Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. In this case-control study, we analyzed genes associated with microangiopathy—VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme — a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. Eighty-four Indian patients with liver biopsy–proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

Acute fatty liver of pregnancy (AFLP) is a rare cause of catastrophic liver dysfunction and failure in late pregnancy. Defective mitochondrial fatty acid oxidation (FAO) seems to be the underlying pathogenic mechanism. Stressors of both late pregnancy (increased maternal dependence on fats as energy source) and fetus with homozygous defect in mitochondrial FAO, precipitate AFLP in a woman who was previously asymptomatic. Mitochondrial disorders exhibit significant clinical heterogeneity, but many of these primary and secondary disorders have liver as the primary organ affected. The liver injury pattern in these patients also has a varied spectrum and course. Unlike other primary mitochondrial disorders affecting the liver, AFLP represents a potentially completely reversible form of liver injury. Thus, AFLP behaves as a secondary mitochondrial disorder precipitated by inciting factors from fetus and placenta. In this review, we attempt to highlight the varied aspects of mitochondrial dysfunction in AFLP. Mitochondrial injury is the mainstay of pathogenesis and can be recognized in typical clinical features and histopathological findings in patients with AFLP. We also present the consequent impact of recognizing underlying mitochondrial injury on clinical diagnosis and management strategies employed in AFLP.

Aim and Objective: Oral submucous fibrosis (OSMF) is a potentially premalignant disorder affecting the oral cavity and its adjacent structures. The present study was aimed at a comparative evaluation of eustachian tube (ET) changes in OSMF patients using audiometry and cone-beam computed tomography (CBCT). Materials and Methods: A total of 40 patients who were clinically diagnosed with OSMF were taken for the study and were graded into clinical and functional staging. After grading, the patients were subjected to audiometry to evaluate their hearing deficit. Subsequently, the patients were subjected to CBCT analysis for the evaluation of the length and volume of the ET. The length of ET was measured in the axial sections of the full-face CBCT images taken at the level of the root tip of the upper first molar. The radiolucency from the nasopharyngeal opening to the maximum distance was considered. The volume of ET was measured using third-party software (ITK-SNAP) in the radiolucent area. Result: The age group in which a higher number of OSMF cases were seen was between 41 and 50 years. There was mild to moderate hearing loss observed in the right and/or left ear, with little variation between right and left ear changes in audiometry. The CBCT analysis did not show a significant difference in the mean length of the eustachian tube when comparing OSMF cases with normal. However, as the disease worsened, the length on the right and left sides significantly decreased. Additionally, there was no statistically significant difference in the mean eustachian tube volume between disease cases and controls. According to the clinical subgrades, the overall volume decreased from lower grade to higher grade, but there was no discernible difference between the left and right ear. The volume on function sub-grading between the right and left ear, however, was significantly reduced. Thus, the length and volume of ET decreased as the disease severity increased, but the mild to moderate hearing loss found in different clinical and functional grades of OSMF cases was not statistically significant. Conclusion: Therefore, from the present study, it can be concluded that all OSMF cases should be evaluated for hearing deficit, and imaging of the eustachian tube should be part of the OSMF assessment for morphological changes of the ET that may cause hearing deficit.

Abstract Introduction: Cholestasis may increase the difficulty of diagnosing Wilson’s disease (WD). We aimed to compare Leipzig score including hepatic parenchymal copper concentration or rhodanine stain, to diagnose hepatic WD, in noncholestatic patients with fibrosis. Materials and Methods: We defined cholestasis by biochemical and/or histological criteria. Of noncholestatic patients who had liver fibrosis and liver copper estimation, those with isolated hepatic WD comprised WD study group and those with liver disease other than WD, with either low serum ceruloplasmin, high urinary copper, or Kayser–Fleischer ring, were controls. WD diagnosis by Leipzig score was labeled highly likely, probable, or unlikely. Results: Twenty WD study group patients (12 males; 21 [6–52] years; median [range]) and 18 controls (13 males; 32 [10–69] years, all had high urinary copper) were recruited. Rhodanine stain was positive in 60% WD patients and in 33% of controls. With rhodanine stain, Leipzig score had sensitivity of 100% (95% confidence interval: 83.2%–100%), specificity of 66.7% (41%–86.7%), and positive likelihood ratio of 3 (1.56–5.77) to diagnose probable/highly likely WD. In contrast, on adding hepatic parenchymal copper concentration, Leipzig score had sensitivity of 100% (83.2%–100%), but specificity was 38.9% (17.3%–64.2%). In controls, Leipzig score (including rhodanine stain) of ≤ 2 ruled out WD. Conclusion: On excluding cholestatic patients, rhodanine stain performs better than hepatic parenchymal copper concentration to diagnose hepatic WD using Leipzig score in patients with fibrosis. Widespread availability is an added advantage of rhodanine stain.

Objective Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC).We aimed to examine the effect of fecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC.Design This open-labelled randomized controlled trial (RCT), randomized patients with mild-moderate (simple clinical colitis activity index [SCCAI] 3 -9) endoscopically active UC (ulcerative colitis endoscopic index of severity [UCEIS] >1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) vs. optimized standard medical therapy (SMT).FMT-AID arm received 7 weekly colonoscopic infusions of freshly-prepared FMT from multiple rural donors (week 0-6) with anti-inflammatory diet.Baseline medications were optimized in SMT arm.Clinical responders (decline in SCCAI >3) at 8 weeks in both arms were followed till 48 weeks on baseline medications (with anti-inflammatory diet in FMT-AID arm).Primary outcome measures were clinical response and deep remission (clinical-SCCAI <2 and endoscopic-UCEIS <1) at 8 weeks, and deep remission and steroid free clinical remission at 48 weeks.Results Of 113 patients screened, 73 were randomized, and 66 were included in (35-FMT-AID; 31-SMT) modified intention-to-treat analysis (age-35.7+11.1 years; males-60.1%;disease duration-48 [IQR:24-84] months; pancolitis-34.8%;SCCAI-6 [IQR:5-7]; UCEIS-4 [IQR:3-5]) (Fig. 1).Baseline characteristics were comparable.FMT-AID was superior to SMT in inducing clinical response (23/35 [65.7%] vs. 11/31 [35.5%], p=0.01,OR-3.5 [95% CI:1.3-9.6]),remission (21/35 [60%] vs. 10/31[32.3%],p=0.02,OR-3.2 [95% CI:1.1 -8.7]), and deep remission (12/33 [36.4%] vs. 2/23 [8.7%], p=0.03,OR-6.0 [95% CI:1.2 -30.2]) at 8 weeks.Anti-inflammatory diet was superior to SMT in maintaining deep remission till 48 weeks (6/24 [25%] vs. 0/27, p=0.007) (Figs. 2 and 3).Conclusion Multi-donor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over one year.

Developing countries such as India, harbor almost a quarter of global tuberculosis (TB) burden. Esophageal involvement in TB, itself is a rare entity with primary esophageal TB reported only as isolated case reports. We report a case of an immunocompetent young adult who presented with dysphagia as the solitary symptom. Upper GI endoscopy and barium swallow showed a midthoracic esophageal stricture. He was subsequently diagnosed with “primary” esophageal TB based on histological examination of endoscopic biopsy showing features consistent with TB and demonstration of normal adjacent pulmonary parenchyma and lymph nodes on a computed tomography scan of the thorax. He showed marked symptomatic improvement with temporary esophageal dilation and stenting which helped in the effective administration of antituberculous therapy as well as attaining nutritional recovery. Our case report emphasizes on this rare scenario of “primary” involvement of esophagus in an otherwise common disease such as TB and its management strategy.

Hepatocellular adenoma (HCA), a benign tumor arising in a noncirrhotic liver occurs typically in women of reproductive age group. Cystic degeneration in HCA is a rare complication. Bone marrow metaplasia in HCA is also uncommon. We present a 25-year-old male with abdominal pain who was found to have a large solid and cystic lesion in the liver, which was diagnosed as HCA with cystic degeneration and bone marrow metaplasia.

Background Paraganglioma of the urinary bladder is a very rare benign tumor that constitutes less than 0.5% of all bladder tumors. It can be functional and non-functional. Functional tumors present with symptoms of catecholamine excess, and non-functional tumors usually remain asymptomatic. Case presentation Here, we present a case of non-functional urinary bladder paraganglioma in a 36-year-old female who presented to us with a history of intermittent hematuria. The routine hematological and biochemical parameters were within normal limits. Diagnostic computed tomography (CT) revealed a hypervascular lesion in the urinary bladder dome with no significant uptake in gallium-68-labelled-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid peptides-NaI3-octreotide positron emission tomography (DOTA-NOC PET/CT). Histopathology and immunohistochemistry confirmed the diagnosis of paraganglioma. Conclusion We present this case because of the rare location of paraganglioma in the urinary bladder and being non-functional with low/absent somatostatin receptor expression.

Goel, Ashish; Zachariah, Uday; Ramakrishna, Banumathi; Elias, Elwyn; Eapen, CE Author Information

Pseudomembranous colitis (PMC) is a well-known entity with an increasing prevalence in the current post antibiotic era. Its endoscopic and histological morphology is often considered synonymous with Clostridioides difficile -associated colitis. Cytomegalovirus (CMV) infection is a less commonly reported cause of PMC. We report an interesting case of a 61-year-old gentleman with an acute-onset, inflammatory diarrhea during SARS COVID-19 convalescence who was found to have features consistent with PMC on colonoscopy. However, histological and immunohistochemistry analysis of colonic biopsies revealed the presence of CMV infection in the absence of C. difficile toxins on stool assay.

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

ABSTRACT Metastases from pancreatic malignancy are commonly known to occur in the regional lymph nodes, liver, lung, and peritoneum. Synchronous or metachronous metastasis from the pancreas to the colon is rare, with only 6 cases reported in the literature. We report a man who was found to have adenocarcinoma on biopsies from synchronous lesions in the colon and the pancreas. The immunohistochemistry report revealed the diagnosis of a primary pancreatic malignancy with synchronous colonic metastases.

Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) have been associated with dysregulation of iron metabolism. The basis for this association is not completely understood. To attempt to investigate this, we studied temporal associations between onset of insulin resistance (IR) and dysregulated iron homeostasis, in a mouse model of T2DM. Male C57Bl/6 mice (aged 8 weeks) were fed a high-fat diet (HFD; 60% energy from fat) or a control diet (CD; 10% energy from fat) for 4, 8, 12, 16, 20 and 24 weeks. Development of IR was documented, and various metabolic, inflammatory and iron-related parameters were studied in these mice. HFD-feeding induced weight gain, hepato-steatosis and IR in the mice. Onset of IR occurred from 12 weeks onwards. Hepatic iron stores progressively declined from 16 weeks onwards. Accompanying changes included a decrease in hepatic hepcidin (Hamp1) mRNA expression and serum hepcidin levels and an increase in iron content in the epididymal white adipose tissue (eWAT). Iron content in the liver negatively correlated with that in the eWAT. Factors known to regulate hepatic Hamp1 expression (such as serum iron levels, systemic inflammation, and bone marrow-derived erythroid regulators) were not affected by HFD-feeding. In conclusion, the results show that the onset of IR in HFD-fed mice preceded dysregulation of iron homeostasis, evidence of which were found both in the liver and visceral adipose tissue.

In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.

Background Hepatoblastoma (HB) has different histological subtypes, with varying prognosis. Though the survival has drastically improved, subsets of patients are not responsive to therapy. Therefore, it becomes important to determine the factors which affect the behaviour of the tumour. This study was aimed to look at the histopathological subtypes and compare with immunohistochemical (IHC) expression of CK19, beta-catenin and EpCAM and survival. Methods This study included 55 cases of HB. IHC expression of CK19, beta-catenin and EpCAM were correlated with histological subtypes, tumour behaviour, response to chemotherapy and survival. Results Most common epithelial subtype was fetal (43.2%) and mixed epithelial (54.8%) in pre- and post-chemotherapy groups respectively. Microvascular invasion (MVI) was present in 14/33 resected tumours. CK19 expression was seen in 54.2% and 72.2% of embryonal subtype, nuclear beta-catenin expression in 48.7% and 57.1% and EpCAM in 100% and 82.1% of tumours in pre- and post-chemotherapy groups, respectively. Fetal subtype had a lesser chance of MVI, recurrence, metastasis and death. Beta-catenin expression was associated with lower event free survival (EFS) and EpCAM with ≥50% viable tumour following chemotherapy (P=0.04). Age at diagnosis ≤2 years, male sex, alpha-fetoprotein <10,000 IU/mL following chemotherapy, solitary tumour (P=0.001), size ≤5 cm, pretreatment extent of disease (PRETEXT) I&II, mitosis ≤2/10 high power fields (hpf), viable tumour <50% (P=0.04) and absent nuclear expression of beta-catenin, predicted a higher EFS rate. Conclusions Beta-catenin expression is associated with lower EFS and EpCAM expression with tumour viability. Multifocality and viable tumour ≥50% were significant factors predicting lower EFS. These factors should be included in the prognostication of HBs.

© 2018 Indian Journal of Medical Research, published by Wolters Kluwer Medknow for Director-General, Indian Council of Medical Research Fatty liver is now a commonly encountered finding on ultrasound scan of abdomen during routine health check-up. Histological studies reveal a spectrum of changes in non-alcoholic fatty liver disease (NAFLD). On liver biopsy, the presence of fat droplets in ≥5 per cent of hepatocytes is considered as pathological, and when it is not accompanied by markers of hepatocellular injury such as ballooning of hepatocytes, it is called simple steatosis. In addition to steatosis, the presence of hepatocellular injury and inflammation with or without fibrosis is categorized as steatohepatitis1.

The immune system evolved to protect multicellular organisms from pathogens. It defends the body against invaders, and generates an enormous variety of cells and molecules capable of specifically recognizing and eliminating foreign invaders, all of which act together in a dynamic network. Neutrophils have been referred to as a first line of defense, meaning that they are first defensive cells to be recruited to a site of inflammation; however the resident leukocytes are cells which normally exist at the sites of inflammation. Neutrophils exhibit their antibacterial action with the help of granules or by virtue of its ability to reduce dioxygen to hydrogen peroxide. The primary mission of neutrophils is to find bacteria and neutralize them by phagocytosis.

The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC).

Non-cirrhotic intrahepatic portal hypertension (NCIPH) is characterized by thrombotic microangiopathy of the portal venous system, low ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs–13), and high vWF (von Willebrand factor) levels. This study aimed to screen for ADAMTS13 mutations, focusing on the CUB domain, in these patients.

Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.