Hana Park

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir.

Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment‐naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen–positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04‐9.11 copies/mL), 3.58 IU/mL (1.17‐5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (−0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(−) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on‐treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (Hepatology 2011;)

Normal liver elasticity values using acoustic radiation force impulse imaging: A prospective study in healthy living liver and kidney donors

Background and Aim:  Although several studies have investigated the normal range of liver elasticity using acoustic radiation force impulse (ARFI) elastography in healthy volunteers, they could not strictly exclude the morphological and functional liver abnormalities. The aim of this study was to identify the normal range of ARFI velocity by recruiting healthy living liver and kidney donors who passed the full laboratory tests and imaging studies.

Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial.

Bone marrow‐derived mesenchymal stem cell (BM‐MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM‐MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy‐two patients with baseline biopsy‐proven alcoholic cirrhosis who had been alcohol‐abstinent for more than 6 months underwent a multicenter, randomized, open‐label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM‐MSC groups that underwent either one‐time or two‐time hepatic arterial injections of 5 × 107 BM‐MSCs 30 days after BM aspiration. A follow‐up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child‐Pugh score, and Model for End‐stage Liver Disease score. Outcomes were analyzed by per‐protocol analysis. In terms of fibrosis quantification (before versus after), the one‐time and two‐time BM‐MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two‐time BM‐MSC transplantation in comparison with one‐time BM‐MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child‐Pugh scores of both BM‐MSC groups (one‐time 7.6 ± 1.0 versus 6.3 ± 1.3 and two‐time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM‐MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM‐MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185‐2197)

Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicentre, retrospective study

Transient elastography (TE) has become an alternative to liver biopsy (LB). This study investigated the diagnostic performance of liver stiffness (LS) measurement using TE in Korean patients with chronic hepatitis B and C (CHB and CHC).

Predictive value of HBsAg quantification for determining the clinical course of genotype C HBeAg-negative carriers

Hepatitis B virus surface antigen (HBsAg) quantification has been suggested to discriminate inactive carriers from hepatitis e antigen (HBeAg) negative chronic hepatitis, but it could be genotype‐dependent. We studied the predictive value of HBsAg quantification in genotype C HBeAg‐negative hepatitis B virus (HBV) carriers.

Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis

Objective Foxp3+CD4+CD25+ regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. Design The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry. Results The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis. Conclusions The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.

Hepatocellular carcinoma in Budd-Chiari syndrome: A single center experience with long-term follow-up in South Korea

AIM To evaluate long-term clinical course of Budd-Chiari syndrome (BCS) and predictive factors associated with the development of hepatocellular carcinoma (HCC) and survival. METHODS We analyzed 67 patients with BCS between June 1988 and May 2008. The diagnosis of BCS was confirmed by hepatic venous outflow obstruction shown on abdominal ultrasound sonography, computed tomography, magnetic resonance imaging, or venography. The median follow-up period was 103 ± 156 [interquartile range (IQR)] mo. RESULTS The median age of the patients was 47 ± 16 (IQR) years. At diagnosis, 54 patients had cirrhosis, 25 (37.3%) Child-Pugh class A, 23 (34.3%) Child-Pugh class B, and six (9.0%) patients Child-Pugh class C. During the follow-up period, HCC was developed in 17 patients, and the annual incidence of HCC in patients with BCS was 2.8%. Patients in HCC group (n = 17) had higher hepatic venous pressure gradient (HVPG) than those in non-HCC group (n = 50) (21 ± 12 mmHg vs 14 ± 7 mmHg, P = 0.019). The survival rate of BCS patients was 86.2% for 5 years, 73.8% for 10 years, and 61.2% for 15 years. In patients with BCS and HCC, survival was 79% for 5 years, 43.1% for 10 years, and 21.5% for 15 years. CONCLUSION The incidence of HCC in patients with BCS was similar to that in patients with other etiologic cirrhosis in South Korea. The HVPG is expected to provide additional information for predicting HCC development in BCS patients.

Clinicopathological Characteristics in Combined Hepatocellular-Cholangiocarcinoma: A Single Center Study in Korea

Purpose Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of cancer, and its clinicopathological features have rarely been reported in detail. This study was undertaken to evaluate the clinicopathological characteristics and prognostic factors of CHCC. Materials and Methods The clinicopathological features of patients diagnosed with CHCC at Severance Hospital between January 1996 and December 2007 were retrospectively studied by comparing them with the features of patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) who had undergone a hepatic resection during the same period. Results Forty-three patients diagnosed with CHCC were included in this study (M : F=35 : 8, median age, 55 years). According to the parameters of the American Joint Committee on Cancer staging, there were 6 (14.0%), 9 (20.9%), 25 (58.1%), and 3 (7.0%) patients with stages I, II, III, and IV cancer, respectively. Thirty-two of the 43 patients underwent resection with curative intent. After resection, 27 patients (84.4%) had tumor recurrence during the follow-up period of 18 months (range: 6-106 months), and the median time to recurrence was 13 months. Overall median survival periods after hepatic resection of CHCC, HCC and CC were 34, 103 and 38.9 months, respectively (p<0.001). The median overall survival for all patients with CHCC was 21 months, and the 5-year survival rate was 18.1%. The presence of portal vein thrombosis and distant metastasis were independent prognostic factors of poor survival. Conclusion Even after curative hepatic resection, the presence of a cholangiocellular component appeared to be a poor prognostic indicator in patients with primary liver cancer.

Discrimination of Nonalcoholic Steatohepatitis Using Transient Elastography in Patients with Nonalcoholic Fatty Liver Disease

Background/aims The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). Methods The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. Results The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P<0.001) and fibrosis (r = 0.714, P<0.001), respectively. The optimal cut-off values for steatosis were 247 dB/m for S1, 280 dB/m for S2, and 300 dB/m for S3. Based on the independent predictors derived from multivariate analysis [P = 0.044, odds ratio (OR) 4.133, 95% confidence interval (CI) 1.037–16.470 for CAP>250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295–8.291 for LS>7.0 kPa; and P<0.001, OR 7.557, 95% CI 2.997–19.059 for Alanine aminotransferase>60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724–0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740–0.893). Conclusion This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation.

Optimal Time for Restoring the Reliability of Liver Stiffness Measurement in Patients With Chronic Hepatitis B Experiencing Acute Exacerbation

Background/aims: Liver stiffness measurement (LSM) using transient elastography (FibroScan) is influenced by major changes in aminotransferase. We aimed to determine the optimal time for restoring the reliability of LSM for assessing liver fibrosis in patients with chronic hepatitis B experiencing acute exacerbation. Methods: Twenty-one patients with acute exacerbation of chronic hepatitis B [alanine aminotransferase (ALT)>5× upper limit of normal (ULN)] were prospectively recruited. Serial LSM and biochemical tests were performed at the time of admission and after 1, 3, 6, 9, and 12 months. The ULN of ALT was defined as 40 IU/L. The cutoff LSM value for cirrhosis was defined as 10.3 kPa. Results: The median age (9 male) was 49 years. The median ALT and LSM in the baseline were 522 IU/L and 15.1 kPa, respectively. Three months after acute exacerbation, ALT had decreased significantly below 2× ULN and stabilized (median: 522, 43, 21, 19, 18, and 16 IU/L at baseline, 1, 3, 6, 9, and 12 mo, respectively). However, LSM needed 3 more months (6 mo after exacerbation) for stabilization (median: 15.1, 10.0, 7.4, 7.1, 6.3, and 5.8 kPa at baseline, 1, 3, 6, 9, and 12 mo, respectively). Conclusions: LSM should be postponed for at least 3 months after stabilization of ALT below 2× ULN to restore the reliability of LSM in assessing liver fibrosis.