Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis.

BACKGROUND AND AIMS: There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. METHODS: Online survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). RESULTS: 25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment. AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response. Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response. Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. CONCLUSION: Among 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response.

Patient-reported quality of care in primary sclerosing cholangitis.

BACKGROUND: Management and follow-up strategies for primary sclerosing cholangitis (PSC) vary. The aim of the present study was to assess patient-reported quality of care to identify the most important areas for improvement. METHODS: Data were collected via an online survey hosted on the EU Survey platform in 11 languages between October 2021 and January 2022. Questions were asked about the disease, symptoms, treatment, investigations and quality of care. RESULTS: In total, 798 nontransplanted people with PSC from 33 countries responded. Eighty-six per cent of respondents reported having had at least one symptom. Twenty-four per cent had never undergone an elastography, and 8% had not had a colonoscopy. Nearly half (49%) had never undergone a bone density scan. Ursodeoxycholic acid (UDCA) was used in 90-93% in France, Netherlands and Germany, and 49-50% in the United Kingdom and Sweden. Itch was common (60%), and 50% of those had received any medication. Antihistamines were taken by 27%, cholestyramine by 21%, rifampicin by 13% and bezafibrate by 6.5%. Forty-one per cent had been offered participation in a clinical trial or research. The majority (91%) reported that they were confident with their care although half of the individuals reported the need for more information on disease prognosis and diet. CONCLUSION: Symptom burden in PSC is high, and the most important areas of improvement are disease monitoring with more widespread use of elastography, bone density scan and appropriate treatment for itch. Personalised prognostic information should be offered to all individuals with PSC and include information on how they can improve their health.

Plasma osteopontin is a biomarker for the severity of alcoholic liver cirrhosis, not for hepatocellular carcinoma screening.

BACKGROUND: Implementation of surveillance programs for at-risk populations and identification of biomarkers for early hepatocellular carcinoma (HCC) detection are a major public health goal. Recently, osteopontin (OPN) has attracted attention as a promising biomarker, with some potential advantages compared to alpha-fetoprotein (AFP), but its role in the context of alcoholic cirrhosis has never been assessed. The aims of this study are to assess the utility of plasma OPN in the diagnosis of HCC in alcoholic cirrhotic patients and to investigate whether increased values are due to the tumor or underlying liver disease severity. METHODS: A total of 90 consecutively alcoholic cirrhosis patients, observed between Jun 2013 and May 2014 at a Liver Disease Unit, were included and divided into two groups: 45 without (group I) and 45 with HCC (group II). Plasma levels of OPN (ELISA, Immuno-Biological Laboratories, Gunma, Japan) and AFP (IMMULITE® 2000 AFP, Siemens Healthcare Diagnostics, Tarrytown, New York) were assessed. The diagnostic accuracy of each marker was evaluated using Receiver-Operating Characteristic (ROC) curve analysis (AUC) and its 95 % Confidence Interval (CI). RESULTS: Plasma OPN levels in group I patients (1176.28 +/-744.59 ng/mL) weren't significantly different from those of group II (1210.75 +/-800.60 ng/mL) (p = 0.826). OPN levels significantly increased with advancing BCLC tumor stage and with advancing Child-Pugh class, in both groups. Comparing the two groups, AUC for OPN and AFP were 0.51 (95 % CI: 0.39-0.63) and 0.79 (95 % CI: 0.70-0.89), respectively. Based on the ROC analysis, there were no satisfactory cut-off values for OPN that would distinguish patients with from those without tumour. CONCLUSIONS: Despite having a correlation with BCLC stage, the same was observed with progressive deterioration of underlying liver function in terms of Child-Pugh class and MELD score, and isn't a useful diagnostic biomarker for HCC in alcoholic cirrhotic patients, particularly in the early stages. AFP confirms the performance evidenced in other studies, being superior to OPN. Searching more specific biomarkers for early diagnosis of HCC in alcoholic cirrhosis is still warranted.

Different locations but common associations in subcortical hypodensities of presumed vascular origin: cross-sectional study on clinical and neurosonologic correlates.

BACKGROUND: Subcortical hypodensities of presumed vascular etiology (SHPVO) are a clinical, radiological and neuropathological syndrome with a still largely unexplained pathophysiology. Parallel to the clinical heterogeneity, there is also recognised cerebral topographical diversity with undetermined etiological implications. Our aim is to assess clinical and neurosonological predictors of SHPVO according to their location. METHODS: Cross sectional analysis of consecutive patients that underwent neurosonologic evaluation and head CT within one month, during a one year period. We excluded patients with absent temporal sonographic window, any pathology with a possible confounding effect on cerebral arterial pulsatility, atrial fibrillation and other etiologies of white matter diseases. The mean pulsatility index (PI) of both middle cerebral arteries was measured in the middle third of the M1 segment; intima media thickness was evaluated in the far wall of both common carotid arteries. SHPVO were rated by analysis of head CT in deep white matter (DWMH), periventricular white matter (PVWMH) and basal ganglia (BGH). We conducted a multivariate ordinal logistic regression model including all clinical, demographic and ultrasonographic characteristics to determine independent associations with SHPVO. RESULTS: We included 439 patients, mean age 63.47 (SD: 14.94) years, 294 (67.0%) male. The independent predictors of SHPVO were age (OR = 1.067, 95% CI: 1.047-1.088, p < 0.001 for DWMH; OR = 1.068, 95% CI: 1.049-1.088, p < 0.001 for PVWMH; OR = 1.05, 95% CI: 1.03-1.071, p < 0.001 for BGH), hypertension (OR = 1.909, 95% CI: 1.222-2.981, p = 0.004 for DWMH; OR = 1.907, 95% CI: 1.238-2.938, p = 0.003 for PVWMH; OR = 1.775, 95% CI: 1.109-2.843, p = 0.017 for BGH) and PI (OR = 17.994, 95% CI: 6.875-47.1, p < 0.001 for DWMH; OR = 5.739, 95%CI: 2.288-14.397, p < 0.001 for PVWMH; OR = 11.844, 95% CI: 4.486-31.268, p < 0.001 for BGH) for all locations of SHPVO. CONCLUSIONS: Age, hypertension and intracranial pulsatility are the main independent predictors of SHPVO across different topographic involvement and irrespective of extracranial atherosclerotic involvement.

Prolonged arthralgias in Whipple's disease - A common but often overlooked symptom of a rare disease.

Whipple's disease is a multisystemic chronic infectious condition caused by Tropheryma whipplei (T. whipplei). Though characterised often by insidious weight loss, diarrhoea, and arthralgia, three other distinct manifestations can be observed, namely localised disease, acute infection and asymptomatic carriage. The diagnosis relies on histopathological examination of duodenal biopsies and polymerase chain reaction analysis of the 16S rRNA gene for T. whipplei. We report the case of a middle-aged man admitted for etiologic investigation of prolonged, migrating, and inflammatory arthralgias and subsequent development of gastrointestinal symptoms. Despite its reputation as a great mimicker of many different illnesses, the difficulty in diagnosis probably lies with its rarity rather than its masking.

Autoimmune Hepatitis on a Living Liver Donor: An Unexpected Long-Term Complication.

In Western countries, deceased donor liver transplantation remains the standard of care for patients with end-stage liver disease. Living donor liver transplantation is a viable and feasible strategy for patients with end-stage liver disease designed to mitigate the deceased organ shortage. Donor safety is the primary concern because liver donors, ideally, should not have any complication. We report a case of middle-aged woman without a history of chronic liver disease who developed autoimmune hepatitis more than 20 years after live liver donation. Changes in these patients' liver enzymes should prompt swift referral to an hepatologist for initial liver disease work-up.

Occult hepatitis C infection identified in injection drug users with direct antiviral agents therapy and spontaneous resolution of hepatitis C virus infection.

BACKGROUND: Occult hepatitis C infection (OCI) is characterized by the detection of hepatitis C virus (HCV) RNA in hepatocytes and in peripheral blood mononuclear cells (PBMCs) without detection in serum. We aimed to evaluate OCI in drug and no drug users who achieved sustained virological response (SVR) after therapy with direct-acting antivirals (DAAs) and with HCV spontaneous resolution. METHODS: Twenty-four patients in the AVP group (who achieved a SVR after DAAs therapy), 13 in the NAVP group (with HCV spontaneous resolution) and 7 HCV-RNA positive patients (CPP, control positive group) were included in the study. HCV/OCI-RNA was screened in serum and PBMCs samples of the patients by ddPCR for OCI patients' identification. Plasma and red blood cells (RBCs) samples of the patients were also evaluated for HCV/OCI-RNA detection by ddPCR. RESULTS: OCI was presented in injection drug users (IDUs) in the AVP (20.8%) and NAVP (23.1%) groups by ddPCR with a higher statistically significant percentage detected in RBCs samples of the patients in the AVP group comparatively to NAVP (p<0.01) and CPP (p < 0.05) groups. CONCLUSION: OCI was identified in IDUs patients of the AVP and NAVP groups by ddPCR. These results suggest that OCI patients in the AVP group might not be entirely cured, and that OCI patients in the NAVP group were not identified at clinical evaluation time when just serum samples were analysed. A higher percentage of HCV/OCI-RNA was detected in RBCs samples. Overall results recommends that HCV/OCI identification in patients with DAAs therapy and spontaneous resolution of HCV infection should be studied more accurately in future and in larger patient groups if possible. Additionally, suggest also PBMCs and RBCs samples as predictors for HCV/OCI diagnosis and management.

Encephalitis: A rare complication of mediterranean spotted fever.

Mediterranean spotted fever (MSF) is an emerging zoonosis caused by Rickettsia conorii. The MSF typically presents with a triad of fever, generalized cutaneous rash and inoculation eschar, but its clinical spectrum may range from a mild febrile illness to a potentially life-threatening condition, being central nervous system involvement highly rare. We report the clinical case of a 63-year-old male patient with MSF complicated by acute encephalitis and multi-organic failure.

Mondor's Disease: A Rare Cause of Chest Pain.

INTRODUCTION: Chest pain is a very frequent reason for seeking medical care. When there is no obvious cause, patients are sometimes subjected to tests and treatments that may be unnecessary and potentially harmful. Mondor's disease is a rare but usually benign and self-limited entity characterized by thrombophlebitis in a specific region. CASE REPORT: We report the clinical case of a 51-year-old man admitted to the emergency department with a 24-hour history of left chest pain with no other symptoms. Physical examination revealed a palpable subcutaneous cord-like structure that ultrasound confirmed to be thrombophlebitis of a superficial vein in the mammary region. Secondary causes were ruled out, and the condition resolved with ibuprofen and the application of local ice. DISCUSSION: Mondor's disease can be associated with neoplasms, trauma or hyperviscosity states, but it is mostly idiopathic. Usually, it resolves completely in 4-8 weeks without specific treatment. Because this infrequent diagnosis mainly relies on clinical findings, it is important that clinicians can recognize the syndrome. LEARNING POINTS: Mondor's disease is a rare but benign disease, with no proof that specific treatment, such as anticoagulation, is beneficial.It may be secondary to underlying disease as malignancy, vasculitis, trauma or hyperviscosity states, which should be excluded.Treatment in the majority of the cases is symptomatic, but if it is secondary Mondor's disease, the underlying problem should be investigated. Physicians should be aware of this condition in order to address patient concerns and avoid unnecessary treatments or investigations.

Keeping prognostic assessment simple: The value of clinical features in normotensive cancer patients with pulmonary embolism.

INTRODUCTION: Although normotensive cancer patients with acute pulmonary embolism (PE) are a heterogeneous population, most validated clinical prognostic scores classify these patients as high-risk individuals, which limits their usefulness in this setting. In this study, we aimed to identify readily available clinical predictors of overall 30-day and one-year mortality in normotensive cancer patients with PE. METHODS AND RESULTS: We performed a retrospective single-center study that included all normotensive cancer patients with PE diagnosed by multidetector computed tomography (MDCT) during emergency department stay between January 2010 and December 2011. Clinical, MDCT and laboratory variables were collected for all patients. A total of 69 patients were included. All-cause mortality was 28% and 55% at 30 days and one year of follow-up, respectively. Lower mean arterial pressure, higher lactate level and a higher Shock Index (SI) at hospital admission were associated with increased all-cause mortality at 30 days and one year of follow-up. The simplified Pulmonary Embolism Severity Index was not a predictor of short- or long-term mortality. An SI of ≥0.7 was found to be associated with lower event-free survival in both short- and long-term follow-up (hazard ratio 7.20 [95% CI, 1.66-31.21, p<0.01] and 3.51 [95% CI, 1.70-7.25, p<0.01], respectively). CONCLUSIONS: This is the first article reporting the value of the SI, a user-friendly and readily available clinical tool, as an independent and accurate predictor of 30-day and one-year all-cause mortality in normotensive cancer patients with symptomatic PE.

Polymyositis and the Spectrum of Scleroderma Disorders.

Polymyositis (PM) is usually associated to other autoimmune or connective tissue diseases. The authors report the case of a 59-year-old man with pulmonary fibrosis, who presented with constitutional symptoms and gradually developed proximal muscle weakness, Raynaud phenomenon, and dysphagia. Besides creatine kinase (CK) elevation, he had positive anti-Polymyositis-Scleromyositis (PM-Scl) and anti-Sjögren's-syndrome A (SSA) antibodies. Nailfold capillaroscopy showed a scleroderma pattern and muscle biopsy revealed necrosis, regeneration of muscle fibers, and inflammatory infiltrate. Prednisolone was started, with great improvement. Taking into account the overlap features between PM and systemic sclerosis sine scleroderma, it is important to closely monitor the patient for signs of pulmonary and cardiac decompensation. LEARNING POINTS: Polymyositis (PM) may be associated with connective tissue diseases such as systemic sclerosis, including its variant without skin involvement.Necrotizing muscle fibers are typically found in patients with overlap syndrome, in opposition to patients only with polymyositis.PM-Scl antibodies are associated to a good response to corticoids.