HPHS Journal Watch March/April 2020

Modern pathology

Utility of glutamine synthetase immunohistochemistry in identifying features of regressed cirrhosis.
Hadi R, Shin K, Reder N, et al. Mod Pathol 2020 Mar; 33(3): 448-455.

The authors hypothesized that aberrant glutamine synthetase positivity adjacent to portal tracts would help identify regressed cirrhosis. They performed glutamine synthetase immunohistochemistry on 49 liver specimens (16 regressed cirrhosis, 18 cirrhotic, and 15 normal livers).

Malignant transformation of liver fatty acid binding protein-deficient hepatocellular adenomas: histopathologic spectrum of a rare phenomenon.
Putra J, Ferrell LK, Gouw ASH, et al.  Mod Pathol 2020 Apr; 33(4): 665-675.

Malignant transformation is an exceptionally rare complication of hepatocyte nuclear factor 1α (HNF1A)-inactivated hepatocellular adenomas. The authors characterized the histopathologic spectrum of 13 liver fatty acid binding protein-deficient hepatocellular adenoma cases showing malignant transformation from multiple centers. Molecular studies confirmed somatic inactivation of HNF1A in 3 cases and absence of TERT promotor and exon 3 CTNNB1 mutations in five cases.

Journal of Gastroenterology and Hepatology

Interaction between the tumor microenvironment and resection margin in different gross types of hepatocellular carcinoma.
Cha SW, Sohn JH, Kim SH, et al. J Gastroenterol Hepatol 2020 Apr; 35(4): 648-653.

There is no consensus regarding a safe resection margin in hepatocellular carcinoma (HCC). Several studies have reported that different gross types require different resection margins. The authors investigated the changes in the tumor microenvironment (TME) in different gross types of HCC. They divided the patients into two groups: group 1 included expanding and vaguely nodular types, whereas group 2 included nodular with perinodular extension, multinodular confluent, and infiltrative types. The authors evaluated 5‐year disease‐free survival (DFS) and overall survival (OS) rates.

Hepatocellular adenoma in Taiwan: Distinct ensemble of male predominance, overweight/obesity, and inflammatory subtype.
Huang WC, Liau JY, Jeng YM, et al. J Gastroenterol Hepatol 2020 Apr; 35(4): 680-688.

The authors evaluated the clinicopathologic features of hepatocellular adenoma in a single institution in Taiwan.

Hepatology Communications

Primary Sclerosing Cholangitis With Features of Autoimmune Hepatitis: Exploring the Global Variation in Management.
Milkiewicz P, Krawczyk M, Wunsch E, et al. Hepatol Commun. 2020 Jan 16; 4(3): 399-408.

The study in this paper involved sending a survey to 80 participates (primarily hepatologists) where they were presented the laboratory studies and histopathologic features from several cases of primary sclerosing cholangitis (PSC), some of which had features suggestive of overlap with autoimmune hepatitis (AIH).  They asked the clinicians if they thought that liver biopsies were indicated in order to confirm the diagnosis, and also what treatment regimen they would recommend.  The results varied widely; however, most of the clinicians answered that they would order liver biopsies to assist with the diagnosis.  The criteria for PSC/AIH overlap from EASL were stated as “AIH/PSC variant can be diagnosed in a patient with cholangiographic or histological features of PSC alongside robust biochemical, serological and histological features of AIH.” This entity is a challenging diagnosis for both clinicians and pathologists.  However, an important point was that many patients with PSC have elevated serologic studies that are just part of active PSC-related injury and do not indicate a component of AIH.  Further studies at more centers are needed to better understand and diagnosis this overlap syndrome.


Applying Machine Learning in Liver Disease and Transplantation: A Comprehensive Review.
Spann A, Yasodhara A, Kang J, et al. Hepatology 2020 Mar; 71(3): 1093-1105.

Machine learning (ML) utilizes artificial intelligence to generate predictive models efficiently and more effectively than conventional methods through detection of hidden patterns within large data sets. This review examined the literature pertaining to machine learning in hepatology and liver transplant medicine. The authors provide an overview of strengths, limitations, and potential applications to both clinical and molecular data in hepatology. The review provides readers with the opportunity to learn about the ML tools available, and potential applications to questions of interest in hepatology.

Liver Diseases in the Perinatal Period: Interactions Between Mother and Infant.
Ibrahim SH, Jonas MM, Taylor SA, et al. Hepatology 2020 Apr; 71(4): 1474-1485.

This is a review article with focus on perinatal liver diseases. Liver diseases affecting the mother and infant dyad may present in the perinatal period from 20 weeks of gestation to 28 days of life. This review focuses on the current approach to neonatal acute liver failure as well as diagnosis and management of gestational alloimmune liver disease. The article discusses a broad differential diagnosis including nonalcoholic fatty liver disease, viral hepatitis, acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy.

New Insights Into Intestinal Failure-Associated Liver Disease in Children.
Khalaf RT, Sokol RJ. Hepatology 2020 Apr; 71(4): 1486-1498.

Development of intestinal failure–associated liver disease (IFALD) is a common complication of long-term parenteral nutrition (PN) in children and adults. This review provides an update on advances in the pathogenesis of IFALD, newer therapeutic and preventative strategies, and challenges that confront managing patients with IFALD.

Journal of Hepatology

Hepatitis A and E – Differences and commonalities.
Gottlieb N, Moradpour D, Shouval D. J Hepatol 2020 Mar; 72(3): 578-580.

This article focuses on distinctions between the two most common causes of acute hepatitis globally in humans, HAV and HEV.  Both are enterically transmitted hepatotropic viruses, usually self-limited, and are mainly transmitted through contaminated water and food.  Large, predominantly water-borne outbreaks of HEV genotypes (gt) 1 and 2 occur in resource limited settings, while gt 3 and 4 are zoonotic infections in middle and high income regions.  Zoonotic transmission of HAV is unknown. HEV gt 3 and 4 infection mainly occurs through the consumption of raw or undercooked pork or game meat but likely also through other routes, including transmission through transfusion of blood products. Risk groups for HAV infection in middle- and high-income regions include persons who inject drugs, men who have sex with men, homeless persons, and travelers to areas of high endemicity. AntiHEV(IgG) antibody seroprevalence rates vary between 5 and 20% in many developed countries and reach 86% in the South of France.  While HAV infection with recovery, and probably immunization too, provide life-long immunity against HAV, re-infection with HEV is possible.

NAFLD as a driver of chronic kidney disease.
Byrne CD, Targher G. J Hepatol 2020 Apr; 72(4): 785-801.

Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), conditions afflicting up to 25–30% (NAFLD), and up to 10–15% (CKD) of the general population, have recently been shown to have a strong association. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, and aging processes are contributory. Follow the link and learn more.


Recent Advances in Alcohol-Related Liver Disease (ALD): Summary of a Gut Round Table Meeting.
Avila MA, Dufour J, Gerbes AL, et al. Gut 2020 Apr; 69(4) :764-780.

This paper provides a good up to date review of ALD and includes a discussion of the role of liver biopsy in its diagnosis and management. The text states: “Liver biopsy is still considered the gold standard for the definite diagnosis and for assessing the fibrosis stage of ALD. However, as it is an invasive procedure, it is associated with side effects and therefore not always recommended.” Attention is drawn to identifying co-existing liver diseases especially iron overload and alpha-1 antitrypsin deficiency.

American Journal of Gastroenterology

Immunosuppression in Autoimmune Hepatitis: Is There an End Game?
Moon AM, Spiritos Z, King LY, et al. Am J Gastroenterol 2020 Apr; 115(4): 498-501.

The role of liver biopsy in the management of autoimmune hepatitis has a long literature. In this paper, the authors show that those patients who demonstrate biochemical and histological remission before treatment is withdrawn are at lower risk for relapse compared with those who have either had an incomplete response or have failed treatment. Histological remission therefore remains an important treatment endpoint.

Prepared by:
Nafis Shafizadeh MD (Editor); Southern California Permanente Medical Group
Daniela Allende MD; Cleveland Clinic
Vishal Chandan MBBS; University of California Irvine
Robert Goldin MD; Imperial College, London
Bella Goyal MD; California Pacific Pathology Medical Group
Cynthia Guy MD; Duke University
Grace Guzman MD; University of Illinois
Mojgan Hosseini MD; University of California San Diego
Heather Stevenson-Lerner MD PhD; University of Texas

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