Hemorragia por hipertensión portal (HTP) secundaria a variz éctopica en ureteroileostomía tipo Bricker en un paciente con dos trombosis precoces consecutivas de la derivación portosistémica intrahepática transyugular (TIPS) / Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS)

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.(AU)

Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS).

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.

Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis.

Iron overload caused by hereditary hemochromatosis (HH) increases free reactive oxygen species that, in turn, induce lipid peroxidation. Its 4-hydroxynonenal (HNE) by-product is a well-established marker of lipid peroxidation since it reacts with accessible proteins with deleterious consequences. Indeed, elevated levels of HNE are often detected in a wide variety of human diseases related to oxidative stress. Here, we evaluated HNE-modified proteins in the membrane of erythrocytes from HH patients and in organs of Hfe-/- male and female mice, a mouse model of HH. For this purpose, we used one- and two-dimensional gel electrophoresis, immunoblotting and MALDI-TOF/TOF analysis. We identified cytoskeletal membrane proteins and membrane receptors of erythrocytes bound to HNE exclusively in HH patients. Furthermore, kidney and brain of Hfe-/- mice contained more HNE-adducted protein than healthy controls. Our results identified main HNE-modified proteins suggesting that HH favours preferred protein targets for oxidation by HNE.

Resolución endoscópica de cuadro de obstrucción intestinal secundario a íleo biliar colónico y estenosis rádica en sigma / Endoscopic resolution of intestinal obstruction secondary to colonic gallstone ileus and radicular stenosis of the sigma

Mujer, 93 años, con antecedentes de adenocarcinoma de endometrio tratado con cirugía y radioterapia pélvica que condiciona estenosis rádica en sigma y pancreatitis aguda biliar, sin colecistectomía posterior. Acude a Urgencias por cuadro de dolor abdominal, vómitos y distensión abdominal, con ruidos metálicos. En TC abdominal se objetiva vesícula con colelitiasis, en amplio contacto con el marco cólico y dilatación de asas colónicas con niveles hidroaéreos con imagen parcialmente calcificada enclavada en la estenosis de sigma conocida, compatible con obstrucción intestinal. Dado el elevado riesgo quirúrgico, se realiza colonoscopia que identifica estenosis puntiforme infranqueable de aspecto fibroso. Se procede a dilatación neumática y posterior retirada de cálculos biliares con pinza de biopsia, con adecuada evolución. Mientras que el íleo biliar es un cuadro raro que condiciona el 5% de los episodios de obstrucción intestinal, su localización en el colon es aún más infrecuente. Su manejo habitual es quirúrgico, con significativo impacto en morbilidad. Este caso resulta de interés por lo infrecuente de la obstrucción secundaria a estas dos causas concomitantes y la posible utilidad del tratamiento endoscópico en pacientes de alto riesgo quirúrgico. (AU)

Endoscopic resolution of intestinal obstruction secondary to colonic gallstone ileus and radicular stenosis of the sigma.

A 93-year-old woman with a history of endometrial adenocarcinoma treated with surgery and pelvic radiotherapy that led to radicular stenosis in the sigma and acute biliary pancreatitis, without subsequent cholecystectomy. She attended the emergency department for abdominal pain, vomiting and abdominal distension, with metallic noises. An abdominal CT scan showed a gallbladder with cholelithiasis, in wide contact with the colonic framework and dilation of the colonic loops with hydro-aerial levels with a partially calcified image embedded in the known sigmoid stenosis, compatible with intestinal obstruction. Given the high surgical risk, colonoscopy was performed, which identified an impassable punctate stricture with a fibrous appearance. Pneumatic dilatation and subsequent removal of gallstones with biopsy forceps was performed, with an adequate evolution. While gallstone ileus is a rare condition that accounts for 5% of episodes of intestinal obstruction, its location in the colon is even rarer. It is usually managed surgically, with a significant impact on morbidity. This case is of interest because of the infrequent occurrence of obstruction secondary to these two concomitant causes and the possible usefulness of endoscopic treatment in patients at high surgical risk.

SARS-CoV-2 vaccine, a new autoimmune hepatitis trigger?

SARS-CoV2 infection and vaccination against this virus have been related to the development of autoimmune diseases. We report a case of autoimmune hepatitis (AIH) after SARS-COV2 vaccine. Male, 76 years old, with a history of hepatic cirrhosis secondary to primary biliary cholangitis (PBC), compensated, treated with ursodeoxycholic acid and obeticholic acid. The patient received the third dose of the SARS-CoV2 vaccine (BioNTech/Pfizer) in December 2021. In subsequent analytical control, the patient presented altered liver test, with elevation of ALT and AST. Ultrasound was performed, without alterations, and viral causes were ruled out. IgG elevation and positive antinuclear antibodies were observed. A liver biopsy was performed, with findings of intense interface and lobular hepatitis and areas of centrilobular necrosis. The inflammation was predominantly lymphoplasmacytic. The patient was diagnosed with AIH and initiated therapy with steroids and azathioprine, currently with an adequate response. AIH is an immune-mediated disease of uncertain etiology. Cases of AIH with SARS-CoV2 vaccination as a possible trigger have recently been published, with characteristics similar to ours. Some of them had a history of autoimmune pathology, such as this case (PBC). Therefore, it is suggested that vaccination can induce the development of autoimmune pathology in patients at risk. Our reported case reinforces the hypothesis of an association between AIH and the SARS-CoV2 vaccine.

Ustekinumab for corticodependent immune-mediated colitis by pembrolizumab, an alternative for patients with concomitant liver injury.

Pembrolizumab, a programmed cell death receptor (PD-1) inhibitor, have improved the prognosis in several types of cancer. Despite the important clinical benefits, checkpoint inhibition have been associated with inflammatory and immune-related side effects (irAE).

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study.

INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.

Curación de la hepatitis autoinmune asociada a hepatitis C con antivirales de acción directa / Healing of autoimmune hepatitis associated with hepatitis C virus infection treated with direct-acting antivirals

La aparición de los nuevos antivirales de acción directa (AAD) para el tratamiento del virus de la hepatitis C (VHC) supone un gran avance para pacientes con hepatitis autoinmune e infectados, ya que hasta el momento no se disponía de opciones terapéuticas libres de interferón. Presentamos el caso de una paciente con infección por VHC que sufrió una HAI desencadenada por interferón, sin conseguir suspender el tratamiento inmunosupresor durante años. Gracias a los AAD, se alcanzó una respuesta viral sostenida y, posteriormente, una remisión clínica completa de su enfermedad autoinmune, sin tratamiento actualmente

The use of direct-acting antivirals (DAA) for the hepatitis C virus (HCV) has yielded a significant improvement in the treatment of autoimmune hepatitis (AIH) associated with HCV infection. Interferon was the cornerstone of HCV therapy before the introduction of these agents into the clinical practice. Herein, we report the case of an HCV-infected patient who developed an interferon-induced AIH and since then, has received immunosuppressive therapy. Administration of DAA resulted in a sustained virologic response (SVR) and clinical AIH remission which allowed a discontinuation of immunosuppressive treatment

Healing of autoimmune hepatitis associated with hepatitis C virus infection treated with direct-acting antivirals.

The use of direct-acting antivirals (DAA) for the hepatitis C virus (HCV) has yielded a significant improvement in the treatment of autoimmune hepatitis (AIH) associated with HCV infection. Interferon was the cornerstone of HCV therapy before the introduction of these agents into the clinical practice. Herein, we report the case of an HCV-infected patient who developed an interferon-induced AIH and since then, has received immunosuppressive therapy. Administration of DAA resulted in a sustained virologic response (SVR) and clinical AIH remission which allowed a discontinuation of immunosuppressive treatment.

Hipertensión portal secundaria a hemangiomatosis hepática múltiple / Portal hypertension secondary to multiple hepatic hemangiomatosis

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Colestasis tras la colocación de un TIPS en paciente con colangitis esclerosante primaria; una complicación infrecuente / Cholestasis after TIPS placement in a patient with primary sclerosing cholangitis: an uncommon complication

Presentamos el caso de un paciente con colangitis esclerosante primaria que presentó un síndrome colestásico de rápida evolución, con hiperbilirrubinemia grave tras colocar un TIPS que se resolvió con una prótesis biliar mediante CPRE. Hasta la fecha no se han descrito casos similares en la literatura, ya que se trata de una complicación rara y, por otro lado, la experiencia con el TIPS en pacientes con CEP es limitada. Las causas de hiperbilirrubinemia tras realizar un TIPS son muy variadas y es crucial realizar un diagnóstico diferencial para instaurar un tratamiento precoz (AU)

We present the case of a patient with primary sclerosing cholangitis who presented a rapidly evolving cholestatic syndrome, with severe hyperbilirubinemia after placing a TIPS. It was resolved with a biliary prosthesis inserted by ERCP. To date, no similar cases have been described in the literature, as it is a rare complication and, on the other hand, the experience with TIPS in patients with PSC is limited. The causes of hyperbilirubinemia after TIPS placement are very varied and it is crucial to perform a differential diagnosis to establish an early treatment (AU)

Cholestasis after TIPS placement in a patient with primary sclerosing cholangitis: an uncommon complication.

We present the case of a patient with primary sclerosing cholangitis who presented a rapidly evolving cholestatic syndrome, with severe hyperbilirubinemia after placing a TIPS. It was resolved with a biliary prosthesis inserted by ERCP. To date, no similar cases have been described in the literature, as it is a rare complication and, on the other hand, the experience with TIPS in patients with PSC is limited. The causes of hyperbilirubinemia after TIPS placement are very varied and it is crucial to perform a differential diagnosis to establish an early treatment.

Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury.

BACKGROUND & AIMS: Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS: 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS: Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS: One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY: Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

Is interferon-beta an alternative treatment for chronic hepatitis C?

The treatment of chronic hepatitis C (CHC) is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-alpha (IFNalpha) plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNbeta could represent an interesting alternative for treating CHC patients. Controversial data about IFNbeta efficacy in CHC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNalpha. Additionally, the good tolerability of IFNbeta represents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNbeta plus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.