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.

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

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.

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: To assess the proportion of patients with cirrhosis up to date with vaccinations and associations of vaccination with age, sex, race, ethnicity, marital status, and type of provider follow-up.
UNASSIGNED: Patients with cirrhosis diagnosed at Mayo Clinic in Rochester and Mayo Clinic Health System in Minnesota from January 1, 2007, to December 31, 2009, were followed up from diagnosis until May 31, 2015. Data were abstracted from Mayo Clinic and Minnesota State records. Factors determining vaccination coverage were assessed.
UNASSIGNED: At the end of the study period (8 years follow-up), 26.4% (95 of 360), 24.7% (82 of 332), 63.2% (180 of 285), and 25.5% (54 of 212) of patients with cirrhosis were up to date with hepatitis A virus (HAV), hepatitis B virus, pneumococcal pneumonia (PN), and herpes zoster vaccinations, respectively. Influenza (FLU) vaccine coverage increased from 36.1% (57 of 158) in 2007 to 2008 to 65.8% (106 of 161) in 2014 to 2015. Of those unvaccinated for HAV and hepatitis B virus before cirrhosis diagnosis, 18.6% (59 of 318) and 23.4% (71 of 304) completed vaccination. For HAV, more whites than nonwhites (28.3% [91 of 322] vs 10.5% [4 of 38]; odds ratio [OR], 3.35; 95% CI, 1.29 to 11.45; P=.02) and more non-Hispanics than Hispanics (27.4% [95 of 347] vs 0% [0 of 13]; OR, 0.00; 95% CI, 0.00 to 0.43; P=.03) were vaccinated. For PN, more younger than elderly people (66.8% [135 of 202] vs 54.2% [45 of 83]; OR, 1.70; 95% CI, 1.01 to 2.87; P=.04) and married vs single people (56.8% [100 of 176] vs 73.4% [80 of 109]; OR, 2.10; 95% CI, 1.26 to 3.56; P=.005) were vaccinated. For FLU, in 2013 to 2014, more elderly (72.0% [54 of 75] vs 58.0% [69 of 119]; OR, 0.54; 95% CI, 0.28 to 0.99; P=.05); in 2008 to 2009, more Hispanics (100% [4 of 4] vs 41.6% [116 of 279]; OR, ∞; 95% CI, 2.25 to ∞; P=.02); and in 2011 to 2012, more married people (62.4% [101 of 162] vs 50.5% [56 of 111]; OR, 1.63; 95% CI, 0.1.0 to 2.66; P=.05) were vaccinated. For FLU in 2008 to 2009, coverage was higher in the primary care than the specialist setting (55.8% [48 of 86] vs 36.6% [72 of 197]; P=.003).
UNASSIGNED: Except for PN and FLU, vaccination coverage in patients with cirrhosis falls short of Healthy People 2020 target. Specific interventions are needed to improve vaccination coverage in patients with cirrhosis.

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.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists.
UNASSIGNED: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review.
CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.