Prevalence and outcomes of extrahepatic primary malignancy associated with hepatocellular carcinoma in a Korean population.

BACKGROUND: With advances in hepatocellular carcinoma (HCC) screening and treatment, the incidence of diagnosing a case of extrahepatic primary malignancy (EHPM) in patients with HCC has increased. This study aimed to elucidate the prevalence and clinical outcomes of EHPM in patients with HCC who underwent curative resection in Korea. METHODS: The clinical data of 250 patients with HCC who underwent curative resection in our hospital from May 2003 to December 2011 were retrospectively analyzed. The clinical features, overall survival, and causes of death were compared between patients with HCC with or without EHPM. RESULTS: The prevalence of EHPM among the 250 patients was 13.2% (n = 33). The most common site of EHPM was the colorectal (n = 10), followed by the stomach (n = 9), breasts (n = 4), and kidneys (n = 3). Patients with EHPM were significantly older, and they presented with higher rates of comorbidities, a different etiology of HCC, and better liver function than patients without EHPM. Interestingly, overall survival was significantly lower in the EHPM group, which more frequently displayed extrahepatic causes of death. Moreover, the presence of EHPM was an independent factor for overall survival in the study population. CONCLUSIONS: The prevalence of EHPM in patients with HCC who underwent curative surgical resection was 13.2% in Korea, with colorectal and stomach cancers comprising most EHPMs (88%). The patients with EHPM displayed significantly worse survival because of extrahepatic causes of death, which should be considered in the management of HCC in the future.

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.

The feasibility of discontinuing lamivudine in lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir combination therapy.

OBJECTIVES: This study investigated the antiviral efficacy of adefovir (ADV) rescue therapy and the feasibility of lamivudine (LAM) discontinuation in LAM-resistant chronic hepatitis B (CH-B) patients who had attained a virological response (VR) with LAM + ADV combination therapy. METHODS: The VR and virological breakthrough (VBT) were analyzed in 106 consecutively enrolled LAM-resistant CH-B patients who received ADV rescue therapy during a mean follow-up period of 55.2 months. Seventy-four patients achieved VR, and were divided into the LAM-discontinuation group (n = 39) and the LAM-continuation group (n = 35). The VR and VBT between the 2 groups were compared. RESULTS: For all 106 LAM-resistant CH-B patients, the overall cumulative probabilities of VR at 1, 2, 3 and 5 years of ADV rescue therapy were 40.6, 55.7, 64.6 and 81.3%, respectively. The cumulative probabilities of VBT at 1, 2, 3 and 5 years were 0, 2.9, 8.8 and 13.9%, respectively. Whether they discontinued or continued LAM after achieving VR on LAM + ADV therapy, VR and VBT were not significantly different during a mean follow-up period of 40.4 months. CONCLUSIONS: There was a good long-term VR with ADV rescue therapy for LAM-resistant CH-B patients. Moreover, discontinuing LAM was found to be feasible for patients who attained VR during ADV + LAM therapy.

Treatment outcomes of transcatheter arterial chemoembolization for hepatocellular carcinoma that invades hepatic vein or inferior vena cava.

PURPOSE: We aimed to elucidate the treatment outcomes of transcatheter arterial chemoembolization (TACE) and survival-associated factors in hepatocellular carcinoma (HCC) patients with hepatic vein (HV) and/or inferior vena cava (IVC) invasion. METHODS: The subjects were consecutively enrolled, newly diagnosed HCC patients with HV/IVC invasion who underwent TACE (n = 62) at the Seoul National University Bundang Hospital from May 2003 to October 2012. Clinical characteristics, treatment responses, overall survival, and survival-related factors were analyzed. RESULTS: The mean subject age was 56.6 years, 82.3% were hepatitis B surface antigen-positive, and 76.2% were classified as Child-Pugh class A. The tumor volume was ≥50% of the liver in 64.5% of patients, and 79, 41.9, and 9.7% of patients had accompanying portal vein, IVC, and right atrial invasion, respectively. TACE response rates for primary tumors and tumor thrombi in HV or IVC were 55.6 and 13%, respectively. Median overall survival was 10.9 months (range 0.1-23.0 months). Multivariate analysis showed that Child-Pugh class A (hazard ratio [HR] = 0.31; 95% confidence interval [CI] 0.14-0.72; p = 0.007), tumor volume <50% of liver (HR = 0.31; 95% CI 0.11-0.83; p = 0.019), alpha-fetoprotein (AFP) response (HR = 0.28; 95% CI 0.11-0.69; p = 0.006), and tumor thrombi treatment response (HR = 0.09; 95% CI 0.01-0.77; p = 0.027) were independent survival-related factors. CONCLUSIONS: TACE seems effective for HCC with HV/IVC invasion, especially in patients with preserved hepatic function, a treatment response for tumor thrombi, and an AFP response.

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.

[Fulminant hepatic failure with hepatitis B virus reactivation after rituximab treatment in a patient with resolved hepatitis B].

It is well known that the reactivation of hepatitis B virus (HBV) may occur as an acute hepatitis after chemotherapy or immunosuppressive therapy. Although most of these cases have been reported in HBsAg-positive patients, there have been a few reports of HBV reactivation in HBsAg-negative patients. There have been concerns for the need to screen the reactivation as well as anti-viral prophylaxis in HBsAg-negative patients with possible HBV occult infection who are planning to undergo chemotherapy or immunosuppressive therapy. Rituximab, an anti-CD20 monoclonal antibody, is effective in the treatment of non-Hodgkins lymphoma. However, rituximab can affect the immunity against HBV, consequently increasing viral replication. In fact, there have been reports of HBV reactivation after treatment with rituximab. Here, we report a case of HBV reactivation following rituximab plus systemic chemotherapy in diffuse large B cell lymphoma patient who was HBsAg negative, anti-HBs positive, and anti-HBc positive, ultimately leading to treatment-unresponsive fulminant hepatic failure.

[A case of extranodal histiocytic sarcoma of stomach mimicking gastric adenocarcinoma].

Histiocytic sarcoma is a rare malignant neoplasm that originates from a histiocytic hematopoietic lineage characterized by histiocytic differentiation and its corresponding immunophenotypic features. Patients with histiocytic sarcoma usually have a poor prognosis due to its aggressive clinical behavior. Here we report a rare case of extranodal histiocytic sarcoma of the stomach which was confirmed through immunohistochemical staining. A 71-year- old man was presented with epigastric pain. Gastroscopy, abdominal CT, and EUS revealed a mass located on the posterior wall of upper body and fundus of the stomach. Grossly, grayish white solid masses were seen extending down to the submucosal layer. Microscopically, the tumor cells had eosinophilic cytoplasm, abundant vacuole, and mitosis. Immunohistochemical staining revealed that the tumor cells were positive for LCA, CD68, and lysozyme. Early detection and accurate diagnosis of this rare neoplasm is important because it can make a great difference in prognostic outcomes. To make an accurate and definitive diagnosis, immunohistochemical staining is essential in the confirmation of histiocytic origin.