Episodes Of Jaundice Research Articles

A vaccine for Beethoven's vulnerable liver.

Dear EJCI Editor, The recent report1 presenting a thorough analysis of Ludwig van Beethoven's genome has made headlines in scientific and non-scientific journals. The famous composer is known to have suffered, among other ailments, from cirrhosis, and the study by Begg et al.1 adds a few exciting new details to this picture. In brief, the authors showed that Beethoven carried a combination of genetic variants (i.e. HFE p.His63Asp and p.Cys282Tyr as well as PNPLA3 p.I148M) that rendered his liver particularly vulnerable to external noxae, here iron, alcohol and caloric overload.2 Hence, regular alcohol consumption, probably combined with rich food over many years is likely to represent the major cause for his chronic liver disease. Interestingly, Begg et al.1 also performed a metagenomic analysis of Beethoven's hair locks and found that in the last months of his life, he might have suffered from hepatitis B virus (HBV) infection. Although the mass media and the authors of the report1 seem to have focused on the analysis of Beethoven's genome, the detection of HBV infection should not be overseen as it might be highly relevant to Beethoven's death, but also to our everyday liver patients. Apparently, the composer experienced a first episode of jaundice 6 years before his death in 1827, possibly a first sign of decompensation. The fact that it took a couple of decades of chronic alcohol consumption on the background of his high-risk genotype to develop clinical liver disease shows the organ's enormous regenerative capacity. This proverbial resilience has been known for a long time and features prominently in the Prometheus saga from 800 BC, which Beethoven refers to in his ballet ‘The Creatures of Prometheus Op. 43’, composed in 1801. One could speculate that during the last months of his life, the composer might have suffered from acute-on-chronic liver failure (ACLF) caused by the HBV infection on top of his alcohol-induced progressive liver damage. This additional insult precipitated the lethal deterioration of liver function (Figure 1). ACLF is a new disease entity,3 defined as acute liver failure in patients with chronic liver diseases. Bajaj et al.4 described ACLF ‘as a potentially reversible condition in patients with chronic liver disease with or without cirrhosis that is associated with the potential for multiple organ failure and mortality within 3 months in the absence of treatment of the underlying liver disease, liver support, or liver transplantation’. The data available in Begg's paper1 are not sufficient to determine if Beethoven suffered from multiple organ failure or only liver failure. Of note, acute viral infections have been identified as precipitating events of ACLF.5, 6 In terms of hepatitis B, acute infection is rare but can result in rapid dysfunction of pre-injured liver, and flares of chronic HBV infection have been described as triggers of ACLF.7 Patients with HBV-ACLF have been reported to suffer from high short-term mortality,8 in line with the data from the metagenomic analyses revealing the viral infection, and Beethoven's rapid demise. Begg's study1 is a major success of molecular genetic analyses. However, we reckon the observation that Beethoven suffered from HBV infection and that ACLF can be triggered by acute viral infections deserves more prominence. This finding might be used as a motivational lever to promote wider acceptance for vaccination against viral infections. Indeed, as highlighted by the pandemic and reviewed recently by Jeng et al.,9 vaccinations represent an effective means to prevent severe viral infections. Regardless of how long Beethoven suffered from HBV infection, one can imagine that prior vaccination against HBV, if it had been available at the time, might have prevented the acute deterioration of his vulnerable liver, which was challenged by the “devil's triangle” of gene variants, environmental toxins, and virus. This represents an important positive message, which is urgently needed in view of the persisting vaccine hesitancy following COVID-19.10 Portrait of Beethoven by Stieler was reproduced in Figure 1 with kind permission of Beethoven Haus Bonn. Open Access funding enabled and organized by Projekt DEAL. The authors have no conflict of interest to declare.

Clinical, Biochemical, and Molecular Characterization of Neonatal-Onset Dubin-Johnson Syndrome in a Large Case Series From the Arabs.

Background: There are only a few case reports and small case series on neonatal-onset Dubin–Johnson syndrome (DJS), particularly from Far-East Asia, Iranian and Moroccan Jews, and Europe.Objectives: In this first study from the Arabs and the largest series reported to date, we characterized the clinical, laboratory, and molecular features and outcome of gene-confirmed neonatal-onset DJS.Methods: We reviewed our database of 533 cases of neonatal cholestasis that presented to our center during the period from 2008 to 2019. We identified neonates with a disease-causing mutation in ABCC2 gene.Results: Twenty-eight neonates with DJS were diagnosed (5.3%). All of the 28 were full-term, well looking neonates without hepatosplenomegaly, with cholestasis, and normal liver synthetic function since the 1 week of life that resolved within 3–6 months of age, followed by a benign course punctuated by recurrent episodes of jaundice in 43% during a median follow up period of 9.25 (range 2.5–14 years). Alanine aminotransferase levels were within normal range in 26 patients (92%) and mildly elevated in two patients. ALT levels were significantly lower in neonates with DJS than in other cases with neonatal cholestasis from other causes (p < 0.001). The median urinary coproporphyrin I% was 88% (IQ1–IQ3 = 84.2–92.7%). We identified four homozygous variants in the ABCC2 gene (from 22 unrelated families), one splicing variant (c.3258+1G>A; p.?), and three were missense variants; two of which were novel missense variants [c.1594G>A (p.Glu532Lys) and c.2439G>C (p.Lys813Asn)]. The p.Gly758Val mutation has occurred in 23 patients (from 19 unrelated families).Conclusions: Our study suggests that normal ALT-cholestasis in a well-looking neonate should trigger evaluation for DJS. The p.Gly758Val variant in ABCC2 is the most predominant mutation among Arabs with “founder effects.” Identification of the predominant ABCC2 variant in any population is likely to facilitate rapid molecular analysis by future targeting of that specific mutation.

Cytokeratin 7 and Copper Stains Facilitate Diagnosis of Small Duct Primary Sclerosing Cholangitis

Abstract Introduction/Objective Classic primary sclerosing cholangitis (PSC) involves extrahepatic and/or intrahepatic biliary ducts with segmental biliary strictures and dilatations that often allow the diagnosis to be made via cholangiogram. Small duct PSC (sdPSC) is a rare subtype that presents similarly with a cholestatic pattern of injury, yet due to the small size of involved ducts, a cholangiogram is non-diagnostic and diagnosis is dependent on clinical suspicion and liver biopsy. The histopathological features of sdPSC are often subtle and may easily be overlooked. Diagnosis of this entity- though difficult- is important, as early recognition can facilitate the identification of associated disease processes and life-threatening complications. Methods/Case Report We encountered a 33-year-old female presenting with intermittent pruritis, episodes of jaundice, and persistently elevated alkaline phosphatase who was misdiagnosed with only fatty liver at an outside institution. Evaluation with MRCP showed no abnormalities within the biliary tract and a liver biopsy was performed to aid in the diagnosis. The H&amp;E and trichrome findings of atrophic bile ducts and some peribiliary sclerosis were extremely subtle and may have been overlooked without clinical suspicion. Cytokeratin 7 (CK7) highlighted cholangiolar metaplasia in hepatocytes and the bile ductular reaction that occurs in cholestatic disease states. A Rhodamine copper stain showed periportal deposition suggestive of chronic biliary obstruction. Use of CK7 and copper stains supported the presence of chronic biliary injury and suboptimal bile flow, confirming the diagnosis of sdPSC. Results (if a Case Study enter NA) NA Conclusion Diagnosis of sdPSC has historically relied on H&amp;E and trichrome stains. In this case, the findings on H&amp;E and trichrome stains were non-diagnostic, while the use of CK7 and copper stains confirmed the diagnosis of sdPSC. We recommend using CK7 and copper stains to evaluate for sdPSC.

Синдром Жильбера: клініка, діагностика, диференціальна діагностика та лікування (частина 2)

роведений огляд наукової літератури за ключовими словами «синдром Жильбера», «клініка», «діагностика», «лікування» з використанням як пошукової системи PubMed. Беручи до уваги дослідження, що проведені за останні 10 років, проаналізовано тези 123 статей. Критерій відбору статей для дослідження був заснований на актуальності їх теми. Більш детально вивчено результати дослідження, що висвітлені в 50 статтях. Клінічні прояви синдрому Жильбера (CЖ) можливі як при гомозиготному статусі за геном UGT1А1, так і при гетерозиготному. У осіб із гетерозиготним статусом переважає латентний варіант перебігу захворювання. У 30 % гомозиготних осіб за дефектним геном СЖ хвороба також перебігає безсимптомно. Клінічні варіанти перебігу СЖ: диспептичний — 43,2 %, астеновегетативний — 15,9 %, жовтяничний — 14,8 %, безсимптомний — 26,1 %. Провокуючими факторами є погрішності в харчуванні, розумова перевтома, стрес, травми, гострі інфекції, зокрема вірусний гепатит, прийом деяких препаратів. У 86,4 % дітей із СЖ виявлена патологія верхніх відділів шлунково-кишкового тракту: дуоденіт — у 58 %, гастрит — у 56,8 %, езофагіт — у 12,5 %, виразкова хвороба дванадцятипалої кишки — у 2,3 %, у 39,7 % хворих зареєстровані сфінктерні порушення (гастроезофагеальний, дуоденогастральний рефлюкси). Для пацієнтів із СЖ характерно зниження детоксикаційної функції печінки, зокрема у 2/3 хворих відзначається порушення поглинальної здатності гепатоцитів, у половини — страждає екскреторна функція печінкових клітин, у 88 % спостерігаються дисфункція жовчовивідних шляхів, підвищений ризик утворення жовчних каменів. В окремих пацієнтів із СЖ відзначають особливості психіки, зокрема наявність тривожності. Діагностичні критерії СЖ: 1) своєрідний світло-жовтуватий колір шкіри (teinte bilieuse), особливо обличчя, кистей і стоп, без вираженої жовтяниці склер. Іноді розвиваються повторно інтермітуючі напади жовтяниці з високою білірубінемією (непрямий білірубін) без ознак гемолізу (диференціально-діагностична ознака); 2) схильність до розвитку пігментних і судинних невусів і ксантелазм у ділянці повік, а також гіперпігментації навколо очей, до брадикардії, гіпотермії, мігрені, ортостатичної, переміжної альбумінурії або аліментарної глюкозурії; 3) посилена тенденція до пігментоутворення під впливом світла та тепла, а також хімічних і механічних подразників; 4) нейром’язова гіперзбудливість; 5) підвищена чутливість до холоду; 6) диспептичні скарги (біль, нудота, відчуття повноти шлунка, пронос або запор); 7) відсутність ознак підвищеного гемолізу (диференціально-діагностична ознака) при збільшенні вмісту в сироватці непрямого білірубіну (диференціально-діагностична ознака); 8) у більшості хворих функціональні проби печінки нормальні (диференціально-діагностична ознака), проба з виділенням бромсульфалену також зазвичай нормальна (диференціально-діагностична ознака); 9) біохімічна аномалія не виявляється гістологічними методами (диференціально-діагностична ознака); 10) часто виявляють сімейну захворюваність печінки. Диференціальну діагностику СЖ проводять з усіма типами гіпербілірубінемій, гемолітичними анеміями, уродженим цирозом печінки, гепатитами, холецистопатіями, атрезією жовчних ходів або тонкої кишки. Медикаментозні препарати застосовують виключно при вираженій гіпербілірубінемії та як супутню терапію за наявності в клінічній картині симптомів гіповітамінозу, порушень моторно-евакуаторної функції верхніх відділів травного тракту, для запобігання ускладненням (жовчнокам’яна хвороба).

How dangerous Gilbert's syndrome is

Gilbert's syndrome is a benign (functional) hyperbilirubinemia, which is based on a hereditary disorder of bilirubin metabolism, as a result of which the concentration of unbound bilirubin can increase several times. Bilirubin, being a breakdown product of hemoglobin, circulates through the bloodstream, combining with albumin molecules. Such bilirubin is called indirect. In the endoplasmic reticulum, it is conjugated; the enzyme glucuronyltransferase is responsible for this process. In Gilbert's syndrome, as a result of insufficient production of this enzyme, the conjugation process is disrupted, and, as a result, the concentration of unconjugated bilirubin increases. According to statistics, this pathological condition is observed in about 5 % of Russians. This syndrome was first described in 1901 by the French physician Augustin Nicolas Gilbert, and was subsequently named after him. The literature also contains references to this syndrome, described as «constitutional hepatic dysfunction», «familial non-hemolytic hyperbilirubinemia», «idiopathic non-conjugated hyperbilirubinemia». Gilbert's syndrome is inherited in an autosomal recessive manner; men get ill 3–4 times more often than women. A number of scientists associate this with a possible inhibitory effect of testosterone on the enzyme UDP-GT1, which breaks down bilirubin. Clinically, Gilbert's syndrome is manifested by episodes of jaundice caused by an increase in the level of unconjugated bilirubin in the blood serum. Against the background of icterus of the sclera and skin, there is increased fatigue, the appearance of a feeling of bitterness in the mouth, loss of appetite, nausea, and sometimes vomiting. The association of Gilbert's syndrome with functional disorders of the biliary tract, in particular, with gallbladder dyskinesia, is often noted.

Transduodenal laparoscopic papillectomy for adenoma of major duodenal papilla

A 60-year-old man admitted to the clinical center due to weakness, episodes of jaundice. The laboratory date revealed elevated levels of total bilirubin—112.5 μmol/l (range 8,5–20,5 μmol/l) and direct bilirubin—60.8 μmol/l (range 4,3–4,6 μmol/l), elevated hepatic enzymes (aspartate aminotransferase [AST]: 95 U/l (range ≤ 40 U/L), alanine aminotransferase [ALT]: 301 U/l (range ≤ 30 U/L). When performing esophagogastroduodenoscopy, a polyp of the large duodenal papilla with a spread to the terminal parts of the bile and pancreatic ducts was revealed, and a biopsy was taken. Histological examination detected tubulovillous adenoma with epithelial dysplasia II–III stage. DS: “Tubulovillous adenoma of the major duodenal papilla with epithelial dysplasia II–III”. Complications: “Multiple choledocholithiasis. Mechanical jaundice. Liver failure.” Considering the inability to carry out endoscopic treatment, recurrent nature of the jaundice it was decided to perform surgery: laparoscopic duodenotomy, papillectomy, choledocholithotomy, performing of choledochoduodenal anastomosis, duodenoplasty and abdominal drainage. The postoperative period was taking its normal course. Duration of staying in the intensive care unit—4 days. Enteral fluid intake started on the 2-nd postoperative day. Enteral feeding was restored in a 3 days. Polyps of the large duodenal papilla are relatively rare form of tumors of the gastrointestinal tract, which may not manifest clinically, or, as the above case, lead to severe pathological conditions. Currently, there is no single approach to the treatment of this group of diseases. Some authors propose a pancreatoduodenal resection, but the risks of this operation associated with high postoperative morbidity and mortality are not always justified. The case is unique because the described procedure is less invasive and affects the minimum number of organs. Laparoscopic approach has significant advantages in the treatment of this infrequent pathology.

Physiological and Hereditary Hyperbilirubinemia in Athletes: Role in Reducing Efficiency and Correction Methodology

Under high-intensity loads, the athlete's bodies take place a number of biochemical reactions and physiological processes that can lead to hyperbilirubinemia. The factors that can initiate the onset of this phenomenon include the syndrome of micro-damage muscle, violation of the integrity of erythrocyte membranes, decreased blood pH, malnutrition and increase oxygen demand of the body. Degree of expression of manifestations of physiological bilirubinemia depends on the level of adaptation of the athlete to the physical activities offered. Hyperbilirubinemia in athletes can be one of the components of the deterioration of the functional state, forming the symptoms of endogenous intoxication. The relevance of this problem in sport lies in the relatively low detection rate of hyperbilirubinemia due to the lack of regular screening studies. However, in drawing up a plan of nutritional- metabolic support for training and competitive activity and recovery measures, must not only the individual reaction of the athlete body to physical activity, but also the severity of shifts in the indicators of bilirubin metabolism and their ratio. The article describes the reasons for the increase in bilirubin levels, which can be caused by both the effect of physical activity and by the presence of pathological processes in athletes. The factors influencing the blood serum’s bilirubin content are also highlighted, which include the state of erythrocyte cell membranes and the rate of hemoglobin destruction, the functional state of the liver, the specifics of physical loads and the use of ergogenic pharmacological agents by athletes. Particular accent has been placed on the illumination of hereditary hyperbilirubinemias, which may have been detected at the stage of selection of athletes. The most common phenomenon is Gilbert's syndrome, which occurs in 2-5% of cases in the general population, is characterized in the clinic by a benign flow and is manifested by episodes of jaundice and an increase in total bilirubin content to moderate values due to indirect. The frequency of detection of hyperbilirubinemias in the population of athletes is 4.68%, among which Gilbert's disease accounts for almost half (48.7%). Conclusion. The work highlighted the pathogenesis and diagnostic algorithm of Gilbert's disease, and also emphasized that its drug prevention and correction in athletes to maintain functional and physical fitness should be carried out taking into account anti-doping rules, which requires upon diagnosis timely receipt of a therapeutic exclusion

Role of biopsy in Benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is an inherited self limiting cholestatic disorder. It is very rare and less common than its severe form, Progressive familial intrahepatic cholestasis (PFIC). Due to impaired canalicular biliary excretion, patients develop recurrent episodes of jaundice and intense pruritus with characteristic symptom free intervals. Most of the cases have a benign course and are managed symptomatically. Histopathological examination of liver biopsy is essential in cases of recurrent intrahepatic cholestasis to confirm the diagnosis. Here we report two cases of biopsy confirmed Benign recurrent intrahepatic cholestasis for its rarity.

The frequency, clinical course, and health related quality of life in adults with Gilbert\u2019s syndrome: a longitudinal study

BackgroundGilbert syndrome (GS) is an autosomal recessive inherited disorder of bilirubin glucuronidation which has not been investigated in Egypt. This longitudinal study investigated the frequency, clinical course, genetic profile and health related quality of life in Egyptian adults.MethodsAn initial cross-sectional study was conducted to assess the frequency of Gilbert syndrome among Egyptian adults. Subjects fulfilling the criteria of GS were enrolled into the study and prospectively followed for the clinical features, risk factors for hyperbilirubinemia, health related quality of life [Short form-36 Health Survey version 2 (SF-36v2) and Chronic Liver Disease Questionnaire (CLDQ)], vitamins assessment and UGT1A1 polymorphisms.ResultsOne hundred and one subjects fulfilled the criteria of GS with a prevalence of 8.016%. Recurrent jaundice was the only presentation in 47 (56.627%) GS subjects and jaundice was associated with abdominal pain, dyspepsia or loss of appetite in 54 (53.465%) subjects. A significant difference in 25-Hydroxyvitamin D3 levels was detected between GS patients and control subjects (P < 00001). Twelve subjects with GS developed significant unconjugated bilirubinemia during direct antiviral therapy (DAAs) therapy for HCV despite achieving sustained virologic response. Pregnancy was associated with significant exacerbation of unconjugated bilirubin which persisted through pregnancy. Risk factors for clinical jaundice included general anesthesia, pregnancy, fasting > 12 h, pregnancy, and low calorie weight losing plans, systemic infections, and intensive physical effort. During jaundice attacks, subjects with GS had significant differences in vitality, role emotional, social functioning, worry and general health domains of the SF-36v2 and CLDQ compared to controls. The homozygous polymorphism A(TA)7TAA was the most frequent polymorphism in Egyptians with GS.ConclusionGilbert syndrome is a frequent inherited disorder in Egypt. In a substantial percentage of subjects with GS, episodes of jaundice are associated with other symptoms and nutritional deficiencies which result in impairment of HRQOL. Screening, counseling, monitoring and individualized health care are recommended for subjects with GS in the setting of anesthesia, pregnancy, treatment with DAAs, deliveries, surgery and weight loss plans.

Hemoglobin-D Punjab—rare hemolytic anemia in the elderly: a case report

A 62-year-old woman with no comorbidity presented with dyspnea since 2 months and fatigue since 1 month. She was having severe anemia with hepatosplenomegaly and icterus. Anemia due to blood loss was ruled out. With a history of blood transfusions and episodes of jaundice in the past, evaluation of hemolytic anemia was carried out. Her serum iron level was normal. Serum lactate dehydrogenase level was raised, and extracorpuscular causes were absent. Hemoglobin electrophoresis was performed in view of suspected hemoglobinopathy. It showed hemoglobin-D Punjab homozygous type, which is very rare. Its presentation in older age is even rarer to warrant this report.

36. An interesting case of jaundice in an adult

Background: Dianosis of recurrent cholestatic jaundice in an adult is often challenging. We report an interesting case of recurrent cholestatic jaundice in a young adult. Case Summary: A 24-year-old male presented with jaundice with itching and clay colored stool since 3 months. He took complementary alternative medicine in the form of Phyllantus niruri with other treatment for 10 days followed by which his jaundice deepened and was referred to Chennai. Patient had a past history of 6 similar episodes spanning over 10 years with complete recovery in between. Each episode of jaundice had maximum bilirubin ranging from 2 mg/dl to 25 mg/dl and duration from 7 to 45 days followed by complete normalization of LFTs after each episode. No significant addiction or family or perinatal history. Labs suggestive of cholestatic jaundice with high serum bile acids and high triglycerides. Based on this history of recurrent jaundice with complete recovery after each episode, BRIC was considered and after exhaustive work up excluding other etiologies, mutational analysis for ATP8B1 was sent which came positive for a missense mutation in JAG1 gene consistent with Alagille syndrome. Clinically this was labeled as BRIC with incidentally detected incomplete penetrance of JAG1 gene. Patient was managed conservatively and on follow up after 45 days he again had normal LFTs. Conclusions: Recurrent cholestatic jaundice in an adult requires workup for common followed by uncommon and genetic causes. These patients require regular follow up to see for worsening LFTs as BRIC can progress to PFIC in a small number of patients. The authors have none to declare.

Dubin\u2013Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report

BackgroundDubin–Johnson syndrome and intrahepatic cholestasis of pregnancy are rare chronic liver disorders. Dubin–Johnson syndrome may manifest as conjugated hyperbilirubinemia, darkly pigmented liver, presence of abnormal pigment in the parenchyma of hepatocytes and abnormal distribution of the coproporphyrin isomers I and III in the urine. Intrahepatic cholestatic jaundice of pregnancy presents as pruritus, abnormal liver biochemistry and increased serum bile acids.Case presentationA Sri Lankan girl presented with recurrent episodes of jaundice. She had conjugated hyperbilirubinaemia with diffuse, coarse brown pigments in the hepatocytes. Urine coproporphyrin examination suggested Dubin–Johnson syndrome. Genetic studies confirmed missense homozygous variant p.Trp709Arg in the ATP-binding cassette sub-family C member 2 gene ABCC2 that encodes the Multidrug resistance-associated protein 2 that causes Dubin–Johnson syndrome. The gene study of the mother revealed the same missense variant in ABCC2/MRP2 but with a heterozygous status, and in addition a homozygous missense variant p.Val444Ala in the ATP-binding cassette, sub-family B member 11 gene ABCB11 that encodes the bile salt export pump.ConclusionDubin–Johnson syndrome should be considered when the common causes for conjugated hyperbilirubinaemia have been excluded, and patient has an increased percentage of direct bilirubin relative to total bilirubin concentration. Its early diagnosis prevents repeated hospital admissions and investigations. Knowledge of a well known homozygous variant in ABCB11 gene could help in the management of pregnancy.

Etiological spectrum of recurrent jaundice in adults: A retrospective observational study from a tertiary care center

Introduction: Studies regarding etiological spectrum of recurrent jaundice are rare. We conducted this study to identify the causes of recurrent jaundice in a tertiary care center. Materials and Methods: Frequency of different causes of recurrent jaundice was assessed from 130 patients attended General Medicine Department over a period of 3 years. Recurrent jaundice was considered when patients had more than one episodes of jaundice with serum bilirubin ≥3 mg/dl since childhood. Recurrent jaundice was diagnosed from past medical records, records of follow-up visits, and current clinical presentation. Causes were identified from past and present medical records of history, clinical and laboratory examinations. Results: Causes of recurrent jaundice included prehepatic (30%), hepatic (59.23%), and posthepatic (10.77 %) disorders. Prehepatic disorders were Gilbert's syndrome (GS), megaloblastic anemia, autoimmune haemolytic anemia, Wilson's disease, G6PD deficiency, etc. Hepatic disorders were exacerbations of alcoholic hepatitis, hepatitis B and C, autoimmune hepatitis, congestive cardiac failure, sarcoidosis, benign recurrent intrahepatic cholestasis, eclampsia, pregnancy induced cholestasis, falciparum malaria, drug induced liver injury (DILI), etc. Posthepatic causes were choledocholithiasis, recurrent pancreatitis, periampullary carcinoma, choledochal cyst, ascariasis, hemobilia, HIV cholangiopathy, autoimmune pancreatitis, etc. Prehepatic jaundice cases were younger. The highest level of total bilirubin was seen in alcoholic hepatitis, DILI, and hepatitis B. Alcoholic hepatitis was the most common cause of recurrent jaundice (19.23%). GS was the most common prehepatic cause. Mean age was lowest in GS and highest in DILI. Conclusion: Etiological spectrum of recurrent jaundice includes many prehepatic, hepatic or posthepatic disorders. A larger study may enlarge the spectrum.

Severe Aplastic Anemia and Seronegative Autoimmune Hepatitis: A Concurrence or Consequence?

Hepatitis-associated aplastic anemia (HAAA) is a variant of bone marrow failure that usually follows an acute attack of hepatitis. It usually affects children and young adolescents and is uncommon in adults. The causative factor in the majority of cases remains unknown. The efficacy of immunosuppressive regimens suggests autoimmunity as a key mechanism of HAAA. Although rare, seronegative autoimmune hepatitis can be a cause of bone marrow failure.A 43-year-old Caucasian male patient with a past medical history of hypertension was admitted due to abdominal pain of two-week duration and progressive jaundice. He denied alcohol, smoking, illicit drug use, foreign travel, recent bites, scrapes, or injuries. His medications included hydrochlorothiazide, lisinopril and hydrocodone/acetaminophen. On physical exam, there was right upper-quadrant tenderness and notable jaundice but no hepato-splenomegaly. Admission laboratory data showed transaminitis and pancytopenia without neutropenia. The white blood cell count was 3.7×103/µl, hemoglobin 13.6 mg/dl, platelets 69×103/µl, ALT 2451 IU/l, AST 1573 IU/l, total bilirubin 7.7 mg/dl, alkaline phosphatase 185 IU/l and lipase 172. Further investigations included serological markers of viral hepatitis which were negative. Urine histoplasma and Cryptococcus antigens were negative. Anti-nuclear, anti-smooth muscle, anti-LKM and anti-mitochondrial antibodies were negative. Serum immunoglobulins, ceruloplasmin, acetaminophen level, DIC panel and anti-tissue transglutaminase (anti-tTG) IgA were normal. Liver ultrasound, endoscopic ultrasound, and MRI of the liver did not show any acute process. A liver biopsy showed autoimmune hepatitis (AIH). Four weeks later, pancytopenia worsened with severe neutropenia, but showed significant improvement in transaminases. Laboratory data showed white blood cell count of 1.1×103/µl, absolute neutrophil count 418, hemoglobin 10.7 mg/dl, platelets 19×103/µl, ALT 164 IU/l, and AST 50 IU/l. Peripheral blood workup for pancytopenia was unremarkable. Bone marrow biopsy showed aplastic anemia. The patient was started on steroids, cyclosporine, and anti-thymocyte globulin (ATG). His counts improved after staring immunosuppressive therapy and his liver function returned to normal. Cyclosporine was stopped because patient developed microangiopathic hemolytic anemia. Three months after initiation of therapy, his counts were stable and immunosuppressive therapy was stopped. He required no further therapy or transfusion.Aplastic anemia (AA) may develop in as many as 1 in 3 cases of seronegative clinically identifiable hepatitis. In most cases, the hepatitis is self-limiting, but the liver disease may be prolonged or recurrent. AA is characterized by diminished number or total lack of hematopoietic precursors in the bone marrow. In most cases, stem-cell failure is acquired as a consequence to exposure to ionizing radiation, environmental chemicals, drugs, or viruses. However, in some patients AA seems to be immune mediated, with active destruction of blood-forming cells. Up to 13% of patients are diagnosed with autoimmune hepatitis and have no typical antibodies or hypergammaglobulinemia at presentation. Our patient was seronegative for known hepatotoxic viruses. Although he had negative autoantibody markers, liver biopsy showed autoimmune hepatitis, thus confirming the diagnosis of seronegative autoimmune hepatitis (SAIH). Clinically, the disease presented as a protracted hepatitis with episodes of jaundice and very high transaminases. Usually bone marrow failure follows SAIH, but in our case the patient had mild bone marrow failure on admission and severe hepatitis. It is unknown whether the immune mediated mechanism targets the liver and bone marrow simultaneously or aplastic anemia is a consequence of SAIH. The hepatitis and aplastic anemia responded well to immunosuppressive therapy which confirmed autoimmunity as the etiology of aplastic anemia and hepatitis in our patient.The major pathogenic mechanisms leading to the liver injury and bone marrow destruction in SAIH patients seem to have an immune nature. Patients with SAIH should be monitored carefully, and in the presence of cytopenia directed to hematologist. Early treatment of SAIH with corticosteroids could prevent development of end stage liver disease and aplastic anemia. DisclosuresNo relevant conflicts of interest to declare.

Chronic pancreatitis with benign biliary obstruction: management issues.

Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP. Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012. Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11-90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10-89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP. BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.

Chronic pancreatitis with benign biliary obstruction: management issues

Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP. Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012. Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11–90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10–89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP. BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.

Incidence of Hepatitis B Surface Antigen among Sickle Cell Disease Patients Receiving Transfusion Therapy

Sickle cell disease (SCD) patients deserve serious attention regarding their Hepatitis B status because episodes of jaundice in the disease may be misleading in many cases. It may either be part of the chronic haemolysis they experience or due to blood transfusion (supportive therapy) related hepatotropic viral infections (Hepatitis-B). The aim of the study was to determine the incidence of Hepatitis B virus infection due to transfusion therapy among SCD patients. Venous blood samples were taken from 202 consenting SCD patients. Haemoglobin-electrophoresis was done to determine the sickling status and Haemoglobin (Hb) genotype of each patient. The samples were then tested for Hepatitis B Surface antigen (HBsAg) using the immunochromatographic method. A questionnaire correlating Hepatitis-B infection and history of blood transfusion was used to obtain other data from the patients. Out of 202 patients who participated in the study, 87 were males and 115 females. The Hb genotype distributions were as follows: SS (128), SC (66), S-β thal (5), CC (2) and SE (1). 99 out of the 202 had a history of blood transfusion. The frequency of HBsAg in the participants was 3.5% and the relative risk of infection by blood transfusion was 2%. It was found that sickle cell disease patients are not at a major risk of hepatitis B viral infection due to transfusion therapy because of the use of properly screened donor blood. However, there remains a significant risk by donations from infected donors who have not yet developed detectable HBsAg levels.

Potential benefits of palliative care for polysymptomatic patients with late-stage nonmalignant disease in Taiwan

Taiwan is only now beginning to offer palliative care to patients who do not have cancer. This study aimed to document the polysymptomatic presentation of illness in Taiwanese patients with late-stage nonmalignant disease and to evaluate the potential benefits of palliative care for these patients. The results may help to educate healthcare personnel regarding the need for and importance of palliative treatment as comprehensive, appropriate end-of-life care for patients with nonmalignant disease. We retrospectively analyzed 115 patients without cancer hospitalized in a community hospital in Taiwan: 61 had organic brain disease, 31 had chronic obstructive pulmonary disease, 17 had chronic renal failure, 14 had congestive heart failure, 12 had liver cirrhosis, and 20 had multiple illnesses. The median age was 81 years (interquartile range 69-86 years), and 51% of patients were enrolled from intensive care. Symptoms and their severity were analyzed. Patients' and their families' understanding of the diagnosis and prognosis and "Do Not Resuscitate" (DNR) consent were evaluated pre- and post-palliative care. The four leading symptoms were fatigue (96%), fever (86%), cough (81%), and dyspnea (79%). No significant differences in symptom prevalence were found between different sexes, ages, performance statuses, ward locations, or underlying diseases, except for fewer episodes of dizziness, more frequent episodes of cough in patients older than 80 years, and more episodes of jaundice in ward service subjects. Only the presence of abdominal distension differed significantly between surviving and deceased patients (22.9% vs. 40.3%; p=0.004). After the start of palliative care, patients' DNR consent increased (105/115 before, 114/115 after). Patients' recognition of the diagnosis and prognosis increased from 13 to 64, respectively, with a simultaneous increase in family members' recognition (66 before, 114 after). Hospice care with good symptom control is warranted for patients with late-stage nonmalignant disease who need appropriate end-of-life care. Medical personnel need education in the importance of palliative care and the identification of patients who could benefit from it. In addition, patients should be informed of its availability.

A novel technique for treatment of intrahepatic biliary obstruction using an endobronchial ultrasound system.

Biliary obstruction (BO) is one of the complications after hepatobiliary surgery decreasing patients' quality of life. Existing interventional methods, such as endoscopic retrograde biliary drainage, occasionally fail to treat this condition. This is the first report of treatment of BO using an endobronchial ultrasound (EBUS) system. A 65-year-old woman developed BO at the confluence of the bile duct of segment 3 of the liver (B3) and segment 2 (B2) after extended right hepatectomy for hepatocellular carcinoma. Percutaneous transhepatic biliary drainage (PTBD) was performed through B3, and its fistula was dilated up to the size of an 18-Fr PTBD silicone catheter. An EBUS endoscope was inserted through the dilated PTBD route. B2 was punctured through the EBUS endoscope inserted to B3 just before the obstruction with a needle for fine-needle aspiration biopsy. A guidewire was inserted to the common bile duct through the needle, and a 7.2-Fr PTBD catheter was placed over the guidewire. The inserted PTBD catheter was clamped, and internal biliary drainage was established. The catheter was patent for 24months, and the patient had no episodes of jaundice or cholangitis. This technique using the EBUS system can be a treatment option for BO.

Intraductal Hepatocellular Carcinoma without Parenchymal Tumor: A Case Report

Obstructive jaundice due to hepatocellular carcinoma is rare. We present a case of hepatocellular carcinoma presenting as an intraductal tumor, which was clinically and radiologically diagnosed as cholangiocarcinoma. A 59-year-old male was admitted with recurrent episodes of jaundice. He was found to have a tumor in the right hepatic duct extending into intrahepatic ducts, which was clinically and radiologically diagnosed as cholangiocarcinoma. The patient underwent right hepatectomy with excision of the bile duct and left hepaticojejunostomy. Histological examination revealed an intraductal moderately differentiated hepatocellular carcinoma. The rest of the liver parenchyma showed features secondary to biliary obstruction but no tumor. A case of hepatocellular carcinoma presenting as an intraductal tumor with obstructive jaundice and no evidence of parenchymal tumor is presented.