Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Large Anorectal Venous Malformation Treated With Microfoam Therapy.

Deficiency of smooth muscle cells can lead to dysfunction and engorgement of blood vessels termed as hemangioma, arteriovenous malformations, and venous malformations (VMs). Anorectal VM is a rare disease. It can present with massive hematochezia. An optimal treatment of anorectal VMs has not been defined. Surgery is an option if the lesion can be resected completely. Endoscopic injection sclerotherapy has been reported to be effective in treating small colorectal VMs. However, it has rarely been described in the treatment of large VMs. In this study, we describe a rare case of large anorectal VMs treated with microfoam sclerotherapy.

Study of Adherence to Medication in Pediatric Liver Diseases ("SAMPLD" Study) in Indian Children.

Background/objectives: Adherence to medication(s) is an essential component of holistic management in any chronic disease including in post liver transplant (LT) patients. Thus, this study aimed to assess adherence to medications in Indian pediatric liver disease patients (including post LT recipients) and to identify variables affecting its occurrence. Methods: A cross-sectional study was conducted among pediatric (<18 years of age) subjects with Wilson disease (WD) and autoimmune liver disease (AILD) along with post LT recipients from May 2021 to October 2021. Structured tools using prevalidated questionnaires (Medication adherence measure and the Child & Adolescent Adherence to Medication Questionnaire) were used to collect data related to nonadherence prevalence (based on missed and late doses) and factors influencing the adherence. Results: A total of 152 children were included in the study (WD 39.5%, AILD 32.9%, and post LT 27.6%). Prevalence of missed and late dose nonadherence (at a cut-off of ≥20%) was 12.5% and 16.4%, respectively. Older age (odd's ratio/O.R 1.185), stay in a rural area (O.R 5.08), and barriers like bad taste of medication (O.R 4.728) and hard to remember the medication (O.R 7.180) were independently associated with nonadherence (P < 0.05). Conclusions: Overall, nonadherence was seen in 12-16%, i.e., around one-sixth of the patients, with least nonadherence seen in post LT recipients (0-2.4%). Older age of the patient, rural place of stay and personal barriers like hard to remember/forgetfulness and bad medication taste were identified as factors independently leading to nonadherence.

Torsion of spleen and portal hypertension: Pathophysiology and clinical implications.

The displacement of spleen from its normal location to other places is known as wandering spleen (WS) and is a rare disease. The repeated torsion of WS is due to the presence of long pedicle and absence/laxity of anchoring ligaments. A WS is an extremely rare cause of left-sided portal hypertension (PHT) and severe gastric variceal bleeding. Left-sided PHT usually occurs as a result of splenic vein occlusion caused by splenic torsion, extrinsic compression of the splenic pedicle by enlarged spleen, and splenic vein thrombosis. There is a paucity of data on WS-related PHT, and these data are mostly in the form of case reports. In this review, we have analyzed the data of 20 reported cases of WS-related PHT. The mechanisms of pathogenesis, clinico-demographic profile, and clinical implications are described in this article. The majority of patients were diagnosed in the second to third decade of life (mean age: 26 years), with a strong female preponderance (M:F = 1:9). Eleven of the 20 WS patients with left-sided PHT presented with abdominal pain and mass. In 6 of the 11 patients, varices were detected incidentally on preoperative imaging studies or discovered intraoperatively. Therefore, pre-operative search for varices is required in patients with splenic torsion.

Neurological manifestations of hepatitis E virus infection: An overview.

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.

Endotherapy for pancreatic necrosis: An update.

Approximately 20% of patients with acute pancreatitis develop pancreatic necrosis. The presence of necrosis in a pancreatic collection significantly worsens the prognosis. Pancreatic necrosis is associated with high mortality and morbidity. In the last few decades, there has been a significant revolution in the treatment of infected pancreatic necrosis. A step-up approach has been proposed, from less invasive procedures to the operative intervention. Minimally invasive treatment modalities such as endoscopic drainage and necrosectomy, percutaneous drainage, and minimally invasive surgery have recently replaced open surgical necrosectomy as the first-line treatment option. Endoscopic intervention for pancreatic necrosis is being increasingly performed with good success and a lower complication rate. However, techniques of endotherapy are still not uniform and vary as per local expertise, and there are still many unresolved questions with regard to the interventions in patients with pancreatic necrosis. The objective of this paper is to critically review the literature and update the concepts of endoscopic interventional therapy of pancreatic necrosis.

Spectrum of gastrointestinal involvement in Stevens - Johnson syndrome.

Stevens - Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is a severe adverse drug reaction associated with involvement of skin and mucosal membranes, and carries significant risk of mortality and morbidity. Mucus membrane lesions usually involve the oral cavity, lips, bulbar conjunctiva and the anogenitalia. The oral/anal mucosa and liver are commonly involved in SJS or TEN. However, intestinal involvement is distinctly rare. We herein review the current literature regarding the gastrointestinal involvement in SJS or TEN. This review focuses mainly on the small bowel and colonic involvement in patients with SJS or TEN.

Clinical correlates of trichuriasis diagnosed at colonoscopy.

Diagnosis of Trichuris trichiura infestations is usually based on identification of barrel-shaped ova in stool, but is frequently missed on stool microscopy. We describe the clinical profile of patients in whom Trichuris infection was incidentally diagnosed at colonoscopy. In a cross-sectional study, patients with colonoscopic diagnosis of trichuriasis were enrolled from the endoscopy unit in a tertiary care center. Blood and stool samples were collected from all those who were willing to participate and provide samples. Sixty-two patients participated, with mean (SD) age of 50.5 (13.6) years and male to female ratio of 40:22. Abdominal pain (61.2%) and/or altered bowel habits (32.2%) were the most common indication for colonoscopy. Most (66.6%) of the Trichuris were located in the cecum and ascending colon. Majority of the patients had live worms, either motile or adhering to the colonic mucosa. The number of worms was single or a few (<15) in 74.2% of patients. Out of 62 patients, 16 (25.8%) had relatively heavy load of parasites. Most patients had normal colonoscopic findings (80.6%). Periappendicular and/or cecal ulcerations/erosions were the most common (16.1%) abnormalities noted. Stool examination showed parasite ova only in four (6.4%) patients. In conclusion, colonoscopy was better than stool microscopy for the diagnosis of trichuriasis in our study.

Etiology, clinical profile, and inhospital mortality of acute-on-chronic liver failure: a prospective study.

BACKGROUND: The causes of acute injury in acute-on-chronic liver failure (ACLF) are variable. There may be simultaneous presence of more than one acute insult. We describe the clinical profile of ACLF and the effect of dual acute insult on the natural history. METHODS: Patients with jaundice diagnosed to have ACLF were prospectively enrolled. Patients were evaluated for the clinical presentation, etiology of acute decompensation and underlying chronic liver disease, and inhospital mortality. We compared the clinical profile of patients who had dual acute insult with those of single/unknown insult. RESULTS: Fifty-two patients with ACLF (mean age 38.6 ± 16.7 years; M/F 41:11) were included. Hepatitis virus infection (46.1 %) and bacterial infection (36.5 %) were the most common acute insults. Hepatitis virus infections were the sole acute insult in 34.6 % and associated with another injury in 11.5 %. Bacterial infections were identified as acute insult in 19 patients (sole acute insult in 13). Drugs, autoimmune disease, surgery, malaria, and dengue were other acute injuries identified. The cause of acute decompensation was unknown in 11.5 %. Mortality (66.6 % vs. 51.1 %) was higher in patients with dual insult (n=9) as compared with single/unknown insult (n=43). CONCLUSIONS: Hepatitis virus and bacterial infection/sepsis were the common acute insults in ACLF. Dual acute insult is not uncommon, poses diagnostic dilemma, and may increase mortality in these patients. Plasmodium falciparum infection and dengue fever may be associated with ACLF.

Association of Bell's Palsy with Hepatitis E Virus Infection: A Rare Entity.

Hepatitis E virus (HEV) infection is a common cause of acute hepatitis in India and other developing countries. The data regarding the neurologic manifestation of HEV infection are limited. The neurologic disorders including Guillain-Barré syndrome, polyradiculopathy, neuralgic amyotrophy, encephalitis, bilateral brachial neuritis, ataxia/proximal myopathy, and acute transverse myelitis have been described. Bell's palsy and other cranial nerve involvement in hepatitis A virus (HAV) and HEV infection are rare. We present the second case of Bell's palsy associated with HEV.