Autoimmune Hepatitis (AIH) is a chronic liver disease Characterized by interface hepatitis, lymphoplasmacytic infiltrate, and hepatic rosettes. HIV infection is a state of immunosuppression; hence, the possibility of AIH is relatively rare, especially in patients with low CD4 counts. Therefore, we present an interesting case series of four patients with autoimmune liver disease with myriad presentations for the first time from India. We propose that despite the rarity of this presentation with immunosuppression, one should never miss such a treatable cause of liver disease leading to good clinical outcomes.

UNASSIGNED: HEV variants such as swine genotypes within Paslahepevirus species balayani (HEV-A) and rat HEV (Rocahepevirus ratti; HEV-C1) cause chronic hepatitis E in immunocompromised individuals. There are few reliable and accessible small animal models that accurately reflect chronic HEV infection. We aimed to develop an immunocompromised rat model of chronic hepatitis E infection.
UNASSIGNED: In this animal model infection study, rats were immunosuppressed with a drug combination (prednisolone, tacrolimus, and mycophenolate mofetil) commonly taken by transplant recipients. Rats were challenged with human- and rat-derived HEV-C1 strains or a human-derived HEV-A strain. Viral load, liver function, liver histology, humoural, and cellular immune responses were monitored.
UNASSIGNED: A high-dose (HD) immunosuppressive regimen consistently prolonged human- and rat-derived HEV-C1 infection in rats (up to 12 weeks post infection) compared with transient infections in low-dose (LD) immunosuppressant-treated and immunocompetent (IC) rats. Mean HEV-C1 viral loads in stool, serum, and liver tissue were higher in HD regimen-treated rats than in LD or IC rats (p <0.05). Alanine aminotransferase elevation was observed in chronically infected rats, which was consistent with histological hepatitis and HEV-C1 antigen expression in liver tissue. None (0/6) of the HD regimen-treated, 5/6 LD regimen-treated, and 6/6 IC rats developed antibodies to HEV-C1 in species-specific immunoblots. Reversal of immunosuppression was associated with clearance of viraemia and restoration of HEV-C1-specific humoural and cellular immune responses in HD regimen-treated rats, mimicking patterns in treated patients with chronic hepatitis E. Viral load suppression was observed with i.p. ribavirin treatment. HD regimen-treated rats remained unsusceptible to HEV-A infection.
UNASSIGNED: We developed a scalable immunosuppressed rat model of chronic hepatitis E that closely mimics this infection phenotype in transplant recipients.
UNASSIGNED: Convenient small animal models are required for the study of chronic hepatitis E in humans. We developed an animal model of chronic hepatitis E by suppressing immune responses of rats with drugs commonly taken by humans as organ transplant rejection prophylaxis. This model closely mimicked features of chronic hepatitis E in humans.

Zoonotic transmission of hepatitis E virus (HEV), in particular the genotype (GT) 3 and GT4 strains, constitutes a major one health issue. Swine serves as an important reservoir and the processed pork products essentially contribute to foodborne transmission. This study comprehensively estimated HEV prevalence in domestic pigs, wild boars, and pork products. At global level, we found nearly 60% domestic pigs and 27% wild boars have ever encountered HEV infection based seroprevalence rate. Nearly 13% domestic and 9.5% wild swine are actively infected based on HEV RNA positivity. Importantly, about 10% of commercial pork products are HEV RNA positive, although available data are limited in this respect. Our results indicate the high prevalence rate of HEV infection in pigs and widespread contamination in pork products, although there are substantial variations at regional and country levels. These findings are important for better understanding the global epidemiology and clinical burden of HEV infection in human population related to zoonotic transmission.

Cyproterone acetate (CPA), a hydroxyprogesterone derivative, is used to treat advanced prostate cancer and infrequently in women for acne, breast cancer and hirsutism. Transient mild elevation in levels of liver enzymes is reported in 10-30% of patients, and acute liver failure (ALF) is uncommon. Here, we discuss the first case of CPA-induced ALF from India and the available literature.

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.

Hepatic involvement in systemic lupus erythematosus (SLE) is common but described infrequently. Liver is usually never the primary organ to be affected in lupus. Again hepatic involvement probably does not carry much prognostic importance though it may correlate with lupus activity. We here report a case of 21-year-old man with no prior comorbidity or addiction who presented to us with acute hepatic illness with jaundice. He also had malar rash and arthralgia. Viral markers were negative. Antinuclear antibody and anti-double-stranded DNA (dsDNA) were strongly positive. Liver biopsy was consistent with autoimmune hepatitis, whereas skin biopsy was suggestive of SLE. He had a brisk and complete recovery with prompt use of immunosuppressive agents (corticosteroids and azathioprine). Cyclophosphamide was started latter in view of lupus nephritis. This is probably the fourth reported case of SLE presenting as acute hepatic illness with jaundice.

Sickle hepatopathy is an umbrella term describing various pattern of liver injury seen in patients with sickle cell disease. The disease is not uncommon in India; in terms of prevalence, India is second only to Sub-Saharan Africa where sickle cell disease is most prevalent. Hepatic involvement in sickle cell disease is not uncommon. Liver disease may result from viral hepatitis and iron overload due to multiple transfusions of blood products or due to disease activity causing varying changes in vasculature. The clinical spectrum of disease ranges from ischemic injury due to sickling of red blood cells in hepatic sinusoids, pigment gall stones, and acute/chronic sequestration syndromes. The sequestration syndromes are usually episodic and self-limiting requiring conservative management such as antibiotics and intravenous fluids or packed red cell transfusions. However, rarely these episodes may present with coagulopathy and encephalopathy like acute liver failure, which are life-threatening, requiring exchange transfusions or even liver transplantation. However, evidence for their benefits, optimal indications, and threshold to start exchange transfusion is limited. Similarly, there is paucity of the literature regarding the end point of exchange transfusion in this scenario. Liver transplantation may also be beneficial in end-stage liver disease. Hydroxyurea, the antitumor agent, which is popularly used to prevent life-threatening complications such as acute chest syndrome or stroke in these patients, has been used only sparingly in hepatic sequestrations. The purpose of this review is to provide insights into epidemiology of sickle cell disease in India and pathogenesis and classification of hepatobiliary involvement in sickle cell disease. Finally, various management options including exchange transfusion, liver transplantation, and hydroxyurea in hepatic sequestration syndromes will be discussed in brief.

UNASSIGNED: Hematopoietic stem cell transplantation (HSCT) is an established curative modality for various hematological malignancies and other diseases. Hepatobiliary dysfunction and subsequent sequelae constitute a common cause of morbidity and mortality in post-transplant scenario. However, data among Indian HSCT recipients is lacking.
UNASSIGNED: One hundred and one HSCT recipients (37 prospective and 64 retrospective) were followed up for hepatobiliary dysfunction in the post-transplant period. The causes for hepatobiliary dysfunction were categorized as sinusoidal obstruction syndrome (SOS), formerly known as veno-occlusive disease (VOD); acute and chronic graft-versus- host disease (GVHD); drug-induced liver injury (DILI); viral infections and miscellaneous causes including bacterial, fungal and unknown causes based on clinical and laboratory evidence.
UNASSIGNED: Among the 101 transplants, 56.44% (n = 57) were allogenic transplants, and 43.56% (n = 44) were autologous transplants. Hepatobiliary dysfunction was observed among 71 (70.30%) patients in first 30 days and overall, among 78 (77.23%) patients. Incidence of hepatobiliary dysfunction was higher among allogenic transplant patients compared to autologous transplants (91.23% vs. 59.09%, p < 0.001). The most common cause of hepatobiliary dysfunction reported was Drug-induced liver injury (DILI). In most cases, however, hepatobiliary dysfunction was multifactorial. Sinusoidal obstruction syndrome (15.79%), acute liver GVHD (31.58%), chronic liver GVHD (33.33%) and viral infection/reactivation (26.32%) were reported only in allogenic transplant patients. 15 (14.85%) patients died of which 14 patients had hepatobiliary dysfunction, commonest cause being infections.
UNASSIGNED: Our study reported a higher incidence of hepatobiliary dysfunction among Indian population post HSCT and was associated with significant mortality. In majority of the cases, the cause is multifactorial and pose a diagnostic dilemma and challenges in therapy.

UNASSIGNED: Acute liver failure (ALF) is rare and associated with poor outcomes. The outcomes of ALF and predictors of outcome may vary as per the etiology. There are limited data on the predictors of spontaneous survival among patients with ALF of non-A-E hepatitis or cryptogenic etiology. We aimed to assess clinical course, complications, and outcome of non-A-E etiology ALF.
UNASSIGNED: In this prospective analysis, all consecutive ALF patients (n = 1555; January 1986-June 2018) were analyzed. Non-A-E-ALF was defined as ALF that could not be attributed to known etiologies such as drugs, viral hepatitis, autoimmune hepatitis, and Wilson\'s disease. Clinical course, complications, and outcomes of non-A-E-ALF patients who did not undergo liver transplantation were analyzed. Unadjusted and adjusted odds ratios (ORs) were calculated.
UNASSIGNED: Non-A-E-ALF constituted 34.6% (n = 538) of all ALF patients, whereas hepatitis E virus (HEV), hepatitis B virus (HBV), and anti-tuberculosis therapy (ATT) accounted for 29.5% (n = 459), 8.6% (n = 134), and 7.4% (n = 115), respectively. Among non-A-E-ALF patients, mean age was 28.8 ± 12.0 years, 50.9% females, majority (63.1%) had hyperacute presentation, and 79.2% had advanced encephalopathy at presentation. The frequency of cerebral edema in non-A-E-ALF (53.3%) was higher than that in HEV-ALF (41.2%) and ATT-ALF (44.2%), P < 0.001. The survival rate in non-A-E-ALF (37.5%) was poorer than HEV-ALF (54.9%) and was comparable to that in HBV (35.8%) and ATT (29.6%) induced ALF. The baseline prothrombin time prolongation (odds ratio [OR] 1.041; 95% confidence intervals [CI], 1.017-1.065) and infection (OR 2.366; 95%CI, 1.107-5.055) were independent predictors of outcome in non-A-E-ALF. The 3-days acute liver failure early dynamic model had the best value in predicting the outcome.
UNASSIGNED: Non-A-E-ALF accounts for one-third of all cases of ALF and is associated with poor spontaneous survival.

The unprecedented global spread of the severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 is depicting the distressing pandemic consequence on human health, economy as well as ecosystem services. So far novel coronavirus (CoV) outbreaks were associated with SARS-CoV-2 (2019), middle east respiratory syndrome coronavirus (MERS-CoV, 2012), and SARS-CoV-1 (2003) events. CoV relates to the enveloped family of Betacoronavirus (βCoV) with positive-sense single-stranded RNA (+ssRNA). Knowing well the persistence, transmission, and spread of SARS-CoV-2 through proximity, the faecal-oral route is now emerging as a major environmental concern to community transmission. The replication and persistence of CoV in the gastrointestinal (GI) tract and shedding through stools is indicating a potential transmission route to the environment settings. Despite of the evidence, based on fewer reports on SARS-CoV-2 occurrence and persistence in wastewater/sewage/water, the transmission of the infective virus to the community is yet to be established. In this realm, this communication attempted to review the possible influx route of the enteric enveloped viral transmission in the environmental settings with reference to its occurrence, persistence, detection, and inactivation based on the published literature so far. The possibilities of airborne transmission through enteric virus-laden aerosols, environmental factors that may influence the viral transmission, and disinfection methods (conventional and emerging) as well as the inactivation mechanism with reference to the enveloped virus were reviewed. The need for wastewater epidemiology (WBE) studies for surveillance as well as for early warning signal was elaborated. This communication will provide a basis to understand the SARS-CoV-2 as well as other viruses in the context of the environmental engineering perspective to design effective strategies to counter the enteric virus transmission and also serves as a working paper for researchers, policy makers and regulators.