Risk Factors for Asymptomatic Colon Diverticulosis.

BACKGROUNDS/AIMS: The etiology of colon diverticulosis is related to a range of genetic, biological, and environmental factors, but the risk factors for asymptomatic diverticulosis of the colon are unclear. This study examined the risk factors for asymptomatic colon diverticulosis. METHODS: This retrospective study included examinees who underwent a colonoscopy for screening at the health check-up center of SAM Hospital between January 2016 and December 2016. The examinees with colon diverticulosis found by colonoscopy were compared with those without diverticulosis. The comparison factors were age, gender, alcohol consumption, smoking status, medical history, lipid profile, body mass index, visceral fat area, waist-hip ratio, and severity of a fatty liver. RESULTS: This study included 937 examinees and the overall prevalence of diverticulosis was 8.1% (76/937). Fatty liver was found in 69.7% (53/76) in cases of colon diverticulosis and 50.3% (433/861) in the control group (p=0.001). The average waist-hip ratio was 0.92±0.051 in colon diverticulosis and 0.90±0.052 in the control group (p=0.052). Multivariate analysis revealed the waist-hip ratio (OR=1.035, 95% CI 1.000-1.070, p=0.043), moderate fatty liver (OR=2.238, 95% CI 1.026-4.882, p=0.043), and severe fatty liver (OR=5.519, 95% CI 1.236-21.803, p=0.025) to be associated with an increased risk of asymptomatic colon diverticulosis. CONCLUSIONS: The waist-hip ratio, moderate fatty liver, and severe fatty liver are risk factors for asymptomatic colon diverticulosis. Central obesity, which can be estimated by the waist-hip ratio, and fatty liver might affect the pathogenesis of asymptomatic colon diverticulosis.

Aspartate Aminotransferase-to-Platelet Ratio or Fibros-4 Index Predicts the Development of Hepatocellular Carcinoma in Chronic Hepatitis C Patients with Sustained Virologic Response to Interferon Therapy.

The risk of hepatocellular carcinoma (HCC) is not completely eliminated in chronic hepatitis C (CHC) patients even after viral eradication. There are few studies in predicting the development of HCC using biomarker in CHC patients with sustained virologic response (SVR). We evaluated the role of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) in predicting HCC development in 295 patients with SVR after interferon therapy. The annual incidence of HCC was 0.55% (95% confidence interval: 0.31-0.96). It was higher in patients with a pretreatment APRI ≥2.0 than in those with an APRI <2.0 (1.82% versus 0.17%; P = 0.0001) and in patients with a FIB-4 ≥ 3.25 compared with those with a FIB-4 < 3.25. (1.50% versus 0.07%; P = 0.0001). The annual incidence of HCC was higher in patients with a post-treatment APRI ≥0.5 than in those with an APRI <0.5 (1.67% versus 0.07%; P < 0.0001) and in patients with a post-treatment FIB-4 ≥ 2.5 compared with those with a FIB-4 < 2.5 (1.49% versus 0.01%; P = 0.0003). Among pretreatment variables, male gender, albumin, APRI, or FIB-4 were independent predictors for HCC. Among post-treatment variables, APRI or FIB-4 was an independent predictor for HCC. HCC surveillance should be performed in these high-risk patients.

Increased Osteoblastic Activity Suppressed Proliferation of Multiple Myeloma Plasma Cells.

STUDY DESIGN: In vitro experimental study. OBJECTIVE: To investigate the impact of increased osteoblastic activity on the proliferation and survival of multiple myeloma (MM) plasma cells in vitro SUMMARY OF BACKGROUND DATA.: MM is one of representative hematologic malignancies that cause skeletal-related events (SREs) and dysregulation of bone remodeling is known as a key pathomechanism of disease progression and skeletal-related events. However, decreased proliferation of MM at fracture sites is frequently noted in clinical situations regardless of systemic disease activity. METHODS: Co-culture under various conditions was used to investigate effects of increased osteoblastic activity on survival and proliferation of MM plasma cells. MM plasma cells were cultured in culture media (control) and co-cultured with human mesenchymal stem cells (hMSCs, group I), osteoblasts (OBs) induced from hMSCs (group II) or bone morphogenic protein-2 (BMP-2, group III). Proliferation measured as extracellular signal-regulated kinase (ERK) and immunoglobulin G (Ig G) expression and apoptosis measured as fluorescence-activated cell sorting (FACS) with annexin V method, caspase-3, and stat-3 expression were assessed for cultured MM plasma cells, along with expression of sclerostin. RESULTS: After 72 hours of co-culture, group II and III showed decreased ERK expression compared with controls. Lower Ig G expression was also noted for groups II and III compared with controls. Group I did not show significantly decreased Ig G and ERK expression compared with controls. Expressions of caspase-3 in groups II and III were higher than controls. Co-culture with hMSCs showed decreased caspase-3 expression compared with control. FACS with annexin V showed higher apoptosis in groups II and III. Sclerostin expression was also decreased in osteoblastic conditions compared with the control and hMSCs co-culture condition. CONCLUSION: Collectively, our data suggest that increased osteoblastic conditions may provide not only prevention of SREs but also anti-tumor effects on MM cells in the bone marrow environment. LEVEL OF EVIDENCE: N/A.

Induction of Endogenous Neural Stem Cells By Extracorporeal Shock Waves After Spinal Cord Injury.

STUDY DESIGN: Animal experimental study OBJECTIVES.: The purpose of this study is to investigate the effects of extracorporeal shock waves (ESWs) on endogenous neural stem cells (NSCs) proliferation after spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Exogenous stem cell transplantation for SCI still has many limitations to be addressed such as ideal cell sources, timing of transplantation, and fate of the transplanted cells. Moreover, the efficacy is another issue owing to a peculiar pathologic condition in the chronic phase of SCI. METHODS: Contusive SCI was made using 24 Sprague-Dawley rats, and ESWs were applied at post-injury 4 weeks in rats. Proliferation and differentiation of endogenous NSCs (DCX, Sox-2) and axonal sprouting (GAP-43 and MAP-2) were observed at 6 weeks after application of ESWs. Differentiation of the activated neural stem cells was also investigated by coexpression of neuronal/glial cell markers (GFAP, Neu N, and CC-1). Immunofluorescence staining and western blotting were performed for quantitative analysis, and these results were compared with those in the control group. For clinical assessment, the BBB locomotor rating scale was performed. RESULTS: More proliferation of endogenous neural stem cells was noted in the experimental groups, and these activated cells were mainly founded in the ependymal layer of the central canal and the injured posterior horn. Differentiation into neuronal and glial cells was also noted in a limited number of cells. With respect to axonal regeneration, GAP-43 and MAP-2 expressions in the experimental groups were also significantly higher than those in the control group. During 6 weeks' clinical observation following ESWs application, functional improvement of the hindlimb was observed without clinical deterioration by trials. CONCLUSION: Collectively, these findings indicate that ESWs on the chronic phase of SCI induce activation of endogenous NSCs and consequent functional improvement. LEVEL OF EVIDENCE: N/A.

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis.

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.

Erratum.

[This corrects the article on p. 355 in vol. 20, PMID: 25548741.][This corrects the article on p. 368 in vol. 20, PMID: 25548743.].

Influence of the basal core promoter and precore mutation on replication of hepatitis B virus and antiviral susceptibility of different genotypes.

Mutations in the basal core promoter (BCP) and precore (PC) regions of the hepatitis B virus (HBV) are more common in genotypes B and C than in genotype A, suggesting that these mutations might affect replication competency depending on genotype. The purpose of the study was to investigate the influence of these mutations on the capacity of HBV for replication and antiviral drug susceptibility according to genotype. Genotypes A, B, and C of HBV strains with a BCP mutation, PC mutation, or BCP + PC mutation were made by site-directed mutagenesis. Replication competency of each construct and susceptibility to nucleos(t) ide analogues were tested in an Huh7 cell line. In genotype A, the BCP and BCP + PC mutations increased the viral replication around 6.5 times compared with the wild type, and the PC mutation alone similarly increased the viral replication around three times. In genotypes B and C, all three mutant types increased viral replication to a similar extent, regardless of mutation pattern. Interestingly, the BCP mutation appeared to have a greater effect on viral replication in genotype A than in genotypes B and C. This finding was unexpected because the BCP mutation is more common in HBV genotypes B and C. Moreover, the BCP, PC, and BCP + PC mutations decreased the sensitivity of HBV to antiviral agents to various degrees (2- to 10-fold) regardless of genotype. In conclusion, BCP and PC mutations increased viral replication regardless of HBV genotype and decreased in vitro antiviral susceptibility to the nucleos(t) ide analogues.

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

BACKGROUND/AIMS: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. METHODS: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. RESULTS: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥ 5.1 × 10(7) IU/mL and ALT ≥ 5 × ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. CONCLUSIONS: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.

Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection.

BACKGROUND/AIMS: This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥ 12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. METHODS: Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. RESULTS: HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥ 2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. CONCLUSIONS: Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥ 2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.

Different mechanism of selection of adefovir-resistant mutant viruses during adefovir monotherapy in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND: Adefovir (ADV) resistance is more frequent in lamivudine (LMV)-resistant chronic hepatitis B (CHB) patients than in nucleos(t)ide analogue-naïve patients. The majority of LMV-resistant mutants harbor the rtM204V/I mutation, while a minor fraction harbor the rtA181V/T mutation. We aimed to elucidate the mechanism of the high rate of ADV resistance in LMV-resistant patients during ADV therapy. METHODS: We performed a clonal analysis of HBV reverse transcriptase in treatment-naïve (n = 3) and LMV-resistant patients before ADV therapy (n = 14). Dynamic changes in the viral population (n = 9) during ADV therapy were also analyzed. RESULTS: Before ADV therapy, rtA181V/T was observed in 30 of 680 clones (4.4%) from 7 patients with LMV resistance under dominant rt204V/I mutation and in one of 150 clones in treatment-naïve patients. The rtA181V/T mutation was more frequently found in clones from LMV-resistant patients than in treatment-naïve patients (p = 0.029). The rtN236T mutation was not observed in any clone. During ADV therapy, most rtM204V/I mutants were replaced by wild type in all 3 patients without the rtA181V/T mutation and in one patient with the rtA181V/T mutation. Subsequently, wild type was replaced by the rtN236T and/or rtA181V/T mutant. In patients with the rtA181V/T mutation (n = 6), the rtA181V/T mutant overtook the rtM204V/I mutant in 3 of 4 patients with ADV resistance. In 2 patients without ADV resistance, most of the viral population was replaced by wild type by the last follow-up. CONCLUSION: The high rate of ADV resistance in patients with LMV-resistance might be attributable to preexisting rtA181V/T mutant virus.

Effect of pronase premedication on narrow-band imaging endoscopy in patients with precancerous conditions of stomach.

BACKGROUND: Narrow-band imaging (NBI) endoscopy improves the detection of intestinal metaplasia. However, strategies to improve the visibility and diagnostic performance of NBI should be sought, as endoscopic views are often obscured by the presence of mucus. AIM: To compare the visibility and diagnostic performance of NBI endoscopy according to pronase premedication in patients with precancerous conditions of the stomach. METHODS: Consecutive outpatients with a previous diagnosis of precancerous condition of the stomach were invited to undergo a surveillance NBI endoscopy between June and December 2012. Enrolled subjects were randomly assigned to pronase or control groups before NBI endoscopy. The visibility score and diagnostic performance of NBI endoscopy were compared between the two groups. RESULTS: Patients' endoscopic and histopathological characteristics were similar between the two groups. Visibility score in the proximal part of the stomach and satisfaction score of the endoscopist were significantly higher in the pronase group than in the control group (p = 0.014 and p = 0.034, respectively). The diagnostic performance of NBI endoscopy to detect intestinal metaplasia was not different in either group (both p > 0.1). However, the negative predictive value of NBI endoscopy was much improved over that of white light endoscopy only in the pronase group (p = 0.013). CONCLUSION: Pronase premedication increased the visibility of the proximal part of the stomach and the satisfaction score during NBI endoscopy. Furthermore, negative predictive value of NBI endoscopy was much improved compared with that of white light endoscopy after pronase premedication.

Small cell carcinoma of the liver and biliary tract without jaundice.

An 80-year-old woman presenting with chest pain was found to have a large, lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography (CT). The tumor had invaded the common hepatic artery and main portal vein. Jaundice developed 4 wk later, at which point, a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction, which was found to be a small cell carcinoma. Despite its rarity, liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.

[A case of acute pancreatitis and acute hepatitis caused by ingestion of Ceramium kondoi].

In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoifor 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement.

[Clarithromycin-resistant Helicobacter pylori associated with 23S rRNA point mutations in Jeju Island].

BACKGROUND/AIMS: The point mutations in 23S rRNA gene accounts for the majority of the clarithromycin resistance of Helicobacter pylori. This study aimed to investigate the association between the clarithromycin-resistance of H. pylori and the failure of primary H. pylori eradication therapy in Jeju Island. METHODS: Between April 2011 and October 2012, 6,937 patients underwent endoscopy, and H. pylori infection was evaluated in 2,287 patients (33.0%). Total of 110 patients with H. pylori infection were treated with proton pump inhibitor (PPI)-based triple therapy. The result of eradication was evaluated with urea breath test, histology and PCR which were conducted 4 weeks from the last dose of medicine. RESULTS: The patients who had point mutations were 33 (26.0%). A2142G and A2143G mutations were observed in 10 patients (7.9%) and 23 patients (18.1%). Among 110 patients treated with PPI-based triple therapy, the success rate of the eradication therapy was 52.7% (58/110) and 70.7% (58/82) by intention-to-treat and per-protocol analysis, respectively. Fifteen of the 24 patients who failed the eradication therapy showed point mutations; 1 patient (4.2%) showed A2142G mutation and 14 patients (58.3%) showed A2143G mutation. Patients with A2143G mutation H. pylori showed higher failure rate of 87.5%. Patients with A2142G mutation H. pylori showed similar failure rate compared to those of the patients with wild type H. pylori. CONCLUSIONS: In Jeju Island, the frequency of 23S rRNA point mutations is similar (26.0%) with other regions of Korea (15.8-31.3%). A2143G mutation is associated with the failure of H. pylori eradication.

Comparison of the clinical characteristics of patients with small bowel and gastric anisakiasis in jeju island.

BACKGROUND/AIMS: Anisakiasis is frequent in Jeju Island because of the people's habit of ingesting raw fish. This study evaluated the clinical characteristics of patients with small bowel anisakiasis and compared them with those of patients with gastric anisakiasis. METHODS: We retrospectively reviewed the medical records of 109 patients diagnosed with anisakiasis between May 2003 and November 2011. RESULTS: Of the 109 patients diagnosed with anisakiasis, those with suspicious anisakiasis (n=38) or possible anisakiasis (n=12) were excluded. The age and gender distributions did not differ between patients with small bowel anisakiasis (n=30; age, 45±13 years) and those with gastric anisakiasis (n=29; age, 46±10 years). The mean duration of hospitalization was 5.4±4.3 days for patients with small bowel anisakiasis and 0.5±1.7 days for patients with gastric anisakiasis. Small bowel anisakiasis was accompanied by leukocytosis (76.7% vs 25.5%, p=0.003) and elevated C-reactive protein levels (3.4±3.2 mg/dL vs 0.5±0.3 mg/dL, p=0.009). Contrast-enhanced abdominopelvic computed tomography showed small bowel wall thickening with dilatation in 93.3% (28/30) of patients and a small amount of ascites in 80.0% (24/30) of patients with small bowel anisakiasis. CONCLUSIONS: Compared with gastric anisakiasis patients, small bowel anisakiasis patients had a longer hospitalization time, higher inflammatory marker levels, and small bowel wall thickening with ascites.

Massive life-threatening lower gastrointestinal hemorrhage caused by an internal hemorrhoid in a patient receiving antiplatelet therapy: a case report.

A Dieulafoy lesion in the rectum is a very rare and it can cause massive lower gastrointestinal bleeding. An 83-year-old man visited our hospital. He had chronic constipation and had taken aspirin for about 10 years because of a previous brain infarction. He was admitted because of a recent brain stroke. On the third hospital day, he had massive hematochezia and suddenly developed hypovolemic shock. Abdominal computed tomography showed active arterial bleeding on the left side of the mid-rectum. Emergency sigmoidoscopy showed an exposed vessel with blood spurting from the rectal wall. The active bleeding was controlled successfully by an injection of epinephrine and two hemoclippings. On the fourth day after the procedure, he had massive recurrent hematochezia, and his vital signs were unstable. Doppler-guided hemorrhoidal artery band ligation was performed urgently at two sites. However, he rebled on the third postoperative day. Selective inferior mesenteric angiography revealed an arterial pseudoaneurysm in a branch of the superior rectal artery, as the cause of rectal bleeding, and this was embolized successfully. We report a rare case of life-threatening rectal bleeding caused by a Dieulafoy lesion combined with pseudoaneurysm of the superior rectal artery which was treated successfully with embolization.

[New insight for HBV DNA and HBsAg quantitation during antiviral therapy in patients with chronic hepatitis B].

Over the past decade, advances in the antiviral therapy in patients with chronic hepatitis B have enabled the sustained suppression of hepatitis B viral replication and the prevention of progressive liver disease. Hepatitis B surface antigen (HBsAg) has been used to diagnose patients with hepatitis B virus infection. Recently, test for quantitative HBsAg titers are available and on-treatment HBsAg quantitations are used to predict treatment outcome. Serum HBV DNA levels have been shown to predict natural course of chronic hepatitis B infection. The HBV DNA levels have been reported to be positively correlated with the development of cirrhosis, hepatocellular carcinoma and related death. The baseline and on-treatment levels of HBV DNA are important factors for predicting treatment outcomes. In this article, we will discuss the role of HBV DNA and HBsAg quantitation during antiviral therapy.

Gender disparity in distribution of the major hydrophilic region variants of hepatitis B virus genotype C according to hepatitis B e antigen serostatus.

Hepatitis B virus (HBV) e antigen (HBeAg) seroconversion during chronic HBV infection is known to play an important role in disease progression and patient response to antiviral agents. The aim of the present study was to analyze gender disparity in distribution of major hydrophilic region (MHR) variants according to HBeAg serostatus. Prevalence of MHR variants from 68 Korean patients with chronic hepatitis (31 HBeAg-positive and 37 HBeAg-negative) was examined in terms of HBeAg serostatus and sex by direct sequencing analysis of the MHR. Gender disparity was observed in the distribution of MHR variants according to HBeAg serostatus. In male patients, the prevalence of MHR variants was significantly higher in HBeAg negative patients than in HBeAg positive patients [58.8% (10/17 patients) vs. 14.3% (3/21 patients), P=0.004]. However, the same was not true in female patients [55.0% (11/20 patients) vs. 60.0% (6/10 patients), P=1.000)]. In addition, 2 mutation types (L110I and G145A) related to HBeAg serostatus were found. In conclusion, HBeAg seroconversion in male chronic patients infected with genotype C could lead to mutations of MHR, major target to host immune response, which might in turn contribute to HBV persistence and immune evasion.

Response to adefovir depends on mutation patterns in precore region, basal core promoter and reverse transcriptase, and on-treatment responses in Lamivudine-resistant chronic hepatitis B patients.

OBJECTIVE: In vitro studies showed that mutations in the basal core promoter (BCP) or precore (PC) region restore the replication inefficiency of the lamivudine-resistant mutant. The aim of this study was to clarify the effect of molecular characteristics on the antiviral response to adefovir in patients with lamivudine-resistant chronic hepatitis B (CHB). METHODS: Sixty-six lamivudine-resistant patients who were treated with adefovir monotherapy were studied. Sequences of BCP, PC region and reverse transcriptase were determined before adefovir therapy. In patients with virologic breakthrough, reverse transcriptase sequencing was performed. RESULTS: The cumulative probabilities of virologic response were 23.3, 46, 52.7 and 59.5% at years 1, 2, 3 and 4, respectively. PC mutation, the absence of compensatory mutations (rtL80I/V or rtV173L), and a decrease in serum hepatitis B virus (HBV) DNA by 3 log or greater at 6 months were independent predictors of virologic response. The cumulative probabilities of virologic breakthrough were 0, 12.9, 30.7 and 44.5% at years 1, 2, 3 and 4, respectively. BCP mutation and a less than 3 log decrease in serum HBV DNA at 6 months were 2 independent risk factors for virologic breakthrough. CONCLUSION: Response to adefovir depends on mutation patterns in the BCP, PC region and reverse transcriptase, and on-treatment decreases in serum HBV DNA in lamivudine-resistant CHB patients.