Cyriac Abby Philips

Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis

Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and portal hypertension that profoundly affects quality of life and improves only with liver transplantation. We present a case where progressive severe spastic paraparesis due to HM was substantially reversed with partial splenic artery emobilization (PSAE). (Hepatology 2018;67:1169–1171)

Dermatitis Herpetiformis as the Initial Presentation of Primary Biliary Cholangitis in a Male with Gluten Sensitivity

Celiac disease is commonly associated with elevated liver enzymes that normalize on a gluten-free diet. Celiac disease is rarely described in patients with primary biliary cholangitis. Dermatitis herpetiformis is the skin manifestation of the celiac disease that is very rarely associated with primary biliary cirrhosis. We present the case of a 62-year-old man who presented with severe chronic pruritus, in whom a diagnosis of primary biliary cholangitis was made initially. However, in the presence of atypical skin lesions, not confirming to chronic cholestasis, an in-depth evaluation including histopathological examination led to the diagnosis of dermatitis herpetiformis associated with gluten sensitivity. Gluten-free diet and medical treatment with dapsone led to beneficial clinical outcomes.

Endoscopic Ultrasound-Guided Management of Bleeding Rectal Varices

Rectal variceal bleeding, though rare, can pose significant morbidity and mortality in the wake of treatment failure. Conventional treatment utilizing endoscopic glue injection might not be feasible in all cases due to poor visualization and inadvertent missing of variceal source of bleed. Endoscopic ultrasound (EUS)-guided rectal variceal management is a promising and effective modality. We provide real-time images and a video of EUS-guided precision management of rectal variceal bleed using coiling and glue in a cirrhotic.

Severe Alcoholic Hepatitis in a Teetotaler

To the Editor: Severe alcoholic hepatitis (AH) is a serious form of alcoholic liver disease associated with rapid onset of jaundice and tender hepatomegaly within 60 days of heavy alcohol consumption (>50 g/day) for minimum of 6 months and serum bilirubin >3 mg/ dL, an elevated aspartate transaminase (AST), an AST: alanine transaminase (ALT) ratio > 1.5, in the absence of other obvious causes of hepatitis and classical histologic features [1]. We describe similar findings in a patient, in the absence of alcohol use. A 44-year-old teetotaler male, pineapple farmer by occupation presented with classical clinical and biochemical features of severe alcoholic hepatitis associated with pruritus for 3 days (Table 1a). He denied over the counter medication use, was not overweight, lacked stigmata of chronic liver disease and portal hypertension, and did not suffer from metabolic syndrome. Blood investigations for acute and chronic viral hepatitis including herpes simplex and zoster, cytomegalovirus, parvovirus, human immunodeficiency virus, human T-cell lymphotropic virus and Table 1 a: Blood investigations of the patient at admission, at discharge and on follow up; b: chemical and toxicology analysis of pineapple samples farmed by the patient and consumed on a daily basis prior to development of symptoms

Chemical Analysis of Weight Loss Herbal Supplement Safe Lean™ Associated With Acute Liver Injury – A Concern for Spurious Drug, Misbranding and Adulteration

Liver injury due to herbal and dietary supplements are well described in literature and its incidence has been on the rise in the past decade. Labelling an herbal product as non-medicinal and as a supplement precludes protocols needed for testing, trials and marketing criteria. This has led to rampant use of clinically unproven multi-herb-based drugs use for a myriad of lifestyle diseases. In this report, we discuss a new dietary weight loss supplement, Safe Lean™ that was found to be the cause of liver injury in a young obese woman, that resolved after discontinuation, and discuss current literature on component, toxicology and chemical analysis of the offending drug.

Slimming to the Death: Herbalife®-Associated Fatal Acute Liver Failure—Heavy Metals, Toxic Compounds, Bacterial Contaminants and Psychotropic Agents in Products Sold in India

Herbalife® is a global nutrition and weight management company selling and marketing nutritional and weight loss supplements. The United States Federal Trade Commission described Herbalife® in 2016 as a scam disguised as healthy living. Herbalife®-associated liver injury was reported from multiple countries in the West. India is fast becoming the largest growing market for Herbalife® products, expected to surpass the United States in sales revenue. We report the first case of a fatal acute liver failure from the Asia-Pacific region, in a young woman who consumed Herbalife® products over 2 months. We also present unsettling data that showcase heavy metal contamination, toxic compounds, psychotropic substances, and pathogenic bacterial contamination in similar Herbalife® products in India. The growth of Herbalife® in India and expansion of its nutrition clubs in major cities that promise fake health benefits portend a serious public health concern.

Reply to: Safety in Ayurveda—Need to bring the house in order by Dr. Sanjeev Rastogi

Sir, We thank Dr. Rastogi for his interest in our recently published study in the Journal [1]. We agree to support his initial opinions in the letter that truly reflects and echoes our study findings. However, we disagree with his statements on causality and subsequent conclusions. For a clear understanding of drug-induced liver injury (DILI), one must be able to fathom the complexities associated with this condition that could clinically mimic almost all other liver disorders [2]. With this in mind, the Roussel Uclaf Causality Assessment Method (RUCAM) and Maria and Victorino systems help to facilitate the causality attribution in suspected DILI. Even though both perform reasonably well in comparison with the Bgold standard^ of expert consensus opinion, the RUCAM is most widely used. Recently, the updated RUCAM was recommended for use in clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected herbal-induced liver injury, facilitating an internationally accepted approach to causality assessment [3]. As per RUCAM, DILI scores are often grouped into likelihood levels of excluded (score ≤ 0), unlikely (1–2), possible (3–5), probable (6–8), and definite or highly probable (> 8). Confirmation of DILI requires the gold standard of drug Brechallenge^ which a patient/family member may not consent to and which is currently frowned upon [4]. In our study, we do not consider this a lacuna, but an interest in patient safety, which is why Bdefinite^ DILI was not ascertained. However, significant scores, along with strong clinical suspicion and meticulous investigations including liver biopsy findings (established and novel patterns) that excluded classical causes of liver injury strongly supported Ayurvedic herbal medicines (AHMs) as the potential cause of DILI in our patients. Hence, our results clearly established causality and justify our conclusions on AHM-related DILI in contrast to what Dr. Rastogi opines. Dr. Rastogi’s confidence in concluding the role of Ayurvedic formulations in themanagement of hepatic encephalopathy and metastatic liver disease is surprising. Both the self-quoted references are case reports—a form of publication with the lowest quality in evidence-based medicine and hence such strong conclusions on the effectiveness of Ayurvedic formulations cannot be made [5]. Both case reports are meddled with confounding factors such as continuation of conventional (or modern) medical management along with introduction of Ayurvedic formulations that defeats the purpose of understanding the true effect of AHM, while the follow up period of supposed Ayurveda management of metastatic liver disease was only ten days which is far from the ideal clinical endpoint in such condition. This aspect in contrivingmediocre conclusions can be considered an enlightenment with regard to the paucity of ideal research methodology in Ayurveda practice: a serious concern which officials of the AYUSH concur with [6]. Dr. Rastogi further describes the effectiveness of Ayurvedic medications in a multitude of liver disorders but does not quote any reference to support his statements. Ayurveda and herbal medicines formed the majority of drugs retrieved from our cohort of patients suspected to have severe liver injury and hence it was only logical to include this aspect in the title while our results and discussions have shed light on every aspect of the retrieved drugs. Ayurveda treatment focuses on symptoms rather than disease or syndromes, because of which multiple AHM use was noted in each patient. Hence, identifying a Bclinical condition^ for AHM use was impossible and a simpler representation of predominant symptoms for * Cyriac Abby Philips abbyphilips@gmail.com

Branch duct-type intraductal papillary mucinous neoplasm presenting as paraneoplastic small plaque para-psoriasis

To present and discuss a novel association between branch duct-type intraductal papillary mucinous neoplasm and paraneoplastic parapsoriasis. We present the case of a middle-aged male presenting with skin lesions that were suggestive of parapsoriasis, resistant to treatment, and in whom a diagnosis of branch-type intraductal papillary mucinous neoplasm of the pancreas was eventually made. A curative Whipples surgery led to complete resolution of the skin lesions within 3 weeks. Paraneoplastic parapsoriasis in association with intraductal papillary mucinous pancreatic neoplasm has never been reported before.

Growth factor therapy for decompensated cirrhosis: Much ado about nothing?

We read with interest, the study by Verma et al., on the utility of granulocyte colony-stimulating factor (GCSF) and growth hormone (GH) (Group A) or GCSF alone (Group B) versus standard medical treatment (SMT) (Group C) in patients with decompensated cirrhosis (DC). The use of GCSF is welldocumented in acute on chronic liver failure, alcoholic hepatitis and reactivation of chronic hepatitis B, in which, control of acute insult along with exogenously administered growth factors lead to activation of hepatic progenitor and bone marrow-derived cells to supplement hepatic regeneration. However, in DC, this proof of concept is lacking, which the authors try to bridge. The recommended dose of GCSF for mobilization of bone marrow cells is 10 mg/kg. The present study utilized suboptimal doses after the initial induction period that was less relevant to disease modulation in the long term. Persistence of elevated levels of CD341 hematopoietic stem cells were not studied and the overall long-term effect of presumed hypothesis of clinical improvement is not clear. Control of etiology improves clinical events and lowers liver stiffness (LSM) in compliant cirrhosis patients. In the present study, LSM in groups A, B and C decrease by 33.1, 31.4 and 5.4 kPa at the end of 12 months. This level of improvement may be biased; it is outside what would be expected as per current literature (Table 1) and requires the much-lacking histological data to support its validity. Nutritional parameters in Group A and Group B improved over time in comparison to SMT, in which it worsened—an important observation closely related to improved outcomes, unexplained with the study treatment protocol. A recent study by Newsome et al. demonstrated that neither G-CSF alone nor combined with autologous stem-cell infusions improved liver function or stiffness in DC. The conclusion of the current study must be taken with a pinch of salt, since the study failed to address confounding factors and the degree of improvements remain to be validated by other independent groups of investigators.

Plasma biomarkers to diagnose alcoholic hepatitis: Are we there yet?

We read with interest the study by Bissonnette et al. that was published recently in HEPATOLOGY. The authors attempted to fill the gap in noninvasive diagnosis of alcoholic hepatitis in a prospective study. They demonstrate that circulating fragments of cytokeratin-18 (CK-18), especially the M65 component, had good diagnostic performance for estimating the presence of alcoholic hepatitis (AH) among patients with clinical suspicion in a test and validation cohort. This was particularly true in patients without recent bacterial infection. They also concluded that analyzing CK-18 fragment levels could help avoid transjugular liver biopsy (TJLB) in two thirds of AH patients. CK-18 is not an exclusively validated biomarker for AH but is a direct marker of hepatocyte apoptosis and, as such, probably should not be considered a diagnostic tool. High levels of CK-18 has been most validated in patients with nonalcoholic steatohepatitis (versus simple steatosis) and toxinassociated steatohepatitis. Obese alcoholics with AH could have components of nonalcoholic steatohepatitis and AH working in tandem. The current study does not shed light on this matter, hence the proposal of CK-18 fragments in noninvasive diagnosis of AH should remain a research tool. With an overall incidence of infections approaching approximately 50% in AH, the noninvasive utility of CK-18 becomes superficial. Discriminating primary liver insults (e.g., druginduced liver injury) among heavy drinkers versus AH still requires a liver biopsy for clarity. In the current study, the authors state that the proposed upper limit cutoffs for CK-18 M65 fragments had a low negative predictive value and that the diagnostic performance was much lower in the validation cohort in which the results were not reproducible using the proposed algorithm, and most patients underwent TJLB. Currently, TJLB is no longer a “cry for the moon,” and most liver units have the expertise to implement it. On the contrary, performing advanced laboratory testing for CK-18 fragments requires more prowess with regard to research personnel, equipment, and costs and is less available at many centers. Diagnosing AH relies on astute history taking—including attention to drug history, careful biochemical interpretation, and histopathology—to be certain in cases where multiple insults or a mimic of AH is expected.