Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B.

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.

Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy.

BACKGROUND AND AIMS: Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. METHODS: All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. RESULTS: Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. CONCLUSIONS: Delayed AFP response to ETV may serve as an indicator of high HCC risk.

Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.

BACKGROUND: The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression. METHODS: Ninety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation. RESULTS: The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance. CONCLUSIONS: NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.

Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma.

BACKGROUND: Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea. METHODS: The clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio. RESULTS: Cryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology. CONCLUSIONS: Cryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.

Senile Cardiac Calcification Syndrome: A Rare Case of Extensive Calcification of Left Ventricular Papillary Muscle.

Extensive papillary muscle calcification is uncommon and only scarce literature about causes and the clinical significance is available, whereas small calcific deposits are common findings in elderly people and are located most commonly at the apex. Papillary muscle calcification has been associated with coronary artery disease, dilated cardiomyopathy, mitral valve disease, hypercalcemia, and increased calcium phosphate product in end stage renal disease. We reported a rare case of extensive calcification of anterolateral papillary muscle diagnosed by echocardiography and multidetector computed tomography.

A Case of Cardiac Amyloidosis Initially Misdiagnosed as Syndrome X.

Cardiac infiltration of amyloid fibril results in progressive cardiomyopathy with a grave prognosis and results in cardiac diseases such as congestive heart disease, cardiomyopathy, valvular heart disease, and arrhythmias. We present a rare case of cardiac amyloidosis initially misdiagnosed as syndrome X in which recurrent chest pain and progressive heart failure could be managed finally by heart transplantation.