Mi Na Kim

Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography–defined subclinical cirrhosis

Early detection of liver cirrhosis in its subclinical stage is of paramount importance to identify high‐risk individuals for developing hepatocellular carcinoma (HCC). This study investigated whether transient elastography (TE) can identify patients with subclinical cirrhosis (SCC) who are at increased risk of developing HCC among chronic hepatitis B (CHB) patients without clinical evidence of cirrhosis. A total of 2,876 CHB patients without clinical cirrhosis who received TE examinations between April 2006 and December 2012 were enrolled in this prospective study. SCC was defined as a nonclinical cirrhosis, but with a liver stiffness (LS) value ≥13 kilopascals (kPa). Mean age of the study population was 46.1 years, and male gender was predominant (nu2009=u20091,775; 61.7%). Mean LS value was 7.9 kPa, and SCC was identified in 285 (9.9%) patients. During the median follow‐up period of 48.9 months (range, 6.6‐96.2), HCC developed in 16 patients (13.3 per 1,000 person‐years) in the SCC group and 36 (3.4 per 1,000 person‐years) in the non‐SCC group. Cumulative incidence rate of HCC in the SCC group was significantly higher than that in the non‐SCC group (Pu2009<u20090.001, log‐rank test). On multivariate analysis, SCC was independently associated with a risk of developing HCC, regardless of antiviral therapy (without antiviral therapy: hazard ratio [HR]: 4.680; 95% confidence interval [CI]: 1.187‐18.441; Pu2009=u20090.027; with antiviral therapy: HR, 3.344; 95% CI: 1.526‐7.328; Pu2009=u20090.003). Conclusion: TE can identify CHB patients with SCC who are at increased risk of developing HCC, even when cirrhosis is not clinically apparent. (Hepatology 2015;61:1851‐1859)

Hepatocellular carcinoma in patients with chronic hepatitis C virus infection in the Asia–Pacific region

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide. Although hepatitis B still remains the most common risk factor worldwide, chronic hepatitis C virus (HCV) infection is the driving force for the increased incidence of HCC especially in Western countries and Japan. In hepatitis B virus (HBV)-endemic areas, after successful vaccination programs against HBV, chronic HCV infection is now emerging as an important cause of chronic liver diseases. Unlike patients with chronic hepatitis B, those with chronic hepatitis C (CHC) develop HCC in the presence of established cirrhosis in most cases. However, a significant minority of CHC develops HCC in the absence of cirrhosis. Although HCV is a RNA virus with little potential for integrating its genetic material into host genome, various HCV proteins, including core, envelope, and nonstructural proteins, have oncogenic properties by inducing oxidative stress, disturbing cellular regulatory pathways associated with proliferation and apoptosis, and suppressing host immune responses. Overall, a combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine progression to HCC. Strategies aimed at eliminating the virus may provide opportunities for effective prevention of the development of HCC. Pegylated interferon plus ribavirin therapy appears to be effective at reducing the risk of HCC in patients who achieve sustained virologic responses. In summary, with the emerging importance of CHC, mechanisms of HCV-associated hepatocellular carcinogenesis should be clarified to provide insight into advanced therapeutic and preventive approaches, which eventually decrease the incidence and mortality of HCC.

Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment

Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases (CLD) is crucial, as liver fibrosis is important in determining the prognosis of liver diseases. Currently, liver biopsy (LB) is considered the gold standard for staging liver fibrosis or cirrhosis. However, utilization of LB in clinical practice is often limited because of its invasive nature, sampling error and interobserver variability. Recently, transient elastography (TE) was introduced as a noninvasive, highly reproducible technique for assessing the degree of liver fibrosis. After extensive studies, TE is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in patients with CLD. In the past few years, the role of TE in monitoring liver stiffness and determining prognosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who are undergoing antiviral treatment has been investigated. In patients with CHB, liver stiffness values decrease with antiviral treatment. TE can also be used to predict the incidence of liver‐related events during antiviral treatment. In patients with CHC, TE can be used to monitor potential regression of liver fibrosis after antiviral treatment and may predict the treatment outcome of CHC. In addition, TE is an adjunct tool for distinguishing inactive hepatitis B virus carriers from patients with chronic active hepatitis. This review article discusses the important findings from recent studies focusing on the clinical application of TE in patients with chronic viral hepatitis who are undergoing antiviral treatments.

Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir

Liver stiffness (LS) measurement using transient elastography allows for accurate evaluation of liver fibrosis in patients with chronic liver disease. We aimed to investigate the influence of antiviral treatment using entecavir (ETV) on LS values in patients with chronic hepatitis B (CHB).

Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma: considerations for tumor response assessment

Radiological response assessment criteria in hepatocellular carcinoma (HCC) have evolved to accurately evaluate tumor responses. The WHO criteria and the subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change in tumor size; however, these criteria generally ignore tumor necrosis and therefore may underestimate treatment responses. Thus, a panel of experts of the European Association for the Study of Liver (EASL) amended the response criteria to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was developed, which consider both the concept of tumor viability based on arterial enhancement and single linear summation, ultimately simplifying EASL criteria. Currently, the mRECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment. Here, the authors review application and performance of mRECIST as well as other HCC response assessment criteria and discuss unmet and open issues regarding response evaluation for HCC treatments.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

Goals: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). Background: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. Methods: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. Results: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). Conclusions: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Risk Assessment of Hepatocellular Carcinoma Using Transient Elastography Vs. Liver Biopsy in Chronic Hepatitis B Patients Receiving Antiviral Therapy

AbstractLiver stiffness (LS) assessed using transient elastography (TE) can assess the risk of developing hepatocellular carcinoma (HCC). We evaluated whether TE, when compared with histological data as a reference standard, can predict the risk of HCC development in chronic hepatitis B (CHB) patients starting antiviral therapy.Observational cohort database of 381 patients with CHB who underwent liver biopsy (LB) and TE were reviewed. All patients underwent surveillance for HCC development using ultrasonography and alpha-fetoprotein.During the median follow-up period of 48.1 (interquartile range 30.3–69.3) months, HCC developed in 34 (8.9%) patients. In patients with HCC development, age, proportion of diabetes mellitus, histological fibrosis stage, and LS value were significantly higher than those in patients without (all Pu200a<0.05). The cumulative incidence rates of HCC increased significantly in association with elevated LS value in 3 stratified groups (LS value <8, 8–13, and >13 kPa; log-rank test, Pu200a<0.001), and with higher histological fibrosis stage in 3 stratified groups (F0–2, F3, and F4; log-rank test, Pu200a<0.001). On multivariate analysis, along with age, LS value was an independent predictor of HCC development (hazard ratio 1.041, Pu200a<0.001), whereas histological staging was not (Pu200a>0.05).TE predicted HCC development independently in patients with CHB starting antiviral therapy. However, further investigation is needed to determine whether the current surveillance strategy can be optimized based on the LS value at the time of starting antiviral therapy.

Prevention of Hepatocellular Carcinoma: Beyond Hepatitis B Vaccination

Chronic hepatitis B (CHB) infection is the major cause of hepatocellular carcinoma (HCC), accounting for approximately 50% of the underlying etiologies. We reviewed the primary, secondary, and tertiary measures for the prevention of hepatitis B virus (HBV)-related HCC. The most effective method for preventing HBV-related HCC is vaccination. Universal hepatitis B vaccination has been shown to reduce the rates of HBV infection and HCC significantly. Once chronic HBV infection is established, antiviral treatment using interferon or nucleos(t)ide analogs is used to prevent disease progression to cirrhosis, HCC, or both. Studies have found viral replication indicated by HBV DNA level to be a strong risk factor for development of HCC. Additionally, periodic surveillance using ultrasonography and serum α-fetoprotein for earlier detection of HCC is also important so that curative treatments with survival benefit can be possible. Finally, adjuvant antiviral treatment using interferon or nucleos(t)ide analogs is used to prevent tumor recurrence after curative resection. Adjuvant interferon treatment prevented early recurrence, not late recurrence, probably due to its antiangiogenetic and antiproliferative effects. Adjuvant nucleos(t)ide analogs demonstrated promising results for preventing late recurrence, probably due to effective suppression of viral replication. Further investigations are required to establish the optimal preventive plans for HBV-related HCC.

Maintaining remission in lamivudine-resistant patients with a virological response to adefovir add-on lamivudine after stopping lamivudine therapy.

We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD‐resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy.

Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea

AIMnTo investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea.nnnMETHODSnHepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC.nnnRESULTSnNone of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323).nnnCONCLUSIONnAlthough no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.