A prospective study of the correlation between hepatic fibrosis and noninvasively measured fibrosis markers including serum M2BPGi and acoustic radiation force impulse elastography / 고신대학교의과대학학술지

Background@#Mac-2 binding protein glycosylation isomer (M2BPGi) was introduced as a noninvasively measurable serologic marker for liver fibrosis. Acoustic radiation force impulse imaging (ARFI) elastography is another noninvasive method of measuring hepatic fibrosis. There are limited data about the correlations between histologic fibrosis grade and noninvasively measured markers, including M2BPGi and ARFI. @*Methods@#This prospective study was conducted among patients admitted consecutively for liver resection, cholecystectomy, or liver biopsy. ARFI elastography, serum M2BPGi levels, and the AST to Platelet Ratio Index (APRI) score were evaluated before histologic evaluation. Histologic interpretation was performed by a single pathologist using the METAVIR scoring system. @*Results@#In patients with high METAVIR scores, M2BPGi levels and ARFI values showed statistically significant differences between patients with fibrosis and those without fibrosis. In 41 patients with hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels also tended to increase (p=0.161). ARFI values changed significantly as METAVIR scores increased (p=0.039). In 33 patients without hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels significantly increased (p=0.040). ARFI values also changed significantly as METAVIR scores increased (p=0.033). M2BPGi levels were significantly correlated with ARFI values (r=0.604, p<0.001), and APRI values (r=0.704, p<0.001), respectively. @*Conclusions@#Serum M2BPGi levels increased with liver fibrosis severity and could be a good marker for diagnosing advanced hepatic fibrosis regardless of the cause of liver disease.

Effectiveness of Albumin-bilirubin Score as a Predictor of Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma / 대한소화기학회지

Background/Aims@#Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea. @*Methods@#Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study. @*Results@#A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%. @*Conclusions@#The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

Gallbladder Perforation after Transarterial Chemoembolization in a Patient with a Huge Hepatocellular Carcinoma / 대한소화기학회지

Transarterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). The most common complications after TACE are non-specific symptoms called post-embolization syndrome, such as abdominal pain or fever. Rare complications, such as liver failure, liver abscess, sepsis, pulmonary embolism, cholecystitis, can also occur. On the other hand, gallbladder perforation is quite rare. This paper reports a case of gallbladder perforation following TACE. A 76-year-old male with a single 9-cm-sized HCC underwent TACE. Five days after TACE, he developed persistent right upper quadrant pain and ileus. An abdomen CT scan confirmed gallbladder perforation with bile in the right paracolic gutter and pelvic cavity. Percutaneous transhepatic gallbladder drainage was performed with the intravenous administration of antibiotics. After 1 month, the patient underwent right hemihepatectomy and cholecystectomy. Physicians should consider the possibility of gallbladder perforation, which is a rare complication after TACE, when unexplained abdominal pain persists.

Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients: A Randomized, Multicenter, Phase IIIb Open-Label Study (POTENT Study) / 中华医学杂志(英文版)

<p><b>Background</b>Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.</p><p><b>Methods</b>Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.</p><p><b>Results</b>HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.</p><p><b>Conclusions</b>The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.</p><p><b>Trial Registration</b>ClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.</p>

Two Cases of Autoimmune Hepatitis Accompanied by Connective Tissue Diseases / 대한내과학회지

Autoimmune hepatitis is a generally progressive chronic hepatitis of unknown etiology. Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic, multifaceted inflammatory diseases that can affect every organ system, although hepatic involvement is rare. Here, we report two rare cases: autoimmune hepatitis associated with SLE and with primary Sjogren's syndrome. A 52-year-old woman and a 60-year-old woman were admitted our hospital with jaundice and pruritus. They had no history of viral hepatitis, alcohol consumption, or drug use. The pathological findings, clinical manifestations, and laboratory findings satisfied each of the diagnostic criteria for autoimmune hepatitis as well as for SLE and Sjogren's syndrome in the first and second cases, respectively. These patients were treated with prednisolone, and then followed regularly.

Comparison of Long-term Complication of Malignant Biliary Obstruction after Percutaneous Transhepatic Biliary Drainage Versus Metallic Biliary Drainage / 고신대학교의과대학학술지

OBJECTIVES: Several advances in the diagnosis, therapy and palliation of patients affected by malignant biliary obstruction have occurred during the last decades. Unresectable malignant biliary obstruction has usually been treated by percutaneous transhepatic biliary drainage (PTBD) versus metallic biliary drainage (MBD). The optimal management of complications after biliary drainage is still an unresolved problem. To compare the complications of malignant biliary obstruction after PTBD and MBD. METHODS: We enrolled 51 patients of malignant biliary obstruction after biliary drainage. The clinical characteristics and complications of each groups were assessed and compared. RESULTS: The complications after biliary drainage of MBD are lower than those of PTBD (59.1% vs 82.8%, P = 0.06, respectively). Patients with PTBD tended to have a shorter event of complication time compared to MBD patients (2.9 months vs 7.1 months, P < 0.01). Patients with older age in PTBD tended to have a longer event of complication time compared to younger patients (4.6 months vs 2.3 months, P < 0.01). CONCLUSIONS: The method of biliary drainage in malignant biliary obstruction have statistically significant impact on the complication time. The clinical efficacy of metallic stent in patients with malignant biliary obstruction is better than that of PTBD.

The Efficacy of Antiviral Agents in Patients with Hepatitis B-related Liver Cirrhosis / 고신대학교의과대학학술지

OBJECTIVES: Improvement of liver synthetic function and the incidence of complication in the patients with hepatitis B-related liver cirrhosis is important. In this study, we study whether antiviral therapy was effective in patients with hepatitis B-related liver cirrhosis. METHODS: 103 patients with hepatitis B-related liver cirrhosis treated with lamivudine 100mg daily over 6 months and followed up over 30 months. 71 patients were positive for serum HBeAg. HBeAg, HBV DNA , CBC, prothrombin time, biochemistry, ultrasonography and endoscopy were tested every 6 months. RESULTS: The medians of ALT, albumin improved after 6 months and then aggravated after 18 months, but they didn't aggravated at 30 months compared with initial test. The median of Child-turcotte-pugh (CTP) score imporved after 6 months and then aggravated after 12 months, but they didn't aggravated at 30 months compared with initial test. The CTP score improved (2 point reduction) in 29 patients. The finding of ultrasonography didn't aggravaed (improved or didn't changed) in 58 patients. The 5 year incidence rate of hepatocelluar carcinoma was 8.3%. CONCLUSIONS: The antiviral therapy in patients with hepatitis B-related liver cirrhosis is improved CTP score and biochmical data. The improvement is more useful in decompensated cirrhosis the compensated cirrhosis. The incidence of hepatocellular carcinoma decreases than other studies. Therefore, the antiviral medication in patients with hepatitis B-related liver cirrhosis is helpful to consider more aggressively.

A left-sided gallbladder accompanying atrophy of the lateral inferior segment of the liver / 대한내과학회지

A left-sided gallbladder occurring in the absence of situs inversus is a rare anomaly. This anomaly was found in a 50-year-old man without any evidence of pancreatobiliary disease. Epigastric transverse ultrasonography showed a normal gallbladder with its fundus extending past the left lateral end of the liver. Abdominal computed tomography (CT) revealed that the gallbladder was located beneath the quadrate lobe (S4) of the liver to the left of the left branch of the portal vein, and S4 was hypertrophied to compensate for atrophy of the lateral inferior segment (S3) of the liver. Magnetic resonance cholangiopancreatography (MRCP) showed that the gallbladder and pancreatobiliary tree were normal, and that the cystic duct joined the common bile duct from the right side making a characteristic U-shaped hairpin bend.

Two Cases of Endoscopically Diagnosed Gastric Metastatic Malignant Melanoma of Unknown Origin / 대한소화기내시경학회지

Although malignant melanoma involving the stomach is commonly mentioned in association with autopsies, endoscopic experience in this gastric malignancy is still limited, and few cases have been illustrated in the literature. This clinical condition is even rarer in Asians who are much less vulnerable to malignant melanoma than Caucasians. We experienced two cases of gastric metastases of malignant melanoma which presented as indigestion and epigastric pain. In the first case, a 75-year-old man visited because of indigestion persisting for 2 months. He had a history of multiple gastric ulcer and was treated at a local medical center, but symptoms did not improved. Endoscopic finding revealed multiple and elevated lesions with central black pigmented bases. In the second case, a 47-year-old man visited because of epigastric soreness and intermittent pain for 1 month. Metastatic melanoma in the stomach was noticed by endoscopic examination. Both patients had multiple metastatic lesions in the liver, thyroid, and brain. These two cases were diagnosed as having metastatic malignant melanoma in the stomach of unknown origin. Therefore, we report these cases with a brief review of the related literature.

The Clinical Meaning of the Emergence of Viral Breakthrough during Lamivudine Treatment in Patients with Hepatitis B Virus Related Chronic Liver Disease / 대한간학회지

BACKGROUND/AIMS: Viral breakthrough has been considered a major limitation of lamivudine in the treatment of hepatitis B virus related chronic liver disease. Its clinical meaning has not been thoroughly assessed. METHODS: 64 patients who showed viral breakthrough during lamivudine treatment were retrospectively reviewed. We evaluated the rate of HBeAg seroconversion and hepatic decompensation after viral breakthrough. RESULTS: After viral breakthrough, serum alanine transaminase (ALT) elevation more than 1.2X upper limit of normal (ULN) was noticed in 40 patients (62.5%). Acute flare (serum ALT elevation >X5 ULN, or serum bilirubin >3 mg/dL) occured in 15 patients (23.4%). During the period of follow up (15.0 +/- 9.7 months; range, 0-31 months) since viral breakthrough, decreased serum HBV-DNA level to below the detection limit and serum ALT normalization was seen in 15 patients (23.4%). HBeAg seroconversion was noticed in 7 (13.7%) of a total of 51 HBeAg positive patients at base line; in 4 (15.4%) of 26 patients with non-hepatic failure (chronic hepatitis or Child-Pugh class A liver cirrhosis) at base line; and in 2 (40.0%) of 5 patients with non-hepatic failure at base line and acute flare after viral breakthrough. During this period, terminal hepatic decompensation (Child-Pugh class C) or death was noticed in 9 (90.0%) of 10 patients who had hepatic decompensation (Child-Pugh class B or C) at baseline and acute flare after viral breakthrough. CONCLUSIONS: Acute flare after viral breakthrough seemed to continue during HBeAg seroconversion and rarely developed into terminal hepatic decompensation or death in patients with non-hepatic decompensation at baseline. Its incidence is not only high but lethal to most patients with hepatic decompensation at baseline.

A Case of Bile Duct Cancer Arising in Choledochal Cyst in a 13-Year-Old Girl / 대한소화기내시경학회지

Choledochal cyst, also referred to as cystic dilatation of the extrahepatic bile duct, is a rare malformation most frequently seen in female. Malignant changes in choledochal cyst have frequently been described, but only one case of malignant change in childhood has been reported till now. Recently, we experienced a case of bile duct cancer arising in choledochal cyst in a 13-year-old girl. She had been complaining of right upper abdominal pain for 15 days. Abdominal CT scan and ERCP showed a cylindrical dilatation of extrahepatic bile duct with irregular cystic wall mass and multiple liver metastasis which was confirmed as adenocarcinoma by ultrasono-guided needle biopsy. Anomalous pancreaticobiliary ductal union was not seen. This patient was the youngest case of bile duct carcinoma arising in choledochal cyst in Korea.

Insulin Resistance and Coronary Artery Disease

BACKGROUND: Insulin resistance has been identified as one of the risk factor of atherosclerosis. Hypertension, obesity, glucose intolerance and dyslipidemia could induce atherosclerosis through mechanism of insulin resistance. And there are some reports that hyperinsulinemia itself could induce coronary artery disease(CAD). Then we planed to investigate relationship between CAD and insulin resistance. And smoking is also known as one major risk factor of CAD. So we also investigated the relationship between smoking and insulin resistance in the CAD patients. METHODS: Among 36 subjects in whom coronary angiography was done, we grouped 25 subjects who had stenotic coronary artery as a CAD group and 11 subjects without stenosis as control group. We compared insulin and glucose response to oral glucose load(75g), serum lipid concentrations, blood pressure, and degree of obesity between two groups. We also divided CAD group into smoking and nonsmoking subgroups, compared the above parameters. RESULTS: 1) There were no significant difference in body mass index, blood pressure, creatinine, cholesterol, HDL-cholesterol, between the CAD group and the control group. There were significantly higher incidence of smokers in CAD group. 2) Insulin concentration at 120 minutes after glucose load were significantly higher in the CAD group than the control group. 3) In the CAD group, fasting plasma insulin concentration insulin area, peak plasma insulin concentration and insulin concentration at 60,90,120 minutes after glucose load were significantly higher in non-smoking group. CONCLUSION: Enhanced insulin reponse such as higher insulin concentration 60 minutes after glucose load in the CAD group suggests that insulin resistance is a risk factor of CAD. And insulin response was more pronounced in the non-smoker subgroup than smoker subgroup in the CAD patients. Thus role of insulin resistance in provoking coronary artery disease is more important in the non-smoker.