Publications by authors named "Hidehiro Kamezaki"

15 Publications

  • Page 1 of 1

[Current state of hepatocellular carcinoma surveillance for chronic liver disease in 91 cases of primary hepatocellular carcinoma].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(1):55-60

Department of Gastroenterology, Eastern Chiba Medical Center.

We retrospectively evaluated the effect of follow-up for chronic liver disease in 91 patients with primary hepatocellular carcinoma. Of these patients, 38 (41.8%) were followed-up for chronic liver disease, while 53 patients (58.2%) were not followed-up. Regarding the baseline status of the liver, the proportion of patients with non-viral hepatitis was significantly higher among patients who were not followed-up (p<0.001). Furthermore, the cumulative survival rate was significantly lower among patients who were not followed-up (p=0.013). Among the 53 patients who were not followed-up, 20 (37.7%) patients did not undergo abdominal imaging for hepatic evaluation despite recorded hepatic issues, and 31 patients (58.5%) were treated by a primary care doctor. Our study suggests that the identification of patients with non-viral hepatitis and confirmation that they are followed-up are vital for improving the prognosis of patients with chronic liver disease.
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http://dx.doi.org/10.11405/nisshoshi.118.55DOI Listing
January 2021

Safety and Efficacy of Early Tube Removal Following Percutaneous Transhepatic Gallbladder Drainage: an Observational Study.

Surg Laparosc Endosc Percutan Tech 2020 Apr;30(2):164-168

Department of Gastroenterology, Graduate School of Medicine, Chiba University Hospital, Chiba Prefecture.

Background: There are currently no guidelines concerning the advisability and timing of tube removal following percutaneous transhepatic gallbladder drainage (PTGBD). The present study aimed to assess the feasibility and risks of early removal of the PTGBD tube under the scenario of subsiding inflammation, patent cystic and common bile ducts, and absence of intraperitoneal leakage.

Methods: Patient background and outcomes were assessed retrospectively in 701 cases of acute cholecystitis treated with PTGBD. The median times until tube removal and tube dislodgement and the cumulative rates of tube dislodgement were calculated.

Results: Tube removal was performed in 275 patients after a median time of 16 days (range: 6 to 213 d); biliary peritonitis was observed in 2 patients following tube removal. Tubes were removed in 8 and 35 patients within 7 and 10 days, respectively. Tube dislodgement was observed in 82 patients after a median time of 12 days (range: 1 to 125 d).

Conclusion: The present study suggests that drainage tube removal is safe and effective when performed after a short drainage period of 7 to 10 days if the criteria for the removal of the drainage tube were met.
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http://dx.doi.org/10.1097/SLE.0000000000000761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147403PMC
April 2020

Suspicion of superior mesenteric artery syndrome in a patient with severe gastric dilatation after catheter ablation.

Intern Med 2015 15;54(6):605-9. Epub 2015 Jan 15.

Department of Gastroenterology, Kimitsu Chuo Hospital, Japan; Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Japan.

Catheter ablation is a widely used treatment for atrial fibrillation. Gastric hypomotility due to periesophageal vagal plexus injury is a consequence of the extracardiac penetration of ablative energy. Some affected patients develop severe gastric dilatation requiring hospitalization. However, most previous reports have stated the cause of the subject's condition to be "unknown" or described the symptoms using obscure terms, such as "paralytic" or "gastroparesis." For example, one report stated that a few sites of severe gastric dilatation were secondary to "pyloric spasms;" however, no illustrations were provided in the paper. "Superior mesenteric artery syndrome" is a suspected cause of such dilatation.
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http://dx.doi.org/10.2169/internalmedicine.54.3276DOI Listing
September 2015

The potential of transabdominal 3D color doppler ultrasonography for diagnosis of gastric varices.

J Clin Gastroenterol 2014 Aug;48(7):629-34

Department of Gastroenterology and Hepatology, Chiba University Graduate School of Medicine, Chiba, Japan.

Goals/background: To examine the potential of transabdominal 3-dimensional (3D) color Doppler ultrasonography (3D-US) as a noninvasive tool to characterize gastric varices.

Study: This was a prospective study in which endoscopy was performed on 107 patients with chronic liver disease. Among these patients, 70 (42 males, 28 females) had gastric varices (46 fundal varices, 24 cardia varices; 30 small, 28 medium, and 12 large), and the 37 patients (25 males, 12 females) without gastric varices served as controls. The 3D-US data and endoscopic findings were compared with respect to grade, location, and similarity of varices.

Results: The sensitivity and specificity of the 3D-US technique to detect gastric varices were 88.6% (62/70) and 100% (37/37), respectively. Although all fundal varices appeared adjacent to the posterior gastric wall, cardia varices were detected separately from the wall with a mean distance of 21.2 mm. The vascular volumes (mL) were 0.84±0.71 in small varices, 5.52±3.81 in medium varices, and 10.9±6.3 in large varices, with significant differences between different grades. The best cutoff value to detect medium-grade/large-grade gastric varices was 2.0 mL, with 83.3% sensitivity and 95.8% specificity. Seventy-nine percent (55/70) of patients showed partial resemblance or better between the 3D images and the endoscopic findings with good interreviewer agreement.

Conclusions: 3D-US can quantitatively characterize gastric varices noninvasively in terms of grade, location, and appearance. This approach has the potential to improve objectivity and reduce invasiveness in the management of gastric varices.
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http://dx.doi.org/10.1097/MCG.0b013e3182a47a1cDOI Listing
August 2014

Effects of inferior mesenteric vein flow in patients with cirrhosis.

Clin Gastroenterol Hepatol 2013 Dec 20;11(12):1648-54. Epub 2013 Jul 20.

Department of Gastroenterology and Hepatology, Chiba University Graduate School of Medicine, Inohana, Chuou-ku, Chiba, Japan. Electronic address:

Background & Aims: The inferior mesenteric vein (IMV) is detected in more than 90% of computed tomography images. Little is known about the hemodynamic features of IMV as a collateral vessel in portal hypertension, or its effects in clinical presentation and outcome. We investigated the roles of the IMV in portal hemodynamics, clinical presentation, and outcomes of patients with cirrhosis.

Methods: We performed a prospective study of 467 patients with cirrhosis (274 men; age, 64.6 ± 10.9 y). We assessed hemodynamics in the IMV using Doppler sonography and compared these data with patients' clinical presentation and patient outcome.

Results: IMV was detected in 94 patients (20.1%); 51 patients had hepatopetal flow, 33 patients had hepatofugal flow, and 10 patients had to-and-fro flow. Those with hepatofugal flow had a significantly greater number of ascites than those with hepatopetal flow, higher Child classification (P = .004), and a higher incidence of decompensated liver (51.5% vs 27.5%; P = .015) and rectal varices (56.3% vs 13.3%; P = .013). The incidence of gastroesophageal varices was lower among those with hepatofugal flow (51.5%; P = .005) or to-and-fro flow (40%; P = .008) than those with hepatopetal flow (80.4%). IMV had similar effects after adjustment for liver function. There were no differences in the cumulative rates of survival during the median 17.2 months of follow-up evaluation, when the patients with and without IMV were stratified by Child classification.

Conclusions: In patients with cirrhosis, hepatofugal flow of the IMV appears to increase the risk of ascites and liver decompensation but reduce the risk for gastroesophageal varices. Although IMV is associated with reduced liver function, it does not affect survival.
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http://dx.doi.org/10.1016/j.cgh.2013.06.026DOI Listing
December 2013

Magnitude of contrast-enhanced ultrasonography as a noninvasive predictor for hepatic fibrosis: comparison with liver stiffness measurement and serum-based models.

Hepatol Int 2013 Jun 27;7(2):749-57. Epub 2012 Apr 27.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.

Purpose: To elucidate the efficiency of contrast-enhanced ultrasonography alone and in combination with other noninvasive models for grading hepatic fibrosis.

Methods: This prospective study included 74 patients with four grades (F1-F4) of chronic liver disease (17, 20, 18, and 19 patients, respectively). Diagnostic performances of the contrast parameter (time to the maximum intensity ratio between the right portal vein and liver parenchyma from the onset of contrast enhancement in the right portal vein) assessed by ultrasonography, liver stiffness measurement (LSM), FIB-4 test, and type IV collagen 7s were compared with histological findings.

Results: Greatest areas under the receiver operating characteristics curve (Az) with the single model were 0.83 (95 % confidence interval 0.71-0.91) for marked fibrosis (≥F2) by FIB-4 test; 0.85 (0.73-0.92) for advanced fibrosis (≥F3) by LSM, and 0.92 (0.83-0.96) by type IV collagen 7s for cirrhosis (F4). When combined, Az for marked fibrosis was ≥0.82; the best Az value was 0.87 (0.74-0.94) for the combination of contrast parameter with FIB-4. Similarly, the Az for advanced fibrosis was ≥0.82, and the best Az value was 0.89 (0.78-0.94) for the combination of contrast parameter with LSM. The Az for cirrhosis was ≥0.95, and the best Az was 0.99 (0.97-1.00) for the combination of contrast parameter with LSM.

Conclusions: The contrast parameter is a promising predictor for grading hepatic fibrosis when combined with LSM or FIB-4.
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http://dx.doi.org/10.1007/s12072-012-9370-7DOI Listing
June 2013

The application of transabdominal 3D ultrasound for the diagnosis of gastric varices: a preliminary study.

Eur J Radiol 2013 Sep 22;82(9):e400-4. Epub 2013 May 22.

Department of Gastroenterology and Hepatology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba 260-8670, Japan.

Objective: The aim of this study was to determine the feasibility of using transabdominal three-dimensional (3D) colour Doppler ultrasound as a non-invasive tool to demonstrate and quantify gastric varices.

Subjects And Methods: A phantom study compared the 3D water flow volume data in a hose with the actual volume inside the hose at three different flow velocities. The prospective clinical study examined the reliability and reproducibility of 3D volume data for gastric varices (mild 28, moderate 26, large 8) in 62 patients. The 3D images were acquired using the colour Doppler with both convex and micro-convex probes.

Results: The phantom study showed a 12.4-17.6% difference between the 3D data and the actual volume with no difference between the two types of probes or three velocities. The detectability of gastric varices was identical between the two probes (54/62, 87.1%). However, the scanning efficiency was significantly greater for the micro-convex probe (66.9 ± 14.1%) than the convex probe (57.3 ± 14%, p=0.012). Body mass index was the only factor that had a significant relationship with the detectability of varices. The mean volume (mL) of the 3D signal was 0.82 ± 0.74 for mild varices, 5.48 ± 3.84 for moderate varices, and 10.63 ± 6.67 for large varices with significant differences between different grades. The intra-/inter-rater reliability was excellent.

Conclusion: The method of 3D colour Doppler ultrasound is reliable and reproducible in the quantitative assessment of vascular volume and is applicable for grading gastric varices. This study may offer a practical usefulness for 3D ultrasonography as an alternative to endoscopy.
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http://dx.doi.org/10.1016/j.ejrad.2013.04.028DOI Listing
September 2013

Efficacy of lamivudine or entecavir against virological rebound after achieving HBV DNA negativity in chronic hepatitis B patients.

Int J Med Sci 2013 1;10(6):647-52. Epub 2013 Apr 1.

Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8677, Japan.

Nucleos(t)ide analogues (NAs) lead to viral suppression and undetectable hepatitis B virus (HBV) DNA in some individuals infected with HBV, but the rate of virological rebound has been unknown in such patients. We examined the prevalence of virological rebound of HBV DNA among NA-treated patients with undetectable HBV DNA. We retrospectively analyzed 303 consecutive patients [158 entecavir (ETV)- and 145 lamivudine (LAM)-treated] who achieved HBV DNA negativity, defined as HBV DNA < 3.7 log IU/mL for at least 3 months. They were followed up and their features, including their rates of viral breakthrough, were determined. Viral rebound after HBV DNA negativity was not observed in the ETV-group. Viral rebound after HBV DNA negativity occurred in 38.7% of 62 HBe antigen-positive patients in the LAM-group. On multivariate analysis, age was an independent factor for viral breakthrough among these patients (P = 0.035). Viral rebound after HBV DNA negativity occurred in 29.1% of 79 HBe antigen-negative patients in the LAM-group. Differently from LAM, ETV could inhibit HBV replication once HBV DNA negativity was achieved. In contrast, LAM could not inhibit HBV replication even if HBV negativity was achieved in the early phase. Attention should be paid to these features in clinical practice.
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http://dx.doi.org/10.7150/ijms.5904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619113PMC
November 2013

Adherence to medication is a more important contributor to viral breakthrough in chronic hepatitis B patients treated with entecavir than in those with Lamivudine.

Int J Med Sci 2013 15;10(5):567-74. Epub 2013 Mar 15.

Departments of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Viral breakthrough is related to poor adherence to medication in some chronic hepatitis B patients treated with nucleos(t)ide analogues (NAs). Our study aimed to examine how adherence to medication is associated with viral breakthrough in patients treated with NAs. A total of 203 patients (135 ETV and 68 LAM) were analyzed in this retrospective analysis. Physical examination, serum liver enzyme tests, and hepatitis B virus marker tests were performed at least every 3 months. We reviewed medical records and performed medical interviews regarding to patients' adherence to medication. Adherence rates <90% were defined as poor adherence in the present study. Cumulative viral breakthrough rates were lower in the ETV-treated patients than in the LAM-treated patients (P<0.001). Seven ETV-treated (5.1%) and 6 LAM-treated patients (8.8%) revealed poor adherence to medication (P=0.48). Among ETV-treated patients, 4 (3.1%) of 128 patients without poor adherence experienced viral breakthrough and 3 (42.8%) of 7 patients with poor adherence experienced viral breakthrough (P<0.001). Only 3 of 38 (7.8%) LAM-treated patients with viral breakthrough had poor adherence, a lower rate than the ETV-treated patients (P=0.039). Nucleoside analogue resistance mutations were observed in 50.0% of ETV- and 94.1% of LAM-treated patients with viral breakthrough (P=0.047). Viral breakthrough associated with poor adherence could be a more important issue in the treatment with especially stronger NAs, such as ETV.
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http://dx.doi.org/10.7150/ijms.5795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607242PMC
September 2013

Short- and long-term clinical outcome after balloon-occluded retrograde transvenous obliteration: is pretreatment portal flow direction a predictive factor?

Hepatol Int 2013 Mar 19;7(1):241-7. Epub 2012 May 19.

Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Purpose: To determine whether pretreatment portal flow direction can predict different clinical manifestations or prognosis after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices.

Methods: The subjects were 103 cirrhotic patients with medium- or large-grade gastric varices treated by B-RTO. Short- and long-term clinical outcomes were compared among patients with forward portal flow (F group) and those with reversed or to-and-fro portal flow (R group) on color Doppler sonography before B-RTO.

Results: Deterioration of liver function reserve 1 year after B-RTO was more frequent in the R group (34.7 %) than in the F group (11.1 %, p = 0.0251). Thrombotic disorders within 1 year after B-RTO were also more frequent in the R group (20.7 %) than in the F group (2.7 %, p = 0.0079). There was no significant difference in cumulative survival rate of Child class A patients between the two groups. In Child class B or class C patients, however, the cumulative survival rate was poorer in the R group (68.7, 30.5, and 30.5 % at 1, 5, and 9 years, respectively) than in the F group (94.9, 58.8, and 37.8 % and 1, 5, and 9 years, respectively; p = 0.0097).

Conclusions: Hemodynamic assessment of portal flow direction is important before B-RTO, and care should be taken to manage thrombotic disorders in the perioperative period in patients with reversed portal flow after B-RTO. Another treatment option might be preferred for gastric varices in Child classes B and C patients with reversed portal flow instead of B-RTO, which may have a poor prognosis.
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http://dx.doi.org/10.1007/s12072-012-9376-1DOI Listing
March 2013

Characterization of hepatic lesions (≤ 30 mm) with liver-specific contrast agents: a comparison between ultrasound and magnetic resonance imaging.

Eur J Radiol 2013 Jan 29;82(1):75-84. Epub 2012 Oct 29.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Purpose: Imaging-based differentiation of hepatic lesions (≤ 30 mm) between well-differentiated hepatocellular carcinomas (w-HCC) and regenerative nodules (RN) presents difficulties. The aim was to compare the diagnostic abilities to differentiate w-HCC from RN using contrast-enhanced ultrasound and magnetic resonance imaging (MRI) both with liver-specific contrast agents.

Materials And Methods: This prospective study included 67 pathologically proven hepatic lesions (17.5 ± 5.4mm, 54 w-HCCs, 13 RNs) in 56 patients with chronic hepatitis/cirrhosis (male 40, female 16; 29-79y). Hepatic-arterial/liver-specific phase enhancements were assessed quantitatively by ultrasound with perflubutane microbubble agent and MRI with gadolinium-ethoxybenzyl-diethylenetriamine with respect to the histological findings.

Results: Sensitivity, specificity and accuracy of hepatic-arterial phase hyper-enhancement for w-HCC were 59.3%, 100% and 67.2% by ultrasound and 46.3%, 100% and 56.7% by MRI without significant difference. Meanwhile, those of liver-specific-phase hypo-enhancement for w-HCC were 44.4%, 100% and 55.2% by ultrasound and 87.0% (p<0.0001), 46.2% (p=0.0052) and 79.1% (p=0.0032) by MRI. Diagnostic accuracies for w-HCC by area under the receiver operating characteristic curves were higher in the hepatic-arterial phase in ultrasound (0.8316) than MRI (0.6659, p=0.0101) and similar in the liver-specific phase in ultrasound (0.7225) and MRI (0.7347, p=0.8814).

Conclusions: Hypervascularity is a significant feature which distinguishes w-HCC from RN, and ultrasound exerts a beneficial impact better than MRI for such characterization. However, both imaging have comparable abilities in the characterization of non-hypervascular lesions, compensating mutually for the poor sensitivity of ultrasound and the poor specificity of MRI in the liver-specific phase.
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http://dx.doi.org/10.1016/j.ejrad.2012.05.035DOI Listing
January 2013

Linear enhancement after radio-frequency ablation for hepatocellular carcinoma: is it a sign of recurrence?

Ultrasound Med Biol 2012 Nov;38(11):1902-10

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chiba, Japan.

This prospective study was performed in 179 hepatocellular carcinoma (HCC) lesions treated by radio-frequency ablation (RFA) to explore the clinical outcome of "linear enhancement" on contrast-enhanced sonogram. Thirty-three lesions (18.4%) showed linear enhancement, a linear-shaped positive enhancement in the RFA-treated area. Seventeen of them were followed up with no treatment (remaining 16; dropout in eight, additional RFA in six and ineffective treatment in two) and three lesions (3/17, 17.6%) showed local tumor progression corresponding to linear enhancement at 7, 14, 19 months after RFA. Although there was no significant difference in local recurrence rate between the lesions with (3/17) and without linear enhancement (10/35), local tumor progression inside the ablation zone occurred only in the lesions with linear enhancement. In conclusion, linear enhancement inside the RFA-treated area should be followed up within 7 months because it has a risk of local tumor progression. Histology of linear enhancement and its influence on distant recurrence remain to be solved.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.07.003DOI Listing
November 2012

Heterogeneous staining in the liver parenchyma after the injection of perflubutane microbubble contrast agent.

Ultrasound Med Biol 2012 Aug 12;38(8):1317-23. Epub 2012 Jun 12.

Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chuou-ku, Chiba, Japan.

This study aimed to characterize the features of heterogeneous staining in the liver after injection of perflubutane microbubble agent (Sonazoid(TM), 0.0075 mL/kg). Digitized hepatic contrast sonograms from 906 subjects were reviewed to assess time-related changes in heterogeneous staining and the possible association between this effect and the clinical backgrounds was analyzed. Heterogeneous staining was found in seven subjects (0.77%) on 15-min phase sonograms. The staining initially appeared as hyper-enhanced circular spots in the liver 10 min or later after the agent injection. The number of spots increased gradually with unequally-spaced distribution. Although the staining pattern did not improve during the examination, there were no abnormal findings in vital signs or symptoms on the day and blood test results or sonograms on the following day. Heterogeneous staining is a side effect that impedes ultrasound examination. However, at present, the precise causes and underlying mechanisms of this event are unknown.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.04.001DOI Listing
August 2012

Efficacy of lamivudine or entecavir on acute exacerbation of chronic hepatitis B.

Int J Med Sci 2012 10;9(1):27-32. Epub 2011 Nov 10.

Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Background/aims: Spontaneous acute exacerbation of chronic hepatitis B virus (HBV) infection occasionally occurs in its natural history, sometimes leading rapidly to fatal hepatic failure. We compared the effects of lamivudine (LAM) with those of entecavir (ETV) treatments in acute exacerbation of chronic hepatitis B with 500 IU/L or higher alanine aminotransferase (ALT) levels.

Methods: Thirty-four patients with acute exacerbation were consecutively treated with LAM /ETV. Their clinical improvements were compared.

Results: Among LAM-treated and ETV-treated patients, none showed a reduction of <1 log IU/mL in HBV DNA after 1 or 3 months of treatment. Initial virological response, defined as a reduction of 4 log IU/mL in HBV DNA at 6 months, with LAM and ETV, respectively, was 83.3% and 100%. One LAM patient developed hepatic encephalopathy, but all patients in both groups survived. Twelve months after treatment, 41.6% of 24 LAM group patients switched to another drug or added adefovir to their treatment due to the emergence of LAM-resistant mutants. On the other hand, patients receiving ETV did not need to change drugs.

Conclusions: ETV appears to be as effective as LAM in the treatment of patients with acute exacerbation of chronic hepatitis B. Clinicians should carefully start to treat these patients as soon as possible.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222087PMC
http://dx.doi.org/10.7150/ijms.9.27DOI Listing
June 2012

Emergence of entecavir-resistant mutations in nucleos(t)ide-naive Japanese patients infected with hepatitis B virus: virological breakthrough is also dependent on adherence to medication.

Scand J Gastroenterol 2011 Sep 30;46(9):1111-7. Epub 2011 May 30.

Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Objective: Currently, five nucleos(t)ide analogues (NUCs) are available for the treatment of chronic hepatitis B in the world. We examined the prevalence of hepatitis B virus (HBV) DNA and alanine aminotransferase normalization in patients receiving entecavir (ETV) and the frequency of ETV-resistant mutations during an approximately 27-month use of ETV in chronic hepatitis B patients in an urban hospital in Japan.

Materials And Methods: A retrospective analysis of 81 NUC-naive chronic hepatitis B patients who received 0.5 mg of ETV daily was performed. HBV DNA was measured and sequence analysis of HBV DNA was performed in virological breakthrough patients.

Results: Hepatitis B e antigen (HBeAg)-positive patients with HBV DNA 5.0-7.0 log IU/mL group and all HBeAg-negative patients achieved serum HBV DNA negativity by 12 months. Four patients experienced virological breakthrough during ETV therapy. Two patients had no genotypic mutations, and medical interviews revealed that they had poor adherence to ETV.

Conclusions: We found that some of the HBV virological breakthroughs during ETV treatment were related to poor adherence to medication, highlighting that clinicians should pay attention to the emergence of resistant mutants as well as adherence to ETV.
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http://dx.doi.org/10.3109/00365521.2011.584898DOI Listing
September 2011