Fulminant hepatitis due to spontaneous reactivation of virus B in an immunocompetent patient

We present the case of a 52-year-old woman with a history of HBeAg-negative chronic hepatitis B virus (HBV) infection, viral load (VL) Z+<20,000U.l/ml with no evidence of liver fibrosis and, therefore, untreated. She presented to the emergency department with jaundice, epigastric pain, nausea, and vomiting. On admission, blood analysis revealed ALT 3982U/l, AST 3221U/l, Gamma-GT 80U/l, alkaline phosphatase 252U/l, LDH 960U/l, bilirrubin12.5mg/dl; no elevation of acute phase reactants, 141,000 platelets and coagulopathy with a prothrombin activity of 29%. Abdominal ultrasound showed no relevant findings. The serological profile revealed AgHBs+, anti-HBe+ y anti-HBc IgM+ and VL VHB>100 mills. Ul/ml, the remaining serology was negative and other causes of liver disease were ruled out. With the diagnosis of severe acute hepatitis (SAH) due to HBV reactivation (HBVR) treatment with entecavir was initiated. Given the analytical evolution (Table 1) and the appearance of encephalopathy grade I-II/IV, an urgent liver transplant was performed. The histological result of the explant was conclusive with intense interphase and lobular hepatitis with extensive areas of massive necrosis in both lobes, without hepatic fibrosis compatible with fulminant hepatitis (FH). (AU)

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy / Seguimiento a largo plazo de pacientes infectados por el virus de la hepatitis C con insuficiencia renal crónica terminal tras una respuesta virológica sostenida con tratamiento antiviral de acción directa

Background and aim: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. Methods: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. Results: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver–kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. Conclusions: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function. (AU)

Introducción y objetivo: Los pacientes con insuficiencia renal crónica (IRC) e infección por el virus de la hepatitis C (VHC) pueden ser tratados de forma efectiva y segura con antivirales de acción directa (AAD). El objetivo de este estudio fue evaluar la mortalidad y la evolución de la función renal y hepática a largo plazo en una cohorte de pacientes con infección por VHC e IRC tratados con AAD. Métodos: Se analizó la evolución de la función hepática y renal, así como la mortalidad en 135 pacientes con infección por VHC e IRC estadio 3b-5 que recibieron ombitasvir/paritaprevir/ritonavir±dasabuvir en un estudio multicéntrico. Resultados: Ciento veinticinco pacientes se curaron (RVS), y 66 de ellos fueron incluidos. Antes de RVS, 53 estaban bajo terapia renal sustitutiva (TRS) y 25 (37,8%) tenían cirrosis hepática. Tras un seguimiento medio de 4,5 años, 25 (38%) requirieron trasplante renal, pero ninguno combinado renal-hepático. No se observaron cambios en la función renal entre aquellos 51 pacientes que no recibieron trasplante renal a pesar de que los valores de eFGR mejoraron en aquellos pacientes con IRC estadio 3b-4 de base. Tres (5,6%) pacientes pudieron dejar la TRS. Dieciocho (27,3%) pacientes fallecieron, principalmente por eventos cardiovasculares, 2 presentaron descompensación hepática y uno carcinoma hepatocelular. No se observó ninguna reinfección por VHC. Conclusiones: La mortalidad a largo-plazo fue alta. Globalmente no se objetivó una mejora en la función renal. A pesar de ello, en estadios 3b-4, la curación del VHC podría tener un papel positivo en la función renal. (AU)

Fulminant hepatitis due to spontaneous reactivation of virus B in an immunocompetent patient.

We present the case of a 52-year-old woman with a history of HBeAg-negative chronic hepatitis B virus (HBV) infection, viral load (VL) Z+<20,000U.l/ml with no evidence of liver fibrosis and, therefore, untreated. She presented to the emergency department with jaundice, epigastric pain, nausea, and vomiting. On admission, blood analysis revealed ALT 3982U/l, AST 3221U/l, Gamma-GT 80U/l, alkaline phosphatase 252U/l, LDH 960U/l, bilirrubin12.5mg/dl; no elevation of acute phase reactants, 141,000 platelets and coagulopathy with a prothrombin activity of 29%. Abdominal ultrasound showed no relevant findings. The serological profile revealed AgHBs+, anti-HBe+ y anti-HBc IgM+ and VL VHB>100 mills. Ul/ml, the remaining serology was negative and other causes of liver disease were ruled out. With the diagnosis of severe acute hepatitis (SAH) due to HBV reactivation (HBVR) treatment with entecavir was initiated. Given the analytical evolution (Table 1) and the appearance of encephalopathy grade I-II/IV, an urgent liver transplant was performed. The histological result of the explant was conclusive with intense interphase and lobular hepatitis with extensive areas of massive necrosis in both lobes, without hepatic fibrosis compatible with fulminant hepatitis (FH).

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. METHODS: 135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. RESULTS: 125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver-kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. CONCLUSIONS: Long-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

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.

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study.

BACKGROUND AND AIMS: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. MATERIAL AND METHODS: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. RESULTS: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. CONCLUSIONS: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.

Hepatitis B en pacientes con hepatitis C tratados con agentes antivirales directos / Hepatitis B virus in patients with chronic hepatitis C treated with direct antiviral agents

Introducción: se han comunicado casos de reactivación de virus de la hepatitis B (VHB) en pacientes con virus de la hepatitis C (VHC) tratados con agentes antivirales directos (AAD). Objetivos y métodos: los objetivos del presente estudio son: a) conocer la prevalencia de la coinfección VHB/VHC en pacientes VHC tratados con AAD en la Comunidad de Madrid (CM) y determinar la incidencia y relevancia clínica de la reactivación del VHB; y b) conocer las tasas de cribado del VHB en pacientes VHC en nuestra comunidad. Se evaluaron 1.337 pacientes VHC consecutivos tratados con AAD en dos hospitales del sur de la CM desde enero de 2015 hasta junio de 2017. Resultados: nueve de los 1.337 (0,67%) presentaban HBsAg positivo y 356 (26,6%) presentaban algún marcador de infección VHB pasada. Dos de los cuatro (50%) pacientes HBsAg positivo sin tratamiento desarrollaron reactivación virológica VHB pero no bioquímica. De los 356 con patrón de infección VHB pasada, el 100% presentó transaminasas normales al finalizar el tratamiento y durante el seguimiento. La tasa de cribado VHB ascendió al 92,9% de la cohorte. Conclusiones: la prevalencia de infección VHB (HBsAg positivos) en pacientes con hepatitis crónica por VHC en la zona sur de la CM es baja. La reactivación del VHB en pacientes HBsAg positivo que reciben AAD es frecuente, pero sin relevancia clínica. En nuestro medio existe una alta tasa de cribado del VHB en pacientes con VHC candidatos a recibir AAD

Introduction: cases of hepatitis B virus (HBV) reactivation have been reported in patients with hepatitis C virus (HCV) treated with direct antiviral agents (DAA). Objectives and methods: the main objectives of the present study are: a) to determine the prevalence of HBV/HCV coinfection in HCV patients treated with DAAs in the Autonomous Community of Madrid (CM) and also to determine the incidence and clinical relevance of HBV reactivation; and b) to determine the HBV screening rates in HCV patients in our region. For that purpose, 1,337 HCV patients were consecutively treated with DAAs in two hospitals located in South CM between January 2015 and June 2017. Results: nine of the 1,337 (0.67%) participants were HBsAg positive and 356 (26.6%) had previous HBV infection markers. Two of the four (50%) HBsAg positive patients with untreated HBV developed a virological reactivation, but not a biochemical reaction. Of the 356 patients with previous HBV infection markers, all had normal transaminases at the end of treatment and during follow-up. The HBV screening rate amounted to 92.9% of the cohort. Conclusions: the prevalence of HBV (HBsAg positive) infection in patients with chronic hepatitis C in the southern area of the CM is low. HBV reactivation in HBsAg positive patients treated with DAAs is common, although without clinical relevance. In our region, there is a high rate of HBV screening in patients with HCV that are likely treated with DAAs

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.

Hepatitis B virus in patients with chronic hepatitis C treated with direct antiviral agents.

INTRODUCTION: cases of hepatitis B virus (HBV) reactivation have been reported in patients with hepatitis C virus (HCV) treated with direct antiviral agents (DAA). OBJECTIVES AND METHODS: the main objectives of the present study are: a) to determine the prevalence of HBV/HCV coinfection in HCV patients treated with DAAs in the Autonomous Community of Madrid (CM) and also to determine the incidence and clinical relevance of HBV reactivation; and b) to determine the HBV screening rates in HCV patients in our region. For that purpose, 1,337 HCV patients were consecutively treated with DAAs in two hospitals located in South CM between January 2015 and June 2017. RESULTS: nine of the 1,337 (0.67%) participants were HBsAg positive and 356 (26.6%) had previous HBV infection markers. Two of the four (50%) HBsAg positive patients with untreated HBV developed a virological reactivation, but not a biochemical reaction. Of the 356 patients with previous HBV infection markers, all had normal transaminases at the end of treatment and during follow-up. The HBV screening rate amounted to 92.9% of the cohort. CONCLUSIONS: the prevalence of HBV (HBsAg positive) infection in patients with chronic hepatitis C in the southern area of the CM is low. HBV reactivation in HBsAg positive patients treated with DAAs is common, although without clinical relevance. In our region, there is a high rate of HBV screening in patients with HCV that are likely treated with DAAs.

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

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Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. METHODS: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. RESULTS: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). CONCLUSIONS: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. LAY SUMMARY: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

Fallo hepático agudo en paciente consumidora de productos de Herbalife y zumo de Noni / Fallo hepático agudo en paciente consumidora de productos de Herbalife y zumo de Noni

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Rechazo agudo del injerto renal no funcionante en pacientes en diálisis después de iniciar tratamiento con interferón y ribavirina / Acute rejection of non-functional renal grafts in dialysis patients after starting treatment with interferon and ribavirin

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