Isolated hepatic sarcoidosis: A case series.

Sarcoidosis is a multi-organ inflammatory disease that can have hepatic involvement in up to 80% of cases. Rarely, sarcoidosis can manifest with only confined disease to the liver. While most patients with hepatic sarcoidosis are clinically silent, certain cases can have insidious onset leading to cirrhosis and secondary complications. Here, we describe three cases of isolated hepatic sarcoidosis to illustrate the range of presentations that may be associated with this condition. Clinicians should be vigilant in consideration of hepatic sarcoidosis as a culprit when investigating patients with undifferentiated liver disease.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Non-Mass-Forming Myeloid Sarcoma of the Colon Presenting With Diarrhea.

A female patient in her mid-70s, with a history of diverticulosis, presented with a 2-month history of severe diarrhea, left lower quadrant abdominal pain, decreased appetite, and fever. She was treated for diverticulitis, but did not improve. Subsequent workup revealed leukocytosis and circulating myeloblasts on a peripheral blood smear. Bone marrow evaluation and flow cytometry confirmed the diagnosis of acute myeloid leukemia. Abdominal computed tomography and sigmoidoscopy were performed for her persistent diarrhea. While both failed to show an obvious mass or anatomical abnormality, pathology from the colorectum showed infiltration by leukemic cells consistent with myeloid sarcoma. The diarrhea improved with acute myeloid leukemia chemotherapy.

Sarcomatoid carcinoma of the common bile duct presenting as painless jaundice.

A woman in her 70s presented with painless jaundice and index biopsy of a common bile duct (CBD) mass obtained by endoscopic retrograde cholangiopancreatography was suspicious for malignant peripheral nerve sheath tumour. Treatment consisted of pancreaticoduodenectomy, and final pathology results were consistent with sarcomatoid carcinoma. Postoperative complications included pancreaticojejunal leak, surgical wound infection, bacteraemia, myocardial injury, and significant ulceration and stricturing of the oesophagus. 14 weeks post-pancreaticoduodenectomy, the patient was found to have a perforated viscus, gastroduodenal leak and diffuse small bowel ischaemia-the patient passed away following emergent laparotomy. We aim to add to the limited literature surrounding this rare CBD neoplasm.

Hepatic graft-versus-host disease: what we know, when to biopsy, and how to diagnose.

Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens, which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD, which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction. Particularly challenging among the various conditions that give rise to liver dysfunction is differentiating sinusoidal obstruction syndrome and drug-induced liver injury (DILI) from hGVHD on clinical grounds and laboratory tests. Despite the minimal risks involved in performing a liver biopsy, the information gleaned from the histopathologic changes may help in the management of these very complex patients. There is a spectrum of histologic features found in hGVHD, and most involve histopathologic changes affecting the interlobular bile ducts. These include nuclear and cytoplasmic abnormalities including dysmorphic bile ducts, apoptosis, and cholangiocyte necrosis, among others. The hepatitic form of hGVHD typically shows severe acute hepatitis. With chronic hGVHD, there is progressive bile duct loss and eventually fibrosis. Accurate diagnosis of hGVHD is paramount so that timely treatment and management can be initiated. Techniques to prevent and lower the risk of GVHD from developing have recently evolved. If a diagnosis of acute GVHD is made, the first-line of treatment is steroids. Recurrence is common and steroid resistance or dependency is not unusual in this setting. Second-line therapies differ among institutions and have not been uniformly established. The development of GVHD, particularly hGVHD, is associated with increased morbidity and mortality.

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis.

BACKGROUND: Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). AIMS: To identify risk factors for new-onset HCC in patients cured of hepatitis C. METHODS: Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. RESULTS: Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59-67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25-4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/µL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. CONCLUSIONS: One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.

Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death.

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b-/- mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b-/- mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

Liver Transplantation for Extra-Hepatic Manifestation of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disorder distinguished by multiple arteriovenous malformations that can affect the liver and lungs, and additionally cause high-output heart failure. Effective medical treatment for HHT-related heart failure is limited. While most types of heart failure are contraindications in liver transplants, HHT-related high-output heart failure is an indication for a liver transplant. However, this is rarely performed as it poses a higher-than-average intraoperative risk. We present a case of a 57-year-old female patient with HHT and high-output heart failure from HHT who underwent a successful orthotopic liver transplant to significantly improve her heart function. Incidentally, the patient had a concomitant diagnosis of primary biliary cholangitis (PBC) from her explanted liver. We review the literature on liver transplants related to HHT and perioperative risks associated with heart failure and pulmonary hypertension that may be associated with both HHT and PBC.

Liver biopsy complication rates in patients with non-alcoholic fatty liver disease.

BACKGROUND: With new treatments for non-alcoholic fatty liver disease (NAFLD) on the horizon, it will be important to risk-stratify patients based on degree of fibrosis to allocate treatment to those at highest risk. No studies have examined the complication rates of liver biopsies in patients with NAFLD in the outpatient setting. METHODS: We conducted a retrospective chart review of all outpatient elective liver biopsies for NAFLD at a tertiary care centre over a 10-year period. Demographic variables and stage of fibrosis were recorded. Complications up to 1 week post-procedure were recorded. We used univariate logistic regression models to estimate the odds of major complications by fibrosis stage, age, sex, platelets, and international normalized ratio (INR). RESULTS: There were 582 biopsies reviewed in total. The mean age was 53 years. There was an even proportion of males to females. The mean fibrosis stage was 1.9; platelet count was 223.9, INR was 1, and partial thromboplastin time (PTT) was 31. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. There were no statistically significant associations between age (odds ratio [OR] 0.97, 95% CI 0.92-1.03), female sex (OR 1.00, 95% CI 0.25-4.04), platelet count <150 (OR 0.59, 95% CI [-inf.], 3.86), INR >1.3 (OR 0.47, 95% CI 0.057-3.85), fibrosis stage, and complication rate. CONCLUSIONS: Our results are consistent with previous studies examining complication rates in other patient populations and clinical settings and support the overall safety of liver biopsies.

PAXgene Fixation for Pancreatic Cancer: Implications for Molecular and Surgical Pathology.

Genomic profiling of pancreatic cancer using small core biopsies has taken an increasingly prominent role in precision medicine. However, if not appropriately preserved, nucleic acids (NA) from pancreatic tissues are known to be susceptible to degradation due to high intrinsic levels of nucleases. PAXgene fixation (PreAnalytix, Switzerland) represents a novel formalin-free tissue preservation method. We sought to compare the NA and histomorphological preservation of pancreatic cancer tissues preserved with PAXgene-fixed paraffin-embedding (PFPE) and formalin-fixed paraffin-embedding (FFPE). Tissues from 19 patients were obtained prospectively from pancreaticoduodenectomy specimens and evaluated by four gastrointestinal pathologists. The extracted NA were quantified by Nanodrop and Qubit and assessed for quality by qPCR, targeted next-generation sequencing (NGS) assay, and RNA-sequencing. Our results demonstrated that, when assessed blindly for morphological quality, the four pathologists deemed the PFPE slides adequate for diagnostic purposes. PFPE tissues enable greater yields of less fragmented and more amplifiable DNA. PFPE tissues demonstrated significantly improved quality control (QC) metrics in a targeted NGS assay including Median Absolute Pair-wise Difference (MAPD) scores. Our results support the use of PAXgene fixative for the processing of specimens from pancreatic cancers with the potential benefits of improved yields for more amplifiable DNA in low-yield biopsy specimens and its ideal use for amplicon-based NGS assays.

Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature review.

Gastrointestinal stromal tumors (GISTs) are usually caused by somatic mutations, but there are rare germline variants that predispose patients to the development of one or, more commonly, multiple GISTs. We present 2 cases of multifocal GISTs related to previously unreported germline variants. The first case is a 28-year-old female who developed multiple gastric GISTs with widespread abdominal metastases that were resistant to imatinib. Assessment by Medical Genetics identified a germline SDHB splice site mutation (NM_003000.3, c.286 + 2T > G, p.?). The second case is a 64-year-old male who presented with multiple gastric tumors that were resistant to imatinib. Next-generation sequencing revealed a germline KIT exon 17 mutation (NM_000222.3, c.2459A > T, p.D820V). These cases highlight the diverse clinical presentations of patients with germline variants and raise several important points about the diagnosis and management of these patients, in particular: mutation in the SDH family of genes (somatic or germline) should be suspected in KIT and PDGFRA wild-type tumors; germline testing should be considered in patients with multiple GISTs or those who present with disease at a young age; and somatic next-generation sequencing cannot only help identify optimal therapy in all patients with GISTs but also help guide referral to Medical Genetics for appropriate patients.

Isolated metastatic melanoma to the pancreas in the context of myeloproliferative neoplasm: a rare occurrence.

Isolated metastatic melanoma to the pancreas is a rare occurrence, representing less than 1 per cent of metastatic melanoma. This case describes the clinical presentation and course of illness of a patient who was diagnosed with a solitary metastasis to the pancreas 11 months after a clear margin resection of a pT1b, stage IB melanoma. Her melanoma metastasis was diagnosed on Endoscopic Ultrasound-Fine Needle Biopsy (EUS-FNB). This patient was found to have a concurrent myeloproliferative neoplasm (MPN) at the time of diagnosis. This case importantly highlights the course of a rare finding in isolated metastatic melanoma to the pancreas that may have been accelerated by the patient's immunocompromised state with concurrent MPN. A high index of suspicion must be raised in patients with abdominal symptoms and melanoma history as the therapeutic window for these patients is quite narrow.

Prospective Evaluation of Virtual MR Elastography With Diffusion-Weighted Imaging in Subjects With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and can lead to the development of cirrhosis, liver failure and cancer. Virtual magnetic resonance elastography (VMRE), which is based on a shifted apparent diffusion coefficient (sADC), is a potential noninvasive method to assess liver fibrosis without the specialized hardware and expertise required to implement traditional MR elastography (MRE). Although hepatic steatosis is known to confound ADC measurements, previous studies using VMRE have not corrected for hepatic fat fraction. PURPOSE: To compare VMRE, corrected for the confounding effects of unsuppressed fat signal, to MRE and biopsy in subjects with suspected NAFLD. STUDY TYPE: Prospective, cross-sectional. POPULATION: A total of 49 adult subjects with suspected NAFLD (18 male; median age 55 years, range 33-74 years) who underwent liver biopsy. FIELD STRENGTH/SEQUENCE: 3T, diffusion-weighted spin echo planar, chemical-shift encoded (IDEAL IQ) and MRE sequences. ASSESSMENT: Two observers drew regions of interest on sADC, proton density fat fraction and MRE-derived stiffness maps. Fat-corrected sADC values were used to calculate the diffusion-based shear modulus according to the VMRE method. Predicted fibrosis stage for MRE and VMRE was determined using previously published cut-off values. STATISTICAL TESTS: The relationship between VMRE and MRE was assessed with least-squares linear regression (coefficient of determination, R2 ). Agreement between MRE and VMRE-predicted fibrosis stage was evaluated with a kappa coefficient and accuracy compared using McNemar's test. A one-way ANOVA determined if the fat-corrected sADC (VMRE) and MRE differed by fibrosis stage. A P value < 0.05 was considered statistically significant. RESULTS: Least squares regression of VMRE vs. MRE revealed R2  = 0.046 and a slope that was not significantly different from zero (P = 0.14). There was no agreement between MRE and VMRE-predicted fibrosis stage (kappa = -0.01). The proportion of correctly predicted fibrosis stage was significantly higher for MRE compared to VMRE. MRE was significantly associated with fibrosis stage, but fat-corrected sADC was not (P = 0.24). DATA CONCLUSION: Fat-corrected VMRE was not associated with fibrosis stage in NAFLD. Further investigation is required if VMRE is to be considered in subjects with NAFLD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Hepatic Secondary Syphilis Can Cause a Variety of Histologic Patterns and May Be Negative for Treponeme Immunohistochemistry.

The rate of syphilis in the United States has been increasing steadily in the past decade, but it remains an uncommon diagnosis in tissue biopsies. Most of the pathology literature on hepatic syphilis consists of older series or case reports. This study aimed to systematically characterize the histologic spectrum of hepatic syphilis in a contemporary cohort. Clinicopathologic features of 14 hepatic syphilis cases between 2012 and 2018 were analyzed to characterize the broad spectrum of histologic changes. Thirteen patients were men (age range: 19 to 59 y); 6 had known human immunodeficiency virus, 7 were men known to have sex with men, and no patient had known prior syphilis. Hepatic syphilis was the primary clinical suspicion in only 1 patient. Common symptoms included jaundice, rash, and abdominal pain. Thirteen had elevated transaminases, and 12 had elevated alkaline phosphatase. Pathologic changes were grouped into 5 histologic patterns: biliary-pattern injury (n=5), acute hepatitis (n=4), autoimmune hepatitis-like (n=1), fibroinflammatory mass-forming lesion (n=2), and no particular pattern (n=2). Nearly all showed portal and lobular lymphocytes and plasma cells; 12 had prominent histiocytes/Kupffer cells, 9 had ductular reaction, and 7 had duct inflammation. Occasional focal findings included dropout (n=7), phlebitis (n=7), and loose granulomata (n=5). Treponeme immunohistochemistry was positive in 10 and negative in 4, though treatment was given before biopsy in 3 of those 4. Thirteen patients had rapid plasma reagin testing either before or after biopsy, with 1:64 or higher titer. All patients who received treatment recovered. Hepatic syphilis is rare but likely underrecognized. It exhibits a variety of histologic appearances and therefore should be considered in several hepatic differential diagnoses, especially in men who have sex with men. Kupffer cells, granulomata, and phlebitis may suggest the diagnosis regardless of predominant histologic pattern. Negative treponeme immunohistochemical staining does not exclude the diagnosis, including in untreated patients.

Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver.

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

Benign Neoplasms, Mass-Like Infections, and Pseudotumors That Mimic Hepatic Malignancy at MRI.

A variety of conditions may mimic hepatic malignancy at MRI. These include benign hepatic tumors and tumor-like entities such as focal nodular hyperplasia-like lesions, hepatocellular adenoma, hepatic infections, inflammatory pseudotumor, vascular entities, and in the cirrhotic liver, confluent fibrosis, and hypertrophic pseudomass. These conditions demonstrate MRI features that overlap with hepatic malignancy, and can be challenging for radiologists to diagnose accurately. In this review we discuss the MRI manifestations of various conditions that mimic hepatic malignancy, and highlight features that may allow distinction from malignancy. Level of Evidence 5 Technical Efficacy Stage 3.

Iron Chelation in Murine Models of Systemic Inflammation Induced by Gram-Positive and Gram-Negative Toxins.

Iron is an essential element for various physiological processes, but its levels must remain tightly regulated to avoid cellular damage. Similarly, iron plays a dual role in systemic inflammation, such as with sepsis. Leukocytes utilize iron to produce reactive oxygen species (ROS) to kill bacteria, but pathologically increased iron-catalyzed ROS production in sepsis can lead to damage of host cells, multi-organ failure and death. Temporary reduction in bioavailable iron represents a potential therapeutic target in sepsis. This study investigates the effect of the novel iron chelator, DIBI, in murine models of systemic (hyper-)inflammation: C57BL/6 mice were challenged with toxins from Gram-positive (Staphylococcus aureus: lipoteichoic acid, peptidoglycan) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae: lipopolysaccharide). Intravital microscopy (IVM) was performed to assess immune cell activation and its impact on microvascular blood flow in vivo in the microcirculation of the gut. Plasma inflammatory mediators were measured via multiplex assay, and morphologic change in intestinal tissue was evaluated. DIBI treatment decreased leukocyte (hyper-)activation induced by Gram-positive and Gram-negative toxins. In some cases, it preserved capillary perfusion, reduced plasma inflammatory markers and attenuated tissue damage. These findings support the utility of DIBI as a novel treatment for systemic inflammation, e.g., sepsis.

Intratumoral heterogeneity and clonal evolution in liver cancer.

Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.

Direct-Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis.

Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV-positive (HCV+) study group that had elevated serum markers of AIH before starting direct-acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre-DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow-up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.

Rat Hepatitis E Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient.

Hepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan, and the United States, with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat HEV with a considerably divergent genomic sequence compared with other rat HEV strains. It is possible that rat HEV is an underrecognized cause of hepatitis infection, and further studies are necessary to elucidate its potential risk and mode of transmission.