Effects of Entecavir and Tenofovir on Renal Function in Patients with Hepatitis B Virus-Related Compensated and Decompensated Cirrhosis

BACKGROUND/AIMS: The renal effects of nucleos(t)ide analogs in patients with chronic hepatitis B are controversial. We aimed to compare the impact of entecavir (ETV) and tenofovir (TDF) on renal function in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: We performed a retrospective cohort study of 235 consecutive treatment-naïve patients with HBV-related cirrhosis who were treated with ETV or TDF between December 2012 and November 2013 at Severance Hospital, Seoul, Korea. RESULTS: Compensated cirrhosis was noted in 183 patients (ETV 130, TDF 53), and decompensated cirrhosis was noted in 52 patients (ETV 32, TDF 20). There were no significant changes in estimated glomerular filtration rates (eGFR) from baseline in either the ETV- or TDF-treated groups at week 96 (Chronic Kidney Disease Epidemiology Collaboration, ETV −1.68% and TDF −5.03%, p=0.358). Using a multivariate analysis, the significant factors associated with a decrease in eGFR >20% were baseline eGFR, diabetes mellitus (DM), and the use of diuretics. The use of antiviral agents and baseline decompensation were not determined to be significant factors. CONCLUSIONS: In patients with HBV-related cirrhosis, TDF has shown similar renal safety to that of ETV over a 2-year period. Renal function should be closely monitored, especially in patients who exhibit decreasing eGFR, DM, and the use of diuretics.

Erratum: Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response

On the pages 432 and 434, Figures 2 and 3 were incorrectly reproduced in the publishing process.

Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response

BACKGROUND/AIMS: Few studies have investigated prognostic factors for the development of liver-related events (LREs) in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). METHODS: We analyzed 190 patients with CHC who achieved SVR after treatment with pegylated interferon (peg-IFN) plus ribavirin. LREs were defined as any complications related to cirrhosis, hepatocellular carcinoma (HCC), or liver-related mortality. RESULTS: The mean age was 54.1 years, and 84 of the patients (44.2%) were male. The mean liver stiffness (LS) value at SVR was 7.1±5.4 kPa. During the follow-up period (median, 43.0 months), LREs occurred in 10 patients (5.3%; HCC in eight patients, ascites in one patient, and liver-related mortality in one patient). By multivariate Cox regression analysis, age, α-fetoprotein level, and LS value were independent predictors for LRE development (all p<0.05). Patients with LS values ≥7.0 kPa had a greater risk (hazard ratio, 9.472; 95% confidence interval, 1.018 to 88.126; p=0.048) for LRE development compared to those with LS values <7.0 kPa. CONCLUSIONS: The LS value at SVR is useful for predicting LRE development in CHC patients who achieve SVR after treatment with peg-IFN plus ribavirin. Thus, LRE surveillance strategies might be optimized according to the LS values at SVR, even with complete viral eradication.

The Relationship between Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Measured by Controlled Attenuation Parameter

PURPOSE: The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). MATERIALS AND METHODS: Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). RESULTS: Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (ρ=0.407) or fasting C-peptide (ρ=0.402) were demonstrated. CONCLUSION: Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.

Treatment of Chronic Hepatitis C Using Newly Developed Oral Antiviral Agents / 대한내과학회지

Standard care for chronic hepatitis C has been a combination of pegylated interferon-alpha and ribavirin, although this treatment has suboptimal antiviral efficacy and significant adverse events. The hepatitis C virus treatment landscape has been transformed recently by the development of direct-acting antiviral agents (DAAs) that target NS3 protease, NS5A protein, and NS5B polymerase. Several DAAs showed potent antiviral activity leading to increased rates of sustained virological response (SVR), even in difficult-to-treat patients such as older patients and those with advanced liver disease and prior failed peg-interferon/ribavirin treatment. Use of multiple DAAs without pegylated interferon has shown dramatically high SVR rates (up to nearly 100%) with negligible side effects. Interferon-free regimens are close to becoming the new standard of care for patients with chronic hepatitis C in USA and Europe. Similarly, several DAAs are near clinical use in Korea. This review discusses DAAs that have been approved or are under investigation for approval in Korea.

A Case of Rapidly Recurred Hepatocellular Carcinoma with Distant Metastasis after Surgical Resection

Hepatocellular carcinoma (HCC) is one of the cancers with poor prognosis. However, surgical resection is the treatment of choice as curative aim for early HCC with preserved liver function. A 5 year survival rate after curative resection is over 50%. We experienced a case of rapidly recurred HCC with bone metastasis after surgical resection. In our case, microscopically microvessel invasion was present after resection. Microvascular invasion (MVI) is an important factor to influence survival and/or HCC recurrence. So we suggested the patients with MVI need to follow up intensively and adjuvant therapy may be considered.

A case of isolated metastatic hepatocellular carcinoma arising from the pelvic bone / 대한간학회지

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13x10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.

Spontaneous Bacterial Peritonitis in Patients with Hepatitis B Virus-Related Liver Cirrhosis: Community-Acquired versus Nosocomial

PURPOSE: Spontaneous bacterial peritonitis (SBP) frequently develops in patients with liver cirrhosis; however, there is little data to suggest whether the acquisition site of infection influences the prognosis. This study compared the bacteriology, clinical characteristics and treatment outcomes of community-acquired SBP (CA-SBP) and nosocomial SBP (N-SBP). MATERIALS AND METHODS: The medical records of 130 patients with hepatitis B virus (HBV)-related liver cirrhosis, who had experienced a first episode of SBP between January 1999 and December 2008, were reviewed. RESULTS: The study population included 111 (85.4%) patients with CA-SBP and 19 (14.6%) patients with N-SBP. Baseline and microbiological characteristics as well as clinical course, including in-hospital mortality, did not differ between patients with CA-SBP and those with N-SBP (all p>0.05). The median survival time was 6.5 months, and 117 (90.0%) patients died during the follow-up period. Patients with CA-SBP and N-SBP survived for median periods of 6.6 and 6.2 months, respectively, without significant difference (p=0.569). Time to recurrence did not differ between patients with CA-SBP and N-SBP (4.7 vs. 3.6 months, p=0.925). CONCLUSION: The acquisition site of infection did not affect clinical outcomes for patients with HBV-related liver cirrhosis who had experienced their first episode of SBP. Third-generation cephalosporins may be effective in empirically treating these patients, regardless of the acquisition site of the infection.

Clinical applications of transient elastography

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan(R)) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.

A Case of Esophageal Intramural Pseudodiverticulosis

Esophageal intramural pseudodiverticulosis (EIP) is a rare benign disease that is characterized by multiple tiny flask-shaped outpouching lesions of the esophageal wall. The etiology is unknown, but the pathologic findings include dilatation of excretory ducts of submucosal glands. The predominant symptom is dysphagia, and esophageal stricture occurs frequently. Diseases such as diabetes mellitus, esophageal candidiasis, gastroesophageal reflux disease, and chronic alcoholism are often combined. Since most EIP cases are benign, the mainstream treatment is symptom relief by endoscopic dilatation or medical treatment of accompanied diseases. This report describes the case of a 68-year-old male patient who suffered from chest tightness for 2 months and was diagnosed with EIP. This symptom disappeared after 2 months of medical treatment, and the patient is now being regularly followed up.

Risk Factors for Treatment Failure and Recurrence after Metronidazole Treatment for Clostridium difficile-associated Diarrhea

BACKGROUND/AIMS: The incidence of treatment failure or recurrence of Clostridium difficile-associated diarrhea (CDAD) following metronidazole treatment has increased recently. We studied the treatment failure, recurrence rate, and risk factors predictive of treatment failure and recurrence after metronidazole treatment for CDAD. METHODS: We retrospectively identified consecutive patients who were admitted and treated for CDAD at a single tertiary institution in Korea over a recent 10-year period (i.e., 1998-2008). RESULTS: Metronidazole was administered as the initial treatment to 111 of 117 patients (94.9%) with CDAD. Fourteen patients (12.6%) had no clinical response to the metronidazole treatment, and in 13 patients (13.4%) CDAD recurred after successful metronidazole treatment. Diabetes mellitus (p=0.014) and sepsis (p=0.002) were independent risk factors for metronidazole treatment failure. Patients who had received surgery within 1 month before CDAD developed were more likely to experience a recurrence after metronidazole treatment (p=0.032). Vancomycin exhibited a higher response rate after treatment failure, and metronidazole showed a reasonable response rate in the treatment of recurrence. Treatment failure and recurrence rates increased with time after metronidazole treatment for CDAD over the 10-year study period. CONCLUSIONS: Our data suggest that diabetes mellitus and sepsis are independent risk factors for metronidazole treatment failure, and that operation history within 1 month of development of CDAD is a predictor of a recurrence after metronidazole treatment.

Clinical Experience of Thalidomide in the Treatment of Korean Patients with Intestinal Behcet's Disease: Pilot Experience in a Single Center

Intestinal Behcet's disease (BD) often leads to severe complications, such as perforation or massive bleeding, and therefore is one of the major causes of morbidity and mortality. As thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified, this drug has been used in cases of systemic BD with some success. Herein we report a case series of four patients with intestinal BD to share our clinical experience with thalidomide treatment. We studied the effects of thalidomide in four patients who had a chronic relapse of intestinal BD requiring the frequent use of systemic steroids due to refractoriness to prior treatments, such as 5-aminosalycylic acid and immunosuppressants. Pre- and post-treatment clinical and laboratory data, including clinical symptoms, laboratory data, disease activity index for intestinal BD, and thalidomide toxicity were recorded. Three of the four patients had a clinical and radiologic improvement after thalidomide treatment and all of the patients discontinued steroid therapy. Although two patients tolerated thalidomide, two patients could not continue the treatment because they suffered from edema and neutropenia. Thalidomide could be considered a therapeutic option for the treatment of intestinal BD.

Clinical Experience of Thalidomide in the Treatment of Korean Patients with Intestinal Behcet's Disease: Pilot Experience in a Single Center

Intestinal Behcet's disease (BD) often leads to severe complications, such as perforation or massive bleeding, and therefore is one of the major causes of morbidity and mortality. As thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified, this drug has been used in cases of systemic BD with some success. Herein we report a case series of four patients with intestinal BD to share our clinical experience with thalidomide treatment. We studied the effects of thalidomide in four patients who had a chronic relapse of intestinal BD requiring the frequent use of systemic steroids due to refractoriness to prior treatments, such as 5-aminosalycylic acid and immunosuppressants. Pre- and post-treatment clinical and laboratory data, including clinical symptoms, laboratory data, disease activity index for intestinal BD, and thalidomide toxicity were recorded. Three of the four patients had a clinical and radiologic improvement after thalidomide treatment and all of the patients discontinued steroid therapy. Although two patients tolerated thalidomide, two patients could not continue the treatment because they suffered from edema and neutropenia. Thalidomide could be considered a therapeutic option for the treatment of intestinal BD.

Bilioptysis Caused by Bronchobiliary Fistula Secondary to Sclerosing Therapy of Liver Cyst / 결핵및호흡기질환

Bronchobiliary fistula is a rare disorder consisting of an abnormal communication between the bronchial tree and the biliary duct. In Western countries, trauma, postoperative biliary stenosis, and biliary lithiasis are the predominant causative factors of bronchobiliary fistula. Bilioptysis (bile stained sputum) is a pathognomic finding for bronchobiliary fistula. To date, there are just a few reported cases of bronchobiliary fistula after sclerosis of a liver cyst. We describe the case of a 74-year-old woman who developed bronchobiliary fistula after sclerosing therapy of a liver cyst. The diagnosis was confirmed by the presence of bilioptysis and the chest and dynamic liver CT findings. The patient was successfully treated with antibiotics and percutaneous transhepatic catheter drainage.

Colitis Cystica Profunda Masquerading as a Pneumatosis Cystoides Intestinalis: A Case Report

Colitis Cystica Profunda (CCP) is an uncommon and benign disease entity characterized by mucoid cysts located in the submucosal layer of the colon. It can mimic cystic submucosal tumors or mucinous adenocarcinoma and is usually located in the rectum. CCP is found in the ascending colon less frequently. CCP manifesting as multiple cystic tumors, similar to pneumatosis cystoides intestinalis, has not yet been reported. Recently, a case of CCP mimicking pneumatosis cystoides intestinalis in the ascending colon was treated. Here this case is reported and the literature reviewed.

Influence of synovial Joint Fluid of Rheumatic and Osteoarthritic on Chondrocyte in vitro / 대한정형외과연구학회지

PURPOSE: Earlier work suggested that two cytokines inhibit synthesis of type II collagen and of aggrecans by chondrocytes and they depress chondrocyte proliferation, but there was little report how the chondrocyte is modulated by culture conditions such as the joint fluids of the rheumatoid arthritis and that of the osteoarthritis. The purpose of this investigation was to determine whether RA(rheumatic arthritis) or OA(Osteoarthritis) joint fluid influence proliferation and differentiation in cultured human articular chondrocytes. MATERIALS AND METHODS: Human chondrocytes were cultured in a standard media (DMEM and 10% FBS), RA and OA joint fluid were added to media at the concentration of 20, 40 and 60% respectively for 1, 3 and 6days. 3H-thymidine and 3H-uridine uptake of cultured chondrocytes were measured as indicators of cell proliferation. Synthesis of human collagen type I, II was estimated by the RT-PCR procedures. RESULTS: 3H-thymidine uptake of the chondrocyte cultured in RA SF(synovial fluid) medium at 2 and 4 days; its uptake in the group treated by RA SF 20%, 40%, 60% increased more significantly than that in control group (P0.05). 3H-uridine uptake of the chondrocyte cultured in RA SF medium at 2 and 4 days; its uptake of the group treated by RA SF 20%, 40%, 60% increased more significantly than that of control group (P0.05). Human type I collagen mRNA expressions of the chondrocyte markedly increased in RA and OA SF mixed groups. Human type II collagen mRNA expressions of the chondrocyte were reduced in RA and OA SF mixed groups, especially RA SF 60% mixed groups. CONCLUSION: RA and OA SF increased the proliferation of the articular chondrocyte, but its decreased the differentiation of the chondrocyte. RA and OA SF may change the phenotype of the articular chondrocyte and this phenomenon was more outstanding in RA SF.

Sacrococcygeal Cystic Teratoma / 대한비뇨기과학회지

A case of sacrococcygeal cystic teratoma in a 16 month-old female infant having suffered from urinary retention and severe constipation for 3 days was herein reported. Confirmative diagnosis was possible by barium enema and contrast media injection into cystic mass located in the presacrococcygeal region. Successful removal of the cystic teratoma with the patient in a prone position was performed. Uneventful postoperative course followed.