Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV\'s extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

BACKGROUND: Hepatitis B rarely leads to demyelinating neuropathy, despite peripheral neuropathy being the first symptom of hepatitis B infection.
METHODS: A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves. Serological testing showed that these symptoms were due to hepatitis B. After undergoing treatment involving intravenous immunoglobulin and an antiviral agent, there was a notable improvement in his symptoms.
CONCLUSIONS: Although hepatitis B virus (HBV) infection is known to affect hepatocytes, it is crucial to recognize the range of additional manifestations linked to this infection. The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented; hence, prompt diagnostic and treatment are essential. The patient\'s positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Hepatitis C virus (HCV) is a well-recognized, major cause of various liver-related conditions such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Apart from liver disease, chronic HCV infection is also associated with several extrahepatic manifestations that can lead to significant morbidity and mortality. These extrahepatic manifestations include essential mixed cryoglobulinemia (EMC), lymphomas, porphyria cutanea tarda, lichen planus, necrolytic acral erythema, glomerulonephritis, subclinical autoantibody formation, immune thrombocytopenia, thyroid disease, Sjögren\'s disease/sicca symptoms, diabetes mellitus, ocular diseases, musculoskeletal disorders, cardiovascular diseases, neurocognitive dysfunction, and leukocytoclastic vasculitis. We are presenting a case of chronic HCV infection linked to the extrahepatic manifestations of the disease which can be directly related to HCV or indirectly related to EMC from HCV. An awareness and knowledge of these extrahepatic manifestations will highlight the importance of recognizing the symptoms for an early diagnosis and effective anti-viral treatment in order to improve or resolve the long-term complications of chronic HCV infection.

UNASSIGNED: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality.
UNASSIGNED: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders.
UNASSIGNED: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%).
UNASSIGNED: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health.
UNASSIGNED: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Hepatitis C virus (HCV) is well-known to be associated with multiple extrahepatic manifestations such as arthralgia, myalgia, arthritis, and vasculitis. Many studies reported frequent rheumatologic manifestations among patients infected by HCV. The purpose of this study was to determine the prevalence of HCV among chronic unexplained arthralgia patients in order to aid in the early detection and treatment of silent HCV infection.
This study was a cross-sectional observational study conducted from July 2020 to May 2022. It included 145 individuals suffering from chronic unexplained arthralgia, with vast majority having oligoarticular joint pain (110, 75.9%). They were 103 (71%) females and 42 (29%) males. Serum samples from all patients were examined for the presence of anti-HCV antibodies using a rapid immunochromatographic assay. Seropositive samples were further examined using polymerase chain reaction (PCR) for detection of HCV RNA to confirm HCV infection.
Out of 145 patients who complained of arthralgia, seven patients tested positive for anti-HCV with a seroprevalence of 4.8% while five patients tested positive for HCV-RNA with a molecular prevalence of 3.4%. All positive patients were males (11.9%) with high statistical significance (χ2 = 12.7 and p = 0.002). No association was found between HCV infection and age, blood transfusion, surgery, using personal shaving tools, or being a health-care worker.
The prevalence of HCV was high among males who complained of arthralgia. Patients with arthralgia, especially male patients, are recommended to perform HCV screening test.

UNASSIGNED: HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015.
UNASSIGNED: Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai®) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter®) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test).
UNASSIGNED: 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L\'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described.
UNASSIGNED: More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease.

Hepatitis E virus (HEV) infection is a significant public health problem, which infects 20 million individuals every year. The clinical presentation of acute HEV infection is similar to hepatitis A virus (HAV) infection, and few affected children may progress to develop acute liver failure. Extrahepatic manifestations involving other systems have been reported with acute and chronic HEV genotype 3 infections both in adults and children. Herein we report acute kidney injury as a rare complication of acute hepatitis E in a child who recovered with a medical line of management.

Hepatitis E virus (HEV) infection has many extrahepatic manifestations as well as liver symptoms. Multiple studies have shown that HEV infection has symptoms related to the nervous system, kidneys, cryoglobulinemia, hematological system, reproductive system, autoimmunity and pancreas. Hence, HEV infection should be considered as a systemic disease, rather than solely a liver disease. The extrahepatic manifestations induced by different genotypes of HEV vary. The severity of these diseases does not necessarily correlate with the severity of HEV infection, and even asymptomatic HEV infection may trigger and cause systemic diseases. Patients with systemic manifestations of HEV infection should have priority for antiviral therapy, which could alleviate or improve the extrahepatic manifestations related to HEV infection. However, the extrahepatic manifestations caused by different genotypes of HEV and their corresponding mechanisms have not been clearly identified. This review discusses the extrahepatic manifestations related to HEV infection and their triggering mechanisms.

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.

Despite worldwide vaccination campaigns, hepatitis B virus (HBV) infection remains a major public health problem. The natural history ranges from asymptomatic infection to severe liver injury or failure, chronic complications or reactivation episodes. The effects of HBV on the organism are immunomediated, possibly triggering extrahepatic manifestations. Since 1971, only a few cases of pleural effusion related to HBV infection have been described. We report HBV-associated pleural effusion occurring during a viral reactivation episode. Antiviral treatment directed towards pleural effusion related to HBV infection should be dictated by underlying liver disease severity and not pleural effusion severity.
UNASSIGNED: In the presence of pleural effusion of unknown origin, especially if with simultaneous acute hepatitis, a viral aetiology should be suspected and pursued.The severity of liver disease and not the pleural effusion should guide antiviral treatment.