A rare presentation of vanishing bile duct syndrome in Hodgkin lymphoma: Case report.

In this report, we present the case of vanishing bile duct syndrome in the setting of classical Hodgkin lymphoma. Vanishing bile duct syndrome was diagnosed retrospectively in this patient with Hodgkin lymphoma, who initially presented with a hepatic abnormality presumed to be drug induced. Vanishing bile duct syndrome is characterized by the disappearance of bile ducts, with the progressive damage resulting in cholestasis. Thus, nivolumab therapy was initiated for Hodgkin lymphoma, in place of the standard ABVD (Doxorubicin, bleomycin, vinblastine, dacarbazine) regimen, which resulted in autoimmune hemolytic anemia. Alternatively, GDP (gemcitabine, dexamethasone, and carboplatin) chemotherapy with protocol modification resulted in better tolerance and remission of Hodgkin lymphoma. Granulocyte colony-stimulating factor support and romiplostim supplement were provided to prevent chemotherapy-induced neutropenia and thrombocytopenia, respectively. Due to the deranged liver function in our case, we initially suspected the etiology as drug-induced cholestatic injury. While hepatic failure is the leading cause of mortality among patients with Hodgkin lymphoma-related vanishing bile duct syndrome, our case report suggests a complete remission of vanishing bile duct syndrome following an adequate treatment of Hodgkin lymphoma and an improvement in the hepatic function. To conclude, our report describes the rare case of vanishing bile duct syndrome which heralded the diagnosis of Hodgkin lymphoma, and the effective management of Hodgkin lymphoma which precedes the improvement of hepatic abnormality.

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Atezolizumab-bevacizumab (atezo-bev) is recommended as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, its effectiveness and safety in other populations, including those with Child-Turcotte-Pugh (CTP) class B cirrhosis, is unclear. Methods: For this systematic review and meta-analysis, electronic databases, including PubMed, Embase, and Scopus, were searched from 1st May, 2020 till 5th October, 2022; the last date of access was January 31, 2023. Pooled progression-free survival (PFS), overall survival (OS), and radiological response rate among patients receiving atezo-bev were compared between patients with CTP-A and CTP-B cirrhosis, with tyrosine kinase inhibitors (TKIs) and among those receiving the drug as first-line and later line therapy. The protocol was registered in Prospero (CRD42022364430). Findings: Among 47 studies (n = 5400 patients), pooled PFS and OS were 6.86 (95% CI, 6.31-7.41) and 13.8 months (95% CI, 11.81-15.8), respectively. Objective response rate (ORR) and disease control rate were 26.7% (24.6-29.1) and 75.3% (73.1-77.4) using RECIST criteria, and 34% (30.3-37.8) and 73.6% (68.8-78) using mRECIST criteria, respectively. Among those receiving atezo-bev, patients with CTP-B cirrhosis had similar ORRs by RECIST (odds ratio [OR], 1.42 [0.77-2.6]; P = 0.25) and mRECIST criteria (OR, 1.33 [0.52-3.39]; P = 0.53) but shorter PFS (mean difference [MD]:3.83 months [1.81-5.84]) than those with CTP-A cirrhosis. Compared to patients receiving TKIs, those receiving atezo-bev had longer PFS (MD: 2.27 months [0.94-3.5]) and higher ORR (RECIST: OR, 1.44 [1.01-2.04] and mRECIST: OR, 1.33 [1.01-1.75]). Compared to first-line therapy, later-line therapy had lower ORR (RECIST: OR, 1.82 [1.3-2.53]; P < 0.001 and mRECIST: OR, 2.02 [1.34-3.05]) but comparable PFS (MD: 0.58 months [-0.18 to 1.35]) among nine studies. The incidence of grade ≥3 adverse events among patients with CTP-A and CTP-B cirrhosis was comparable (OR, 0.89 [0.45-1.74]) as it was for patients receiving atezo-bev and TKIs (OR, 0.86 [0.61-1.2]). Interpretation: Our findings suggest that atezo-bev is safe and effective as first-line systemic therapy for patients with uHCC and CTP-A or CTP-B cirrhosis. Funding: An unsolicited grant from ROCHE Products India Pvt Ltd. was received for publication.

Liver Transplantation: Protocol for Recipient Selection, Evaluation, and Assessment.

Liver transplantation (LT) is the definitive therapy for patients with end-stage liver disease, acute liver failure, acute-on-chronic liver failure, hepatocellular carcinoma, and metabolic liver diseases. The acceptance of LT in Asia has been gradually increasing and so is the expertise to perform LT. Preparing a patient with cirrhosis for LT is the most important aspect of a successful LT. The preparation for LT begins with the first index decompensation for a patient with cirrhosis. Patients planned for LT should undergo a thorough screening for infections, and a complete cardiac, pulmonology, and psychosocial evaluation pre-LT. In this review, we discuss the indications and contraindications of LT and the evaluation and assessment of patients with liver disease planned for LT.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease.

Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.

Long-term Outcome of Autologous Hematopoietic Stem Cell Infusion in Cirrhosis: Waning Effect over Time.

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking. Methods: Patients with cirrhosis of non-viral etiology received either standard-of-care (n = 23) or autologous CD34+ cell infusion through the hepatic artery (n = 22). Study patients received granulocyte colony-stimulating factor (commonly known as G-CSF) injections at 520 µgm per day for 3 days, followed by leukapheresis and CD34+ cell infusion into the hepatic artery. The Control group received standard-of-care treatment. Results: Mean CD34+ cell count on the third day of G-CSF injection was 27.00 ± 20.43 cells/µL 81.84 ± 11.99 viability and purity of 80-90%. Significant improvement in the model of end-stage liver disease (commonly known as MELD) score (15.75 ± 5.13 vs. 19.94 ± 6.68, p = 0.04) was noted at end of 3 months and 1 year (15.5 ± 5.3 vs. 19.8 ± 6.4, p = 0.04) but was not statistically different at end of the second (17.2 ± 5.5 vs. 20.3 ± 6.8, p = 0.17) and third-year (18.4 ± 6.1 vs. 21.3 ± 6.4, p = 0.25). No difference in mortality (6/23 vs. 5/23) was noted. Conclusions: Autologous CD34+ cell infusion effectively improved liver function and MELD score up to 1 year but the sustained benefit was not maintained at the end of 3 years, possibly due to ongoing progression of the underlying disease.

Autologous mobilized peripheral blood CD34(+) cell infusion in non-viral decompensated liver cirrhosis.

AIM: To study the effect of mobilized peripheral blood autologous CD34 positive (CD34(+)) cell infusion in patients with non-viral decompensated cirrhosis. METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant (DDLT) (control, n = 23) or to receive autologous CD34(+) cell infusion through the hepatic artery (study group, n = 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 µg/d for 3 consecutive days to mobilize CD34(+) cells from the bone marrow. On day 4, leukapheresis was done and CD34(+) cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34(+) cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo. RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18 (78.2%) and 16 (72.72%) and alcohol related in 5 (21.7%) and 6 (27.27%), respectively. The mean day 3 cell count (cells/µL) was 27.00 ± 20.43 with a viability of 81.84 ± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly (2.83 ± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was, however, not sustained at 3 mo. However, at the end of 3 mo there was a statistically significant improvement in serum creatinine in the study group (0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score (15.75 ± 5.13 vs 19.94 ± 6.68, P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference (P = 0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications. CONCLUSION: Autologous CD 34(+) cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.

The Distribution of Genotype and Allelic Frequency of IL28B Gene Polymorphism in Andhra Pradesh, India.

BACKGROUND: The single nucleotide polymorphism (SNP) of IL28B gene on chromosome 19, encoding for the interferon (IFN)-λ-3 is strongly associated with treatment response to pegylated-IFN and ribavirin in patients infected with different genotypes of hepatitis C virus (HCV). Difference between ethnicity and treatment response rates suggesting a key role of host genetics. The IL28B polymorphism (rs12979860C/T) shows a marked differential distribution between racial groups. AIM: The present study is aimed to evaluate genotype and allelic frequency of IL28B gene polymorphism (rs12979860C/T) in Andhra Pradesh, India. METHODS: A total of 220 healthy controls were recruited for the study. The genotyping of SNP rs12979860C/T on IL28B gene was performed by polymerase chain reaction-direct sequencing method. RESULT: The frequency of CC genotype was found to be significantly (59.09%) higher compared to CT (34.09%) and TT (6.81%) genotypes, respectively. The frequency of major allele C is 0.762 whereas minor allele T is 0.238. CONCLUSION: The higher distribution of genotype 'CC' of SNP, rs12979860C/T of IL28B gene in study subjects is suggestive of better response of HCV patients to standard anti-HCV therapy.