Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

Obstructive Jaundice with skin involvement - An unusual presentation of Myeloid Sarcoma.

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to leukemia, and obstructive jaundice in these patients usually presents late in the course of the disease. We present a rare case of a patient who presented with fever, jaundice, and pruritus with multiple nodular swellings in the left shoulder, left thigh, and lower back. Magnetic resonance cholangiopancreatography (MRCP) revealed periampullary mass lesion causing dilated common bile duct (CBD) and intrahepatic bile ducts; hence, endoscopic retrograde cholangiography with plastic stenting was done. Biopsy from the shoulder lesion revealed a mesenchymal tumor, and immunohistochemistry (IHC) confirmed the lesion as myeloid sarcoma. Myeloid sarcoma is an extramedullary tumor, a subtype of acute myeloid leukemia, and presentation as biliary lesions with multiple anatomical sites is very rare. The patient was started on chemotherapy after the normalization of bilirubin. The patient showed improvement of skin lesions and normalization of liver function test (LFT) after 3 weeks of chemotherapy.

A Prospective Study on the Clinical Significance of Infections in a Hospital Setting Among the Cirrhotic Patients and Their Outcomes.

Aim and objectives The infection of microbial agents in cirrhosis has increased due to poor immunity, which increases morbidities and mortalities worldwide. The present study aimed to assess the incidence, the type of infections, the pattern of resistance, and the course of hospitalization among cirrhotic patients in the Eastern coastal region. Methodology The study was a descriptive cross-sectional study, and the current study was undertaken for 24 months at the Department of Gastroenterology and Hepatobiliary Sciences, IMS, and SUM. Hospital, Bhubaneswar. Consecutive cirrhotic patients admitted with bacterial infection were prospectively evaluated, and the infection patterns were accessed. The data were collected in a well-structured proforma designed by our study team. Results Out of the total 200 cases, a fraction of 72.5% of males outnumbered the females; the mean age of presentation was 59 ± 12 years. A fraction of 59% of cases had the habit of consuming alcohol which amounted to the predominant etiological factor for cirrhosis, followed by non-alcoholic steatohepatitis (NASH). Urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP) were more common types of infections in the healthcare-associated (HCA) group; however, pneumonia and skin and soft tissue infections (SSTI) were predominant types of infections in community-acquired (CA) group. The model for end-stage liver disease (MELD) scores were not significantly different amongst the three groups with infections at the time of Diagnosis infection and at the time of hospitalization. However, the MELD scores were substantially higher at the time of infection diagnosis than the MELD scores at the time of admission amongst the three groups with infection. Conclusion The present study showed that infections in cirrhosis were relatively common. Due to increasing resistance patterns, the judicious usage of antibiotics in cirrhosis could be the need of the hour.

Burkholderia cepacia causing liver and splenic abscess: Two case reports.

Burkholderia cepacia infections are common among immunocompromised patients but multiple reports have shown that it can affect immunocompetent patients also. We are reporting two patients with multiple liver and splenic abscesses caused by Burkholderia cepacia. First case is a 54-year-old diabetic male presenting with fever, abdominal pain, bilateral lower limb weakness, and incontinence of urine. Second case is a 41-year-old male presenting with fever and confusion. Both had liver and splenic abscesses. Pus aspirated from the abscesses grew Burkholderia cepacia. Both responded to cotrimoxazole. Our case report emphasizes growing incidence of Burkholderia cepacia in immunocompetent patients.

Knowledge, Awareness and Prevalence of Hepatitis B Among Urban Slum Dwellers and Residents of Social Welfare Home: A Cross sectional Study From Eastern India.

Background/aims: In view of limited data on the knowledge and awareness of hepatitis B virus (HBV) and the available preventive strategies at the community level, it was aimed to analyse the knowledge and awareness of HBV in the community. Methods: A cross-sectional questionnaire-based survey was conducted among residents of an urban slum and a social welfare home in Bhubaneswar, Odisha, from October 2019 to April 2021. The prevalence of HBV infection was also measured by testing the serum positivity for hepatitis B surface antigen using rapid point-of-care test kits. The statistical analysis was done by using the software SPSS version 20. Results: A total of 370 individuals (mean age 38.7 ± 14.9 years, males: 55.1%) were assessed. Although 18.1% (67) had good knowledge, only 16.7% (62) had good awareness about HBV. Approximately 14.8% (55) knew that a vaccine is available in the country for HBV, and 6.2% (23) identified themselves as being vaccinated. Educational status was a significant independent predictor of knowledge and awareness such that people with education level of matriculation and above had odds of 11.05 (95% confidence interval: 5.3-22.7) and 14.7 (95% confidence interval: 6.5-33.1) for having good knowledge and awareness regarding HBV, respectively. A total of 10 participants tested positive for hepatitis B surface antigen contributing to a point prevalence rate of 2.7%. The proportion of individuals with an education status of matriculation and above was higher in the slum area when compared with the welfare home (67% vs 33%; P < 0.001), the knowledge (71.6% vs 28.4%; P < 0.001) and so was the awareness (71% vs 29%; P < 0.001) about HBV as well. Conclusion: The relatively low figures of knowledge and awareness identified in our study undermine the need for intensification of health education and promotion activities regarding the prevalence of hepatitis B infection on a large scale at the community level.

Evaluating the Association of Genetic Polymorphism of Cytochrome p450 (CYP2C9*3) in Gastric Cancer Using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).

Background and aim As a distinguished system, the cytochrome P450 (CYP) enzyme superfamily is involved in the biotransformation of several endogenous and exogenous substances including drugs, toxins, and carcinogens. Reports on the role of CYP enzyme in gastric cancer (GC) from the Eastern region of India are scarce. The present study aimed to evaluate the effect of single nucleotide polymorphisms (SNP) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9*3) among cases with gastric malignancy. Material and methods The current study is a cross-sectional observational study carried out among 113 GC cases attending the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, and Srirama Chandra Bhanja Medical College and Hospital, Cuttack, India. Two ml of venous blood was collected from the confirmed cases of GC. The samples were subjected to genomic DNA isolation followed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP). Results The prevalence of both homozygous and heterozygous mutation in GC cases is 4% and 8%, respectively. The overall association of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) mutation in GC cases is 12% whereas 88% were detected as wild/standard type. The mutation CYP2C9 SNP has been seen in Helicobacter pylori-infected cases and as well as those without H. pylori infection. Conclusions The CYP2C9*3 genetic polymorphism might play a significant role as a risk factor for the development of gastric malignancy irrespective of H. pylori infection, among the eastern Indian population.

Effect of Dapagliflozin on Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Single-Center Survey.

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 20%-40%. Approximately 40%-60% of patients with type 2 diabetes mellitus (DM2) experience NAFLD; out of which 20%-40% cases may have higher severity. Due to the scarcity of available reports from the eastern part of India, we aimed to evaluate the effects of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor used in these types of cases. Material and methods The study included consecutive patients with DM2 and NAFLD, treated with dapagliflozin at 10 mg daily for six months. All patients underwent detailed anthropometric, biochemical, abdominal ultrasonography, and transient elastography studies at baseline and after therapy as well as a comparative analysis. Results In the 100 patients included in our study, the male patients outnumbered the female patients (male-to-female ratio, 4.27:-1) and the mean age at presentation was 44.11 ± 8.24 years. The mean body mass index significantly decreased over the course of the therapy, from 27.31± 1.87 kg/m2 at baseline to 26.21 ± 1.51 kg/m2 after the therapy. The patients' transaminitis, dyslipidemia, and glycemic status significantly improved over the course of the therapy. We also observed significant (p < 0.05) improvement in hepatic steatosis by the end of the treatment. Although transient elastography by FibroScan-measured hepatic fibrosis score (Echosens, Paris, France) significantly decreased from 6.95 ± 1.42 to 6 ± 1.44 kPa, hepatic fibrosis did not improve significantly (p ≥ 0.05) following therapy. Conclusion Although dapagliflozin improved body mass index, transaminitis, dyslipidemia, glycemic status, and hepatic steatosis, it had a minimal effect on hepatic fibrosis.

SPINK1 Mutation in Idiopathic Chronic Pancreatitis: How Pertinent Is It in Coastal Eastern India?

Background and aim Idiopathic chronic pancreatitis (ICP) is said to be present when no identifiable etiology can be identified. Robust evidence suggested that the serine protease inhibitor nucleus Kazol type 1 (SPINK1) N34S mutation was frequently associated with ICP. As there is a paucity of data on genetic studies in ICP cases from the coastal eastern region of India, we performed this study with an aim to evaluate the SPINK1 genetic mutations and other associated clinical correlates in ICP cases. Material and methods Consecutive ICP cases attending the department of gastroenterology, Institute of Medical Sciences (IMS) and SUM Hospital, were enrolled and evaluated for the pertinent clinical history and undergone detailed biochemical and radiological evaluations. Two ml of venous blood in ethylenediaminetetraacetic acid (EDTA) vials were collected from each case and subjected to a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) test for genetic analysis. Result In this study, the mean age of the cases at the time of the first consultation with us and the age of the first clinical presentation were 34.52±6.44 and 28.73±5.52 years, respectively. Males outnumbered females (Male:Female - 2.12:1). Out of the total of 200 cases, 50% had no SPINK1 mutation, whereas 40% and 10% cases had SPINK1 N34S heterozygous and homozygous mutations, respectively. The mean age of clinical presentation, severe abdominal pain, exocrine and endocrine insufficiency, and parenchymal atrophy were significantly more common in mutants as compared to non-mutants (p-value <0.05). Conclusion In our region, 50% of ICP cases had the SPINK1 N34S mutation. The SPINK1 mutants had a relatively more severe variety of pancreatitis as compared to non-mutants.

Tenofovir is Superior to Entecavir in Patients with Treatment-naïve Hepatitis B e-Antigen-Positive Chronic Hepatitis B.

BACKGROUND AND AIM: Chronic Hepatitis B (CHB) is a global health problem affecting around 400 million of people worldwide. Two available first-line antiviral drugs are tenofovir disoproxil fumarate (TDF) and Entecavir (ETV). Till date,there are few published reports from India comparing efficacy of TDF and ETV in CHB cases. Therefore, this present study was carried out with an aim to compare the efficacy of ETV and TDF in patients with nucleos(t)ide naïve CHB. MATERIALS AND METHODS: This retrospective cohort study was carried out in 192 treatment naïve CHB cases, who completed 24 months of treatment with either TDF or ETV between March 2015 and August 2017. The primary end point of the study was undetectable hepatitis B virus DNA after 24 months of therapy. RESULTS: Of total 192 patients with CHB, 38 hepatitis B e-antigen (HBeAg)-positive and 53 HBeAg-negative patients were treated with tenofovir, whereas 40 HBeAg-positive and 61 HBeAg-negative patients were treated with ETV. Pretreatment characteristics at baseline were not statistically different between the TDF and ETV groups. Patients treated with TDF achieved significantly higher complete viral suppression as compared with ETV-treated patients (Log rank: 7.04, P = 0.008) in HBeAg-positive CHB during the 24 months follow-up time; whereas no significant difference in viral suppression rate could be noticed in HBeAg-negative patients (Log rank: 0.98, P = 0.38). Both univariate and multivariate analysis by cox proportional hazard model confirmed that tenofovir had significant rate of complete viral suppression in comparison with ETV in HBeAg-positive patients (P < 0.05); whereas complete viral suppression rates were similar in HBeAg-negative patients. CONCLUSION: In our study, tenofovir had more effective antiviral suppressive effect compared with ETV in HBeAg-positive, nucleos(t)ide-naïve CHB cases.

Irritable Bowel Syndrome and the Menstrual Cycle.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder. Female patients with bowel disease commonly report worsening of symptoms in the menstrual cycle. However, there is a paucity of data regarding IBS presentations' variation during different phases of the menstrual cycle. The current study aimed to evaluate the same in female IBS patients. MATERIALS AND METHODS: Consecutive premenopausal female patients with the diagnosis of IBS attending the outdoor (OPD) of Department of Gastroenterology and Gynaecology; IMS and SUM Hospital, Bhubaneswar, Odisha from June 2019 to December 2019 were included in the study and evaluated by a set of questionnaires regarding various presentations during all the three phases of the menstrual cycle. RESULTS: Consecutive 102 cases with the diagnosis of IBS were included in the study and evaluated. The mean age of presentation was in mid-30s. Most of the subjects suffered from IBS mixed (IBS-M) type. More patients significantly suffered from constipation (27.27%) during the luteal phase of their menstrual cycles than the menstrual period of their cycles (p - 0.009). More than 50% of all the cases suffered from abdominal bloating during all phases of the menstrual cycle, which was quite disturbing and affected the quality of life. These IBS patients were more symptomatic with more significant limitation of daily activities, suffered from low quality of life, and obtained physician consultation during the menstrual phase as compared to other cycle stages. CONCLUSION: Premenopausal female patients with IBS become much more symptomatic during the menstrual phase of the cycle than other stages of the cycle.

Simple Anthropometric Indices are Useful for Predicting Non-alcoholic Fatty Liver Disease [NAFLD] in Asian Indians.

BACKGROUND AND AIMS: With the rising prevalence of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder in both developed and developing nations. Several studies on NAFLD have described waist circumference, a surrogate marker of visceral fat accumulation and waist height ratio as a better screening tool for NAFLD and metabolic syndrome than body mass index (BMI). We conducted this study to assess simple abdominal obesity indices as a predictor of NAFLD and determine the appropriate cut-off levels with reference to NAFLD. METHODS: 1000 subjects with NAFLD detected ultrasonographically and 360 controls attending a Gastroenterology Clinic at Cuttack, Odisha were included in the study and subjected to detailed anthropometric measurements. The abdominal anthropometric cut offs were determined using ROC analysis. Statistical analysis was performed by using SPSS software version 16. RESULTS: All receiver operating curve (ROC) curves of waist circumference, waist-height ratio and BMI were significantly above the diagonal line. There were no significant differences in the area under the curve values among these abdominal obesity indices in each gender. The appropriate cut-off point of waist circumference in screening for NAFLD was 89 cm for men and 84 cm for women and the optimal cut-off point of waist-height ratio was 0.53 for men and 0.57 for women and the cut-off point of waist to hip ratio was 0.94 for men and 0.87 for women with very good sensitivity and specificity. CONCLUSIONS: The simple anthropometric parameters, such as BMI, waist circumference, waist-hip ratio and waist-height ratio are useful for predicting NAFLD in Indian adults. The anthropometry cut offs would be very useful in setting target points of life style modification and weight reduction. Besides, our study also clearly demonstrated that a simple assessment of BMI is as efficacious as other anthropometry parameters in predicting NAFLD.

Nonalcoholic Fatty Liver Disease in South Asia.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the West, and is also increasing alarmingly in South Asia, reaching an epidemic proportion of 30% because of epidemic of obesity and metabolic syndrome (MS) in younger South Asians in the last two decades. Prevalence of MS and fatty liver is escalating in geometric progression in South Asian countries, such as India, Pakistan, Sri Lanka, Bangladesh, Nepal, Bhutan, Burma, and Maldives because of sedentary lifestyle, poor health awareness, socioeconomic growth, affluence, urbanization, and dietary westernization. Almost 20% of world's population resides in South Asia, making it the most populous and most densely populated geographic region in the world, thereby having most of MS and NAFLD cases within its territory. The risk factors and course of NAFLD do not differ between South Asians and other ethnic populations, but the obesity epidemic is more recent in South Asia than elsewhere in the world. Nonalcoholic fatty liver disease may progress through stages of simple bland steatosis, nonalcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). It is frequently associated with obesity, MS, dyslipidemia, insulin resistance (IR), and type-2 diabetes mellitus (DM). Nonalcoholic fatty liver disease is frequently diagnosed with abdominal ultrasonography (US) study. Despite its high prevalence in the community till now, no definitive pharmacotherapy is available for NAFLD. However, modification of risk factors, such as dyslipidemia, control of diabetes, and weight reduction do help to some extent. The nonobese South Asians are also at increased risk of having NAFLD and NASH as, despite of absence of frank obesity in South Asians, they are metabolically more obese compared to other ethnic population and more prone to develop NAFLD-related complications. Therefore, the cost-effective US abdomen should be included in the list of tests for persons undergoing preemployment or master health checkups for early diagnosis of NAFLD in this resource-constraint South Asian region, so that early necessary measures can be undertaken to reduce NAFLD associated morbidity and mortality in the community. HOW TO CITE THIS ARTICLE: Pati GK, Singh SP. Nonalcoholic Fatty Liver Disease in South Asia. Euroasian J Hepato-Gastroenterol 2016;6(2):154-162.

Risk Factors Associated With Non-Alcoholic Fatty Liver Disease in Indians: A Case-Control Study.

BACKGROUND/AIMS: NAFLD has today emerged as the leading cause of liver disorder. There is scanty data on risk factors associated with NAFLD emanating from India. The present study was conducted to identify the risk factors associated with NAFLD. METHODS: 464 consecutive NAFLD patients and 181 control patients were subjected to detailed questionnaire regarding their lifestyle and dietary risk factors. Anthropometric measurements were obtained and biochemical assays were done. Comparison of different variables was made between NAFLD patients and controls using principal component analysis (PCA). RESULTS: NAFLD patients had higher BMI [26.25 ± 3.80 vs 21.46 ± 3.08 kg/m(2), P = 0.000], waist-hip ratio [0.96 ± 0.12 vs 0.90 ± 0.08, P = 0.000] and waist-height ratio [0.57 ± 0.09 vs 0.50 ± 0.06, P = 0.000] compared to controls. Fasting blood sugar [101.88 ± 31.57 vs 90.87 ± 10.74 mg/dl] and triglyceride levels [196.16 ± 102.66 vs 133.20 ± 58.37 mg/dl] were significantly higher in NAFLD group. HOMA-IR was also higher in NAFLD group [2.53 ± 2.57 vs 1.16 ± 0.58, P = 0.000]. Majority (90.2%) of NAFLD patients were sedentary. Family history of metabolic syndrome (MS) was positively correlated with NAFLD. Dietary risk factors associated with NAFLD were non-vegetarian diet [35% vs 23%, P = 0.002], fried food [35% vs 9%, P = 0.000], spicy foods [51% vs 15%, P = 0.001] and tea [55% vs 39%, P = 0.001]. Diabetes, hypertension, snoring and sleep apnoea syndrome were common factors in NAFLD. On multivariate PCA, waist/height ratio and BMI were significantly higher in the NAFLD patients. CONCLUSION: The risk factors associated with NAFLD are sedentary lifestyle, obesity family history of MS, consumption of meat/fish, spicy foods, fried foods and tea. Other risk factors associated with NAFLD included snoring and MS.