Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. METHODS: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. RESULTS: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47). CONCLUSIONS: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

A Case of Management for Advanced Hepatocellular Carcinoma with Extrahepatic Metastasis by Autologous Natural Killer Cells Combined with Immune Checkpoint Inhibitor

Hepatocellular carcinoma (HCC) has extremely poor prognosis. Immunotherapy has emerged as a new treatment for a number of cancers. Adoptive immunotherapy is one of the important cancer immunotherapy, which relies on the various lymphocytes including cytotoxic T lymphocytes, natural killer (NK) and cytokine induced killer cells. Also, there has been advance in techniques of NK cell activation to more effectively kill the cancer cells. Of note, recently the blocking antibodies targeting programmed cell death protein 1 (PD-1) have shown promising results in diverse cancers including HCC. We report our recent experience of a patient accompanying advanced HCC with extrahepatic metastases. Disease progression had occurred after sorafenib administration, while the patient showed local tumor control and tumor marker decrease by NK cell immunotherapy combined with PD-1 inhibitor therapy. Though, there was no definite survival advantage due to impaired liver function, which might be caused by treatment related toxicities as well as cancer progression.

Sarcopenia Predicts Prognosis in Patients with Newly Diagnosed Hepatocellular Carcinoma, Independent of Tumor Stage and Liver Function / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias. RESULTS: Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m2 for males and ≤ 43.0 cm/m2 for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival. CONCLUSION: The presence of sarcopenia at HCC diagnosis is independently associated with survival.

Fluoroscopy-induced Subacute Radiation Dermatitis in Patient with Hepatocellular Carcinoma / 대한소화기학회지

Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis.

Living Donor Liver Transplantation in a Hepatitis B Patient with Acute on Chronic Liver Failure Accompanying Hepatocellular Carcinoma / 이화의대지

Acute clinical deterioration in patients with chronic liver disease is called acute on chronic liver failure (ACLF). Principles of management of ACLF consist of early identifying etiology of liver disease, rapid intervention of precipitating event and discreet intensive cares. Despite medical intensive cares, if liver failure progresses, liver transplantation could be the other option. Also, liver transplantation is the only treatment that offers a chance of cure for hepatocellular carcinoma (HCC) and the underlying liver cirrhosis simultaneously. Emergent living donor liver transplantation (LDLT) can be performed for patients with acute liver failure and improves survival rate, especially in circumstances which liver graft is often not available because of deceased donors are not affordable. Here, we describe a chronic hepatitis B patient who developed ACLF accompanying early HCC. Because he did not improved with medical care, he received emergent LDLT. After LDLT, he showed great improvement without critical complications.

Hepatic Infarction Caused by Portal Vein Thrombophlebitis Misdiagnosed as Infiltrative Hepatic Malignancy with Neoplastic Thrombus / 대한소화기학회지

Portal vein thrombosis (PVT) is a form of venous thrombosis that usually presents in chronic form without any sequalae in patients with hepatocellular carcinoma (HCC) or liver cirrhosis. Accurate differential diagnosis of bland PVT from neoplastic PVT is an important step for planning treatment options, but the acute form can be challenging. Here we present a case of acute hepatic infarction caused by acute bland PVT combined with pylephlebitis, which was misdiagnosed as infiltrative hepatic malignancy with neoplastic PVT owing to the perplexing imaging results and elevated tumor markers.

A Case of Severe Peripheral Polyneuropathy Occurring after Entecavir Treatment in a Hepatitis B Patient / 대한소화기학회지

Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.

A Case of Concurrent Chemoradiation Therapy for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis

Patients with advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have an extremely poor prognosis. Although the Barcelona Clinic Liver Cancer guideline recommends sorafenib in advanced HCC with PVT, which has provided survival benefits of 2 or 3 months compared to the placebo group, many liver cancer centers in Asia still select multimodality approaches including transarterial chemoembolization, radiofrequency ablation, radiation therapy (RT) as well as systemic/intra-arterial chemotherapy. Recently advanced RT technologies have shown potential to improve survival without severe radiation-related toxicity. For locally advanced HCC patients with PVT, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment and provides potential cures. We herein report our recent experience of a patient accompanying large HCC with PVT who successfully undergone CCRT followed by hepatic arterial infusion chemotherapy.

A Case of Nodular Regenerative Hyperplasia of the Liver Combined with Toxic Hepatitis / 대한소화기학회지

Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.

Prevalence of Occult Hepatitis B Virus Infection in Hemodialysis Patients / 대한소화기학회지

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

BACKGROUND/AIMS: Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B. METHODS: We enrolled 91 patients with treatment-naive chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy. RESULTS: Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy. CONCLUSIONS: Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.

Effects of Metabolic Syndrome on Fibrosis in Chronic Viral Hepatitis

BACKGROUND/AIMS: Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC). METHODS: In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system. RESULTS: Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3+/-2.1 vs 2.4+/-1.3, p=0.025; CHC, 2.6+/-1.5 vs 1.3+/-0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017). CONCLUSIONS: Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.

Efficacy and safety of entecavir plus carnitine complex (GODEX(R)) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex(R)) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-gamma secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

BACKGROUND/AIMS: We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. METHODS: We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. RESULTS: Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was > or =6x10(5) IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). CONCLUSIONS: Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.

The Role of 18F-FDG PET/CT in the Evaluation of Gastric Cancer Recurrence after Curative Gastrectomy

PURPOSE: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans are frequently performed for the screening or staging of malignant tumors. This study aimed to assess the usefulness of 18F-FDG PET/CT in detection of gastric cancer recurrence after curative gastrectomy. MATERIALS AND METHODS: Eighty nine patients who had undergone curative gastrectomy due to gastric cancer and had 18F-FDG PET/CT and contrast CT scans within 2 weeks for surveillance in asymptomatic patients (n = 11) or to clarify suspected recurrence (n = 78) were consecutively collected and retrospectively analyzed. They had clinical follow-up for at least 12 months after PET/CT and CT scans. RESULTS: Fifteen of the 89 patients (16.9%) were diagnosed with recurrent gastric cancer in 21 organs. Forty one organs showed an increase in FDG uptake, and only 9 of these organs were diagnosed with recurrent gastric cancer by 18F-FDG PET/CT. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the 18F-FDG PET/CT were 42.9%, 59.7%, 29.3%, 78.2%, and 57.3%, respectively. On the CT scan, 18 of 21 recurrent gastric cancers were detected, and 7 cases were in agreement with the 18F-FDG PET/CT. The sensitivity and specificity of the CT scan were 85.8% and 87.3%, respectively, which are superior to the 18F-FDG PET/CT. When we diagnosed a recurrence based on either 18F-FDG PET/CT or CT scans, the sensitivity increased to 95.2% and the specificity decreased to 45.6%, when compared with the contrast CT scan alone. CONCLUSION: 18F-FDG PET/CT is an insufficient diagnostic method in detection of recurrence after curative gastrectomy, and even less accurate than contrast CT scan alone.

Fatal Biliary-Systemic Air Embolism during Endoscopic Retrograde Cholangiopancreatography: A Case with Multifocal Liver Abscesses and Choledochoduodenostomy

We report a rare case of a massive fatal embolism that occurred in the middle of endoscopic retrograde cholangiopancreatography (ERCP) and retrospectively examine the significant causes of the event. The patient was a 50-year old female with an uncertain history of previous abdominal surgery for multiple biliary stones 20 years prior. The patient presented with acute right upper quadrant pain. An abdominal computed tomographic (CT) scan revealed the presence of multiple stones in the common bile duct (CBD) and intra-hepatic duct (IHD) with biliary obstruction, multifocal liver abscesses, and air-biliarygram. Emergency ERCP showed a wide and straight opening of choledochoduodenostomy, which may have been created during a previous surgery, and multiple filling defects in the CBD. With the use of a forward endoscope, mud stones were extracted through the opening of the choledochoduodenostomy. Cardiac arrest suddenly developed during the procedure, and despite immediate resuscitation, the patient died due to a massive systemic air embolism. We reviewed previously reported fatal cases and accessed factors facilitating air embolisms in this case.

The Usefulness of F18-FDG PET/CT in Detection of Colonic Neoplasm

BACKGROUND/AIMS: The diagnostic value of 2-18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET)/CT in the detection of colon carcinoma and adenoma was evaluated retrospectively. METHODS: Between May 2007 and June 2008, 102 patients (42 males and 60 females: age range, 28-89 years) underwent both FDG PET/CT and colonoscopy in < a 3 month interval. FDG uptake on PET/CT was divided into physiologic and pathologic uptake by a nuclear medicine specialist. Pathologic confirmation was obtained in all patients. RESULTS: Forty-three patients had no abnormal findings on both FDG PET/CT and colonoscopy. One hundred five and 59 colonic lesions were detected on FDG PET/CT and colonoscopy, respectively. Eleven of 24 lesions with pathologic FDG uptake were histologically-confirmed to be malignancies. Among 18 lesions with physiologic FDG uptake, 1 carcinoma and 1 adenoma were revealed. One carcinoma, 25 adenomas, and 11 hyperplastic polyps did not reveal FDG uptake. Interpretation of pathologic FDG uptake in the colon had a sensitivity of 84.6% and 28.2%, a specificity of 90.4% and 88.1%, a positive predictive value of 45.8% and 45.8%, and a negative predictive value of 98.4% and 77.8% for carcinomas and adenomas, respectively. CONCLUSIONS: FDG PET/CT is a very useful diagnostic method for the detection of colon cancer, but the sensitivity is low for adenomas, which may need further evaluation, such as a screening endoscopy.

The Usefulness of F18-FDG PET/CT in Detection of Colonic Neoplasm

BACKGROUND/AIMS: The diagnostic value of 2-18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET)/CT in the detection of colon carcinoma and adenoma was evaluated retrospectively. METHODS: Between May 2007 and June 2008, 102 patients (42 males and 60 females: age range, 28-89 years) underwent both FDG PET/CT and colonoscopy in < a 3 month interval. FDG uptake on PET/CT was divided into physiologic and pathologic uptake by a nuclear medicine specialist. Pathologic confirmation was obtained in all patients. RESULTS: Forty-three patients had no abnormal findings on both FDG PET/CT and colonoscopy. One hundred five and 59 colonic lesions were detected on FDG PET/CT and colonoscopy, respectively. Eleven of 24 lesions with pathologic FDG uptake were histologically-confirmed to be malignancies. Among 18 lesions with physiologic FDG uptake, 1 carcinoma and 1 adenoma were revealed. One carcinoma, 25 adenomas, and 11 hyperplastic polyps did not reveal FDG uptake. Interpretation of pathologic FDG uptake in the colon had a sensitivity of 84.6% and 28.2%, a specificity of 90.4% and 88.1%, a positive predictive value of 45.8% and 45.8%, and a negative predictive value of 98.4% and 77.8% for carcinomas and adenomas, respectively. CONCLUSIONS: FDG PET/CT is a very useful diagnostic method for the detection of colon cancer, but the sensitivity is low for adenomas, which may need further evaluation, such as a screening endoscopy.

Two Cases of Rectal Vascular Ectasia in Patients with Liver Cirrhosis and Who Were Treated by Argon Plasma Coagulation / 대한소화기내시경학회지

The term "vascular ectasia" is defined to include angiodysplasia, gastric antral vascular ectasia (GAVE) and telangiectasis, and these are the leading causes of acute or chronic gastrointestinal bleeding. We describe here the first 2 Korean cases of GAVE with rectal vascular ectasia in patients with liver cirrhosis. A 70-year-old woman was admitted to the hospital with hematochezia. The finding on endoscopy showed diffuse nonconfluent spots with oozing bleeding on the antrum and several vascular spots with oozing bleeding on the rectum. The lesions were successfully treated by argon plasma coagulation (APC). We report on another case of rectal vascular ectasia in a patient with liver cirrhosis. A 77-year-old man was admitted to the hospital with hematochezia. The findings on colonoscopy showed diffuse vascular spots with oozing bleeding on the rectum. The lesions were successfully treated by APC. These two patients have had no bleeding since their treatment, and they are currently being evaluated by follow-up studies at the outpatient department.

Molecular Epidemiology of Hepatitis A Virus in the South-East Area of Gyeonggi-do in Korea

PURPOSE: Hepatitis A virus (HAV) has been a leading cause of acute hepatitis in Korea. The reported genotypes of acute hepatitis A in Korea are the subgenotype IA and IB. The aim of the present study is to investigate HAV genotypes in the south-east area of Gyeonggi-do in Korea. MATERIALS AND METHODS: From June 2004 to June 2006, 46 acute hepatitis A patients were enrolled prospectively. All had sporadic acute hepatitis A patients. All suspected cases of acute hepatitis A were tested for IgM anti-HAV antibodies. We sequenced 168 bp of nucleotides of the putative VP1/P2A junction and determined the HAV genotype with reverse transcriptase polymerase chain reaction. The clinical and laboratory results of all patients were recorded. RESULTS: HAV-ribonucleic acid (RNA) was detected in 41 samples out of 46 samples. Among the 41 samples, 25 (60%) were shown to have subgenotype IIIA and the other 16 (40%) were subgenotype IA. Several amino acid substitutions were found. CONCLUSION: In these HAV sporadic cases, IIIA and IA were identified, and this may reflect co-circulation of various genotypes in Korea. This study provides valuable new data on the genetic distribution of HAV and important information to help design appropriate public health measures.