Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

Efficacy and safety of intragastric balloon for obesity in Korea.

BACKGROUND/AIMS: Intragastric balloon (IGB) is the only available endoscopic bariatric and metabolic therapy in Korea. End-ball (Endalis) has the longest history of clinical use among the IGBs available in Korea. However, little clinical data on this system have been reported. In this study, we aimed to evaluate the efficacy and safety of End-ball in Korea. METHODS: We performed a retrospective cohort study of patients who underwent IGB insertion (End-ball) from 2013 to 2019. Demographic and anthropometric data were collected. The efficacy and safety of IGB treatment were analyzed. RESULTS: In total, 80 patients were included. Mean age was 33.7 years and 83.8% were female. Initial body mass index was 34.48±4.69 kg/m2. Body mass index reduction was 3.72±2.63 kg/m2 at the time of IGB removal. Percent of total body weight loss (%TBWL) was 10.76%±6.76%. Percentage excess body weight loss was 43.67%±27.59%. Most adverse events were minor, and 71.4% of participants showed nausea, vomiting, or abdominal pain. CONCLUSION: IGB treatment showed good efficacy and safety profile in Korean patients with obesity. In terms of %TBWL and percentage excess body weight loss, the efficacy was similar to that in the Western population.

Serum aminotransferase levels instead of etiology affects the accuracy of transient elastography in chronic viral hepatitis patients.

BACKGROUND AND AIM: It is still uncertain whether the accuracy of transient elastography (TE) in predicting the fibrosis stage is similar in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The present study was carried out to evaluate whether the underlying cause of chronic viral hepatitis affects the predictive accuracy of TE. METHODS: Patients with CHB or CHC who were admitted for a liver biopsy were enrolled. Patients underwent TE and laboratory tests on the same day as the liver biopsy. The predictive accuracy was analyzed by comparing the areas under the receiver-operating characteristic curves (AUCs). RESULTS: Two-hundred and seven patients were enrolled, comprising 121 CHB patients and 86 CHC patients). The patients were aged 44 ± 14 years, and 121 (58.5%) of them were men. AUCs for predicting significant fibrosis were significantly lower in CHB patients than in CHC patients (P = 0.043). The serum alanine aminotransferase (ALT) level was associated with overestimation and underestimation of the fibrosis stage, while the cause of chronic hepatitis was not. AUCs for predicting significant fibrosis were significantly lower in patients with ALT levels >70 IU/L (AUC, 0.830; 95% CI, 0.742-0.898) than in patients with ALT levels ≤70 IU/L (0.944; 0.882-0.979; P = 0.015). CONCLUSIONS: Although the predictive accuracy of TE in predicting significant fibrosis differed significantly with the cause of chronic hepatitis, this difference was due to the degree of serum ALT levels rather than to the cause of hepatitis itself. Avoiding performing TE in patients with elevated ALT levels is recommended to guarantee the predictive accuracy of TE.

Healthy range for serum ALT and the clinical significance of "unhealthy" normal ALT levels in the Korean population.

BACKGROUND AND AIMS: It remains unclear whether the currently-used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. The present study was conducted to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels. METHODS: We reviewed the medical records, including questionnaires and the results of laboratory and radiological tests conducted at the Health Promotion Center at Korea University Anam Hospital between March 2005 and February 2007. The records, written in questionnaire form, included baseline data, such as physical status, social behaviors, medication history, and past and present disease histories. RESULTS: The mean age of the 7403 enrolled patients was 48 years, and 49.9% of these patients were male. A healthy cohort was selected after excluding patients who showed any abnormalities of the factors that were significantly associated with the serum ALT level upon multivariate regression analysis. The upper limit of the healthy range of the serum ALT level (i.e. 95th percentile) in the healthy population was 31 IU/L for males and 23 IU/L for females. The prevalence of metabolic syndrome and insulin resistance (IR) were significantly higher in patients with an 'unhealthy' normal ALT level than in those with a healthy ALT level. CONCLUSION: In our study, the upper limit of the healthy range of the serum ALT level was 31 IU/L for males and 23 IU/L for females. An unhealthy normal ALT level was associated with a higher prevalence of metabolic syndrome and IR.

Dynamic changes in liver stiffness during the course of acute hepatitis A.

OBJECTIVE: Several recent studies have suggested that hepatic necroinflammation can alter the results of liver stiffness measurements (LSMs) obtained using the FibroScan device. However, the precise relationship between acute hepatic inflammation and LSMs remains unclear. The aim of this study was therefore to evaluate the dynamic changes in LSMs during the course of acute hepatic inflammation. MATERIAL AND METHODS: Thirty-one patients with acute hepatitis A (AHA) were enrolled in this study (mean +/- SD age 29 +/- 7 years; 32.3% male). Only AHA patients who visited our hospital before their alanine aminotransferase (ALT) levels peaked were included. The day when AHA-associated symptoms began was considered as Day 0. Serum levels of ALT and bilirubin (BIL), and the international normalized ratio (INR) were measured every 2 days, as were LSMs, until the peak levels of all parameters were identified. Subsequently, these parameters were measured every 1-2 weeks until they had normalized. RESULTS: Peak serum levels of ALT and BIL, the INR, and LSMs were 3723 +/- 1513 IU/l, 5.8 +/- 2.4 mg/dl, 1.3 +/- 0.3, and 11.9 +/- 5.7 kPa, respectively. The time taken for LSMs to peak from Day 0 (8 +/- 2 days) differed significantly from that for ALT (5 +/- 1 days), BIL (10 +/- 4 days), and INR (5 +/- 1 days). LSMs had normalized (< or = 5.5 kPa) in all patients at 34 +/- 17 days after Day 0. ALT level and the INR were significantly associated with peak LSMs and BIL level and the INR with the time taken for normalization of LSMs. CONCLUSIONS: LSMs changed dynamically during the course of AHA. The pattern of change appears to be related to the severity of hepatic necroinflammation.

Terlipressin-induced hyponatremic seizure.

Terlipressin is a splanchnic constrictor that is used to control variceal bleeding and is considered to have a very good safety profile compared to vasopressin. However, side effects such as hyponatremia and seizure, although very rare, can occur. Recently, the authors have experienced a case of hyponatremia induced by infusion of terlipressin which resulted in generalized seizure. On admission, the patient's sodium level was 141 mmol/l but, 4 days after the initiation of terlipressin, it plummeted to 114 mmol/l, with serum osmolality also having fallen to 243 mOsm/kg. Hyponatremia could not be corrected despite correction with hypertonic saline but, after withdrawal of terlipressin, the serum sodium level showed a dramatic increase almost to the normal range the following day. Therefore, it is necessary to carefully monitor patients' electrolyte levels during the course of terlipressin therapy.

Usefulness of non-invasive markers for predicting liver cirrhosis in patients with chronic hepatitis B.

BACKGROUND AND AIM: Recently, various non-invasive blood markers and indices have been studied to overcome the limitations of liver biopsy, such as its invasiveness and sampling errors. However, the majority of these studies have focused on patients with chronic hepatitis C. Accordingly, this study was performed to evaluate the significances of various non-invasive serum markers in terms of predicting the presence of liver cirrhosis in chronic hepatitis B. METHODS: We included 125 chronic hepatitis B patients who had undergone liver biopsy. Fibrosis stage was assessed using the METAVIR scoring system (F0-F4), which defines liver cirrhosis as F4. In addition, we measured various blood markers at times of liver biopsy. RESULTS: Thirty four of the 125 patients (27.2%) were rated as F4 by liver biopsy. Age, platelet, white blood cells, aspartate aminotransferase (AST), alanine aminotransferase, haptoglobin, apolipoprotein-A1 (Apo-A1), collagen-IV, hyaluronic acid, alpha2-macroglobulin, matrix metalloproteinase-2, and YKL-40 were significantly different between patients with chronic hepatitis and those with liver cirrhosis. However, multivariate analysis showed that only platelet, AST, haptoglobin, and Apo-A1 independently predicted the presence of liver cirrhosis. Having identified these four factors, we devised a system, which we refer to as platelet count, AST, haptoglobin, and Apo-A1 (PAHA). The area under the receiver-operating characteristics (AUROC) of PAHA indices for the presence of liver cirrhosis was 0.924 (95% confidence interval, 0.877-0.971), which was significantly greater than the AUROC of other indices of fibrosis. CONCLUSION: The devised PAHA system was found to be useful for predicting the presence of liver cirrhosis in patients with chronic hepatitis B.

[A case of acute cholestatic hepatitis induced by Corydalis speciosa Max].

Herbs are widely used as treatments for various symptoms. However, several herbs have been reported to be inducers of liver injury. We report herein a case of hepatotoxicity induced by Corydalis speciosa Max. A 37-year-old male complained of jaundice and mild abdominal discomfort. A thorough history was taken, and laboratory investigation, diagnostic imaging studies, and percutaneous liver biopsy sampling were conducted to determine the cause of liver injury. An accurate cause was not revealed. We administered supportive management for acute cholestatic hepatitis of unknown origin, after which his symptoms disappeared and serum aminotransferase levels decreased gradually to near normal levels. However, at 2 months after discharge, the symptoms and the elevation of aminotransferase levels recurred. At that time he told us that he had repeatedly but unintentionally eaten a herb called "Hwang-geun cho"(Corydalis speciosa Max.). Thus, we diagnosed his case as herbal hepatotoxicity.

Recurrence rates and factors for recurrence after radiofrequency ablation combined with transarterial chemoembolization for hepatocellular carcinoma: a retrospective cohort study.

PURPOSE: There have been reports that radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) is as equally effective as surgical resection for the treatment of hepatocellular carcinoma (HCC). This study aimed to evaluate recurrence rate and risk factor of recurrence after RFA combined with TACE for early stage HCC. METHODS: We reviewed the medical records of the patients who were diagnosed with early stage HCC between March 2006 and August 2008 at Korea University Medical Center and treated with RFA combined with TACE for curative intent (n = 65). RESULTS: Recurrence rate was 40% (26 cases) and the time to recurrence was 14.9 months. Cumulative recurrence rate at 1 year was 20% (13 cases) and at 2 years was 33.8% (22 cases). Significant variables for recurrence were: (1) RFA repeated more than one session at initial therapy (P < 0.001) and (2) size of main lesion ≥2 cm (P = 0.047). CONCLUSIONS: The recurrence rate of combination therapy was considerably high. Regardless of the therapy used, careful post-RFA follow-up is needed, especially if additional treatment is required after the first session or if the main lesion is ≥2 cm at the time of RFA.

Clinical significance of the detection of antinuclear antibodies in patients with acute hepatitis a.

BACKGROUND/AIMS: The findings of several recent studies suggest that antinuclear antibodies (ANAs) are frequently detected in patients with acute hepatitis A (AHA). However, the clinical significance of a positive ANA test remains uncertain. This study was performed to evaluate the clinical significance of ANAs in AHA patients. METHODS: All patients admitted with AHA were consecutively enrolled in this study. An ANA assay was performed by indirect immunofluorescence during hospitalization. ANA positivity was defined as an ANA titer ≥1:80. The peak international normalized ratio (INR), peak alanine aminotransferase (ALT) and peak bilirubin levels were assessed over the duration of the hospitalization, and the incidence of AHA complications was evaluated. RESULTS: A total of 422 patients were enrolled in this study (age, 31±7 years), of which 260 (61.6%) were men. ANAs were detected in 179 AHA patients (42.4%). The proportion of ANA-positive patients varied significantly with AHA status on the day of the ANA assay (4.7% during the prodromal period vs 52.1% during the icteric or recovery period, p<0.001) and sex (56.2% in women vs 33.8% in men, p<0.001). The ANAs became undetectable in all ANA-positive patients within 3 months. The incidence of complications, including mortality, fulminant hepatic failure, renal dysfunction, relapse, and cholestatic hepatitis, did not differ significantly between ANA-positive and ANA-negative patients. CONCLUSIONS: ANAs were detected frequently and transiently in patients with AHA, especially after their peak-ALT day. The presence of ANAs may not be associated with the clinical outcome of AHA, but simply with AHA status on the ANA assay day.

Virologic response is not durable after adefovir discontinuation in lamivudine-resistant chronic hepatitis B patients.

BACKGROUND/AIMS: We investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. METHODS: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 10(5) copies/mL. RESULTS: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than (5) copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. CONCLUSIONS: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

Liver cirrhosis induced by porphyria cutanea tarda: a case report and review.

Porphyria cutanea tarda (PCT) is a metabolic disorder that results in a decrease in uroporphyrinogen decarboxylase activity. It is characterized by photosensitivity, bullae formation, and skin pigmentation. There are four types of PCT: acquired, familial, toxic, and hepatoerythropoietic. Uroporphyrin levels are elevated in the urine of PCT patients. PCT can be differentiated from other porphyrias by its clinical characteristics and the porphyrin levels in the serum, erythrocytes, urine, and feces. This metabolic disorder can lead to liver dysfunction as well as histological changes such as fatty infiltration or hepatic fibrosis. PCT rarely manifests as liver cirrhosis. We report herein a case of PCT-induced liver cirrhosis that progressed to hepatic failure.

Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.

Solitary pancreatic involvement of tuberculosis is rare, especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms. Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques. However, they are composed of a variety of neoplasms with a wide range of malignant potential, and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so, then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.