Shahinul Alam

Insulin resistance in development and progression of nonalcoholic fatty liver disease

Although insulin resistance (IR) is strongly associated with nonalcoholic fatty liver disease (NAFLD), the association of IR and NAFLD is not universal and correlation between IR and severity of NAFLD is still controversial. In this review, we summarize recent evidence that partially dissociates insulin resistance from NAFLD. It has also been reported that single-nucleotide polymorphisms in the diacylglycerol acyltransferase gene, rather than IR, account for the variability in liver fat content. Polymorphisms of the patatin-like phospholipase 3 gene have also been reported to be associated with NAFLD without metabolic syndrome, which suggests that genetic conditions that promote the development of fatty changes in the liver may occur independently of IR. Moreover, environmental factors such as nutrition and physical activity as well as small intestinal bacterial overgrowth have been linked to the pathogenesis of NAFLD, although some of the data are conflicting. Therefore, findings from both genetically engineered animal models and humans with genetic conditions, as well as recent studies that have explored the role of environmental factors, have confirmed the view that NAFLD is a polygenic disease process caused by both genetic and environmental factors. Therefore, IR is not the sole predictor of the pathogenesis of NAFLD.

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.

Nonalcoholic steatohepatitis in nonalcoholic fatty liver disease patients of Bangladesh

AIM To explore the prevalence and risk factors for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) patients. METHODS We have included 493 patients with sonographic evidence of a fatty change, and 177 of these individuals were evaluated and confirmed after liver biopsy. The exclusion criteria consisted of significant alcohol abuse (< 20 g daily), evidence of hepatitis B and C, evidence of drug-induced fatty liver disease and other specific liver diseases such as hemochromatosis, Wilsons disease or autoimmune liver disease. The patients were assessed for metabolic syndrome, and biochemical, anthropometric and histopathological evaluations were carried out. The degree of disease activity in the NAFLD patients was evaluated using the NAFLD Activity Score. The data were analyzed by SPSS, version 16.0. RESULTS Females predominated among the study participants (250, 57.0%), and the mean age was 40.8 ± 10.2 years. The numbers of overweight, obese I and obese II patients were 58 (13.2%), 237 (53.9%) and 93 (21.2%), respectively. However, there were 422 (96.2%) centrally obese patients. NASH was absent in 10 (5.6%) cases, borderline in 92 (52.6%) cases and present in 75 (42.4%) cases. The presence of diabetes could significantly (P = 0.001) differentiate NASH from simple steatosis. The following parameters did not influence the development of NASH: age, sex, basal metabolic index, waist circumference, serum high-density lipoprotein, triglyceride, insulin resistance index, hypertension and metabolic syndrome. The serum gamma-glutamyl transpeptidase (GGT) level was significantly higher (P = 0.05, 51.7 ± 32.8 and 40.4 ± 22.6 U/L) in the NASH patients, with a sensitivity of 45% and a specificity of only 68%. The serum alanine aminotransferase and aspartate aminotransferase levels were not able to predict NASH. CONCLUSION Females were the predominant sufferers of NAFLD in Bangladesh. The prevalence of NASH was high. Diabetes was found to be the main culprit in developing NASH. GGT was the only biochemical marker of NASH. We recommend liver biopsy in NAFLD patients who have diabetes and elevated GGT.

Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial

Background/Aim: Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. Patients and Methods: A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders. Results: Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and –0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39–6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. Conclusion: Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.

Effect of sitagliptin on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis patients: a 1-year randomized control trial

Background/purpose Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin. Materials and methods In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year. Patients from both groups were encouraged to exercise moderately and advised to avoid saturated fat, excessive sugar, soft drinks, fast food, and refined carbohydrates to reduce weight. Results Steatosis improved in the SL group (from 2.3±0.6 to 1.2±0.8; P=0.000) and the L group (from 2.1±0.6 to 1.6±0.9; P=0.008), ballooning decreased from 1.8±0.6 to 1.3±06 (P=0.002) in the SL group, but not in the L group. Nonalcoholic fatty liver disease activity score (NAS) attenuated in both groups: the SL group (from 5.8±0.9 to 3.9±1.4; P=0.000) and the L group (from 5.3±0.6 to 4.6±1.2; P=0.009). NAS improvement was much higher in the SL group (1.9±1.4) than in the L group (0.7±1.1) (P=0.006), with NAS improving by ≥2 in 13 patients from the SL group and five patients from the L group (P=0.01). Improvement was irrespective of diabetes. Regression analysis explored that sitagliptin had odds of 6.38 and weight reduction had odds of 4.51 for NAS reduction. Conclusion Sitagliptin 100 mg once daily for 1 year ameliorates NAS by improving steatosis and ballooning, irrespective of diabetes. Sitagliptin has stronger efficacy than that of weight reduction.

Effect of pentoxifylline on histological activity and fibrosis of nonalcoholic steatohepatitis patients: A one year randomized control trial

Abstract Background and Objectives To observe the effect of Pentoxifylline for 1 year on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis (NASH). Materials and Methods A single center, open label Randomized Control Trial. Patients were included if they had ultrasonographic evidence of fatty liver and nonalcoholic fatty liver disease activity score (NAS) ≥ 5 on liver histology. A total of 35 patients were selected; 25 of PL (Experimental) group and 10 of L (Control) group. PL group received 400 mg pentoxifylline thrice daily along with lifestyle modification and there was only lifestyle modification for the L group. After one year, NAS and fibrosis was compared in both groups. Results In PL group, NAS improved 2.10 ± 1.07; whereas in L group, NAS was 0.90 ± 0.99 (P = 0.006). As per the protocol analysis, NAS ≥ 2 improved in 15/20 (75%) in PL group and in 3/10 (30%) in L group (P = 0.018). In PL group, the individual component of NAS, steatosis improved from 2.30 ± 0.66 to 0.95 ± 0.76 (P = 0.000), lobular inflammation from 1.65 ± 0.59 to 1.05 ± 0.51 (P = 0.002) and hepatocyte ballooning from 1.50 ± 0.51 to 1.30 ± 0.57 (P = 0.258). In L group, steatosis improved from 2.30 ± 0.68 to 1.40 ± 1.08 (P = 0.01), lobular inflammation and hepatocyte ballooning did not improve. The fibrosis score did not improve in any group. In PL group, NAS improved significantly (P = 0.027; OR=22.76, CI=1.43-362.40) independent of weight reduction. Conclusion Pentoxifylline for 1 year improves the hepatic histological activity but not fibrosis of NASH patients.

Prevalence and risk factors of non‐alcoholic fatty liver disease in Bangladesh

Non‐alcoholic fatty liver disease (NAFLD) is a significant cause of hepatic dysfunction and liver‐related mortality. As there is a lack of population‐based prevalence data in a representative sample of general population, we aimed to estimate the prevalence and risk factors of NAFLD in Bangladesh.

Association of Single Nucleotide Polymorphism At PNPLA3 With Fatty Liver, Steatohepatitis and Cirrhosis of Liver

Background/Purpose The aim of this study was to determine the association of single nucleotide polymorphism (SNP) in patatin-like phospholipase domain-containing 3 (PNPLA3) at I148 with histological severity of non-alcoholic fatty liver disease (NAFLD).