Acute hepatitis caused by a natural lipid-lowering product: When "alternative" medicine is no "alternative" at all

Background/Aims The general public's growing mistrust of the pharmaceutical industry and its perception of the lack of adverse effects of "natural" therapy have lead to the increasing use of "alternative drugs" for hypercholesterolemia. Methods A sixty-three year old woman presented with severe hypertransaminasemia that had developed progressively over a few weeks. For six months she had been taking Equisterol ® , an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract. The product had been prescribed for hypercholesterolemia because the patient had developed hepatotoxicity while on lovastatin. Results Liver biopsy revealed severe lobular necroinflammatory changes with an eosinophilic infiltrate. The episode was regarded as an adverse drug reaction after exclusion of other possible causes of acute liver disease and the prompt normalization of liver function tests after Equisterol ® had been discontinued. Red yeast rice extract's cholesterol-lowering properties are largely due to fungal metabolites known as monacolins, one of which – monacolin K – is identical to lovastatin. Conclusions The choice of an alternative medicine approach in this case subjected the patient to "re-challenge" with the official medicine agent that had previously caused mild hepatotoxicity. Physicians should keep in mind that "alternative" medicine is not always the safest alternative and sometimes it is not even "alternative.

Abdominal angina due to recurrence of cancer of the papilla of Vater: a case report

Abdominal angina is usually caused by atherosclerotic disease, and other causes are considered uncommon. This is the first report of a case of abdominal angina secondary to neoplastic vascular stenosis caused by local recurrence of an adenocarcinoma of the papilla of Vater. CASE PRESENTATION: An 80-year-old woman of Caucasian origin presented with abdominal pain and diarrhea. She had undergone a pancreaticoduodenectomy for adenocarcinoma of the papilla of Vater four years earlier. Computed tomography revealed a mass surrounding her celiac trunk and superior mesenteric artery. Her abdominal pain responded poorly to analgesic drugs, but disappeared when oral feedings were withheld. A duplex ultrasonography of the patient's splanchnic vessels was consistent with vascular stenosis. Parenteral nutrition was started and the patient remained pain free until her death. CONCLUSION: Pain relief is an important therapeutic target in patients with cancer. In this case, abdominal pain was successfully managed only after the ischemic cause had been identified. The conventional analgesic therapy algorithm based on nonsteroidal anti-inflammatory drugs and opioids had been costly and pointless, whereas the simple withdrawal of oral feeding spared the patient of the discomfort of additional invasive procedures and allowed her to spend her remaining days in a completely pain-free state

PGI12 Organizational and Economic Issues Related to the Introduction of Boceprevir in the Treatment of Patients with Genotype 1 Chronic Hepatitis C in Italy

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Splanchnic Artery Stenosis and Abdominal Complaints: Clinical History Is of Limited Value in Detection of Gastrointestinal Ischemia

BACKGROUND: Splanchnic artery stenosis is common and mostly asymptomatic and may lead to gastrointestinal ischemia (chronic splanchnic syndrome, CSS). This study was designed to assess risk factors for CSS in the medical history of patients with splanchnic artery stenosis and whether these risk factors can be used to identify patients with high and low risk of CSS. METHODS: All patients referred for suspected CSS underwent a standardized workup, including a medical history with questionnaire, duplex ultrasound, gastrointestinal tonometry, and angiography. Definitive diagnosis and treatment advice was made in a multidisciplinary team. Patients with confirmed CSS were compared with no-CSS patients. RESULTS: A total of 270 patients (102 M, 168 F; mean age, 53 years) with splanchnic artery stenosis were analyzed, of whom 109 (40%) had CSS and 161 no CSS. CSS-patients more often reported postprandial pain (87% vs. 72%, p = 0.007), weight loss (85% vs. 70%, p = 0.006), adapted eating pattern (90% vs. 79%, p = 0.005) and diarrhea (35% vs. 22%, p = 0.023). If none of these risk factors were present, the probability of CSS was 13%; if all were present, the probability was 60%. Adapted eating pattern (odds ratio (OR) 3.1; 95% confidence interval (CI) 1.08-8.88) and diarrhea (OR 2.6; 95% CI 1.31-5.3) were statistically significant in multivariate analysis. CONCLUSIONS: In patients with splanchnic artery stenosis, the clinical history is of limited value for detection of CSS. A diagnostic test to detect ischemia is indispensable for proper selection of patients with splanchnic artery stenosis who might benefit from treatment

Decline of Prevalence of Resistance Associated Substitutions to NS3 and NS5A inhibitors at DAA-failure in Hepatitis C Virus in Italy over the years 2015 to 2018

Background: A minority of patients fail to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens. Material and methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols. The geno2pheno system was used to infer HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend, predictors of RASs at failure were analysed by logistic regression. Results: We included 386 real-life HCV pts failed to recommended DAA regimens: 92% (271/294) Italians, 75% (286/384) males, median age was 56 years (IQR 52-61); 106 (28%) were treatment-experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAA-based regimens. Metavir fibrosis stage was F4 in 76% (245/322), 65% (240/369) had clinical cirrhosis. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype (G) was G1b in 122 pts (32%), G3a 103 (27%), G1a 97 (25%), G4d 30 (8%), G2c 19 (5%), G3h 5 (1.3%), G4a 4 (1%) and 1 (0.3%) each for G3g, G4n/o/v. DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%). Antiviral treatment was completed by 352 pts (91%), while 34 (9%) discontinued prematurely. The NS5A fasta-sequence was available for all pts, NS5B for 361 (94%), NS3 for 365 (95%). The prevalence of any RASs was 87%, namely 78/135 (58%) in NS3, 303/359 (85%) in NS5A, 114/286 (40%) in NS5B (Tab 1). The prevalence of any RASs significantly declined from 2015 to 2018 (100%, 13/13 vs 81%, 101/125, p=0.01): NS5A RASs from 100%, 13/13 to 76%, 76/100 (p<0.001), NS3 RASs from 88%, 7/8 to 44%, 28/63 (p=0.02), while NS5B RASs remained stable. Independent predictors of any RASs included liver cirrhosis/advanced fibrosis (AOR 3.72, CI 95% 1.51-9.17, p=0.004) and genotype (G2 vs G1a AOR 0.01, CI 95% 0.0-0.3, p<0.001; G3 vs G1a AOR 0.22, CI 95% 0.05-0.98, p<0.047; G4 vs G1a AOR 0.13, CI 95% 0.03-0.63, p<0.011), with a modest effect scored for past treatment (AOR 3.45, CI 95% 1.00-11.92, p=0.05), after adjusting for DAA regimen and year of genotype. Notably, full activity was predicted for GLE/PIB in 75.9% of cases and for at least two components of VEL/SOF/VOX in 59% of cases and no case with full-resistance to either regimen was found (Tab 2). Conclusions: Despite decreasing prevalence over the years, RASs remain a common signature at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. Their distribution may vary according to genotype, so the identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Arterial Embolization Hyperthermia Using As2O3 Nanoparticles in VX2 Carcinoma–Induced Liver Tumors

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis

Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib

Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child-Pugh A, 83% performance status (PS) ≥1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3-4.9) months, resulting from 4.6 (3.3-5.7) months for 123 progressors, 7.3 (6.0-10.0) months in 77 with adverse effects, and 1.8 (1.6-2.4) months in 60 decompensated patients (P<0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 (4.6-7.1) months, which was dependent on reasons of discontinuation (P=0.004), PS (P<0.001), macrovascular invasion (P<0.001), and extrahepatic metastases (P<0.002). Conclusion: Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second-line therapy

Upper limits of downstaging for hepatocellular carcinoma in liver transplantation

In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion