patients reported to have HCC out of 290 patients who were treated with DAA at the Oklahoma City VA Medical Center over 2 years (2014-2015). Descriptive analysis including mean and standard deviation for different variables was performed. Results: All 16 patients were male, with the majority (75%) being white. Mean age was 66 years. All patients had cirrhosis as indicated by Fib-4 score > 3.25 and confirmed by imaging. Average Fib-4 score was 7.88. Most were Child Pugh Class A, with average MELD of 11. 6 (37.5%) were treatment naïve. Majority, 9 (56.25%) were genotype 1a. The frequencies of other HCV genotypes 1b, 2 and 3 were 3 (18.75%), 2 (12.5%) and 2 (12.5%) respectively. The median pretreatment HCV viral load was 1,286,176. EVR(Early viral response) was achieved in all patients. ETR(end treatment response) and Sustained Viral Response (SVR) was achieved in 12 (75%) and 10 (62.5%) patients respectively. In patients who achieved SVR, average number of weeks from SVR to HCC detection was 33.3 weeks. All HCC were diagnosed on surveillance ultrasound (USG) imaging (6 monthly) later confirmed via CT-Scan/MRI. 11/16 had denovo occurance of HCC Average time period from DAA therapy to HCC diagnosis was 48.2 weeks. 9/16 patients had more than 1 nodule at diagnosis, and only 7 fulfilled Milan Criteria. Conclusion: Our case series reiterates previously confirmed concern of increased HCC recurrence in patients with history of eradicated HCC. It may be associated with more aggressive occurance (given multiple nodules in >50% patients). It also adds to growing literature which suggest SVR may not be protective against HCC occurrence. It is unclear if treatment with DAA leads to increased HCC occurrence. There is a need of statistically stronger studies on larger cohorts before further conclusions are drawn.

A Variant in PNPLA3 Associated With Fibrosis Progression but not Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection

A single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain containing 3 gene (PNPLA3, rs738409) has been associated with fibrosis and development of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis, although its association with outcomes in patients with hepatitis C virus (HCV) infection is less clear. We evaluated the association between this SNP in PNPLA3 and fibrosis progression and development of HCC among HCV-infected patients. We performed a secondary analysis of data from participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. Patients were randomly assigned to groups given weekly pegylated interferon or no further therapy for 3.5 y and then followed without further treatment until October 2009. Multivariate logistic regression was used to identify factors associated with fibrosis at baseline, fibrosis progression (defined as 2-point increase in Ishak score), and HCC development. Among 937 HCV patients with known PNPLA3 genotype, 384 (41.0%) had cirrhosis at baseline. The PNPLA3 CG/GG SNP at rs738409 was significantly associated with the presence of cirrhosis (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.34-2.30), after adjusting for age, sex, diabetes, and race. Among 493 patients without cirrhosis at baseline who had at least 1 follow-up biopsy, 142 had fibrosis progression. In multivariate analyses, fibrosis progression was associated with obesity (OR, 1.67; 95% CI, 1.11-2.51) and the PNPLA3 CG/GG genotype (OR, 1.70; 95% CI, 1.13-2.56). PNPLA3 genotype was not associated with HCC development (P = .85). Using these data to update prior meta-analysis results, the rs738409 SNP in PNPLA3 was not significantly associated with development of HCC in HCV-infected patients (OR 1.29; 95% CI, 0.97-1.99). Based on data from the HALT-C trial, the PNPLA3 CG/GG SNP at rs738409 is associated with fibrosis progression but not development of HCC in patients with HCV infection.

Risk factors of hepatocellular carcinoma development in non-cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection.

Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV-infected patients who achieved SVR. The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon-based antiviral therapy for HCV. Patients maintained regular follow-up every 6 months for HCC surveillance. The FIB-4 index and aspartate aminotransferase to platelet count ratio index were calculated based on laboratory data at the time that SVR was documented (SVR24). Patients continued follow-up visits for 1.0-22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at 5 years and 4.3% at 10 years. The use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. The presence of diabetes mellitus (risk ratio 2.08; P = 0.0451) and FIB-4 index calculated at the time of SVR24 (risk ratio 1.73; P = 0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis. Patients with diabetes mellitus and patients with the elevation of FIB-4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.

TGF-β1 polymorphism 509 C>T is associated with an increased risk for hepatocellular carcinoma in HCV-infected patients.

Transforming growth factor-beta 1 (TGF-β1), a member of the transforming growth factor beta family, functions as a multi-functional cytokine and plays a key role in cellular growth, proliferation, and differentiation. The 509 C/T polymorphism in the TGF-β1 gene has been implicated in the outcome of hepatitis C virus (HCV) infection; however, little is known regarding the relationship between TGF-β1 gene mutations and the development of hepatocellular carcinoma (HCC) in HCV-infected patients. The aim of the study was to evaluate the effect of the TGF-β1 polymorphisms 509 C>T on the occurrence of HCC in patients chronically infected with HCV in a Chinese Han population. The results showed that HCC patients had a higher frequency of the TGF-β1 -509 TT genotype distribution of the TGF-β1 -509 polymorphism and a lower frequency of the CC genotype. Serum TGF-β1 levels were significantly higher in patients with the TT genotype than in those with the CC genotype. In this study, we confirmed that the TGF-β1 polymorphism 509 C>T is associated with the risk of HCC in HCV-infected patients.

TP53 polymorphism as a risk factor for hepatocellular carcinoma in hepatitis C virus-infected Egyptian patients

Background and aimsHuman hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Polymorphisms of the TP53 gene are known to play an important role in HCC. It is aimed to investigate the impact of the Arg72Pro polymorphism of TP53 in the development of HCC among chronic hepatitis C patients with different stages of liver disease. Subjects & methodsThis study included 69 HCC patients, 101 liver cirrhosis (LC) patients and 46 healthy, unrelated, age-matched volunteers as controls, from the same locality of Egypt. The HCC and LC patients were suffering from HCV infection. The Arg72Pro polymorphism of codon 72 was tested by PCR, followed by restriction enzyme digestion (PCR-RFLP). ResultsThe results showed that the Proline allele significantly increases the risk of HCC development (OR 2.461, 95% CI 1.391–4.3558, P = 0.002, Z* = 3.094), compared with the development of LC. The variant genotypes were also associated with the risk of HCC (Pro/Pro: OR 3.7956, 95% CI 1.9228–7.4923, P = 0.0001; Arg/Pro: OR 2.099, 95% CI 1.0911–4.0383, P = 0.0263; Arg/Arg: OR 1.9594, 95% CI 1.0023–3.8306, P = 0.0492). There was a significant decrease in the plasma TP53 level in the HCC group when compared with the LC group or with the control group (P = 0.000). ConclusionThis case–control analysis confirmed that the Pro/Pro (C/C) genotype and the Pro (C) allele of TP53 codon 72 are associated with increased risk of HCC in HCV-infected patients. Additionally, the data suggest that the plasma TP53 level is downregulated in HCC.

Effect of occult hepatitis B virus infection on the early-onset of hepatocellular carcinoma in patients with hepatitis C virus infection

Although overt hepatitis B virus (HBV) infection promotes the onset of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients, the effect of occult HBV infection remains unclear. The aim of this study was to investigate the effect of occult HBV infection on the early-onset of HCC in HCV-infected patients. A total of 173 HCC patients with HCV infection were enrolled and classified into 2 groups according to the median age of HCC onset: the early-onset group (n=91; 61.1±5.6 years) and the late-onset group (n=82; 73.8±3.7 years). Independent factors associated with the early-onset of HCC were assessed by multivariate analysis. In the overall analysis, independent risk factors for the early-onset of HCC were the white blood cell count and alanine aminotransferase level, but not the presence of HBV DNA. In a stratification analysis according to albumin levels of ≥3.5 g/dl, the presence of HBV DNA was a significant independent risk factor for the early-onset of HCC (OR 145.18, 95% CI 1.38-15296.61, P=0.036), whereas the presence of antibodies against hepatitis B core antigen was not found to be a risk factor. The presence of HBV DNA was not a risk factor for the early-onset of HCC in the overall analysis. However, its presence was an independent factor for the early-onset of HCC in HCV-infected patients with an albumin level of ≥3.5 g/dl. Thus, occult HBV infection may accelerate hepatocarcino-genesis in HCV-infected patients with relatively low carcinogenic potential.

Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines

This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC). Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n=353), ALT ≤30IU/L and platelet (PLT) ≥15×10(4)/mm(3); group B (n=123), ALT ≤30IU/L and PLT <15×10(4)/mm(3); group C (n=233), 30<ALT≤40IU/L and PLT ≥15×10(4)/mm(3); and group D (n=100), 30<ALT≤40IU/L and PLT <15×10(4)/mm(3). The mean observation period was 36.2±16.5months In groups A and C, the HCC incidence was low even in patients with non-response (NR) (cumulative rates at 3years, 0.0 and 2.9%, respectively). In groups B and D, 14.5 and 5.3% of NR patients had developed HCC at 3years, but none of the patients with sustained virologic response (SVR) or relapse had developed HCC. In group B, no patients with mild fibrosis developed HCC irrespective of the antiviral effect of the treatment. Among patients with PLT <15×10(4)/mm(3) (group B plus group D), the HCC incidence was significantly lower in patients with SVR and relapse than in NR patients (p<0.001, p=0.021, respectively). These results suggest that N-ALT patients with PLT <15×10(4)/mm(3) could be candidates for early antiviral therapy.

The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma

To evaluate the role of chemokine CC ligand 20 (CCL20) as a biomarker for hepatocellular carcinoma (HCC). Ninety patients in four groups were enrolled in this prospective cross-sectional study: 30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C virus infection (group III), and 15 healthy blood donors as controls. Alpha fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were measured in all groups. Serum levels of CCL20 were significantly different among the study groups (F=230.979, p<0.001). The highest level was found in HCC patients (57.305 ± 6.386 pg/mL) followed by patients with cirrhosis (45.999 ± 5.165 pg/mL) compared with 22.781 ± 5.986 pg/mL and 18.585 ± 3.554 pg/mL in asymptomatic patients with HCV infection and controls, respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559, p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV-infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity. In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455, p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). CCL20 may be used for the detection of HCC in HCV-infected patients with comparable specificity and higher sensitivity than AFP.

Increasing Prevalence of HCC and Cirrhosis in Patients With Chronic Hepatitis C Virus Infection

Patients with hepatitis C virus (HCV) infection are at risk for developing costly and morbid complications, although the actual prevalence of these complications is unknown. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular carcinoma (HCC). We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort as well as sex and changes in clinical characteristics. In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly. The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years. An aging cohort of patients with HCV could partly explain our findings. Clinicians and health care systems should develop strategies to provide timely and effective care to this high-risk population of patients.

Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors

It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.

Detection and characterization of focal liver lesions with contrast-enhanced ultrasonography in patients with hepatitis c-induced liver cirrhosis

Hepatitis C virus (HCV)-associated liver cirrhosis provides a major preneoplastic condition for hepatocellular carcinoma (HCC). Ultrasonography (US) is usually used for screening of HCC, but needs improvement. To assess whether use of a second-generation ultrasound contrast agent can improve characterization of focal liver lesions and detection of HCC in HCV-infected patients with liver cirrhosis. In total, 96 US studies in 49 HCV-infected patients with liver cirrhosis were performed. The patients were first examined with a baseline US. After this, a diagnostic decision was made and recorded. The patients were then re-examined with contrast-enhanced ultrasound (CEUS), and the diagnostic triage was repeated. The patients were followed up for at least 1 year. On baseline US, indeterminate focal lesions were found in 27 examinations. After CEUS, a confident diagnosis of HCC was made in eight of these examinations. In an additional eight US examinations, diagnosis of regenerative/dysplastic noduli was established. In one patient with no detectable focal lesion at baseline examination, an indeterminate malignant lesion was detected with CEUS. This lesion was further investigated with computed tomography and diagnosed as HCC. Our study indicates that the use of CEUS significantly improves diagnostic confidence. CEUS improves the detection of HCC in patients with HCV-induced liver cirrhosis. Also, CEUS makes it possible to rule out malignancy in many cases where baseline US shows indeterminate focal lesions. In low-endemic countries, the use of CEUS in screening for HCC may be considered.

Antibody to the Human T-Lymphotropic Virus Type 1 (HTLV-1) Envelope Protein Gp46 in Patients Co-infected with HCV and HTLV-1

Human T-lymphotropic virus type 1 (HTLV-1) infection is known to affect hepatitis C virus (HCV) clearance and to accelerate the development of hepatocellular carcinoma in HCV-infected patients. In this study, we found the prevalence and titer of an antibody recognizing the central region of the HTLV-1 Gp46 protein to be associated with the severity of chronic liver disease. The antibody prevalence was significantly correlated with the stage of chronic liver disease (P < 0.0001): 3 (14.3%) of 21 patients with minimal-mild chronic hepatitis, 12 (24%) of 50 with moderate-severe chronic hepatitis, 7 (87.5%) of 8 with liver cirrhosis, and 13 (100%) of 13 with hepatocellular carcinoma. These results indicate that the antibody may be a useful marker of the deterioration of liver disease in patients co-infected with HCV and HTLV-1. This antibody may be useful for the diagnosis of liver diseases and the development of more effective treatments.

Emerging epidemiologic observations in HCV/HIV coinfection

Recent studies indicate that when HCV-infected patients also are infected with HIV, their risk of chronic liver disease is increased up to twofold compared with the risk for HCV-infected patients without HIV. As a result, consideration for HCV antiviral therapy should not be hindered by HIV status. The data are inconclusive on the role of highly active antiretroviral therapy (HAART) in chronic liver disease progression. The limited data available do not support an HIV-related increase in the risk of hepatocellular carcinoma in HCV-infected patients. Acute hepatotoxicity clearly increases significantly when HAART is administered to patients infected with both HIV and HCV, compared with patients infected with HIV alone. Nonetheless, the overall benefit of HAART in persons with HIV is far greater than the risk of hepatotoxicity, even with coinfection.

Can Therapy of Hepatitis C Affect the Development of Hepatocellular Carcinoma?

Chronic inflammation induced by viral infections and their role in carcinogenesis is well recognized. Two hepatotropic viruses, hepatitis B and hepatitis C (HCV), have been linked worldwide to the development of hepatocellular carcinoma (HCC). Although orthotopic liver transplant offers the best chance for cure and long-term survival, the demand for organs far outweighs the supply. The incidence of HCC in the United States has increased over the past 3 decades. HCV-induced cirrhosis is believed to play a significant role in the rising rate of HCC. Therefore, primary measures to prevent HCC in HCV-infected patients are urgently needed. Numerous studies of the HCV HCC patient have considered primary treatment with interferon-based therapy. However, secondary prevention currently seems to carry more promise. This article evaluates and assesses various treatments for primary and secondary chemoprevention in the setting of HCV.

Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: genes involved in tumor progression.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. The present study aimed to investigate the genes involved in viral carcinogenesis and tumor progression in liver transplant recipients with hepatitis C virus (HCV) and HCC. To accomplish this, we performed the analysis of hepatic gene expression in HCV-infected liver recipient patients with stages of disease ranging from early cirrhosis with preserved volume and function to late cirrhosis with diminished volume and function with and without HCC. We found consistent differences between the gene expression patterns in HCV-HCC and those of early HCV-cirrhosis, late HCV cirrhosis, and normal control livers. The expression patterns in HCC were also readily distinguished between early and advanced HCC tumor stages. Moreover, we found different gene expression patterns between early cirrhosis and late cirrhosis. In conclusion, these findings confirm the presence of multiple molecular alterations during HCV-HCC hepatocarcinogenesis and, clinically, indicate the possibility for identifying prognostic factors associated with HCC progression in liver transplant patients waiting for a donor and/or posttransplantation recurrence.