Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study

Background@#/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. @*Methods@#This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. @*Results@#In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. @*Conclusions@#This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

New Potential Therapies for Chronic Hepatitis B / 대한소화기병학회잡지

A HBV infection is a dynamic disease and long-term liver inflammation contributes to the development of liver cirrhosis and hepatocellular carcinoma. Currently available nucleos(t)ide analogues and pegylated interferon are effective in inhibiting HBV replication but rarely achieve HBsAg clearance. The present article introduces a new definition of HBV cure and several emerging therapies for HBV cure, including direct acting antivirals and immune modulatory antivirals.

New Potential Therapies for Chronic Hepatitis B / 대한소화기학회지

A HBV infection is a dynamic disease and long-term liver inflammation contributes to the development of liver cirrhosis and hepatocellular carcinoma. Currently available nucleos(t)ide analogues and pegylated interferon are effective in inhibiting HBV replication but rarely achieve HBsAg clearance. The present article introduces a new definition of HBV cure and several emerging therapies for HBV cure, including direct acting antivirals and immune modulatory antivirals.

Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.

A case of portal hypertension by presumed as plexiform neurofibroma at the hepatic hilum

Neurofibromas can occur anywhere in the body, but they usually involve the head, neck, pelvis, and extremities. Abdominal visceral involvement is rare, and intrahepatic involvement is even less common. We describe a patient who suffered from plexiform neurofibromatosis with liver involvement. A 49-year-old man, who had previously been diagnosed with neurofibromatosis, underwent esophagogastroduodenoscopy and abdominal ultrasonography for screening purposes. Esophagogastroduodenoscopy showed grade 2 esophageal varices and abdominal ultrasonography showed conglomerated nodules with echogenic appearances in the perihepatic space. Magnetic resonance imaging showed presumed plexiform neurofibroma involving the lesser sac and hepatic hilum and encasing the common hepatic artery celiac trunk and superior mesenteric artery left portal triad. We report an unusual case of portal hypertension attributed to the compressive narrowing of the portal vein by presumed as plexiform neurofibroma at the lesser sac and hepatic hilum.

Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.

Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report

Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

Night Blindness Induced by Long-term External Bile Drainage / 이화의대지

Vitamin A deficiency can occur as a result of malnutrition, malabsorption, or poor vitamin metabolism due to liver disease and night blindness might develop as the first symptom. Although there have been foreign reports about night blindness due to vitamin A deficiency which was derived from liver cirrhosis, primary biliary cirrhosis, intestinal bypass surgery or bariatric operation, it is hard to find reports about night blindness after percutaneous transhepatic biliary drainage for external bile drainage. We report a case of night blindness derived from fat-soluble vitamin A deficiency developed after long-term (18 months) external bile drainage for benign biliary stricture occurred after left hepatic lobectomy and hepaticojejunostomy due to the Klatskin tumor (IIIb). Her night blindness and low serum retinol level (0.02 mg/L) was dramatically improved after vitamin A supplementation. We recommend lipid-soluble vitamin supplementation on the case of long-term external bile drainage.

Chelidonium majus-Induced Acute Hepatitis / 이화의대지

The use of traditional folk remedies is increasing throughout Asia. Chelidonium majus, a popular herbal remedy, is used to treat abdominal pain caused by various gastrointestinal disorders, including gastric ulcer, gastritis, and biliary tract disease, because of its morphine-like effect. We encountered a 62-year-old woman with acute hepatitis, in which C. majus was suspected to be the etiological factor. The patient had taken high dose of C. majus extract for the preceding 60 days. The clinical context and the temporal association between the start of the herbal medicine treatment and her liver injury allowed us to attribute a causative role to C. majus. The diagnosis was confirmed by liver biopsy and the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale. After C. majus was discontinued, the liver function was restored to normal. In conclusion, because the use of phytotherapy is increasing, we wish to raise awareness of the potential adverse effects of C. majus.

DC Bead Transarterial Chemoembolization Is Effective in Hepatocellular Carcinoma Refractory to Conventional Transarteral Chemoembolization: A Pilot Study

BACKGROUND/AIMS: To determine if hepatocellular carcinoma refractory to conventional transarterial chemoembolization (TACE) responds to TACE with DC beads. METHODS: Between July 2008 to June 2010, 435 patients underwent TACE. Of these, 10 patients who had tumors refractory to conventional TACE and who thus were treated with TACE with DC beads were enrolled in this study. The treatment response after TACE with DC beads was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: Ten tumors were treated in 10 patients. Using the mRECIST and the RECICL, a complete response was observed in four (40%) of the tumors, and six tumors (60%) showed a partial response. Eight (80%) out of 10 HCCs showed delayed enhancement patterns upon angiography, and better responses were observed in these cases following DC bead treatment. The adverse effects of treatment with DC beads became tolerable. CONCLUSIONS: TACE with DC beads was effective for HCCs refractory to conventional TACE, and this treatment elicited a better response, especially when the tumors were small and showed a delayed enhancement pattern upon angiography.

Myeloid Sarcoma in Patients with RUNX1/RUNX1T1 Positive AML and a c-kit Mutation / 대한내과학회지

t (8;21)(q22;q22) is the most frequently detected cytogenetic abnormality in patients with acute myeloid leukemia (AML) and accounts for 8-21% of de novo AML. The translocation involves two genes, RUNX1 (formerly AML1) on 21q22 and RUNX1T1 (ETO) on 8q22. RUNX1/RUNX1T1 translocation confers a favorable prognosis, but a subset of patients has a precipitous course with a high incidence of relapse. This patient subset is associated with the presence of a c-kit mutation. c-kit is a proto-oncogene, which encodes a type III transmembrane tyrosine kinase, which elicits a variety of cellular responses essential for the development of bone marrow stem cells. The expression of the c-kit mutation in AML is < 2%, whereas AML with RUNX1/RUNX1T1 shows higher rates of c-kit mutation and is associated with extramedullary leukemia and poor clinical outcome. We report cases of myeloid sarcoma in patients with RUNX1/RUNX1T1-positive AML and a c-kit mutation.

Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization / 대한간학회지

BACKGROUND/AIMS: Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL. METHODS: This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen1-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL. RESULTS: Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036). CONCLUSIONS: TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

Glyphosate Induced Severe Tubulointerstitial Nephritis Requiring Hemodialysis / 대한신장학회지

This is the first case of glyphosate induced severe tubulointerstitial nephritis requiring hemodialysis without cardiovascular collapse. A 67-year-old man presented to the hospital 30 minutes after ingesting 90 mL of glyphosate herbicide. On arrival, his serum creatinine was 0.8 mg/dL and other laboratory findings including liver, cardiac, and muscle enzymes were all normal. Two days after admission, although his vital signs were stable, his creatinine abruptly increased to 8.2 mg/dL and oliguria developed. As a result, we started hemodialysis treatment and two weeks after initiation of hemodialysis, his renal function started to improve slowly. After discontinuation of hemodialysis, his renal function gradually recovered and serum creatinine level decreased to 1.6 mg/dL three weeks after admission.

Complete Fracture of Sirolimus-Eluting Stent in a Saphenous Vein Graft to Left Anterior Descending Artery

Coronary stent fractures have been suggested as a potential new mechanism of restenosis. The mechanical properties of stents were designed not only to prevent vessel recoil, but also to resist the mechanical stress of vessel movement over millions of cardiac cycles. We present a case in which mechanical stress may have contributed to the fracture of a stent implanted in a saphenous vein graft (SVG) to the left coronary artery. The patient was admitted due to chest pain 2 years after receiving a coronary artery bypass graft. A coronary angiography revealed the culprit vessel to be the SVG to the left coronary artery. The graft was stenosed and was stented with a sirolimus-eluting stent. A 6-month follow-up coronary angiography revealed 80% in-stent restenosis with stent fracture. We re-intervened by balloon angioplasty. This is the first report of sirolimus-eluting stent fracture combined with restenosis of SVG in Korea.

Significance of Inflammatory Markers in Diabetic Patients with Stable Coronary Artery Disease

BACKGROUND/AIMS: Patients with diabetes are prone to coronary artery disease (CAD); however, the majority of diabetic patients show normal coronary arteries. We examined differences in the clinical aspects of diabetic patients with insignificant and with significant stenosis of the coronary artery. METHODS: A total of 418 consecutive diabetic patients with stable angina who had undergone coronary angiography from January 2004 to March 2007 were included in this study. Patients were subdivided into control and CAD groups and then clinical characteristics and CAD-associated factors were evaluated. RESULTS: A total of 92 (22%) patients were assigned to the control group and 326 (78%) patients were assigned to the CAD group. Using univariate regression analysis, we found that patients with CAD were significantly older (control vs. CAD; 59+/-21 vs. 64.7+/-33.7, years, p<0.001), had a longer duration of diabetes (8.2+/-21.8 vs. 10.2+/-29.8, years, p=0.027), higher titers of high sensitivity C-reactive protein (hsCRP; 0.3+/-6.79 vs. 0.9+/-12.6, mg/dL, p=0.015), and increased hemoglobin A1c (HbA1c) levels (7.1+/-3.8 vs. 7.5+/-4.8, %, p=0.007) compared to control patients. Multivariate regression analysis showed that only differences in age, hsCRP, and HbA1c were statistically significant. When patients were subdivided into groups based on hsCRP levels (208 patients in the low group [49.8%], 210 patients in the high group [50.2%]), we found that patients with higher hsCRP levels showed more frequent multivessel disease. CONCLUSIONS: In diabetic patients, age, hsCRP, and HbA1c were associated with stable CAD. Among these factors, hsCRP levels were significantly correlated with multivessel involvement in diabetic CAD. Therefore, high hsCRP levels may be a strong predictor for atherosclerotic progression of the coronary arteries in diabetic patients, suggesting that regular screening tests should be performed.