Mobin Khan

A case‐control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D

There are two subtypes of hepatitis B virus genotype A (HBV/A) and they are provisionally designated Aa (“a” standing for Africa/Asia) and Ae (“e” for Europe). In a case‐control study, 78 HBV/Aa, 78HBV/Ae, and 78HBV/D carriers from several countries were compared. The prevalence of HBe antigen (HBeAg) in serum was significantly lower in carriers of HBV/Aa than in carriers of HBV/Ae (31% vs. 49%; P = .033), with a difference more obvious in the carriers aged 30 years or younger (34% vs. 67%; P = .029). HBV DNA levels in the carriers of HBV/Aa (median, 3.46 log copies/mL; 95% CI, 2.93–3.95) were significantly lower than those of carriers of HBV/Ae (6.09 log copies/mL; 95% CI, 4.24–7.64) or of carriers of HBV/D (5.48 log copies/mL; 95% CI, 4.06–7.02), regardless of the HBeAg status (P < .001). The most specific and frequent substitutions in 54 HBV/Aa isolates were double substitutions for T1809 (100%) and T1812 (96%) immediately upstream of the precore initiation codon, which would interfere with the translation of HBeAg in HBV/Aa infections. They were not detected in 57 HBV/Ae or 61 HBV/D isolates examined. The double mutation in the core promoter (T1762/A1764) was more frequent in both HBV/Aa (50%) and HBV/Ae (44%) than in HBV/D isolates (25%; P < .01), whereas the precore mutation (A1896) occurred in HBV/D isolates only (48%; P < .0001). In conclusion, the clearance of HBeAg from serum may occur by different mechanisms in HBV/Aa, HBV/Ae, and HBV/D infections, which may influence clinical manifestations in the Western countries where both genotypes A and D are prevalent. (HEPATOLOGY 2004;40:747–755.)

Frequent coinfection with hepatitis B virus strains of distinct genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support

A genotype-specific probes assay (GSPA) was developed for distinguishing the seven genotypes (A-G) of hepatitis B virus (HBV). Nucleotide (nt) sequences corresponding to preS1 region were amplified by PCR with a primer labeled with biotin, and delivered to eight wells on which complementary sequences specific to one or other genotype had been immobilized. Thereafter, hybridization of HBV DNA sequences amplified from the test serum was detected by colorimetry. When 256 sera from HBV carriers in Bangladesh, Cameroon, Japan, South Africa, USA and Uzbekistan were subjected to GSPA, genotypes were concordant with those of ELISA with monoclonal antibodies to epitopes on preS2-region products in 242 (94.6%) of them; 8 sera (3.1%) were not genotypeable by either method. Cloning analysis confirmed the presence of two distinct HBV genotypes in the seven selected sera with coinfection. There were 7 (2.7%) sera with discordant genotyping results between GSPA and ELISA. When HBV DNA clones propagated from these sera were sequenced and analyzed phylogenetically, the genotypes determined by GSPA were verified. Coinfection with HBV strains of two distinct genotypes was identified by GSPA in 28 (10.9%) sera, while it was suggested by ELISA in only 2 (0.8%) sera. The GSPA method would be particularly useful for detecting the coinfection with distinct HBV genotypes of any clinical relevance, which seems to be more frequent than reported previously.

Evaluation of normal or minimally elevated alanine transaminase, age and DNA level in predicting liver histological changes in chronic hepatitis B

Background: Serum alanine transaminase (ALT), hepatitis B virus (HBV) DNA level and age are used in the evaluation of chronic hepatitis B (CHB).

Comparative study on presentation of biliary ascariasis with dead and living worms.

Background/Aim: Ascariasis is a common parasitic infestation in Asia and Latin America. The most serious presentation is biliary and pancreatic ascariasis (BPA). The aim of the present study was to compare the clinical presentation of BPA with dead worms with that with living worms. Materials and Methods: We included 138 consecutive cases of BPA that occured during the period January 2005 to July 2009. All the patients had endoscopically proven BPA consisting of living or dead worms. Comparison was done by chi-square and independent t tests. Results: The age (mean ± SD) of the patients was 36.8 ± 16.1 years. Prevalence ratio between male and female patients was 1:5. Ninety eight patients contained living worms and 40 had dead worms. Males were more prone to develop dead worm BPA. The commonest presentation was biliary colic (131; 94.9%); others were acute cholangitis (30; 21.7%), obstructive jaundice (19; 13.8%), choledocholithiasis (20; 14.5%), acute pancreatitis (10; 7.2%), acute cholecystitis (6; 4.3%), liver abscess (2; 1.4%), hepatolithiasis (3; 2.2%), stricture of common bile duct (2; 1.4%), pancreatic abscess (1; 0.7%) and cirrhosis of liver (1; 0.7%). Choledocholithiasis, hepatolithiasis, liver abscess and cirrhosis were associated only with dead worms. We could successfully remove all the worms with endoscopic interventions, but 5 patients required surgical intervention as there were strictures and stones within the biliary tree or Ascaris were in gallbladder. Recurrences of stone and cholangitis occurred only in those with dead worms. Conclusion: Biliary ascariasis with dead worms is more dangerous than that with living worms. Endoscopic or surgical intervention may be required repeatedly in those with dead worms.

Natural course of fulminant hepatic failure: The scenario in Bangladesh and the differences from the west

Background/Aim: Fulminant hepatic failure (FHF) is a devastating complication of acute viral hepatitis, leading to death in most cases. The etiology and predictors of outcome differ according to the geographical region. This study was conducted with the aim of evaluating the etiology, complications, and outcome of FHF in Bangladesh. Patients and Methods: In this prospective study, we included 67 consecutive cases of FHF presenting to the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, between November 2003 and May 2008. Thirty-nine of the patients were male and 28 were female. Data was analyzed using SPSS, version 13.0. Results: The mean age of the subjects was 31.9 ± 11.7 years. Hepatitis E virus (HEV) was the commonest etiological factor for FHF (50 cases, 74.6%); of the 50 cases with HEV infection, 43 (64.2%) were not coinfected with any other virus, four cases were Hepatitis B virus (HBV) carriers, and three had coinfection with hepatitis A virus (HAV). HBV was the cause of FHF in nine (13.4%) patients. HCV, paracetamol, and alcohol were not responsible for any of the cases. Most of the patients (57 patients, 85%) developed FHF within 2 weeks of the onset of jaundice. Of the 67 patients, 49 (73.1%) died. Cerebral edema was the single most common cause of death (48 patients, 71.6%). Other complications were renal failure (23 patients, 34.3%), sepsis (15 patients, 22.4%), electrolyte imbalance (12 patients 17.9%), and bleeding tendency (7 patients, 10.4%). Occurrence of cerebral edema, longer prothrombin time, higher grade of encephalopathy, and longer jaundice-to-encephalopathy interval had significant negative influence on outcome. Conclusions: The etiology of FHF in Bangladesh is different from that in the West. Prolongation of prothrombin time and occurrence of cerebral edema are predictors of the worst prognosis.

Precore/Core Promoter Mutant Hepatitis B Virus Produces More Severe Histologic Liver Disease than Wild Type Hepatitis B Virus

Introduction: The aim of this study is to compare Knodell and HAI scores in patients with wild type and precore/core promoter mutant CHB to see if there is any difference in severity of liver injury between these two types of HBV. Methods: We did percutaneous liver biopsies of 155 CHB patients. 102 (65.8%) of them were infected wild type HBV and the rest 53 (34.2%) were infected with precore/core promoter mutant CHB. Results: 11/53 (20.8%) patients with precore/core promoter mutant CHB had moderate to severe CH (HAI score 8–18). In contrast, moderate to severe CH was seen in 19/102 (18.6%) patients with wild type CHB. Fibrosis score was >2 in 15/53 (28.3%) precore/core promoter mutant CHB as opposed to 20/102 (19.6%) patients with wild type CHB. Conclusion: The study shows that precore/core promoter mutant HBV produces more severe histologic liver disease compared to wild type HBV.

Characteristics of treatment naive chronic hepatitis B in Bangladesh: Younger populations are more affected; HBeAg-negatives are more advanced

Background/Aim: Bangladesh is a densely populated country with intermediate endemicity for chronic hepatitis B (CHB). The aim of the present study was to evaluate the biochemical, virological and histological character of CHB patients and to examine the relationship between these indices. Materials and Methods: One thousand and twenty-two patients of CHB fulfilled our inclusion criteria. Inclusion criteria were (1) HBsAg positive for at least 6 months, (2) HBeAg-positive or negative and (3) hepatitis B virus (HBV) DNA positive. Patients with detectable antibodies to human immunodeficiency virus (HIV), hepatitis Delta virus (HDV) or hepatitis C virus (HCV), with previous antiviral treatment, overt cirrhosis and hepatocellular carcinoma, were excluded. Of these, 191 patients were randomly selected for liver biopsy and were evaluated for analysis. Results: In the 191 patients, male to female ratio was 4.6:1; age distribution was 26.5 ± 8.5 (mean ± standard deviation) years. One hundred and seventy-eight (93.2%) patients were under 40 years. Sixty-eight (35.6%) patients were HBeAg-negative, had less DNA load, and were significantly older, more fibrotic and cirrhotic (P < 0.001). Correlation was not found between DNA level and histological activity. Histological activity was not correlated with ALT level in HBeAg-positive patients (P < 0.001). Conclusion: CHB affects the younger population in Bangladesh. HBeAg-positive CHB was associated with more fibrosis and cirrhosis. Serum HBV DNA levels do not correlate with the severity of histological lesions in all patients. Evaluation by liver biopsy remains gold standard for taking decision of treatment.

Genotypes of HCV in Bangladesh: Experience from a Tertiary Centre

Introduction: Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide including Bangladesh. Approximately 0.84% of our population is infected with HCV. Genotypes of HCV are important in the determination of treatment duration and in predicting the response to treatment in HCV infection. Methodology: 61 consecutive patients who presented to us with chronic hepatitis C (CHC) and who could afford treatment and having no features of decompensation were included in the study. Results: Of the 61 study subjects, 46 were males and 15 females. They were between 12 and 70 years of age. Of them 41% had genotype 3, 31% had mixed genotypes 3 + 4 and 21% had genotype 1. Patients also had genotypes 2, 4, 5 and mixed genotypes 5 + 6, the figure being 1.6% in each case. Conclusion: Genotype 3 is the commonest HCV genotype in Bangladesh, while we also have a high prevalence of mixed HCV genotypes.

Serum Interleukin-10 Level in Patients with Chronic Hepatitis B Infection

Background/Aims: Preferential production of immunoregulatory cytokines may play an important role in the pathogenesis of chronic hepatitis B. Patients with chronic hepatitis B infection were evaluated to determine whether serum interleukin-10 (IL-10) levels were changed and whether the degree of these changes in serum levels correlated with HBV DNA levels, histologic activity index (HAI) or serum aminotransferase levels (ALT). Methodology: 15 patients diagnosed of chronic hepatitis B (wild type) with raised ALT, 15 inactive HBsAg carriers, 15 healthy people with resolved acute hepatitis B, and 15 healthy controls without any hepatitis marker positivity were included in the study. Serum IL-10 levels were measured. The associations between liver pathology, HBV DNA and ALT levels were assessed. Result: IL-10 is elevated more in chronic hepatitis B with positive HBeAg and raised ALT in comparison to asymptomatic carrier, resolved acute hepatitis B and control. Conclusions: IL-10 production is increased in chronic hepatitis B patients with HBeAg positivity and raised ALT as compared to other groups (p < 0.01). No correlation between HBV DNA, HAI or ALT could be established through this study. However, as IL-10 is increased in chronic hepatitis B infection with HBeAg positivity, the HBe antigen may be responsible for the raised IL-10 levels.

Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma

Introduction: Hepatitis B virus (HBV) infection is an established cause of hepatocellular carcinoma (HCC) and is associated with poor prognosis. High HBV deoxyribonucleic acid (DNA) load has been identified in HCC and hepatitis B surface antigen-positive patients. Materials and methods: This study was done in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from January 2006 to December 2007. Thirty patients with HBV infection-related HCC were enrolled. Another 30 patients with HBV-related liver diseases without HCC were analyzed as controls. Results: The HCC patients had a high viral load (>105 copies/mL), while all of the controls had low (<105 copies/mL) viral load. Conclusion: It seems that patients with HCC bear high HBV DNA loads in Bangladesh, but the causes underlying this remain to be resolved. How to cite this article: Hussain MM, Al Mahtab M, Islam S, Ahmed N, Rahman S, Khan M. Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2017;7(1):111-112.