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.

Association of GCKR and MBOAT7 genetic polymorphisms with non-alcoholic fatty liver disease.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease (CLD) in both Western and Asian populations. There is wide inter-individual variability in the occurrence of NAFLD and progression to non-alcoholic steatohepatitis (NASH) even after correcting environmental factors, and its true explanation can be provided by heritability. Two such genetic variations, the glucokinase regulator (GCKR) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes, in NAFLD patients were studied in the Indian population. Material and methods: A cross sectional analytical study was conducted in the Department of Gastroenterology at a tertiary care centre. In total 100 subjects in the age range of 18-65 years were included in the study; 50 were patients with NAFLD including fatty liver, NASH and NASH related cirrhosis, and 50 were healthy subjects (No NAFLD). The polymorphisms rs780094 and rs1260326 for GCKR and rs641738 for MBOAT7 were determined using PCR followed by the PCR-RFLP. Results: GCKR rs780094 minor allele A was more common in NAFLD patients (p = 0.00001). Within the spectrum of NAFLD, the A allele was present frequently among cirrhotics as compared to NASH and fatty liver (p = 0.00001). Morbidly obese individuals showed significant association with the homozygous A allele (p = 0.028). These results were not seen with GCKR rs1260326 across all alleles. In MBOAT7 (rs641738) the frequency of the minor allele T for NAFLD was 84% vs. 80% in healthy subjects (p = 0.79). The association of the T allele among the spectrum of NAFLD was not statistically significant (p = 0.79). Conclusions: GCKR genetic variant rs780094 was found to be significantly associated with NAFLD. The MBOAT7 (rs641738) genetic variant was not found to be significantly associated with NAFLD.

Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus Retreatment in Difficult-to-treat Patients: A Real-life Observational Study from India.

Background and aim: Hepatitis C virus (HCV) treatment fails to achieve sustained virological response at 12 weeks (SVR12) in 5-10 % and requires retreatment with second-line drugs. We report our experience of sofosbuvir/velpatasvir/voxilaprevir use for HCV retreatment in a small cohort of difficult-to-treat Indian patients. Methods: We reviewed our HCV databases to identify the patients who had failed to achieve SVR12 after treatment with sofosbuvir in combination with either daclatasvir, ledipasvir, or velpatasvir with/without ribavirin on one or more occasions. Participants were excluded if they had (i) decompensated cirrhosis, (ii) HIV coinfection or (iii) chronic kidney disease, or (iv) prior organ transplantation. All the participants were treated with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks. Treatment outcome was categorized as successful or failure if HCV RNA was undetectable or detectable at SVR12, respectively. Results: Fifteen patients (male 67 %; genotype-3 80 %) were included in the analysis. Ten (67 %) had cirrhosis. Five, eight, and two participants had previously failed one, two, and three courses of pegylated-interferon free, sofosbuvir containing direct acting antiviral (DAA) regimens respectively. Fourteen participants had failed to at least one course of the sofosbuvir/velpatasvir combination. Fourteen patients achieved SVR12, and one patient was lost to follow-up. Treatment was successful in 100 % and 93.3 % of per-protocol (PP) and intention to treat (ITT) analyses, respectively. Conclusion: Sofosbuvir/velpatasvir/voxilaprevir combination is an effective second-line therapy in India for difficult-to-treat HCV patients.

Auxiliary Partial Orthotopic Liver Transplant as a Rescue Procedure for Acute Liver Failure with Extra-Small-for-Size Grafts: A Report of 2 Cases.

Auxiliary partial orthotopic liver transplant is a complex technique whereby a partial liver graft is transplanted in the orthotopic position, leaving behind a portion of the native liver. In acute liver failure, auxiliary partial orthotopic liver transplant serves as a rescue therapy and bridge for the native liver to regenerate. Auxiliary partial orthotopic liver transplant was initially considered a technically challenging procedure with inferior results versus orthotopic liver transplant. However, advancements in surgical techniques have led to improved results with auxiliary partial orthotopic liver transplant. Auxiliary partial orthotopic liver transplant is now increasingly accepted as a valid treatment option for acute liver failure. We present 2 cases of acute liver failure treated with auxiliary partial orthotopic liver transplant using an extra-small-for-size graft. The first case was a 12-year-old female patient who presented with druginduced acute liver failure and required an auxiliary partial orthotopic liver transplant with an extra-small left lobe graft (graft-to-recipient weight ratio of 0.45). The second case was a 23-year-old male patient with acute liver failure of unknown etiology who underwent an auxiliary partial orthotopic liver transplant with a small right lobe graft (graft-torecipient weight ratio of 0.5). In both cases, computed tomography liver volumetry was performed to determine the appropriate graft size for the recipient. Both patients underwent successful auxiliary partial orthotopic liver transplants, with good postoperative recovery. Follow-up examinations showed satisfactory liver function without evidence of graft failure or rejection. Auxiliary partial orthotopic liver transplant using extra-small grafts can be an effective treatment option for acute liver failure when no other suitable option exists, including as a rescue procedure for small grafts. However, careful patient selection and surgical planning are essential to ensure successful outcomes.

Study and Comparison of Metabolic Profile of Lean and Obese Subjects with Non Alcoholic Fatty Liver Disease.

BACKGROUND AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is conventionally considered to be a disease of obese subjects. Recent data suggests increasing incidence of NAFLD among lean subjects also. The aim of this study was to evaluate the metabolic profile of lean subjects with NAFLD and compare it with obese subjects with NAFLD. We also aimed to compare the same with lean subjects without NAFLD. METHODS: This study included 250 subjects with NAFLD and 500 non-NAFLD controls. Clinical, anthropological and biochemical data were collected. Subjects with body mass index (BMI) >= 25 kg/m2 were taken as obese and subjects with BMI <25 kg/m2 were taken as lean. Study population was divided into four groups i.e. lean subjects with NAFLD (LN), obese subjects with NAFLD (ON), lean subjects without NAFLD (LNN) and obese subjects without NAFLD (ONN). RESULTS: Out of 250 NAFLD subjects, 69 (27.6%) were lean. Out of 69 lean subjects with NAFLD, 54 (78.3%) were having diabetes mellitus. Metabolic profile (including lipid profile, diabetic profile) of lean subjects with NAFLD was significantly abnormal in comparison to lean non-NAFLD subjects. Proportion of subjects with metabolic syndrome was also comparable in both lean and obese NAFLD groups. Despite having comparable BMI, LN groups had significantly higher waist circumference (WC) than LNN. Mean total cholesterol, triglyceride, LDL were significantly higher in obese NAFLD in comparison to lean NAFLD. Mean HDL and VLDL were comparable among both groups. Mean FBS, HbA1c, fasting insulin and HOMA-IR were significantly higher among lean NAFLD group in comparison to obese NAFLD group. Obese NAFLD group had significantly higher levels of SGPT and SGOT as compared to lean NAFLD group. CONCLUSION: Lean NAFLD has significantly higher WC in comparison to non-NAFLD counterparts suggesting possible association with central adiposity. Lean and obese NAFLD share common set of metabolic abnormalities, albeit with varying intensity. Lean NAFLD has more severe insulin resistance in comparison to obese NAFLD. Lean NAFLD subjects appeared to have less severe transaminasemia.

The Outcome of Primary Hepatic Neuroendocrine Tumors: A Single-Center Experience.

BACKGROUND: Primary hepatic neuroendocrine tumor is an extremely rare entity. Only case reports are available in the literature. The aim of the study was to analyze the symptoms, diagnosis, management, and the outcome of patients with primary liver neuroendocrine tumors. METHODS: In the study, a total of eight patients were diagnosed with primary liver neuroendocrine tumors between 2001 and 2017 in our center. Data were analyzed from the records available including the presentation, diagnosis, treatment received, and follow-up. RESULTS: Of eight patients, five were males and three were females. The age of presentation was between 35 and 70 years. Two patients had pain in the right side of the abdomen, while it was accidentally detected in two patients in routine checkup. One patient presented with carcinoid syndrome, while two had ascites and one patient presented only with loose motions. Of eight patients, two patients with poorly differentiated neuroendocrine tumor died within 1 month of follow-up. Four patients are still being followed up, while 10-12 years of follow-up data are available for the remaining two patients. Four patients underwent surgery, and three patients received Sandostatin LAR for tumor recurrence after procedure. Transarterial chemoembolization (TACE) of the tumor was performed in two patients for whom resection was not possible. CONCLUSIONS: Our data suggest that the prognosis of the tumor seems favorable. Surgical resection is the curative treatment. TACE is a favorable option in unresectable tumors.

Do additional colonoscopic biopsies increase the yield of Mycobacterium tuberculosis culture in suspected ileo-colonic tuberculosis?

BACKGROUND: Isolation of Mycobacterium tuberculosis on culture is vital for differentiating intestinal tuberculosis (ITB) from Crohn's disease (when histology is not diagnostic) and for diagnosis of multidrug-resistant tuberculosis. The current yield of TB culture (< 50%) from colonoscopic biopsy tissue is not satisfactory. AIM: To determine whether more colonoscopic biopsies can increase the yield of TB culture in patients with ITB. METHODS: In this prospective study, in patients who underwent colonoscopy for suspected ITB, four biopsies were taken (container 1) followed by an additional four biopsies (container 2) for TB culture, from involved regions. The culture was done using Mycobacterium Growth Indicator Tube (MGIT) 960. A final diagnosis of ITB was made if TB culture was positive, there was unequivocal histological evidence of TB, or there was unequivocal evidence of TB elsewhere in the body, in the absence of another diagnosis. RESULTS: Of 182 patients enrolled (mean age 37.5 [SD 17.2] years; 93 [51.5%] women), 70 (38.4%) were finally diagnosed to have ITB. MGIT culture was positive in 29 (41.4%), 27 (38.5%), and 37 (52.8%) of 70 patients from containers 1, container 2, and combined eight biopsies, respectively. The incremental yield of eight biopsies was 11.4% (95% confidence interval [CI] 5.1 to 21.3%) as compared to container 1 and 14.3% (95% CI 7.1 to 24.7%) as compared to container 2. CONCLUSION: Additional four (total eight) colonoscopic biopsies improved the yield of TB culture positivity over four biopsies by 11.4% to 14.3%, to 52.8%; this increase is clinically useful.

An Unusual Case of Chronic Hepatitis E in Haematological Malignancy.

Hepatitis E is an enterically transmitted and typically self-limited infection, that is caused by the hepatitis E virus. Hepatitis E viral infection has traditionally been considered an acute. Chronic hepatitis E is rare and occurs mainly in immunosuppressed individuals such as transplant recipients, HIV patients with low CD4 count and in patients with hematological malignancies receiving chemotherapy.

Model for end-stage liver disease exceptions in the context of the French model for end-stage liver disease score-based liver allocation system.

Model for End-Stage Liver Disease (MELD) score-based allocation systems have been adopted by most countries in Europe and North America. Indeed, the MELD score is a robust marker of early mortality for patients with cirrhosis. Except for extreme values, high pretransplant MELD scores do not significantly affect posttransplant survival. The MELD score can be used to optimize the allocation of allografts according to a sickest first policy. Most often, patients with small hepatocellular carcinomas (HCCs) and low MELD scores receive extra points, which allow them appropriate access to transplantation comparable to the access of patients with advanced cirrhosis and high MELD scores. In addition to patients with advanced cirrhosis and HCC, patients with a number of relatively uncommon conditions have low MELD scores and a poor prognosis in the short term without transplantation but derive excellent benefits from transplantation. These conditions, which correspond to the so-called MELD score exceptions, justify the allocation of a specific score for appropriate access to transplantation. Here we report the conclusions of the French consensus meeting. The goals of this meeting were (1) to identify which conditions merit MELD score exceptions, (2) to list the criteria needed for defining each of these conditions, and (3) to define a reasonable time interval for organ allocation for each MELD exception in the general context of organ shortages. MELD exceptions were discussed in an attempt to reconcile the concepts of transparency, equity, justice, and utility.

Inaccuracies of creatinine and creatinine-based equations in candidates for liver transplantation with low creatinine: impact on the model for end-stage liver disease score.

Renal function has a significant impact on early mortality in patients with cirrhosis. However, creatinine and creatinine-based equations are inaccurate markers of renal function in cirrhosis. The aim of this study was to reassess correlations between creatinine-based equations and measured glomerular filtration rate (GFR) and to investigate the impact of inaccuracies on the Model for End-Stage Liver Disease (MELD) score. GFR was measured using iohexol clearance and calculated with creatinine-based equations in 157 patients with cirrhosis during pretransplant evaluation. We compared the accuracy of creatinine to that of true GFR in a prognostic score also including bilirubin and the international normalized ratio. In patients with creatinine below 1 mg/dL, true GFR ranged from 34-163 mL/minute/1.73 m(2). Cockcroft and Modification of Diet in Renal Disease (MDRD) significantly overestimated true GFR. On multivariate analysis, younger age and ascites were significantly correlated with the overestimation of true GFR by 20% or more. Body mass index was an independent risk factor of overestimation of GFR with Cockcroft but not with MDRD. The accuracy of a prognostic score combining bilirubin, international normalized ratio, and true GFR was superior to that of MELD, whether creatinine was rounded to 1 mg/dL when lower than 1 mg/dL or not (c-statistic of 0.8 versus 0.75 and 0.73, respectively). Creatinine-based formulas overestimate true GFR, especially in patients younger than 50 years or with ascites. In patients with serum creatinine below 1 mg/dL, the spectrum of true GFR is large. True GFR seems to have a better prognostic value than creatinine and creatinine-based equations. Specific equations are needed in patients with cirrhosis to improve prognostic scores.

Celiac crisis with hypokalemic paralysis in a young lady.

Celiac crisis presents as severe acute diarrhea with life-threatening metabolic derangement in a patient with celiac disease. We report a 30-year-old lady who was admitted with one-month history of worsening small bowel-type diarrhea. She developed acute quadriparesis due to refractory hypokalemia. Celiac disease was diagnosed on the basis of positive serology and histological features. She improved with aggressive correction of hypokalemia and gluten-free diet. Celiac crisis is a rare presentation of this heterogeneous disease in adulthood.

Primary malignant melanoma of right colon.

We report a 62-year-old lady who presented with abdominal lump and neurological deficit. Investigations showed ascending colon mass, subcutaneous nodule and right parietal lobe lesion. Histology and immunohistochemistry were suggestive of malignant melanoma. The search for primary site was negative.

Cytomegalovirus involving gastric antrum in immunocompromised hosts: a report of 5 cases.

Cytomegalovirus infection, which is common in immunosuppressed patients, only rarely affects the stomach, especially the gastric antrum. We report five patients with cytomegalovirus infection of the stomach with antral involvement. Of these, four had undergone renal transplant and one had HIV infection. All patients presented with upper gastrointestinal symptoms that did not respond to proton pump inhibitors and prokinetic drugs. In addition, all had systemic symptoms. Diagnosis was made at upper GI endoscopy and biopsy, and ganciclovir treatment led to improvement.