John S, Pratt DS. Jaundice. In: Loscalzo J, Kasper DL, Longo DL, Fauci AS, Hauser SL, Jameson JL, editors. Harrison’s principles of Internal Medicine. 21 ed: Mc Graw Hill Education, 2022;315-20.
Schrumpf E, Elgjo K, Fausa O, Gjone E, Kolmannskog F, Ritland S.
Sclerosing cholangitis in ulcerative colitis.
Scand J Gastroenterol. 1980;15(6):689-97. doi: 10.3109/00365528009181516.
Abstract/Text
In a 5-year period 48 (14%) of 336 patients with ulcerative colitis were found to have hepatobiliary disease. The bile ducts were examined in 35 of these patients, and optimal visualization of both intra- and extra-hepatic bile ducts was obtained in 26. Duct changes compatible with sclerosing cholangitis were found in 14 patients. This finding of sclerosing cholangitis in 4% of all patients admitted with ulcerative colitis by far exceeds previous estimations on the incidence of sclerosing cholangitis in ulcerative colitis. The entire colon was usually affected, and the symptoms of the bowel disease were most often mild or moderate. The age at the onset of the colitis was usually below 20 years in patients with combined ulcerative colitis and hepatobiliary disease. In most patients the hepatobiliary disease gave no symptoms. Biochemical data and the histological findings in the liver biopsies did not distinguish between patients with hepatobiliary disease with and without sclerosing cholangitis. Our follow-up study has so far shown that most patients with sclerosing cholangitis remain asymptomatic for a considerable period of time.
Kumada H, Miyakawa H, Muramatsu T, Ando N, Oh T, Takamori K, Nakamoto H.
Efficacy of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus: A randomized, double-blind trial.
Hepatol Res. 2017 Sep;47(10):972-982. doi: 10.1111/hepr.12830. Epub 2016 Nov 24.
Abstract/Text
AIMS: Patients with chronic liver disease sometimes develop cholestasis, which induces severe whole-body pruritus that may disrupt daily activities and sleep. To determine the efficacy of nalfurafine hydrochloride (5 μg), which is a selective κ-opioid receptor agonist, in improving pruritus, we undertook a double-blind placebo-controlled study in patients with chronic liver disease with refractory pruritus. Nalfurafine hydrochloride at 2.5 μg was also used to evaluate the dose-response relationship.
METHODS: In total, 318 subjects were randomly assigned to receive the placebo or nalfurafine hydrochloride (2.5 or 5 μg) given orally once daily for 84 consecutive days. Pruritus was assessed based on the visual analog scale and pruritus scores.
RESULTS: Changes in the visual analog scale at week 4 (last observation carried forward) were significantly greater in the nalfurafine hydrochloride groups at 28.56 and 27.46 mm in the 2.5 μg and 5 μg groups, respectively, compared to 19.25 mm in the placebo group (P = 0.0022 and 0.0056, respectively). The major adverse drug reactions (ADRs) included pollakiuria (including nocturia), somnolence, insomnia (including middle insomnia), and constipation. Most ADRs were mild.
CONCLUSIONS: Nalfurafine hydrochloride (2.5 or 5 μg daily) was effective in the treatment of refractory pruritus in patients with chronic liver disease. Furthermore, no clinically significant ADRs were observed at either dose.
© 2016 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.
Tseng CW, Chen CC, Chen TS, Chang FY, Lin HC, Lee SD.
Can computed tomography with coronal reconstruction improve the diagnosis of choledocholithiasis?
J Gastroenterol Hepatol. 2008 Oct;23(10):1586-9. doi: 10.1111/j.1440-1746.2008.05547.x. Epub 2008 Aug 17.
Abstract/Text
BACKGROUND AND AIM: Many technical developments of computed tomography (CT) made in recent years have improved imaging quality. However, the diagnostic efficacy of CT with coronal reconstruction for choledocholithiasis remains uncertain. This study aimed to investigate if CT with coronal reconstruction can aid in the diagnosis of choledocholithiasis.
METHODS: Two hundred and sixty-six patients with clinically suspected choledocholithiasis undergoing abdominal CT before endoscopic retrograde cholangiopancreatography were recruited. Among them, 163 patients confirmed with choledocholithiasis were divided into three groups: group 1, 92 patients undergoing CT using 5-mm thick sections with coronal reconstruction; group 2, 32 patients undergoing CT using 5-mm thick sections without coronal reconstruction; and group 3, 39 patients undergoing CT using 7-mm thick sections without coronal reconstruction. The diagnostic rate of CT for choledocholithiasis, the stone size and biochemical data among the three groups were analyzed.
RESULTS: The sensitivity and specificity of CT in diagnosing choledocholithiasis were 77.3% and 72.8%. There was no significant difference of CT diagnostic rate among the three groups (75.0%, 81.2% and 79.5%, respectively). The diameter of common bile duct (CBD), size of CBD stones and white cell count showed significant differences between CT true-positive and false-negative cases in group 1 patients. The CT diagnostic rate was significantly lower in patients with choledocholithiasis of less than 5 mm than in patients with choledocholithiasis of 5 mm or more (56.5% vs 81.2%).
CONCLUSION: The coronal reconstruction of CT imaging did not increase its diagnostic efficacy on choledocholithiasis. The stone size affects the diagnostic rate of abdominal CT for detecting choledocholithiasis.
Shea JA, Berlin JA, Escarce JJ, Clarke JR, Kinosian BP, Cabana MD, Tsai WW, Horangic N, Malet PF, Schwartz JS.
Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.
Arch Intern Med. 1994 Nov 28;154(22):2573-81.
Abstract/Text
BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis.
METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results.
RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98).
CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.
Pickuth D, Spielmann RP.
Detection of choledocholithiasis: comparison of unenhanced spiral CT, US, and ERCP.
Hepatogastroenterology. 2000 Nov-Dec;47(36):1514-7.
Abstract/Text
BACKGROUND/AIMS: ERCP is an established method for the diagnosis and treatment of common bile duct stones, however, it is invasive, time-consuming, and expensive. The purpose of this study was to determine whether unenhanced spiral CT and US, compared with ERCP, have sufficient sensitivity and negative predictive value to be useful screening techniques in patients suspected of having choledocholithiasis.
METHODOLOGY: Over a period of 2 years, 82 patients with clinically suspected choledocholithiasis underwent unenhanced spiral computed tomography and US immediately before undergoing endoscopic retrograde cholangiopancreatography. CT/US scans and ERCP images were evaluated for the presence of bile duct stones, ampullary stones, and extrahepatic biliary dilatation.
RESULTS: Unenhanced spiral computed tomography (US) depicted common bile duct stones in 24 (23) of 28 patients found to have stones at endoscopic retrograde cholangiopancreatography. Five patients had stones impacted at the ampulla, all (two) of which were detected with CT (US). Computed tomography (US) had a sensitivity of 86% (82%) and a specificity of 98% (98%) in the diagnosis of choledocholithiasis.
CONCLUSIONS: Both unenhanced spiral CT and US are useful for evaluating suspected common bile duct stones. Unenhanced spiral CT is especially useful when the patient is likely to have ampullary stones and is a safe, more available and less expensive alternative to magnetic resonance cholangiography.
Scaffidi MG, Luigiano C, Consolo P, Pellicano R, Giacobbe G, Gaeta M, Blandino A, Familiari L.
Magnetic resonance cholangio-pancreatography versus endoscopic retrograde cholangio-pancreatography in the diagnosis of common bile duct stones: a prospective comparative study.
Minerva Med. 2009 Oct;100(5):341-8.
Abstract/Text
AIM: As it is a non-invasive method, magnetic resonance cholangiography (MRCP) has almost completely replaced endoscopic retrograde cholangiography (ERCP) in the diagnosis of pancreato-biliary diseases. The aim of this study was to evaluate sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of MRCP in diagnosis of choledocholithiasis using ERCP/endoscopic sphincterotomy (ES) as gold standard.
METHODS: For this study 140 individuals, suspected for lithiasis of the common bile duct (CBD), were enrolled. After a clinical and biochemical evaluation, patients underwent upper abdominal ultrasonography, then MRCP and diagnostic and/or operative ERCP.
RESULTS: Only 120 out of 140 patients completed the study. MRCP diagnosed lithiasis of CBD in 84. ERCP confirmed the lithiasis in 73/84 patients who were submitted to ES. Eleven were negative after ES. ERCP documented stones in 10 patients among the 36 negative at MRCP; stones were detected only in four patients after ES. In 26 out of 36 patients negative at MRCP, ERCP confirmed this response: only 12 out of 26 patients underwent ES. The sensitivity, specificity, diagnostic accuracy, PPV and NPV of MRCP were: 88%, 72%, 83%, 87%, 72%.
CONCLUSIONS: As the MRCP diagnostic yield is still limited with small stones, the question of which patient is the best candidate to ERCP/ES is still unsolved.
Sjogren MH, Cheatham JG. Hepatitis A. In: Feldman M, Friedman L, Brandt L, Chung R, Rubin D, Wilcox C, editors: Sleisenger and Fordtran’s Gastrointestinal and liver disease. 2. 11 ed: Elsevier, 2021;1210-5.
Perrillo RP, Chau KH, Overby LR, Decker RH.
Anti-hepatitis B core immunoglobulin M in the serologic evaluation of hepatitis B virus infection and simultaneous infection with type B, delta agent, and non-A, non-B viruses.
Gastroenterology. 1983 Jul;85(1):163-7.
Abstract/Text
The clinical value of an enzyme-linked immunosorbent assay for the detection of immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc IgM) was evaluated by testing serum samples from the following groups of patients: (a) 27 individuals who had been diagnosed as having acute hepatitis B virus (HBV) infection, (b) 29 hepatitis B surface antigen (HBsAg) carriers, (c) 6 subjects with acute non-B hepatitis, and (d) 10 HBsAg-negative but anti-HBc-positive subjects who were suspected of being index cases for the intimate transmission of HBV. Whereas 24 of the 27 individuals with presumed acute HBV infection exhibited anti-HBc IgM, only 2 of 29 HBsAg carriers were found to be positive. Hepatitis B surface antigen persisted during an 8-mo observation period in 3 anti-HBc IgM-negative subjects with acute HBsAg-positive hepatitis. Before anti-HBc IgM testing, it was considered that these cases had evolved to the HBsAg carrier state. However, the regular demonstration of anti-HBc IgM in acute type B hepatitis, as well as the failure to detect this antibody in the majority of HBsAg carriers, led to reclassification of these cases as probable instances of acute non-A, non-B or delta-agent hepatitis superimposed on the HBsAg carrier state. Through additional testing, the diagnosis of non-A, non-B (NANB) infection was confirmed in 2 of these cases, and delta-agent infection was identified in the third. None of the non-B hepatitis cases exhibited anti-HBc IgM. However, 5 of the 10 suspected type B index cases were anti-HBc IgM-positive, indicating that they were very recently infected and most likely had infected their cohabiting sexual partners. The results from this study indicate that testing for anti-HBc IgM may improve serodiagnostic accuracy when acute NANB and delta-agent hepatitis occur in previously unrecognized HBsAg carriers. Moreover, it may be a useful test in defining potential high risk sources of exposure to HBV.
Reiss G, Keeffe EB.
Review article: hepatitis vaccination in patients with chronic liver disease.
Aliment Pharmacol Ther. 2004 Apr 1;19(7):715-27. doi: 10.1111/j.1365-2036.2004.01906.x.
Abstract/Text
Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.
Scott JD, Gretch DR.
Molecular diagnostics of hepatitis C virus infection: a systematic review.
JAMA. 2007 Feb 21;297(7):724-32. doi: 10.1001/jama.297.7.724.
Abstract/Text
CONTEXT: Hepatitis C virus (HCV) is a common blood-borne pathogen that relies heavily on nucleic acid testing for confirmation of infection. Nucleic acid tests are invaluable for the diagnosis of HCV infection and provide critical prognostic information for guiding treatment and measuring the response to antiviral therapy.
OBJECTIVE: To review the currently available molecular diagnostic tests for HCV, their clinical applications, and how these tests shed light on the natural history of HCV.
EVIDENCE ACQUISITION: Search of MEDLINE (1966 to July 2006), article reference lists, and national meeting abstracts for the diagnosis and applications of molecular diagnostic tests for HCV. Studies were selected on the basis of clinical relevance.
EVIDENCE SYNTHESIS: Qualitative nucleic acid tests have low limits of detection (<50 IU HCV RNA/mL) and are used for confirmation of HCV infection and for screening blood donations. Hepatitis C virus genotype test results provide important prognostic information related to therapeutic response and are routinely used for selecting treatment regimens. Quantitative HCV RNA testing provides prognostic information regarding likelihood of treatment response and plays an important role in monitoring the antiviral response to treatment. Sustained virological response is defined as testing negative for HCV RNA 6 months after cessation of therapy. Recent studies suggest that the rate of response to therapy is also important. For example, conversion to an HCV RNA negative test result after 4 weeks of therapy constitutes a rapid virological response and is a strong predictor of treatment success. Patients who have not had an early virological response, defined as at least a 2-log decline in HCV RNA after 12 weeks of therapy, are unlikely to respond with an additional 36 weeks of therapy, and should stop therapy.
CONCLUSIONS: A sensitive nucleic acid test should be used to confirm all cases of acute or chronic HCV infection. A genotype test and quantitative HCV RNA test should be performed on all patients prior to therapy to best assess probability of response and to aid in selection of appropriate therapeutic regimen. Monitoring HCV RNA during treatment provides important information on likelihood of sustained virological response. The same type of quantitative HCV RNA test should be used throughout a patient's treatment course.
Ghany MG. Hepatitis D. In: Feldman M, Friedman L, Brandt L, Chung R, Rubin D, Wilcox C, editors : Sleisenger and Fordtran’s Gastrointestinal and liver disease. 2. 11 ed: Elsevier, 2021;1283-91.
Aggarwal R. Hepatitis E. In: Feldman M, Friedman L, Brandt L, Chung R, Rubin D, Wilcox C, editors. Sleisenger and Fordtran’s Gastrointestinal and liver disease. 11 ed: Elsevier, 2021;1292-7.
Reisman Y, Gips CH, Lavelle SM, Wilson JH.
Clinical presentation of (subclinical) jaundice--the Euricterus project in The Netherlands. United Dutch Hospitals and Euricterus Project Management Group.
Hepatogastroenterology. 1996 Sep-Oct;43(11):1190-5.
Abstract/Text
BACKGROUND: From a primary clinical database, we wanted to obtain insight in disease distribution and clinical presentation of adult jaundiced patients in a Western country.
MATERIALS AND METHODS: As part of the Euricterus project, 24 Dutch general and academic hospitals in a period of 2 years gathered prospectively 702 patients on a standard proforma. Patient aged 16 years or more (median 61) and with a serum bilirubin of 20 mmol/l or more (median 83) were included. The final diagnosis was established within 3 months.
RESULTS: Pancreatic or biliary carcinoma (20%), gallstone disease (13%) and alcoholic liver cirrhosis (10%) were the 3 most frequent diagnoses. Imaging (79%), clinical course (63%) and chemistry/serology (57%) were the most used ascertaining methods. Pancreatic or biliary carcinoma and gallstone disease were more common and age higher in general hospitals (p = 0.0001), and 'immunological' liver disease, non-alcoholic cirrhosis and hepatocellular carcinoma (HCC) more common in academic hospitals (p = 0.001). Patients aged 90 years or older (13%) had pancreatic or biliary carcinoma, liver metastases or heart failure and patients with age less than 20 (0.9%) had acute viral hepatitis, nonalcoholic active liver disease or HCC. Risk factors were more apparent (p < 0.02) in those aged less than 61 years. Feeling unwell (78%), dark urine (67%) and anorexia (57%) were the 3 most frequent symptoms; the 3 most frequent signs were liver enlarged (39%), looking ill (29%) and appearing wasted (23%).
CONCLUSIONS: Through Euricterus, fresh clinical knowledge has emerged of symptomatology, age stratification and hospital preponderance of (sub)clinical jaundice in this country. This is important both for teaching and in preparing clinical studies.
Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ.
Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases.
Hepatology. 2020 Aug;72(2):671-722. doi: 10.1002/hep.31065. Epub 2020 May 12.
Abstract/Text
Levy C, Bowlus C. Primary and Secondary Sclerosing Cholangitis. In: Feldman M, Friedman L, Brandt L, Chung R, Rubin D, Wilcox C, editors. Sleisenger and Fordtran’s Gastrointestinal and liver disease. 11 ed: Elsevier, 2021;1094.
Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr M, Notohara K, Okazaki K, Schneider A, Zhang L; International Association of Pancreatology.
International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology.
Pancreas. 2011 Apr;40(3):352-8. doi: 10.1097/MPA.0b013e3182142fd2.
Abstract/Text
OBJECTIVES: To achieve the goal of developing international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP).
METHODS: An international panel of experts met during the 14th Congress of the International Association of Pancreatology held in Fukuoka, Japan, from July 11 through 13, 2010. The proposed criteria represent a consensus opinion of the working group.
RESULTS: Autoimmune pancreatitis was classified into types 1 and 2. The ICDC used 5 cardinal features of AIP, namely, imaging of pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histology, and an optional criterion of response to steroid therapy. Each feature was categorized as level 1 and 2 findings depending on the diagnostic reliability. The diagnosis of type 1 and type 2 AIP can be definitive or probable, and in some cases, the distinction between the subtypes may not be possible (AIP-not otherwise specified).
CONCLUSIONS: The ICDC for AIP were developed based on the agreement of an international panel of experts in the hope that they will promote worldwide recognition of AIP. The categorization of AIP into types 1 and 2 should be helpful for further clarification of the clinical features, pathogenesis, and natural history of these diseases.
Luzzatto L, Franceschi LD. Hemolytic anemia. In: Loscalzo J, Kasper DL, Longo DL, Fauci AS, Hauser SL, Jameson JL, editors. Harrison’s principles of Internal Medicine. 21 ed: Mc Graw Hill Education, 2022;776-91.
Adachi Y, Nanno T, Yamamoto T.
[Japanese clinical statistical data of patients with constitutional jaundice].
Nihon Rinsho. 1992 Nov;50 Suppl:677-85.
Abstract/Text
