Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations.

OBJECTIVE: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. METHODS: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. RESULTS: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). CONCLUSIONS: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

Can "healthy" normal alanine aminotransferase levels identify the metabolically obese phenotype? Findings from the Korea national health and nutrition examination survey 2008-2010.

BACKGROUND: There is no established parameter with which to screen metabolically obese phenotypes. AIM: The aim of the study was to revise the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) and to investigate the predictive value of updated ALT levels for metabolic obese phenotype stratified according to body mass index (BMI). METHODS: We analyzed a nationally representative data from the Fourth Korea National Health and Nutrition Examination Survey. This cross-sectional study included 2,416 healthy people aged 33.9 ± 0.3 years. The ULN of healthy ALT level was set at the 95th percentile of the healthy population. A metabolic obese phenotype was defined as having insulin resistance or metabolic syndrome. A logistic regression analysis was performed to assess the odds ratio for a metabolic obese phenotype according to the healthy ALT level. RESULTS: The revised ULN of serum ALT level in healthy participants were 30 IU/L and 22 IU/L for males and females, respectively. Serum ALT level was higher in individuals with metabolic obesity compared with those without metabolic obesity in both genders, stratified according to BMI. After adjusting for age, BMI, smoking, alcohol drinking, and regular physical activity, unhealthy normal ALT levels (males 30-40 IU/L, females 22-40 IU/L) were significantly associated with metabolic obesity, especially in both obese and non-obese women. CONCLUSIONS: A newly revised threshold for ALT is proposed as a simple clinical metabolic parameter that can identify a metabolic obese phenotype. We suggest that people with unhealthy normal ALT levels may need further investigation for the presence of metabolic obesity.

Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial.

BACKGROUND: Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported. AIMS: This multicentre prospective randomized study was designed to compare the efficacy of these two strategies. METHODS: Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir-lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months. RESULTS: One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir-lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24. CONCLUSION: This study showed that adefovir-lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.

Hepatitis B virus load in serum does not reflect histologic activity in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Little is known about whether histologic data can predict which patients with hepatitis B virus (HBV)-related decompensated cirrhosis will respond to antiviral therapies. We assessed the relationship between serum HBV DNA load and histologic activity by analyzing liver specimens from patients with decompensated cirrhosis. METHODS: The study included 72 consecutive patients who underwent liver transplantation for HBV-related decompensated cirrhosis between November 2000 and March 2008. None of the patients had received nucleoside or nucleotide analogues more than 2 weeks before transplantation. Serum HBV DNA levels at the time of transplantation were compared with histologic activity in explanted liver specimens. RESULTS: The median HBV DNA level of the 72 patients was 5.40 log(10) copies/mL (range, 1.45-8.00 log(10) copies/mL). There were no differences in HBV DNA level between patients grouped according to lobular or portoperiportal activity (P = .678, P = .291, respectively). Of 16 patients (22.2%) with HBV DNA levels less than 2000 copies/mL, 8 patients (50.0%) had moderate or severe portoperiportal activity; their median alanine aminotransferase level was 30.5 U/L (range, 12-135 U/L). CONCLUSIONS: HBV DNA load does not reflect histologic activity in patients with HBV-related decompensated cirrhosis. Although patients with decompensated cirrhosis might have normal levels of alanine aminotransferase and a low level of viremia (<2000 copies/mL), they still can have significant portoperiportal activity.

Impact of serial hepatitis B virus DNA on hepatocellular carcinoma development in patients with liver cirrhosis.

OBJECTIVES: We investigated the pattern of serial HBV DNA levels in known cirrhosis patients and its impact on the development of hepatocellular carcinoma (HCC). METHODS: We analyzed a retrospective case/control study based on 352 HCC patients associated with HBV between 2005 and 2007. Prior to HCC development, 49 cirrhosis patients were tested for HBV DNA levels more than once a year (median 4 times) during the follow-up period. Ninety-eight consecutive cirrhosis patients without HCC, matched for age, sex and HBe Ag status were included as controls. Eighty-three patients in both groups had undergone antiviral therapy. RESULTS: In cirrhosis, the most common HBV DNA pattern was fluctuating (33.3%), followed by persistently high (> or =10(4) copies/ml, 23.8%). Compared to a persistently low pattern (<10(4) copies/ml), the relative risks of HCC in patients with persistently high and fluctuating patterns were 2.650 and 1.475. At multivariate analysis, a persistently high pattern was an independent risk factor for HCC (hazard ratio 3.135). Patients with sustained HBV DNA suppression during antiviral therapy were less likely to develop HCC than those with viral breakthrough/nonresponse. CONCLUSIONS: This study showed that persistent suppression of HBV DNA is also important to prevent the development of HCC in known cirrhosis patients.

Tumor doubling time after initial response to transarterial chemoembolization in patients with hepatocellular carcinoma.

OBJECTIVE: Following initial transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC), these tumors can frequently recur, making it important to determine the appropriate follow-up interval after initial response to TACE. We therefore assessed the time taken by new recurrent HCCs to double in volume after an initial response to TACE. MATERIAL AND METHODS: This retrospective cohort study included 73 patients who achieved an initial response after TACE. After intrahepatic distant recurrence of HCC, dynamic CT scans were reviewed by two radiologists without clinical information, and the doubling time of new recurrent nodules was determined. The relationship between doubling time and clinical factors was also analyzed. RESULTS: In 32 of the 73 patients, 40 intrahepatic distant recurrent (IDR) nodules were detected over a median period of 14 months (range 4-46 months). The 1-, 2- and 3-year cumulative IDR rates of patients were 27%, 45% and 65%, respectively. The doubling time of IDR HCC ranged from 20 to 104 days, with a median of 46 days. Over 90% of IDR HCCs had a doubling time of less than 3 months. The doubling time (median 108 days; range 51-129 days) of primary HCC in five patients for whom we had information regarding primary tumors was longer than that of recurrent nodules (median 28 days; range 24-90 days) in the same five patients (P = 0.022). CONCLUSIONS: The median doubling time of IDR HCCs after an initial response was 47 days (range 20-104 days). These findings indicate that the appropriate follow-up interval for dynamic CT in patients with an initial response after TACE is less than 3 months.

Large-scale surveillance study of the safety and effectiveness of entecavir in Korean patients with chronic hepatitis B.

BACKGROUND/AIMS: Entecavir (ETV) is effective and safe antiviral agent against hepatitis B virus (HBV) in clinical and real-world setting but, most studies were performed in single institute or have limitation in patient's number. A large-scale nation-wide real-world surveillance study was carried out to investigate safety, efficacy and clinical effectiveness of ETV in Korean patients with chronic hepatitis B (CHB). METHODS: Between 2006 and 2012, 3,444 patients were enrolled from 132 Korean institutions. For the safety assessment, investigators recorded the occurrence of observed and patient-reported adverse events (AEs), as well as laboratory abnormalities. Efficacy, which consisted of change in HBV DNA and alanine aminotransferase (ALT), was evaluated in patients who had received at least 16 weeks of ETV treatment. Overall clinical effectiveness, based on improvement of ALT, HBV DNA and patient's symptoms, was evaluated by physicians. RESULTS: Of the patients, 3,367 were evaluated for safety and 3,115 for efficacy and clinical effectiveness. Three hundred and eighty AEs were reported in 255 cases (7.57%), and 67 adverse drug reactions in 54 cases (1.6%). Serious AEs (SAE) were 19 events in nine cases (0.27%). Serious adverse drug reactions (SADR) were three events in two cases (0.06%), and unexpected SAE/SADR were three events in two cases (0.06%). Medical history and concomitant medications were factors inf luencing incidence rates of AEs. Overall clinical effectiveness rate was 96.53%, which was clinically assessed as marked improved or improved state. CONCLUSIONS: This study showed that ETV was well tolerated and clinically effective in Korean patients with CHB in a real-world nation-wide setting.

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients.

BACKGROUND/AIMS: Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. METHODS: We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. RESULTS: Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. CONCLUSIONS: The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A.

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

A Decade-old Change in the Screening Rate for Hepatocellular Carcinoma Among a Hepatitis B Virus-infected Population in Korea.

BACKGROUND: Evaluating a change in the screening rate for hepatocellular carcinoma (HCC) is critical for understanding screening implementation, and whether targeted population groups are receiving proper screening. This study examined recent nationwide changes in HCC screening use among hepatitis B virus (HBV)-infected populations after the introduction of the Korean National Cancer Screening Program and predictors of screening adherence. METHODS: We analyzed 165 and 276 participants ≥40 years of age who were hepatitis B surface antigen-positive from 2001 (14,936 participants) to 2010-2011 (9159 participants) Korea National Health and Nutrition Examination Surveys, respectively. Demographic data, socioeconomic factors, and HCC screening use were collected by means of self-reported questionnaires. RESULTS: The rate of HCC screening within the previous 2 years increased significantly from 17.5% in 2001 to 40.3% in 2010-2011 (P < 0.0001). The rate of HCC screening use increased from 2001 to 2010-2011 in all study populations. Subjects who had a higher income status and were aware of their infection were more likely to have undergone recent HCC screening. CONCLUSIONS: This study showed a substantial increase in HCC screening in high-risk HBV-infected subjects from 2001 to 2010-2011. However, the HCC screening participation rate remained suboptimal despite the introduction of the nationwide screening program. Efforts should be made to identify high-risk individuals and increase attendance at HCC screening events among high-risk groups.

[A case of pulmonary thromboembolism in active ulcerative colitis].

Thromboembolic disease is a significant cause of morbidity and mortality in patients with inflammatory bowel disease. The reported incidence is 1-6%. The most common thromboembolic complications are deep venous thrombosis of legs and pulmonary thromboembolism. Cerebral thrombosis, portal vein thrombosis, retinal venous thrombosis and arterial thrombosis were also reported. We experienced a case of ulcerative colitis complicated with pulmonary thromboembolism. The patient was a 70-year-old woman who was diagnosed as ulcerative colitis on colonoscopy. We used prednisolone and sulfasalazine for the treatment of ulcerative colitis. Twenty five days later, she complained of abrupt dyspnea and chest pain. Chest CT and ventilation-perfusion scan revealed a thromboembolism in both lung. After the treatment of heparin & warfarin therapy, follow-up chest CT showed much regressed pulmonary thromboembolism. We report a 70-year-old woman with ulcerative colitis complicated with pulmonary thromboembolism and treated with heparin & warfarin therapy successfully.

[Prediction of hepatic fibrosis using serum hyaluronic acid in patients with chronic liver disease].

BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is invasive and may not represent the whole liver state. Serum hyaluronic acid (HA), a major component of connective tissues, was introduced as a useful non-invasive index of hepatic fibrosis. The aim of this study was to evaluate the relationship among HA, the degree of fibrosis, several hematologic and biochemical parameters in patients with chronic liver diseases or post state liver transplantation (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured by enzyme-linked binding protein assay and evaluated in relation the degree of fibrosis, several hematologic and biochemical parameters. RESULTS: Among four groups, HCC showed the highest HA and HA of HCC significantly higher than that of CH. The degree of fibrosis were correlated with HA. HA was correlated with age, platelet count and albumin but, not with ALT and PT. There is no significant relation between HA and the presence of acute rejection in liver transplantation. CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of hepatic fibrosis and disease severity.

[A case of inflammatory pseudotumor of the spleen].

Inflammatory pseudotumor is a benign disease, which is histologically composed of the inflammatory cells such as mature lymphocytes, plasma cells, and histiocytes. It usually occurs in the respiratory system, liver, central nervous system, and gastrointestinal tracts. However, inflammatory pseudotumor rarely occurs in the spleen. Pathologic diagnosis is essential for the definitive diagnosis because of the difficulty in distinguishing pseudotumor from lymphoproliferative disorders of the spleen. We report a case of inflammatory pseudotumor of the spleen. A 35-year-old woman complained of the intermittent epigastric pain for several months. Physical examination and laboratory findings were normal. Ultrasonography and abdominal computerized tomography showed a low attenuation splenic mass suggesting lymphoma. However, the pathologic findings of the resected spleen were consistent with those of the inflammatory pseudotumor. The spleen weighed 230 g containing a 6 x 5 x 5 cm-sized, well-circumscribed gray mass. The microscopic findings indicated the inflammatory cell infiltrations.

[Massive bleeding hemobilia occurred in patient with hepatocellular carcinoma].

Massive bleeding hemobilia occurs rarely in patients with hepatocellular carcinoma (HCC) without any invasive procedure. Upper gastrointestinal bleeding in patient with cirrhosis and abdominal pain with progressive jaundice in patient with HCC were usually thought as variceal bleeding and HCC progression respectively. We experienced recently massive bleeding hemobilia in patient with HCC who was a 73-year old man and showed sudden abdominal pain, jaundice and hematochezia. He had alcoholic cirrhosis and history of variceal bleeding. One year ago, he was diagnosed as HCC and treated with transarterial chemoembolization periodically. Sudden right upper abdominal pain occurred then subsided with onset of hemotochezia. Computed tomography showed bile duct thrombosis spreading in the intrahepatic and extrahepatic ducts, while an ampulla of vater bleeding was observed during duodenoscopy. Hemobilia could be one of the causes of massive bleeding in patients with cirrhosis and HCC especially when they had sudden abdominal pain and abrupt elevation of bilirubin.

Outcome after discontinuing antiviral agents during pregnancy in women infected with hepatitis B virus.

BACKGROUND: Women who are taking antiviral agents and become pregnant have several options that include, continuing therapy, ceasing drugs, or switching to safer drugs. However, there are limited data on the outcome in pregnant women after withdrawal of antiviral agents. OBJECTIVES: We aimed to investigate the outcome of stopping antiviral agents in pregnant women with chronic hepatitis B virus (HBV) infection. STUDY DESIGN: In this single-center, retrospective cohort study, 12 pregnant patients who had received antiviral therapy for HBV and cease drugs after awareness of pregnancy between 2003 and 2010 were enrolled. We retrospectively studied virologic and biochemical flares during pregnancy and postpartum period. RESULTS: Median age at pregnancy was 30.5 (range, 24-35) years, median duration of antiviral drug before pregnancy was 15.3 (range, 3.0-131.3) months, and median HBV DNA at withdrawal of therapy was 4.8 (range, 1.7-8.0) log(10) copies/mL. Eight out of twelve patients (66.7%) had a viral rebound after stopping antiviral drugs during pregnancy. Severe hepatitis flares, defined as a 5-fold increase in serum alanine aminotransferase (ALT), were observed in six patients (50%) during pregnancy. However, all of these patients spontaneously recovered without an event of hepatic decompensation. High pretreatment ALT was associated with severe hepatitis flares after cessation of therapy during pregnancy. Five patients with at least 1-year treatment before pregnancy maintained low hepatitis activity after delivery. CONCLUSIONS: Pregnant women with high pretreatment ALT or those treated less than 1 year before pregnancy have high risk of severe hepatitis flares after cessation of antiviral agents.

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease.

BACKGROUND/AIMS: The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH. METHODS: One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea. RESULTS: According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH. CONCLUSIONS: Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Correlation of hepatitis B core antigen and beta-catenin expression on hepatocytes in chronic hepatitis B virus infection: relevance to the severity of liver damage and viral replication.

BACKGROUND AND AIMS: The topographical distribution of hepatitis B core antigen (HBcAg) is related to the pathogenesis of liver damage caused by hepatitis B virus (HBV) infection. beta-catenin plays an important role in both intracellular adhesion and Wnt signaling transduction pathways. This study investigated the intrahepatic expression of HBcAg and beta-catenin in chronic HBV infection, and correlated the results with the degree of liver damage and viral replication. METHOD: Liver sections from 73 patients with chronic HBV infection were examined immunohistochemically for HBcAg and beta-catenin. RESULTS: The distribution of HBcAg could be classified into four types: only nucleus (C-1), both nucleus and cytoplasm (C-2), only cytoplasm (C-3) and all negative for nucleus and cytoplasm (C-4). Significant differences in serum aminotransferase level, HBV DNA and necroinflammatory score were observed among the different distribution types, and as the distribution of HBcAg changed from C-1 to C-4, fibrosis stage and hepatitis B e antigen (HBeAg) negative/anti-HBe positive rate increased concurrently. The distribution of beta-catenin could be classified into two types: only membrane (B-1) and membrane with nucleus or cytoplasm (B-2). B-2 showed higher serum aminotransferase level and necroinflammatory score than B-1. Between B-1 and B-2, there was no significant difference in serum HBV DNA level or fibrosis stage. CONCLUSIONS: In chronic HBV infection, HBcAg distribution may change from C-1 to C-4 gradually, and in correlation with serum aminotransferase, and HBV DNA and HBeAg negative/anti-HBe positive rate. Nuclear or cytoplasmic distribution of beta-catenin, compared with exclusive membranous distribution of beta-catenin, is related to active hepatitis, but not viral replication.

The impact of hepatitis B viral load on recurrence after complete necrosis in patients with hepatocellular carcinoma who receive transarterial chemolipiodolization: implications for viral suppression to reduce the risk of cancer recurrence.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high tendency for recurrence after radical treatment. Apart from tumor and liver function parameters, little is known about the role of hepatitis B virus (HBV) factors in the recurrence of HCC. The objective of this study was to identify the potential relation between viral load and HCC recurrence in patients undergoing transarterial chemolipiodolization. METHODS: This was a cohort study of 62 consecutive patients who had HBV-related HCC and achieved complete necrosis with transarterial chemolipiodolization. Risk factors, including viral load for posttreatment recurrence, were analyzed. RESULTS: Overall, 32 of 62 patients (51.6%) developed a recurrence during the study period (7.2-37.5 months). Multivariate analysis established Child-Pugh Class B (P = .014), multiple tumors (P = .013), and high viral load (HBV DNA levels >10(5) copies/mL) at complete necrosis (P = .001) as independent risk factors for recurrence. On both univariate and multivariate analyses, high viral load at the time of complete necrosis was identified as the strongest factor for recurrence; moreover, its statistically significant effects still were observed even when conducting the analyses separately for both local recurrence (P = .018) and distant recurrence (P = .009). CONCLUSIONS: Among individuals who underwent transarterial chemolipiodolization, high HBV viral load at complete necrosis was among the most important risk factors for posttreatment recurrence, irrespective of the locational pattern of recurrence. The current findings underscored the need for future work that tests the applicability of antiviral therapy to reduce the risk of HCC recurrence in this setting.

Myxedema ascites: case report and literature review.

Myxedema ascites caused by hypothyroidism is rare, so its diagnosis is often delayed and patients frequently receive unnecessary procedures such as liver biopsies and exploratory laparotomies. We report a 71-yr-old man with clinical ascites that was the first manifestation of hypothyroidism, and which resolved completely in response to thyroid hormone replacement therapy. To our knowledge, this is the first report of myxedema ascites in Korea. A review of the literature revealed 51 well-documented cases of myxedema ascites. Analyses of ascites from patients in this condition usually show high protein (>2.5 g/dL) and low white blood cell counts, with a high proportion of lymphocytes. A consistent feature is the good response to thyroid hormone replacement therapy, which has always led to resolution of the ascites. Myxedema ascites is thus rare but easy to treat; it should be borne in mind, especially if the ascites fluid has a high protein content.