Euroasian journal of hepato-gastroenterology

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2012 | July-December | Volume 2 | Issue 2

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ORIGINAL ARTICLE

Ahmet Uyanikoglu, Filiz Akyuz, Fatih Ermis, Fatih Besisik, Binnur Pinarbasi, Sabahattin Kaymakoglu, Kadir Demir, Gungör Boztas

Azathioprine Toxicity in Inflammatory Bowel Disease

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:4] [Pages No:59 - 62]

   DOI: 10.5005/jp-journals-10018-1035  |  Open Access |  How to cite  | 

Abstract

Background/aim: The aim of this study was to evaluate patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) and followed-up in our clinic to adverse effects. Materials and methods: We analyzed patients with IBD who were treated with AZA between April 1998 and April 2008 for adverse events. Results: Four hundred and seventeen patients that included 211 (50.6%) females (age, 38.63 ± 13.32 years) were evaluated. Two hundred and forty-two patients (58%) had ulcerative colitis, 159 (38.1%) patients had Crohn’s disease and 16 (3.8%) patients had undetermined colitis. Mean follow-up period was 42.5 ± 46 months (range, 6-288 months). One hundred and eighty-nine (45.3%) patients used AZA (66% in Crohn’s disease group, 32% in ulcerative colitis group). Mean AZA treatment period was 33.8 ± 32 months (range, 6-160 months). Discontinuing rate was 19.6% (37 cases). Causes of discontinuing AZA were as follows: Adverse events in 15 patients (bone marrow suppression in three, pancreatitis in two, hepatotoxicity in two, related malignancy in three and other events in five patients), inefficacy in 12 patients, postoperation in five patients and other causes in five patients. Major toxicity was seen in seven of 189 patients (3.7%). Conclusion: Half of IBD patients were using AZA and major toxicity and malignancy development rates during AZA treatment were low. AZA is a safe immunosuppressive agent in IBD patients.

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ORIGINAL ARTICLE

Munira Jahan, Shahina Tabassum, Afzalun Nessa, Chowdhury Mohammad Shamim Kabir

High HBcAg Expression in Hepatocytes of Chronic Hepatitis B Patients in Bangladesh

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:7] [Pages No:63 - 69]

   DOI: 10.5005/jp-journals-10018-1036  |  Open Access |  How to cite  | 

Abstract

The present study evaluates the intracellular expression of the hepatitis B Virus (HBV) core antigen in chronic hepatitis B (CHB) patients from Bangladesh in relation with serological, virological and histological variables. A cross-sectional study was carried out among 70 patients incidentally diagnosed as HBV chronic carriers who have undergone liver biopsy. Indirect immunofluorescence technique was used to study the intracellular expression of hepatitis B core antigen (HBcAg). The grade and cellular distribution were semiquantitatively scored according to the percentage of stained cells and their nuclear, cytoplasmic or mixed expression pattern respectively. A higher HBcAg grade was related to higher viral load, alanine aminotransferase levels and histological damage. Higher HBV DNA counts and HBcAg grade were found in hepatitis B e antigen (HBeAg)-positive patients.

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ORIGINAL ARTICLE

Mona Abd Elmonem Hegazy, Nehad Mohamed Tawfik, Hoda Abd-Elstar Elrawi

Liver Injury and Khat Leaves: A Common Toxic Effect

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:6] [Pages No:70 - 75]

   DOI: 10.5005/jp-journals-10018-1037  |  Open Access |  How to cite  | 

Abstract

Background: The evidence of hepatotoxic effects of khat is often based on limited numbers of case reports and animal studies. Aim: To evaluate the prevalence and severity of effects of khat on the liver. Materials and methods: A total of 214 khat users, Yemeni people, included in the study. They were divided into two groups according to the presence or absence of hepatic insult either detected by elevated liver enzymes and/or abnormal hepatic finding on abdominal ultrasonography. Full medical history, clinical examination and calculation of body mass index (BMI) were done. Fasting blood sugar, total lipid profile, liver enzymes were estimated in all patients. Serum albumin, bilirubin and prothrombin time were assessed in patients showing positive hepatic damages (either by elevated liver enzymes and liver ultrasound). Abdominal ultrasound scan was done for all patients. Results: One hundred and forty-four (group I) khat users showed a positive sign of hepatic injury either by elevated liver enzymes in 127 patients and abnormal hepatic scan finding in 89 patients. Four patients (3%) discovered to have liver cirrhosis. Patients showed hepatotoxic effect of khat were significantly older in age than participants without hepatic affection. Both subgroups with variable BMI showed elevated ALT with no significant difference. Liver ultrasound showed positive hepatic insult in 40% of khat chewing patients with normal BMI, meaning that obesity is not the responsible factor for fatty liver in the current study. Conclusion: Hepatotoxic effect of khat is common. Confounding issues other than khat were eliminated in the present study as causative factors, such as alcohol consumption, coexisting disease. Also, the effect of obesity was evaluated.

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ORIGINAL ARTICLE

Md Mokhlesur Rahman, Mizanur Rahman, Niamul Gani Chowdhury, SK Bahar Hossain, Delwar Hossain, Rabiul Hossain, Quadrat E-Elahi

Long-term Follow-up Study of Asymptomatic HBsAg-Positive Carrier

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:3] [Pages No:76 - 78]

   DOI: 10.5005/jp-journals-10018-1038  |  Open Access |  How to cite  | 

Abstract

Objectives: Hepatitis B virus (HBV)-related chronic liver disease is a common health problem in our country. About 5.2 to 7.8% population of Bangladesh is chronic HBV carriers. There is no long-term follow-up study of asymptomatic HBV carriers in our country. Aim of the present study is to know the outcome of these cases in 10 years. Materials and methods: Twelve hundred and eighty-six cases of asymptomatic HBsAg-positive individuals were evaluated and followed up for 10 years at gastroenterology department, combined Military Hospital, Dhaka Cantonment, from January 2000 to December 2009. Results: Age of the patient’s ranges from 3 to 50 years (mean, 27 ± 6 years). Majority cases were males 1,236 (96.12%). Baseline alanine aminotransferase (ALT) >45 IU/l was found in 168 (13.06%) cases. Ultrasonography revealed coarse hepatic echotexture in 62 (5.63%) cases out of 1,200 cases. Hepatic histology revealed chronic hepatitis in 318 cases (35.02%) and cirrhosis of liver in 24 cases (2.64%), hepatocellular carcinoma 1 (0.11%), fatty liver in eight (0.88%) out of 908 cases. After follow-up, compensated cirrhosis of liver was found in 90 (15%) cases, decompensated liver disease in 50 (8.33%) cases and hepatocellular carcinoma (HCC) in 42 (7%) out of 600 cases. Twenty (3.33%) cases died due to liver failure, HCC and other complications. Spontaneous HBsAg seronegativity occurred in five cases out of 600 cases (0.83%), and spontaneous HBeAg seroconversion occurred in 10 cases out of 180 cases (5.55%). Conclusion: Asymptomatic HBsAg-positive carriers should not be considered as inactive disease. They should be followed up every 3 to 6 months to know activity of the disease and development of complications. Antiviral treatment should be instituted in cases of active liver disease.

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ORIGINAL ARTICLE

Mesut Sezikli, Züleyha Akkan Cetinkaya, Fatih Güzelbulut, Demet Özgil Yetkin

Metabolic Syndrome in Inflammatory Bowel Disease: A Real Relationship or Just a Coincidence

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:5] [Pages No:79 - 83]

   DOI: 10.5005/jp-journals-10018-1039  |  Open Access |  How to cite  | 

Abstract

Background and aim: Presence of metabolic syndrome along with inflammatory diseases is being reported with increased frequency. The aim of this study was to investigate the presence of metabolic syndrome in inflammatory bowel disease patients. Materials and methods: Fifty-one patients with ulcerative colitis, 34 patients with Crohn’s disease and 88 healthy controls were included in this study. All of the patients were in remission state. Subjects were classified as having the metabolic syndrome based on the National Cholesterol Education Program (NCEP) and the modified World Health Organization (WHO) definition. Results: The prevalence of metabolic syndrome in patients with ulcerative colitis was 16% according to the NCEP and 23.5% according to the WHO, and that in patients with Crohn’s disease was 8.8% according to the NCEP and 14.7% according to the WHO. The prevalence of metabolic syndrome in control group was 18% according to the NCEP and 15.7% according to the WHO. When inflammatory bowel disease patients and control groups were compared with respect to the presence of metabolic syndrome, there was no statistically significant difference between the two groups according to neither NCEP nor WHO. Conclusion: Although it is predicted that metabolic syndrome develops lesser since inflammatory bowel disease patients as they are considered to have lower body mass index, frequency of metabolic syndrome is not less than control group according to the results of our study. Therefore, possibility of metabolic syndrome in inflammatory bowel disease patients should not be overlooked and it should be considered that it can be used in patient follow-up.

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ORIGINAL ARTICLE

Tarek A Besheer, Mona Arafa, Ghada Elkannishy, Mona A El-hussiny, Ehab B Rakha

Features of Hormonal Disturbances in Cirrhotic Patients with Hepatic Encephalopathy

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:6] [Pages No:84 - 89]

   DOI: 10.5005/jp-journals-10018-1040  |  Open Access |  How to cite  | 

Abstract

Background: Features of hormone disturbances in patients suffering from chronic hepatic failure have been documented for many years. Objective: To evaluate the possible diagnostic and prognostic values of cortisol, total T3, thyroid-stimulating hormone (TSH) and prolactin concentrations in cirrhotic patients for prediction of hepatic encephalopathy (HE) and severity of hepatic diseases. Materials and methods: Study was carried out on 75 (40 males, 35 females) cirrhotic patients (HCV positive) with HE and 50 (28 males, 22 females) cirrhotic patients without HE (HCV positive). Patients underwent clinical evaluation with determination of the degree of HE. The severity of cirrhosis was assessed according to Child-Pugh classification. Immulite 1000 chemiluminescent immunometric assay was used for determination of cortisol, total T3, TSH and prolactin. Results: Cortisol, total T3 concentrations were significantly decreased in cirrhotic patients with HE compared to those without HE. Cutoff value for cortisol was less than 18.3 mg/dl could predict HE in cirrhotic patients according to AUROC curve showing a sensitivity of 52% and a specificity of 61%. Cutoff value for total T3 of less than 45.5 ng/dl could predict HE in cirrhotic patients showing a sensitivity of 64% and a specificity of 80.6%. Whereas prolactin concentration in cirrhotic patients with HE was significantly increased compared to patients without HE and its cutoff value was more than 18.85 ng/dl could predict HE in cirrhotic patients showing a sensitivity of 88% and a specificity of 90.3%. TSH concentration showed no significant difference in patients with HE vs patients without HE. Conclusion: Hormonal abnormalities of cortisol, total T3 and prolactin may represent risk factors and early indicators of impending hepatic encephalopathy and progression of liver disease severity.

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ORIGINAL ARTICLE

Metin Küçükazman, Ayse Kefeli, Sebahat Basyigit, Abdullah Özgür Yeniova, Yasar Nazligül, Ibrahim Halil Akkus, Ayla Tezer, Servet Guresci

Efficacy of Bismuth-Containing Quadruple Therapy as First-line Treatment for Helicobacter pylori Infection

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:4] [Pages No:90 - 93]

   DOI: 10.5005/jp-journals-10018-1041  |  Open Access |  How to cite  | 

Abstract

Background and aim: Helicobacter pylori (H. pylori) infection can cause chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. For this reason, eradication of H. pylori has become an important issue. In recent years, failure of eradication therapy with standard eradication regimes had directed toward new therapeutic alternatives. The present study aimed to show the efficacy of bismuth-containing quadruple regimen for the first-line treatment of H. pylori infection. Materials and methods: H. pylori positive patients received a quadruple therapy consisted of esomeprazole 20 mg bid, colloidal bismuth subcitrate 600 mg bid, tetracycline 500 mg qid and metronidazole 500 mg tid for 7 days. The diagnosis of H. pylori infection was performed by the histopathological assessment of gastric biopsies. Six weeks after completion of therapy, H. pylori status was rechecked by C14 urea-breath test. Results: A total of 115 patients have completed the protocols (upper gastrointestinal endoscopy, treatment, urea-breath test). H. pylori eradication rate was found to be 87%. This eradication rate is significantly higher than those of classic triple therapies in the literature. Conclusion: The bismuth-containing quadruple regimen achieved an acceptable and very higher eradication rate than those of classic triple therapies in the literature. It can recommend as a first-line therapy for Helicobacter pylori infection.

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ORIGINAL ARTICLE

Suresh Kumar Nigam, Huthi Venkatakrishna Bhatt

Structural Changes and Gross Pathology of Gut and associated Organs of Mice on Chronic Exposure to Pan Masala Plain and its Blend (Pan Masala Tobacco): A Review and an Experimental Study

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:4] [Pages No:94 - 97]

   DOI: 10.5005/jp-journals-10018-1042  |  Open Access |  How to cite  | 

Abstract

Swiss albino mice in three groups (control, experimental I and experimental II) of 60 each were fed staple diet (control), diet composed with 2% pan masala plain (PMP) and its blend (tobacco-PMT) for a period of up to 70 weeks with intermittent postmortem at 16, 56 and 70 weeks for assessing histological changes of the gut histopathology of mice. Mice of experimental groups I and II showed progressive advancement of structural changes of stomach during the study period. Fibrosis, thickening of prickle cells and also horney layered cells indicating lesions of acanthosis and hyperkeratosis initially and later prominently ulcers and papillomas which transformed into a peptic tumor occured. Spleen was found enlarged in mice fed with PMT. Animal feeding, hygiene, exploration and environmental care and health protocols were as per the standard guidelines and approved by National Institute of Occupational Health ethical committee. Here, chronic exposure of mice has been consistent in respect of feed and environment, unlike habitual PM users whose consumption is inconsistent depending on the body demand and choice on the variety of the blended PM product. This study endorses generating critical clinically designed case control, cohort data for awareness programs and PM substitutes as well as treatment to PM addicts.

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ORIGINAL ARTICLE

Naffisa Adedin, Abdullah Shahriar, Jafreen Sultana, Akhtar Uddin Ahmed, AS Mohiuddin, Nayeema Rahman

Comparison of Ultrasonography and Computed Tomography to Evaluate the Causes of Biliary Obstruction

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:6] [Pages No:98 - 103]

   DOI: 10.5005/jp-journals-10018-1043  |  Open Access |  How to cite  | 

Abstract

Objective: To observe the role of computed tomographic (CT) scan and ultrasonography (USG) examination to evaluate the causes of biliary obstruction. Materials and methods: This cross-sectional study was conducted in a total of 57 patients clinically suspected of obstructive jaundice. Results: The highest incidence of biliary obstruction was found in the age group between 40 and 49 years and the mean (±SE) age of the patients was 48.4 ± 1.6 years. Serum bilirubin and serum alkaline phosphatase were high in all patients. For evaluation of pancreatic mass, USG found true positive in 13 with no false positive, false negative 2 and true negative 42 cases. Similarly, CT scan found true positive in 15 and no false positive, no false negative and true negative in 42 cases. Sensitivity and specificity of USG in detecting pancreatic mass were 80 and 97.6%. CT scan showed 93.3% sensitivity and 97.6% specificity. In case of gallbladder (GB) mass USG found true positive in 20 and 1 false positive. There was no false negative and true negative in 36 cases. CT scan also revealed better sensitivity. USG could not detect any case of periampulla. Conclusion: Accuracy of USG and CT is high in detecting biliary tree dilatation, with CT scan slightly more accurate than USG. The difference in cost between the two is likely to decline with time and make CT even more attractive and handy for imaging the hepatobiliary system.

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MINI REVIEW

Lionel Bridet, Juan Jose Beitia Martin, Jose Luis Cabriada Nuno

Acute Liver Damage and Anorexia Nervosa: A Case Report and Review of the Literature

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:3] [Pages No:104 - 106]

   DOI: 10.5005/jp-journals-10018-1044  |  Open Access |  How to cite  | 

Abstract

We treated a patient suffering from severe anorexia nervosa [body mass index (BMI), 10.5 kg/m²] complicated with hepatic insufficiency. The treatment consisted of rehydration and the correction of her malnutrition, using adapted protocols to avoid the development of the refeeding syndrome. In view of her successful progress she was discharged from the hospital on day 50. Although we do not perform a hepatic biopsy, the mechanism seems to be related to autophagy more than hypoperfusion because of the extremely low BMI. This observation also highlights the need of following a multidisciplinary approach in these difficult cases (BMI < 13 kg/m²), involving intensive care unit doctors, gastroenterologists, endocrinologists and psychiatrists. Abbreviations: BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CT: Computed tomography.

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MINI REVIEW

Bulent Colak, Harun Erda, Mehmet Arhan, Mehmet Ibis, Selahattin Unal

A Case of Downhill Esophageal Varices associated with Superior Vena Cava Syndrome due to Mediastinal Mass

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:2] [Pages No:107 - 108]

   DOI: 10.5005/jp-journals-10018-1045  |  Open Access |  How to cite  | 

Abstract

Here we report a case of downhill esophageal varices who complained of weight loss, abdominal pain after meals, fatigue, anorexia, dizziness and swollen face for 2 months.

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CASE REPORT

Abdurrahman Sahin, Kamil Ozdil, Resul Kahraman, Turan Calhan, Murat Hakan Karabulut, Recai Gokcan, Haci Mehmet Sokmen

An Unusual Cause of Upper Gastrointestinal Bleeding: Duodenal Vascular Ectasia after Splenectomy

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:4] [Pages No:109 - 112]

   DOI: 10.5005/jp-journals-10018-1046  |  Open Access |  How to cite  | 

Abstract

Cavernomatous transformation of portal vein (CTPV) is characterized by a collateral network of veins in the hepatic hilum that bypasses an obstructed or occluded extrahepatic portal vein. We report a case of CTPV, 25 years after splenectomy in a 39-year-old man with acute and chronic blood loss from duodenal vascular ectasia without esophageal or gastric varices or portal hypertensive gastropathy. This case demonstrates that distal part of duodenum assessment is important in gastrointestinal bleeding of patients with CTPV. Abbreviations: GI: Gastrointestinal; CTPV: Cavernomatous transformation of portal vein; CT: Computed tomography; PHD: Portal hypertensive duodenopathy.

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CASE REPORT

Swapan Chandra Dhar, Chanchal Kumar Ghosh, Sasanka Kumar Saha, Nikhil Chandra Nath, Helal Uddin, Mohammad Wareshuzzaman, Mohammad Omar Faruk

A Female with Benign Recurrent Intrahepatic Cholestasis

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:3] [Pages No:113 - 115]

   DOI: 10.5005/jp-journals-10018-1047  |  Open Access |  How to cite  | 

Abstract

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive or sporadic disorder, characterized by recurrent episodes of intense pruritus and jaundice that resolve spontaneously without any residual liver damage. Episodic attack can occur at any age but is usually seen at 2nd decade of life. We here report a young female with BRIC who presented the recurrent attack of cholestatic jaundice and pruritus, but was negative for all possible etiology. Liver biopsy was consistent with intrahepatic cholestasis. She was improved after 3 months of suffering from jaundice. On follow-up, she was alright after attack.

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CASE REPORT

Necati Örmeci, Onur Keskin

An Interesting Case of Early Multifocal Gastric Cancer

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:3] [Pages No:116 - 118]

   DOI: 10.5005/jp-journals-10018-1048  |  Open Access |  How to cite  | 

Abstract

Early gastric cancer (EGC) is defined as gastric cancer confined to mucosa or submucosa, regardless of the presence or absence of lymph node metastasis. Generally, patients with multifocal EGC have two or three lesions but rarely have more than three lesions. In this article, we present a patient who was admitted to the hospital with complaints of epigastric pain and fatique. His endoscopic examination revealed four EGC lesions. We performed endoscopic mucosectomy for all lesions successfully. Endoscopic mucosal resection is an organ conservative approach and can be performed to patients with early multifocal gastric cancer. During this procedure life-threatening severe complications can occur. In our experience, severe bleeding occured during mucosectomy and our patient underwent subtotal gastrectomy.

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CASE REPORT

Ozlem Ozer Cakir, Huseyin Ataseven, Murat Biyik, Gokhan Gungor, Ali Demir

Autoimmune Cholangiopathy followed with the Diagnosis of Cholangiocarcinoma

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:3] [Pages No:119 - 121]

   DOI: 10.5005/jp-journals-10018-1049  |  Open Access |  How to cite  | 

Abstract

Autoimmune cholangiopathy (IgG4-associated sclerosing cholangitis) can mimic symptoms and signs of many other diseases and thus it remains often undiagnosed or misdiagnosed. The definitive diagnosis is based on pathological findings. Thus, only very few patients have been reported in the literature. We report a case of a 64-year-old female with autoimmune cholangiopathy (IgG4-associated sclerosing cholangitis) that had presented mass-like lesions at liver parenchyma and occlusion of the common bile duct and performed a metal stent inserted in the common bile duct for diagnosis of cholangiocarcinoma in another medical center 5 years ago. High levels of the IgG4 of the patient and pathologic findings of mass-like lesion specimen disclosed severe infiltrations of lymphocytes and plasma cells and suggested an autoimmune cholangiopathy (IgG4-associated cholangiopathy). The patient was treated with prednisolone. The narrowing of the common bile duct, mass-like lesions at liver parenchyma and complaints of the patient improved significantly 1 month after corticosteroid treatment.

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CASE REPORT

Masanori Abe, Hiroshi Onji, Youhei Koizumi, Masakazu Hanayama, Morikazu Onji, Masashi Hirooka, Yoshio Tokumoto

A Case of de novo Hepatitis B Complicated due to Lack of Comprehensive Interventional Approach

[Year:2012] [Month:July-December] [Volume:2] [Number:2] [Pages:4] [Pages No:122 - 125]

   DOI: 10.5005/jp-journals-10018-1050  |  Open Access |  How to cite  | 

Abstract

Here, we report a case of de novo type B hepatitis in a patient with hepatitis B surface antigen (HBsAg) negative but positive for low titer of anti-HBc antibody (anti-HBc titer; dilution 200; negative). As the disease was anticipated in advance, the patient received nucleos(t)ide analogs, but de novo type B hepatitis was developed, because of discontinuation of antiviral drugs. A 59-year-old male with a history of T cell rich diffuse large Bcell lymphoma (DLBCL) and was treated with rituximab plus cyclophosphomide, doxorubicin, vincristine and prednisolone (R-CHOP). The patient responded to anticancer therapy and his complete responder status was confirmed by PET-CT on October 4, 2010. As the patient was expressing low levels of anti-HBc (anti-HBc titer; dilution 200-negative), he was given lamivudine to block HBV reactivation, but the drug was continued after 1 year due to apparent improvement. Stoppage of antiviral drug resulted in detectable HBV DNA and evidences of liver damages and he was referred to our department for specialized consultation about liver-related complications. He was given entecavir at a dose of 1 gm/day from May 2012. However, the parameters of liver function test showed anomaly indicating progressive liver damages. Subsequently, he was given steroid pulse therapy with 1,000 mg of prednisolone and tapered successively. The levels of HBV DNA decreased and parameters of liver function test were improved. A biopsy specimen taken in July 2012 showed the findings compatible with resolved acute hepatitis. To prevent de novo type B hepatitis, critical observation and timely management of the patients are necessary. The administration with nucleoside analogs at least 1 year after R-CHOP therapy is recommended in guideline of Japanese Society of Hepatology. However, we should reconsider the term of administration with nucleoside analogs after R-CHOP therapy.

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