Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.

BACKGROUND AND AIM: In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. METHODS: We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. RESULTS: Over a median 3.5 years of follow-up (range = 0.1-4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. CONCLUSIONS: In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Psychometric hepatic encephalopathy score for the detection of minimal hepatic encephalopathy in Korean patients with liver cirrhosis.

BACKGROUND AND AIM: Although the Psychometric Hepatic Encephalopathy Score (PHES) for the diagnosis of minimal hepatic encephalopathy (MHE) has been validated in several countries, further validation is required for its use in different populations. The aims of this study were thus to standardize the PHES in a healthy Korean population and evaluate the prevalence of MHE among Korean patients with liver cirrhosis. METHODS: Two-hundred healthy subjects without evidence of liver disease and 160 patients with liver cirrhosis without overt HE were included. Blood sampling for routine laboratory tests and determination of venous ammonia concentration was performed on the day of PHES neuropsychological testing. RESULTS: The age and education years of the control group were 41 ± 13 years and 13 ± 3 years, respectively; 100 of the subjects (50.0%) were men. The PHES for the control group was -0.31 ± 2.06 and the normal range was thus set at > -5 points. The age and education years of the liver cirrhosis group were 55 ± 8 and 11 ± 4 years, respectively; 102 of those in this group (63.8%) were men. Of the liver cirrhosis patients, 129 (80.6%), 21 (13.1%), and 10 (6.3%) had Child-Pugh grades A, B, and C, respectively. The PHES of the liver cirrhosis group was -2.94 ± 3.39. MHE was diagnosed in 41 patients (25.6%), of which 26 (20.2%), nine (42.9%), and six (60.0%) had Child-Pugh grades A, B, and C, respectively. CONCLUSIONS: The PHES was useful for detecting patients with MHE. A significant proportion of Korean patients with liver cirrhosis suffer from MHE.

Prognosis of hepatitis B-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents.

BACKGROUND AND AIM: We investigated long-term outcomes and prognostic factors in patients with hepatitis B virus (HBV)-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents. METHODS: Between January 1999 and February 2009, a total of 240 consecutive patients who had HBV-related cirrhosis without malignancy were treated with lamivudine and second line nucleos(t)ide analogs. The group of historical controls consisted of 481 consecutive patients with HBV-related cirrhosis who were managed without any antiviral treatment prior to 1999. RESULTS: In 78% of the patients who received antiviral treatment, sustained viral suppression (serum HBV DNA < 10(5) copies/mL) was achieved during a mean follow-up period of 46 months. The occurrences of death, hepatic decompensation, and hepatocellular carcinoma (HCC) were less frequent in the treated cohort than in untreated historical controls, with the 5-year cumulative incidences being 19.4% versus 43.9% (log-rank P < 0.001), 15.4% versus 45.4% (P = 0.001), and 13.8% versus 23.4% (P = 0.074), respectively. For patients who received antiviral treatment, suboptimal viral suppression (HBV DNA > 10(5) copies/mL at last follow-up) was an important independent risk factor of death (P < 0.001) and hepatic decompensation (P = 0.019), and was linked to an increased risk of HCC (P = 0.042). Although the Child-Pugh grade remained a useful prognostic factor, no significant differences were found between patients with Child-Pugh grade B and C cirrhosis at the beginning of antiviral treatment (P = 0.656). CONCLUSIONS: Oral antiviral agents have improved the prognosis of patients with HBV-related cirrhosis and affected the prognostic values of factors constituting the Child-Pugh system, necessitating a more efficient prognostic system.

Gastrectomy for the treatment of refractory gastric ulceration after radioembolization with 90Y microspheres.

Transcatheter arterial radioembolization (TARE) with Yttrium-90 ((90)Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE.

Computed tomography findings for predicting severe acute hepatitis with prolonged cholestasis.

AIM: To evaluate the significance of computed tomography (CT) findings in relation to liver chemistry and the clinical course of acute hepatitis. METHODS: Four hundred and twelve patients with acute hepatitis who underwent enhanced CT scanning were enrolled retrospectively. Imaging findings were analyzed for the following variables: gallbladder wall thickness (GWT), arterial heterogeneity, periportal tracking, number and maximum size of lymph nodes, presence of ascites, and size of spleen. The serum levels of alanine aminotransferase, alkaline phosphatase, bilirubin, albumin, and prothrombin time were measured on the day of admission and CT scan, and laboratory data were evaluated every 2-4 d for all subjects during hospitalization. RESULTS: The mean age of patients was 34.4 years, and the most common cause of hepatitis was hepatitis A virus (77.4%). The mean GWT was 5.2 mm. The number of patients who had findings of arterial heterogeneity, periportal tracking, lymph node enlargement > 7 mm, and ascites was 294 (80.1%), 348 (84.7%), 346 (84.5%), and 56 (13.6%), respectively. On multivariate logistic regression, male gender [odds ratio (OR) = 2.569, 95%CI: 1.477-4.469, P = 0.001], toxic hepatitis (OR = 3.531, 95%CI: 1.444-8.635, P = 0.006), level of albumin (OR = 2.154, 95%CI: 1.279-3.629, P = 0.004), and GWT (OR = 1.061, 95%CI: 1.015-1.110, P = 0.009) were independent predictive factors for severe hepatitis. The level of bilirubin (OR = 1.628, 95%CI: 1.331-1.991, P < 0.001) and GWT (OR = 1.172, 95%CI: 1.024-1.342, P = 0.021) were independent factors for prolonged cholestasis in multivariate analysis. CONCLUSION: In patients with acute hepatitis, GWT on CT scan was an independent predictor of severe hepatitis and prolonged cholestasis.

Spinal cord injury after conducting transcatheter arterial chemoembolization for costal metastasis of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.

Treatment strategies using adefovir dipivoxil for individuals with lamivudine-resistant chronic hepatitis B.

AIM: To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil (adefovir) in patients with lamivudine-resistant chronic hepatitis B. METHODS: We included 154 consecutive patients in two treatment groups: the "add-on" group (n = 79), in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance, and the "switch/combination" group (n = 75), in which lamivudine was first switched to adefovir and then re-added later as needed. The "switch/combination" group was then divided into two subgroups depending on whether participants followed (group A, n = 30) or violated (group B, n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus (HBV) DNA levels (< 60 IU/mL or not) after 6 mo of treatment (roadmap concept). RESULTS: The cumulative probability of virologic response (HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B (P < 0.001). In contrast, the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B (P = 0.002). Furthermore, the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A (hazard ratio = 0.096; 95%CI, 0.015-0.629; P = 0.015). CONCLUSION: The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.

Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A patients with a negative initial test.

BACKGROUND/AIMS: The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test. METHODS: In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was ≥400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected. RESULTS: The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (ß=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day. CONCLUSIONS: The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.

Solitary primary gastric mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a relatively rare subgroup of non-Hodgkin's lymphoma that is characterized by an aggressive and severe disease course with frequent involvement of regional lymph nodes and/or early metastasis. Because most cases of MCL are diagnosed in the advanced stages, clinical data on extranodal or early stage MCL is lacking, and MCL that is both extranodal and diagnosed during the early stages is even more rare. There have been several case reports on primary gastric MCL, which comprise a type of extranodal MCLs. However, to our knowledge, there have been no reports on solitary primary gastric MCL without regional lymph node involvement or distant metastasis. Recently, the authors experienced an uncommon case of MCL with the aforementioned characteristics that was managed with chemotherapy followed by allogenic stem cell transplantation.

Two cases of incidentally diagnosed idiopathic left atrial appendage ostial stenosis.

We report here on 2 cases of idiopathic left atrial appendage ostial stenosis (LAA), and this rare finding was detected on transesophageal echocardiography. Its clinical implication is still unknown, given the small number of reported cases. Incompletely ligated LAA has characteristics similar to those observed in idiopathic LAA ostial stenosis, including the narrowed orifice, the small LAA cavity and the accelerated blood flow across the stenotic area. Since the incompletely ligated LAA has been reported to be complicated with thromboembolic events, we can assumed that the patients with idiopathic LAA ostial stenosis have a higher risk of thromboembolism than those with a normal LAA structure.