Drug induced autoimmune hepatitis: An unfortunate case of herbal toxicity from Skullcap supplement: A case report.

BACKGROUND: The surge in traditional herbal dietary supplement (HDS) popularity has led to increased drug-induced liver injuries (DILI). Despite lacking evidence of efficacy and being prohibited from making medical claims, their acceptance has risen over sevenfold in the last two decades, with roughly 25% of United States (US) adults using these supplements monthly. An estimated 23000 emergency room visits annually in the US are linked to HDS side effects. NIH-funded research suggests HDS contribute to 7-20% of DILI cases, with similar trends in Europe-Spain reporting 2% and Iceland up to 16%. Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines. Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements, this association appears to be the first documented instance in literature. CASE SUMMARY: A middle-aged Caucasian woman, previously healthy, presented with sudden jaundice. Four months earlier, her liver enzymes were normal. She mentioned recent use of Skullcap mushroom supplements. Tests for chronic liver disease were negative. The first liver biopsy indicated severe resolving drug-induced liver injury. Despite treatment, she was readmitted due to worsening jaundice. Follow-up tests raised concerns about autoimmune hepatitis. A subsequent biopsy confirmed this diagnosis. The patient responded as expected to stopping the medication with improvement in liver enzymes. CONCLUSION: This scenario highlights an uncommon instance of DILI caused by Skullcap supplements. It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

Midnight Report: A Novel Faculty-Guided Night Curriculum to Enhance Resident Nighttime Education.

OBJECTIVES: A large discrepancy exists in resident educational activities between daytime and nighttime medical rotations. The Accreditation Council for Graduate Medical Education duty-hour regulations led to the increased adoption of the dedicated nighttime rotation called night float. Nighttime education has largely been negatively perceived by night float medical residents. Although there have been attempts to improve nighttime education, none of the initiatives included faculty-guided structured night curriculum. Our objective was to improve resident experience with and perception of nighttime education by implementing a structured, faculty-guided, nighttime educational curriculum. METHODS: This was an assessment of an educational initiative at a single academic medical center, Virginia Commonwealth University Health System. The internal medicine residency program implemented a teaching nocturnist program in 2013 and a novel faculty-guided nighttime teaching curriculum in 2016 called midnight report. We then evaluated resident experience with and perception of nighttime education at our institution using anonymous free-response surveys for the academic year July 2016-June 2017. RESULTS: Of the 142 eligible residents, 95 (67%) responded to the survey. The majority of the residents (54%-77%) positively perceived their experience of the nighttime educational environment during their night float rotation after implementation of the teaching nocturnist program and midnight report. CONCLUSIONS: Compared with the published literature reporting negative perceptions of the nighttime educational environment by residents at different academic centers, our results showed that the majority of our residents positively perceived the impact of our new faculty-guided nighttime educational curriculum.

Addition of [18 F]Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography to Cross-Sectional Imaging Improves Staging and Alters Management in Hepatocellular Carcinoma.

In this work, we characterize the value of positron emission tomography (PET) with computed tomography (CT) in combination with cross-sectional imaging for staging and prognostication of hepatocellular carcinoma (HCC) patients. In this retrospective cohort study, HCC patients underwent PET-CT after initial staging with contrast-enhanced CT or magnetic resonance imaging (MRI). The benefit of PET-CT was measured by the identification of new HCC lesions, and potential harm was quantified by the number of false positives and subsequent diagnostic evaluation. We used multivariate Cox regression analysis to evaluate the association between the highest grade on PET-CT with the risk of extrahepatic metastasis, progression-free, and overall survival. Among 148 patients, PET-CT detected additional extrahepatic metastasis in 11.9% of treatment-naïve and 13.8% of treatment-experienced patients. PET-CT changed the Barcelona Clinic Liver Cancer (BCLC) staging in 5.9% of treatment-naïve and 18.8% of treatment-experienced patients compared with CT/MRI alone, changing HCC management in 9.9% and 21.3% of patients, respectively. Of the patients, 5% (n = 8) experienced severe physical harm requiring additional procedures to evaluate extrahepatic findings. High tumor grade on PET-CT was independently associated with a higher likelihood of extrahepatic metastasis (hazard ratio [HR], 17.1; 95% confidence interval [CI], 3.6-81.5) and worse overall survival (HR, 2.4; 95% CI, 1.4-4.3). Treatment-experienced patients (versus treatment-naïve patients; HR, 9.7; 95% CI, 1.9-49.4) and BCLC stage A (HR, 8.2; 95% CI, 1.5-45.9; P < 0.01) and BCLC stage B (HR, 20.6; 95% CI, 1.5-282.2; P < 0.05) were more likely to have an upstaging with PET-CT compared with BCLC stage C (reference). PET-CT provides prognostic information and improves tumor staging beyond CT/MRI alone, with subsequent changes in management for patients with HCC.

Use of Telehealth Expedites Evaluation and Listing of Patients Referred for Liver Transplantation.

BACKGROUND & AIMS: Liver transplantation is the only treatment that increases survival times of patients with decompensated cirrhosis. Patients who live farther away from a transplant center are disadvantaged. Health care delivery via telehealth is an effective way to manage patients with decompensated cirrhosis remotely. We investigated the effects of telehealth on the liver transplant evaluation process. METHODS: We performed a retrospective study of 465 patients who underwent evaluation for liver transplantation at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Of these, 232 patients were evaluated via telehealth, and 233 via in-person evaluation. Using regression models, we evaluated the differential effects of telehealth vs usual care on placement on the liver transplant waitlist. We also investigated the effects of telehealth on time from referral to initial evaluation by a transplant hepatologist, liver transplantation, and mortality. RESULTS: Patients in the telehealth group were evaluated significantly faster than patients evaluated in person, without or with adjustment for potential confounders (21.7 vs 79.5 d; P < .01). Telehealth also was associated with a significantly shorter time on the liver transplant waitlist (138.8 vs 249 d; P < .01). After propensity-matched analysis, telehealth was associated with a reduction in the time from referral to evaluation (hazard ratio, 0.15; 95% CI, 0.09-0.21; P < .01) and listing (hazard ratio, 0.26; 95% CI, 0.12-0.40; P < .01), but not to transplantation. In the intent-to-treat analysis of all referred patients, we found no significant difference in pretransplant mortality between patients evaluated via telehealth vs in-person. There was statistically significant interaction between model for end-stage liver disease (MELD)-Na scores and time to evaluation (P = .009) and placement on the transplant waitlist (P = .002), with telehealth offering greater benefits to patients with low MELD-Na scores. CONCLUSIONS: Use of telehealth is associated with a substantial reduction in time from referral to initial evaluation by a hepatologist and placement on the liver transplant waitlist, especially for patients with low MELD scores, with no changes in time to transplantation or pretransplant mortality. More studies are needed, particularly outside of the Veterans Administration Health System, to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.

Telehealth-Based Evaluation Identifies Patients Who Are Not Candidates for Liver Transplantation.

The burden of chronic liver disease has increased exponentially, driving more patients toward orthotopic liver transplant (OLT) evaluation.1 Because of limited access to transplant centers, patients often travel long distances to be evaluated for OLT.2 Liver transplantation in the VA system is offered at 6 Veterans Affairs transplant centers (VATCs) across the United States, including Richmond. To increase access to specialty care, the VA introduced the Specialty Care Access Network-Extension of Community Healthcare Outcomes (SCAN-ECHO) program,3,4 which was designed to transfer subspecialty knowledge to primary care physicians. In 2011, the Richmond VA introduced SCAN-ECHO for gastroenterology/hepatology providers to facilitate case-based distance learning combined with real-time consultation in hepatology, and the opportunity for an initial triage without completing a formal transplant evaluation. We studied the role of SCAN-ECHO in triaging OLT evaluations and the utility of this health care delivery in the field of transplantation.

Recipient But Not Donor Adiponectin Polymorphisms Are Associated With Early Posttransplant Hepatic Steatosis in Patients Transplanted for Non-Nonalcoholic Fatty Liver Disease Indications.

OBJECTIVES: De novo steatosis after liver transplant is common and can occur in up to one-third of patients who are transplanted for liver disease other than for nonalcoholic fatty liver disease. Genetic factors may influence posttransplant steatosis; in a posttransplant setting, donor or recipient genetic factors could also play roles. Genetic polymorphisms in the adiponectin gene have been associated with metabolic syndrome in the pretransplant setting. We aimed to assess the association between donor and recipient adiponectin polymorphisms and early posttransplant hepatic steatosis identified on liver biopsies. MATERIALS AND METHODS: Clinical data were collected for 302 liver transplant patients who underwent protocol biopsies for hepatitis C. Of these, 111 patients had available biopsies and donor/recipient DNA. Patients with grade 1 steatosis or greater (35% of patients) were compared with patients without posttransplant steatosis with respect to clinical features and donor/recipient adiponectin polymorphism genotypes. RESULTS: Patients who developed posttransplant steatosis and those without steatosis were similar with respect to individual components of metabolic syndrome. The adiponectin polymorphisms rs1501299 G/G and rs17300539 G/G genotypes in recipients were associated with early posttransplant graft steatosis. We found no associations between graft steatosis and donor adiponectin polymorphisms. CONCLUSIONS: Genetic polymorphisms in the adiponectin gene of recipients (but not donors) are associated with early de novo posttransplant hepatic steatosis, independent of components of metabolic syndrome.

A Case of Familial Mediterranean Fever with Extensive Lymphadenopathy and Complex Heterozygous Genotype Presenting in the Fourth Decade.

Familial Mediterranean fever (FMF) is an inherited disease caused by loss of function mutations in the MEFV gene encoding pyrin, a negative regulator of interleukin-1. The disease is characterized by recurrent fever and self-limited attacks of joint, chest, and abdominal pain but lymphadenopathy is an infrequent manifestation. While mesenteric lymphadenopathy has been described in several cases in the literature; hilar, paratracheal, axillary, pelvic, and retroperitoneal lymphadenopathy are extremely rare and have been reported separately in very few individuals. In this report, we present a patient with late-onset FMF with extensive lymphadenopathy in all of the aforementioned anatomic regions. Genetic analysis identified three heterozygous pyrin mutations in a patient with no affected family members. Genetic investigation of the patient's mother identified a novel carrier haplotype E148Q/P369S. The proband also inherited the previously described and rare A744S mutation previously not thought to be a disease-defining lesion. This unique compound heterozygous genotype resulted in a novel genotype-phenotype association producing an atypical clinical presentation of FMF that fits within the pattern of several case reports of late-onset disease with respect to clinical course and therapeutic response.

Primary Pancreatic Burkitt's Lymphoma: A Case Report and Review of the Literature.

Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal site of Non-Hodgkin's lymphoma (NHL). It represents less than 1% of NHL. Out of which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs in children and presenting in adults is uncommon. The prevalence of pancreatic Burkitt lymphoma is not known as the incidence is significantly low. Clinical features of PPL are predominantly nonspecific and can become difficult with associated inflammation of pancreas. Differentiation of lymphoma to adenocarcinoma is important as chemotherapy is the main stay of treatment in lymphoma. We report a case of 68-year-old female who presented with nonspecific symptoms and was found to have obstructive jaundice secondary to pancreatic head neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare presentation.

Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy.

PURPOSE OF REVIEW: The approval of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment. However, the publication of a study from Barcelona in 2016 raised concern for an increased risk of recurrence of hepatocellular carcinoma (HCC) after potentially curative therapy in patients receiving DAAs. This article reviews the current literature on the interaction between HCC and hepatitis C eradication with DAAs. RECENT FINDINGS: Following publication of the initial observation in 2016, a number of studies have looked at the impact of active HCC on the success of antiviral therapy, as well as that of treatment with DAAs on both the occurrence and recurrence of HCC. The presence of active HCC decreases sustained virologic response (SVR) rates with DAAs. However, SVR rates improve in patients who have achieved complete radiological response or are treated post transplantation. With respect to occurrence of HCC after DAAs, many small single-center studies without a control group have documented high incidence. The rates are also higher when compared to those of historical controls treated with interferon, but these patients are not comparable because DAA-treated population is more likely to have advanced fibrosis or decompensation. In large studies that have included a control group (patients treated concurrently who did not achieve SVR), a decrease in the occurrence of HCC has been demonstrated. With regard to recurrence of HCC, while smaller single-center studies have shown an increase, larger studies with control group have not replicated those findings. However, methodological limitations in the published studies limit our ability to make a firm conclusion on both the occurrence and recurrence of HCC after DAA therapy. The presence of active HCC decreases treatment success rates with DAAs. Therefore, it is recommended that treatment of HCV in patients with HCC be deferred till there is complete radiological response. Though there are major limitations with the currently published studies, the data does not support an increase in the occurrence or recurrence of HCC after DAA therapy.

Prognosis of Patients With Fibrolamellar Hepatocellular Carcinoma Versus Conventional Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Emerging data suggest that the fibrolamellar variant of hepatocellular carcinoma (FL-HCC) differs in clinical course and prognosis from conventional (nonfibrolamellar) HCC (NFL-HCC). Although FL-HCC is believed to have a better prognosis than NFL-HCC, data comparing the prognoses of the two types of HCC remain lacking. The aim of this systematic review was to compare the prognosis of FL- vs. NFL-HCC. METHODS: Two of the authors independently conducted a comprehensive search of the Cochrane Library, PubMed, Scopus, and published proceedings from major hepatology and gastrointestinal meetings from January 1980 to October 2013. Outcomes of interest were mean overall survival (OS) and 5-year survival. The analyses were performed with a fixed- or random-effects model, as appropriate. The Begg's and Egger's tests with visual inspection of the funnel plot were used to assess for population bias. All analyses were performed with RevMan 5.1 (Cochrane IMS). RESULTS: Seventeen studies involving 368 patients with FL-HCC and 9877 patients with NFL-HCC were included in the analysis. There was an overall statistically significant increase in the 5-year survival for the FL-HCC vs. the NFL-HCC patients (RR, 2.09; 95% CI, 1.38-3.16). In a subgroup analysis limited to noncirrhotic patients, there was no significant difference in 5-year survival in the FL-HCC group compared to that in the NFL-HCC group (RR, 1.69; 95% CI, 0.69-4.17). A significant increase in mean OS was reported in patients with FL-HCC compared with the survival time of those with NFL-HCC (84.9 ± 15.8 vs. 42.9 ± 6.5 months) undergoing partial hepatectomy, but there was no difference in patients undergoing liver transplantation (51.4 ± 14.4 vs. 47.5 ± 5.5 months). CONCLUSION: Patients with FL-HCC treated with hepatic resection had significantly higher 5-year survival rates than did those with NFL-HCC. However, survival was similar for both FL-HCC and conventional HCC in noncirrhotic patients. There seems to be no difference in survival outcomes for FL- and NFL-HCC when transplantation is used as the therapeutic option.

Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death.

The curious case of a Klatskin tumor.

Klatskin tumors are the most common type of cholangiocarcinomas. They are perihilar tumors usually found at the bifurcation of right and left hepatic ducts. The absence of early symptoms leads to the diagnosis of most Klatskin tumors at an advanced incurable stage. Despite emerging adjuvant treatment regimens, survival outcomes remain poor. Surgery is currently the standard of care and the only curative treatment modality available. In this manuscript, we share our experience with an asymptomatic patient with elevated liver enzymes, who was found to have a Klatskin tumor, extending into the left hepatic duct. The patient's diagnosis, management, and prognosis are discussed. The case highlights the importance of screening for hepato-biliary malignancies in elderly patients with abnormal liver function markers.