Pathobiology of Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is highly associated with the metabolic syndrome. Given its high heterogeneity in patients along with unpredictable clinical outcomes, MAFLD is difficult to diagnose and manage. MAFLD is associated with obesity, diabetes, metabolic derangements, lipid disorders, cardiovascular disorders, sleep apnea, sarcopenia, gut dysbiosis, and sex hormone-related disorders. Identification of risk factors is imperative in understanding disease heterogeneity and clinical presentation to reliably diagnose and manage patients. The complexity of MAFLD pathobiology is discussed in this review in relation to its association with common metabolic and nonmetabolic disorders.

Normative Values for Esophageal Motility Assessed in the Physiological Seated Position for 16-Channel Water Perfused High-resolution Esophageal Manometry System and Postural Variations in Healthy Volunteers.

BACKGROUND/AIMS: Consensus guidelines for performance and analysis of high-resolution esophageal manometry (HREM) recommend use of equipment, population and posture specific normative values. To provide normative values for Chicago classification (CC) metrics in the physiological seated position for a 16-channel water perfused system (Dentsleeve HREM catheter, Advanced Manometry Systems, Melbourne, Australia) widely used in India and other countries with limited access to solid-state equipment. The results are compared with published CC metrics in supine position done using the same system and volunteers. METHODS: HREM tracings of ten 5 mL water swallows in sitting posture were acquired in healthy volunteers and normative values for CC version 3.0 metrics calculated. Individual swallows were paired with previously reported supine swallows for postural variations (Wilcoxon sign rank test) and concordance of CC diagnoses (Pearson coefficient). RESULTS: Analysis of 530 sitting posture water swallows (53 subjects) and comparison with their supine data revealed significantly higher integrated relaxation pressure (IRP; median 6.7 mmHg vs 6.1 mmHg) but lower distal latency (DL; mean 6.3 seconds vs 6.8 seconds) and distal contractile integral (DCI; mean 1224 mmHg∙sec∙cm vs 1456 mmHg∙sec∙cm). Sitting posture normal was defined as: IRP < 13.9, DL > 4.5, and DCI = 115-4500 (absent contractility: DCI < 30). CC diagnoses concordance using posture-specific cut-offs was moderate (k = 0.47). CONCLUSIONS: This paper provides normative values for the Advanced Manometry Systems 16-channel water perfused system in the physiological seated position for CC metrics. Our findings of higher IRP and lower DCI in sitting posture than previously reported supine CC cut-offs, confirm the need to use posture-specific cut-offs for reporting HREM tracings.

HRQOL using SF36 (generic specific) in liver cirrhosis.

Health-related quality of life (HRQOL) is influenced by the disease state, associated complications and their management. In patients with liver cirrhosis co-morbidity, severity of liver disease and their complications are likely to affect the QOL. The aim of the study was to determine the factors that are likely to influence the domains of HRQOL using SF-36 in patients with liver cirrhosis. For the study, 149 patients with liver cirrhosis were compared with age-gender matched healthy controls for physical and mental components of SF-36 score and the effects of age, co-morbidity severity of liver disease and complications of liver cirrhosis on HRQOL were assessed using the same questionnaire. Results of the study showed that except for body pain, all the patients had a significantly low individual and composite domain score (p-value <0.0001) compared to age-gender matched controls. Patients below 45 years, Child-Turcotte-Pugh (CTP) C, a high model for end-stage liver disease (MELD) and higher rates of complication had low scores for body pain (KW p <0.005) and those above 55 years, for physical function (p <0.05). Both the physical components had a major impact on mental composite score (MCS) (KW p <0.05). Co-morbidity that included diabetes, hypertension and hypothyroid states in various combinations had no effect on SF-36 scores while co-morbid conditions like musculoskeletal pain, arthralgia etc. affected physical domains (physical function, body pain and role physical) and physical component score (PCS) (KW p <0.01 to <0.0001). By linear regression, MELD had a direct and significant association with overall PCS and mental component score (MCS).

Malignant Hepatic Epithelioid Hemangioendothelioma with Villaret Syndrome.

Malignant hepatic epithelioid hemangioendothelioma is a rare, vascular tumor of the liver with peak incidence in the middle age with a female preponderance and of unknown etiology. Majority of the tumors are asymptomatic. The gold standard for diagnosis of the tumor is liver histology showing presence of epithelioid tumor cells on a background of a hyaline stroma. Immunohistochemical positivity for CD31, CD34, Factor VIII, and Podoplanin (D2-40) is confirmatory. The treatment of choice is liver transplantation.

Indian Society of Gastroenterology consensus statements on Crohn's disease in India.

In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

Does leptospirosis behave adversely in cirrhosis of the liver?

BACKGROUND AND AIM: Leptospirosis, endemic in India, is complicated by jaundice and renal failure. Whether leptospirosis could result in a worsening of preexisting chronic liver disease (CLD) is not known. Aim of the study was to analyze the clinical profile and natural course of leptospirosis in decompensated CLD in comparison to those acquiring the infection in an otherwise healthy individual. METHODS: Cases were patients with liver cirrhosis who presented with fever and/or jaundice and were screened and found positive for leptospirosis. Controls were patients diagnosed to have leptospirosis during the same period, but in the absence of liver disease. Both cases and controls were followed up until recovery or death. RESULTS: Thirty-one patients had cirrhosis of the liver, and 91 controls had leptospirosis. Significantly more number of cirrhotics had jaundice (87.1 % vs. 16.5 %; p = 0.001), elevated blood urea (41.9 % vs. 18.7 %; p = 0.01), and serum creatinine (41.9 % vs. 19.8 %; p = 0.03) compared to the controls. There were four deaths due to hepatorenal dysfunction and coagulopathy in cirrhotics and no deaths in the control group (4 vs. 0; p = 0.001). CONCLUSION: Leptospirosis should be considered as yet another important cause of acute-on-chronic liver failure in endemic areas associated with poor outcome. Death is often due to hepatorenal dysfunction.

Anti-HBs response to hepatitis B immunoglobulin prophylaxis in liver transplant recipients.

BACKGROUND: Hepatitis B virus (HBV) recurrence after a liver transplant (LT) is a global issue. Several strategies have been adopted to prevent this recurrence. Most strategies recommend a combination of hepatitis B immunoglobulin (HBIG) and or nucleos(t)ide analogue. AIM OF THE STUDY: The aim of the study is to determine the anti-HBs response to HBIG among Indian patients who had undetectable pre-transplant HBV DNA. METHODS: Seven adult HBV-related LT recipients of Indian origin with low pre-transplant HBV titres who had a liver transplant between August 2009 and June 2012 were included in the study. The protocol followed for post-liver transplant HBIG dose was titrated to achieve an anti-HBs titre of at least 100 IU/L. All recipients were on entecavir. Anti-HBs titre, and HBsAg status was checked at regular intervals. A retrospective analysis of the anti-HBs response to a loading and maintenance dose of HBIG was done. RESULTS: Seven adult HBV-related LT recipients on post-transplant prophylaxis with HBIG and nucleoside analogue (entecavir) fulfilled the criteria for the study. The median anti-HBs response to the anhepatic and loading dose of HBIG was high at 555 IU/L. In two, the response was less than 100 IU/L. The median dose of HBIG reduced at end of 1 month to 800 IU, and the median titre was 223 IU/L. For the next 11 months, the median requirement of HBIG was 3,000 and 4,000 IU, and the titre was low at 53.8 and 60.9 IU/L at end of 6 and 12 months, respectively. CONCLUSIONS: The anti-HBs response to HBIG was variable, and titres even below 100 IU/L did not result in HBV recurrence when HBIG was given in combination with entecavir.

Tacrolimus-related adverse effects in liver transplant recipients: its association with trough concentrations.

BACKGROUND: Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects. METHODS: The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM). RESULTS: Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone. CONCLUSION: Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.

HBsAg Positive Patient Characteristics in Hospital and Blood Donation Camps.

Background. Prevention of the residual risk of transfusion transmitted hepatitis B virus infection (HBV) is mostly dependant on serological screening of blood donors for HBsAg and antibody to hepatitis B core antigen (anti-HBc Ab). This study aimed to study the prevalence of HBsAg and anti-HBc Ab and to compare the profile of blood donors attending a blood donation camp and people attending a hospital based camp. Methods. In the blood donor camp, all the blood units were screened for HBV, (HBsAg and anti-HBc), and in the hospital based camp, screening was done for HBsAg alone. Baseline demographic characteristics were noted. Results. The number of blood bank donors was 363 (47.5%) and hospital camp attendees was 402 (52.5%). Prevalence of HBsAg positivity was similar in both the groups at 1.7% and 1.9%, respectively. Anti-HBc Ab positivity (Total) was 6% among the blood donors; Overall prevalence of HBV infection in this group was 3.2%. Conclusion. Policy for checking the collected blood unit by 3 tests for anti-HBc, anti-HBsAb, and HBsAg should be reconsidered to possibly achieve the zero risk goal of transfusion transmitted HBV infection. Blood obtained from a vaccinated donor may give an added protection to the recipient.

Gram-negative bacteria causing infective endocarditis: Rare cardiac complication after liver transplantation.

Bacterial endocarditis is a rare complication amongst solid organ transplant recipients and is often linked to bacteremia. Majority of these recipients do not have underlying valvular heart disease or congenital valvular abnormalities. Staphylococoocusaureus and Enterococcus species are the most commonly isolated organisms. There are very few reports of gram-negative bacteria causing endocarditis in liver transplant recipients. We report a 51-year-old male, a liver transplant recipient, who developed bacterial endocarditis of the mitral valve due to extended spectrum of betalactamase producing strain of Escherichia coli and was managed successfully with antibiotics.

Indian Society of Gastroenterology consensus on ulcerative colitis.

In 2010, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on ulcerative colitis. This consensus, produced through a modified Delphi process, reflects our current understanding of the definition, diagnostic work up, treatment and complications of ulcerative colitis. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

Survey of inflammatory bowel diseases in India.

INTRODUCTION: Inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), once thought to be uncommon, is now seen commonly in India. The Indian Society of Gastroenterology (ISG) Task Force on IBD decided to collate data on the clinical spectrum of IBD currently prevailing in India. METHODS: An open call to members of ISG was given through publication of a proforma questionnaire in the Indian Journal of Gastroenterology and the web portal of ISG. The proforma contained questions related with demographic features, family history, risk factors, clinical manifestations and characteristics, course of disease, and pattern of treatment of IBD. RESULTS: Of 1,255 filled questionnaires received, 96 were rejected and 1,159 (92.3 %) were analyzed. This comprised data on 745 (64.3 %) patients with UC, 409 (35.3 %) with CD, and 5 with indeterminate colitis. The median duration of illness was longer in patients with CD (48 months) compared to those with UC (24 months) (p = 0.002). More than one half of patients (UC 51.6 %, CD 56.9 %) had one or more extraintestinal symptoms. A definite family history of IBD was present in 2.9 % (UC 2.3 % and CD 4.6 %; p = 0.12). The extent of disease in UC was pancolitis 42.8 %, left-sided colitis 38.8 %, and proctitis alone in 18.3 %. The extent of disease involvement in CD was both small and large intestine in 39.6 %, colon alone in 31.4 % and small intestine alone in 28.9 %. Stricturing and fistulizing disease were noted in 18.8 % and 4.4 % of patients with CD respectively. Chronic continuous and intermittent disease course were present in 35.5 % and 47.2 % of UC patients respectively, and in 23.1 % and 68.8 % of CD patients. Four percent of patients with UC had undergone colectomy, while 15.2 % of patients with CD underwent surgical intervention. CONCLUSIONS: The present survey provides a reasonable picture of the demographic features and clinical manifestations of Indian patients with IBD, their risk factors, course of disease, and the treatment given to them.

Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome.

AIM: To assess the symptomatic efficacy of Lactobacillus plantarum 299v (L. plantarum 299v) (DSM 9843) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome (IBS) patients fulfilling the Rome III criteria. METHODS: In this double blind, placebo-controlled, parallel-designed study, subjects were randomized to daily receive either one capsule of L. plantarum 299v (DSM 9843) or placebo for 4 wk. Frequency and intensity of abdominal pain, bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated. RESULTS: Two hundred and fourteen IBS patients were recruited. After 4 wk, both pain severity (0.68 + 0.53 vs 0.92 + 0.57, P < 0.05) and daily frequency (1.01 + 0.77 vs 1.71 + 0.93, P < 0.05) were lower with L. plantarum 299v (DSM 9843) than with placebo. Similar results were obtained for bloating. At week 4, 78.1 % of the patients scored the L. plantarum 299v (DSM 9843) symptomatic effect as excellent or good vs only 8.1 % for placebo (P < 0.01). CONCLUSION: A 4-wk treatment with L. plantarum 299v (DSM 9843) provided effective symptom relief, particularly of abdominal pain and bloating, in IBS patients fulfilling the Rome III criteria.

Perioperative bacterial infections in deceased donor and living donor liver transplant recipients.

BACKGROUND: Deceased donor (DDLT) and living donor (LDLT) liver transplant (LT) is in vogue in several centers in India. Most centers are resorting to LDLT as a preferred surgery due to shortage of deceased donor liver. The risk of infection and its effect on survival in both groups of recipients from the Indian subcontinent are not known. The study was conducted to compare the bacterial infection rates among LDLT and DDLT recipients and their impact on survival at a tertiary referral center. METHODS: Retrospective data on 67 LT recipients were reviewed. Data on pre-, per-, and postoperative bacterial infection rates and the common isolates were obtained. RESULTS: Thirty-five patients had LDLT and 32 had DDLT. The prevalence of pre-operative bacterial infection and the isolates was similar in both groups. The perioperative bacterial infection rates were significantly higher in DDLT recipients (P < 0.01) (relative risk: 1.44 95% confidence interval 1.04-1.9). In both LDLT and DDLT, the common source was urinary tract followed by bloodstream infection. The common bacterial isolates in either transplant were Klebsiella followed by Escherichia coli, Pseudomonas spp. and nonfermenting gram-negative bacteria. Six patients (four LDLT; two DDLT) were treated for tuberculosis. Among the risk factors, cold ischemic time, and duration of stay in the intensive care unit was significantly higher for DDLT (p < 0.01). The death rates were not significantly different in the two groups. However, the odds for death were significantly high at 26.8 (p < 0.05) for postoperative bacterial infection and 1.8 (p < 0.001) for past alcohol. CONCLUSION: Liver transplant recipients are at high-risk for bacterial infection irrespective of type of transplant, more so in DDLT.

Identification of Perforators in Patients with Duodenal Varices by Endoscopic Ultrasound-A Case Series [with video].

BACKGROUND/AIMS: Duodenal varices (DV) are ectopic varices which can cause massive gastrointestinal bleeding. The diagnosis of DV may be difficult; sometimes they can be hidden behind duodenal folds. The aim of the study was to evaluate DV by endoscopic ultrasound. METHODS: Endoscopic ultrasound was done in patients detected or suspected to be having DV. The para duodenal varices were identified and subsequently hemodynamic evaluation of DV was done. RESULTS: Endoscopic ultrasound identified perforators in seven cases of DV. CONCLUSION: The endoscopic ultrasound can help in detection of DV underlying thickened folds. It can also help in hemodynamic evaluation of DV.

Massive infiltration of liver by metastatic adenocarcinoma: a rare cause of acute hepatic failure.

Acute liver cell failure can occur by diffuse infiltration of malignant cells in liver parenchyma. The malignant cells might be either primary hepatocellular carcinoma or metastatic liver disease. Mostly, CT abdomen with intravenous contrast fails to detect liver malignancy. We report a case of liver metastasis masquerading as fulminant hepatic failure.

Antiviral treatment for cirrhosis due to hepatitis C: a review

Chronic hepatitis C infection is an important cause of cirrhosis and hepatocellular carcinoma (HCC). Antiviral therapy (AVT) for patients with cirrhosis due to hepatitis C may retard the progression of cirrhosis and prevent both the development of HCC as well as the recurrence of hepatitis C following liver transplantation. This review highlights the issues associated with AVT for patients with compensated and decompensated cirrhosis due to hepatitis C virus.

Prevalence and risk factors for gastroesophageal reflux in pregnancy.

BACKGROUND AND AIM: Prevalence of gastroesophageal reflux (GER) increases during pregnancy, due to several factors like decreased lower esophageal sphincter pressure, increased intra-abdominal pressure secondary to the enlarged gravid uterus and alteration in gastrointestinal transit. The present study aimed to determine the prevalence of GER in pregnancy in a southern State of the Indian subcontinent and determine the risk factors associated with it. METHODS: Consecutive pregnant females (n = 400) at various stages of pregnancy attending the antenatal clinic or admitted in the antenatal wards were enrolled. Patients with heartburn or regurgitation or both (n = 182) for at least a week were defined as cases, and controls were those without these symptoms (n = 218). Data on demographic variables and symptoms were analyzed using Pearson chi-square, Yates corrected chi-square and Fischer exact test and student independent t-test as appropriate; p < 0.05 was considered significant. RESULTS: Demographic characteristics between cases and controls were similar. The mean age of cases (23.68±3.37 years) was similar to that of controls (23.25±3.31 years). The overall prevalence of GER was 45.5% (182/400), 77 (19.3%) had heartburn (GER-HB), 54 (13.5%) had regurgitation (GER-R) and 51 (12.8%) had both (GER-HB + R). Age and gravida did not influence the frequency of symptoms. Symptoms were more frequent in the second (43.1%) and third trimester (54.1%) as compared to the first trimester (9.5%) in pregnant women with GER (p < 0.001). Atypical symptoms were uncommon. GER was common among non-vegetarians (p = 0.02) and frequent aerated beverage users (p = 0.001). CONCLUSIONS: GER prevalence was high in pregnancy, often in second and third trimester. Non-vegetarianism and aerated beverages increased the risk of reflux in pregnancy.