Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

Effect of probiotics supplementation on liver stiffness and steatosis in patients with NAFLD.

Background and Aim: To compare the effects of probiotics on liver stiffness and steatosis in obese and non-obese patients with nonalcoholic fatty liver disease (NAFLD),the pragmatic clinical trial included 50 obese body mass index (BMI) ≥25 kg/m2 and 50 non-obese NAFLD BMI <25 kg/m2 age and sex-matched patients. Materials and Methods: Fibroscan with controlled attenuated parameter (CAP) was done at day 0 and at the end of 6 months. Probiotics supplementation was provided for both groups for 6 months along with lifestyle modifications. Results: At inclusion, both groups had comparable characteristics except BMI, metabolic syndrome and waist circumference (WC). Beneficial changes occurred in BMI (p=0.024), WC (p=0.045), ALT (p=0.024), total cholesterol (p=0.016), LDL (p=0.025) and triglyceride (p=0.021) of obese group, systolic blood pressure (p=0.003) and LDL level (p=0.018) in non-obese group. No significant change was observed in liver enzymes and glycemic profiles. Significant improvement in CAP was observed in both groups. But after adjusting for changes in BMI and WC, the change in CAP among non-obese participants were significantly higher compared to obese, mean change of 19.33±48.87 and 16.02±51.58 dB/m in non-obese and obese patients, respectively; p=0.044). Conclusion: Probiotics improve CAP/ steatosis in both obese and non-obese NAFLD patients and improvement was higher in non-obese, irrespective of BMI change.

Estimating the cost of illness of non-alcoholic fatty liver disease in Bangladesh.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a growing concern, affecting about 45 million of the Bangladeshi population. There is a paucity of research on the economic burden of NAFLD. The study aims to estimate the cost of illness of NAFLD in Bangladesh. Methods: In this prospective, cross-sectional study, a total of 250 patients of NAFLD, non-alcoholic steatohepatitis (NASH), and NASH cirrhosis were included from public and private hospitals. Costs of hospitalization, physician fees, investigation costs, expenditures on medical procedures, drugs; and nonmedical costs such as transport expenses and other informal payments (tips) were estimated. Results: The overall cost per patient per evaluation was (16.90-46 942.00) USD. The cost in public and private hospitals was 384.76 and 1146.93 USD, respectively. The cost per patient of NAFLD was 157.91 (16.90-955.08) USD, and for NASH cirrhosis was 1783.80 (422.48-46 942) USD. The cost of illness increased to USD 281.18 for diabetics and 254.52 USD for hypertensive. If all the NAFLD patients are evaluated once in healthcare settings, the projected cost will be 7.11 billion USD. In NAFLD, cost for investigations, medicines, transportation, and consultation of physicians was 49.08%, 32.41%, 11.11%, and 6.67%, respectively. Conclusions: NAFLD is causing a huge economic burden to the healthcare system. The cost of illness is increased with NASH cirrhosis. Overall, this study provides valuable insights into the economic burden of NAFLD in Bangladesh and emphasizes the several ways of intervention to reduce the cost by preventive measures and accessible healthcare for affected individuals.

High Prevalence of Hepatitis B and C Virus Infections Among Rohingya Refugees in Bangladesh: A Growing Concern for the Refugees and the Host Communities.

Content available: Audio Recording.

Transition of an acronym from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a global public health concern owing to its substantial contribution to chronic liver diseases. The disease is closely linked to metabolic syndrome (MS), suggesting a common biological pathway and shared disease mechanism for both ailments. Previous studies revealed a close relationship of NAFLD with the components of MS including abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Hence, a group of experts recently renamed NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) in order to encompass a more appropriate pathogenesis of the disease. NAFLD was first named to describe a condition similar to alcoholic hepatitis in absence of significant alcohol consumption. However, knowledge pertaining to the etiopathogenesis of the disease has evolved over the past four decades. Recent evidence endorses NAFLD as a terminology of exclusion and suggests that it may often leads to misdiagnosis or inappropriate management of patients, particularly in clinical practice. On the other hand, the new definition is useful in addressing hepatic steatosis with metabolic dysfunction, which ultimately covers most of the patients with such illness. Therefore, it seems to be helpful in improving clinical diagnosis and managing high-risk patients with fatty liver disease. However, it is imperative to validate the new terminology at the population level to ensure a holistic approach to reduce the global burden of this heterogeneous disease condition.

Risk factors of nonalcoholic fatty liver disease in lean body mass population: A systematic review and meta-analysis.

The pathophysiology and risk factors of nonalcoholic fatty liver disease (NAFLD) among lean patients is poorly understood and therefore investigated. We performed a meta-analysis of observational studies. Of 1175 articles found through searching from Medline/PubMed, Banglajol, and Google Scholar by two independent investigators, 22 were selected. Data from lean (n = 6768) and obese (n = 9253) patients with NAFLD were analyzed; lean (n = 43 398) and obese (n = 9619) subjects without NAFLD served as controls. Age, body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure (DBP) had significantly higher estimates in lean NAFLD patients than in lean non-NAFLD controls. Fasting blood sugar [MD(mean difference) 5.17 mg/dl, 95% CI(confidence interval) 4.14-6.16], HbA1c [MD 0.29%, 95% CI 0.11-0.48], and insulin resistance [HOMA-IR] [MD 0.49 U, 95% CI 0.29-0.68]) were higher in lean NAFLD patients than in lean non-NAFLD controls. All components of the lipid profile were raised significantly in the former group except high-density lipoprotein. An increased uric acid (UA) level was found to be associated with the presence of NAFLD among lean. Cardio-metabolic profiles of nonlean NAFLD patients significantly differs from the counter group. However, the magnitude of the difference of lipid and glycemic profile barely reached statistical significance when subjects were grouped according to lean and nonlean NAFLD. But DBP (slope: 0.19, P < 0.037), HOMA-IR (slope: 0.58, P < 0.001), and UA (slope: 0.36, P = 0.022) were significantly higher if NAFLD was present compared to that of non-NAFLD group. Lean and nonlean NAFLD patients are metabolically similar and share common risk factors.

The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.

Effect of telmisartan and vitamin E on liver histopathology with non-alcoholic steatohepatitis: A randomized, open-label, noninferiority trial.

BACKGROUND AND AIM: To compare the effect of telmisartan and vitamin E on liver histopathology of non-alcoholic steatohepatitis (NASH) patients. METHODS: This noninferiority clinical trial was conducted for 1 year. Fatty liver patients with non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 5 (in liver biopsy) were selected. All methods were in accordance with the Declaration of Helsinki. Patients who received telmisartan and vitamin E were denoted as Group-T and Group-E, respectively. Forty patients >18 years old were assigned and divided into two groups (20 in each group). Histological improvements were primary outcome measures. RESULTS: Significant improvement in NAS score was noted in both groups (Group E [GE]: 6 ± 0.8 to 4.36 ± 1.4; P = 0.00 and Group T [GT]: 5.6 ± 0.7to 4.9 ± 1.2; P = 0.03). Fibrosis score improved from 1.6 ± 0.5 to 1.5 ± 0.5 in GE and from 1.7 ± 0.9 to 1.5 ± 0.7 in GT (P = 0.67 and 0.42, respectively). Steatosis improved in GE from 2.07 ± 0.6 to 1.14 ± 0.66 (P = 0.00) and in GT from 1.94 ± 0.57 to 1.56 ± 0.8 (P = 0.05). Lobular inflammation improved from 2.0 ± 0.4 to 1.6 ± 0.5 in GE (P = 0.02) and from 1.9 ± 0.3 to 1.8 ± 0.4 in GT (P = 0.58). Ballooning score in GE decreased from 1.9 ± 0.3 to 1.7 ± 0.5 (P = 0.03), and in GT, it reduced from 1.9 ± 0.1 to 1.5 ± 0.5 (P = 0.19). NAS improvement was similar in GE (1.6 ± 1.2) and GT (0.6 ± 1.1; P = 0.07) when controlled for weight reduction. CONCLUSION: Telmisartan was similar to vitamin E in improving the histology of NASH patients.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Non-alcoholic fatty liver disease (NAFLD) among underweight adults.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), closely linked to obesity, has also been evident in lean and underweight adults. But data pertaining to NAFLD in underweight adults in Bangladesh is very limited. Therefore, we sought to estimate the prevalence and identify the factors associated with NAFLD in underweight adults in Bangladesh. METHODS: Underweight adults (BMI <18.5 kg/m2) who underwent abdominal imaging from December 2015 to January 2017 were included in this analysis. Multivariable logistic regression was performed to identify the factors associated with NAFLD in underweight adults. RESULTS: Total 286 (female = 117) participants with a mean age of 28.4 (±13.0) years were included in this analysis. The prevalence of NAFLD in underweight adults was 5.2% (95% CI: 2.6, 7.8). The prevalence was higher in adults ≥30 years (9.2 vs. 3.5 p-value = 0.048), married (9.0 vs. 1.4, p-value = 0.004), sedentary workers (8.7 vs. 1.5, p-value = 0.006, and diabetic individuals (60.0 vs. 5.0, p-value<0.001) compared to their counterparts. Multivariable logistic regression model demonstrated that rural residents had higher odds (aOR: 3.93, 95% CI: 1.07, 14.49, p-value = 0.048) of having NAFLD than urban inhabitants. The odds of NAFLD was 5 times higher (aOR: 5.60, 95% CI: 1.04, 30.29, p-value = 0.046) in patients with positive family history of metabolic traits. Being non-diabetic was protective against NAFLD (aOR: 0.06, 95% CI: 0.01, 0.45, p-value = 0.005) in this selected population. CONCLUSION: The study results delineate that underweight adults living in rural areas, with a positive family history of metabolic traits and being diabetic are more likely to develop NAFLD in Bangladesh.

Effect of Weight Reduction on Histological Activity and Fibrosis of Lean Nonalcoholic Steatohepatitis Patient.

BACKGROUND AND OBJECTIVES: Weight reduction has evidenced benefit on attenuation of histological activity and fibrosis of nonalcoholic steatohepatitis (NASH), but there is scarcity of data for lean NASH subgroup. We have designed this study to compare the effects of weight reduction on histological activity and fibrosis of lean and non-lean NASH. METHODS: We have included 20 lean and 20 non-lean histologically proven NASH patients. BMI < 25 kg/m2 was defined as non-lean. Informed consent was taken from each subject. All methods were carried out in accordance with the Declaration of Helsinki. Moderate exercise along with dietary restriction was advised for both groups for weight reduction. After 1 year, 16 non-lean and 15 lean had completed second liver biopsy. RESULTS: Age, sex, alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltrasferase (GGT), Homeostasis model assessment insulin resistance (HOMA-IR), triglyceride and high density lipoprotein (HDL) was similar in both groups. Steatosis, ballooning, lobular inflammation, nonalcoholic fatty liver disease activity score (NAS) and fibrosis was similar in the two groups. In lean/non-lean group, any amount of weight reduction, ≥ 5% weight reduction and ≥ 7% weight reduction was found in respectively 8/11, 5/6 and 2/6 patients. In both lean and non-lean groups, weight reduction of any amount was associated with significant reduction of steatosis, ballooning and NAS, except lobular inflammation and fibrosis. In both groups, weight reduction of ≥ 5% was associated with significant reduction in NAS only. However, significant improvement in NAS was noted with ≥ 7% weight reduction in non-lean group only. CONCLUSION: Smaller amount of weight reduction had the good benefit of improvement in all the segments of histological activity in both lean and non-lean NASH.

Clinical, anthropometric, biochemical and histological character of nonalcoholic fatty liver disease without Insulin Resistance.

OBJECTIVES: Nonalcoholic Fatty Liver Disease (NAFLD) is thought to be a hepatic manifestation of Metabolic Syndrome (MS) or Insulin Resistance (IR). The aim of the study was to explore the clinical, anthropometric, metabolic, biochemical and histological profile of NAFLD patients without IR by comparing it with NAFLD with IR. METHODS: Total 851 patients with sonographic evidence of fatty liver were included. These patients underwent clinical, anthropometric, biochemical and histological evaluation. IR was calculated using the homeostatic model assessment. Liver biopsy done in 285 patients who consented for the procedure and who had MS or raised ALT. RESULTS: Among 851 NAFLD patients, 561(65.9%) patients were without IR and 290 (34.1%) patients were with IR. The proportion of male sex [230 (41.0%) vs. 89 (30.7%); P = 0.046] were higher but diabetes [19.10% vs. 39.0%; P = 0.000] and MS were [58.80%vs. 78.10%; P = 0.014] significantly lower in non IR group. Body Mass Index (BMI) kg/m2 and Waist Circumference (WC) in cm were also lower in non IR group: [26.6 ± 3.5 vs. 27.9 ± 4.3; P = 0.002] and [93.3 ± 8.4 vs. 95.9 ± 8.4; P = .003]. Lipid profile, ALT, AST and ALP were not differed between the groups. Histopathology reports revealed that lobular inflammation, ballooning and fibrosis were similar in two groups, only steatosis score was higher in IR group [2.0 ± 0.7 vs. 1.8 ± 0.8; P = 0.007]. CONCLUSION: There are significant proportion of NAFLD patients without IR in Bangladesh. NAFLD patients without IR predominantly male, had lower BMI, WC, MS and diabetes. Histologically NAFLD without IR equally severe with ballooning, lobular inflammation and fibrosis except steatosis. Insulin resistance is the principal but not the sole factor for NAFLD in our population.

Financing health care in Bangladesh: Policy responses and challenges towards achieving universal health coverage.

Bangladesh has attained notable progress in most of the health indicators, but still, health system of the country is suffering badly from poor funding. Issues like burden of out-of-pocket expenditure, low per capita share in health, inadequate service facilities, and financial barriers in reducing malnutrition are being overlooked due to inadequacy and inappropriate utilization of allocated funds. We aimed to review the current status of health care spending in Bangladesh in response to national health policy (NHP) and determine the future challenges towards achieving universal health coverage (UHC). National health policy suggested a substantial increase in budgetary allocation for health care, although government health care expenditures in proportion to total public spending plummeted down from 6.2% to 4.04% in the past 8 years. Overall, 67% of the health care cost is being paid by people, whereas global standard is below 32%. Only one hospital bed is allocated per 1667 people, and 34% of total posts in health sector are vacant due to scarcity of funds. The country is experiencing demographic dividend with a concurrent rise of aged people, but there seems no financial protection schemes for the aged and working age populations. Such situation results in multiple obstacles in achieving financial risk protection as well as UHC. Policy makers must think effectively to develop and adapt systems in order to achieve UHC and ensure health for all.

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

BACKGROUND AND AIM: 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. METHODS: A cross-sectional study was conducted both in urban and rural areas of Bangladesh from December 2015 to January 2017. Data were collected using a pretested structured questionnaire followed by ultrasonography of hepatobiliary system for screening of NAFLD. Multivariate logistic regression was used to estimate the risk factors of NAFLD. RESULTS: A total of 2782 (1694 men and 1088 women) participants were included in the study, with a mean age of 34.21 (±12.66) years. The overall prevalence of NAFLD was 33.86% (95% confidence interval [CI]: 32.12, 35.64). Females living in the rural areas and midlife adults (45-54 years) had the highest prevalence of NAFLD (P < 0.05). Multivariable logistic regression model demonstrated that increasing age, diabetes, elevated body mass index, and married individuals are significantly associated with NAFLD. Individuals with diabetes (adjusted odds ratio: 2.71, 95% CI: 1.85, 3.97) and hypertension were at a higher risk of having NAFLD. The odds of having NAFLD were 4.51 (95% CI: 3.47, 5.86) and 10.71 (95% CI: 7.80, 14.70) times higher among overweight and obese participants, respectively, as compared to normal-weight participants. CONCLUSIONS: About one-third of the population of Bangladesh is affected by NAFLD. Individuals with higher body mass index (overweight and obese), diabetics, midlife adults, married individuals, and rural women were more at risk of having NAFLD than others.

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.

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.

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). METHODS: Patients were selected for the study if they had histological evidence of NAFLD and clinical evidence of non-alcoholic steatohepatits (NASH) cirrhosis. We included 50 NASH cirrhosis, 99 patients of NAFLD including 36 non-NASH fatty liver (NNFL) along with 63 NASH and 75 healthy controls. PNPLA3 genotyping was done by real-time PCR using a Taqman assay for rs738409. RESULTS: CC, CG, and GG frequencies were 45 (60.0%)/27 (36.0%)/3 (4.0%) in healthy control, 19 (52.8%)/14 (38.9%)/ 3 (8.3%) in NNFL, 18 (28.6%)/29 (46.0%)/16 (25.4%) in NASH, and 7 (14.6%), 25 (52.1%), 16 (33.3%) in cirrhosis. The frequency of G allele was significantly higher (62.6%) in NAFLD than in healthy control. The GG genotype had 20.25 times odds of NAFLD. The GG genotype had 6.53 times odds of having NASH. HOMA-IR > 1.6 had 3.81 times odds of having NASH. Regression analysis revealed that G allele odds of having cirrhosis was 3.9 times compared to C. The G allele was also significantly associated with steatosis, lobular inflammation, NAFLD activity score, and fibrosis. CONCLUSION: PNPLA3 genotype showed an association with NAFLD, NASH, fibrosis, and cirrhosis.

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.

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.