Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS: We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS: Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION: The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Endoscopic Ultrasound-Guided Antegrade Stent Placement in Patients with Failed ERCP as a Modality of Preoperative and Palliative Biliary Drainage.

BACKGROUND: No large studies have addressed the role of endoscopic-ultrasound biliary drainage (EUS-BD) as preoperative biliary drainage (PBD) for malignant extrahepatic biliary obstruction (MEBO). We aimed to discuss the outcomes of EUS antegrade stent placement (EUS-AG) in the preoperative and palliative setting. METHODS: Retrospective review of patients who underwent EUS-AG for MEBO between December 2019 and December 2021 was done. Primary outcome measures were technical success and clinical success. Secondary outcome measures were number of days of hospitalization postprocedure, adverse events related to EUS-AG procedure, morbidity related to surgery, and 3-month mortality after surgery. RESULTS: 54 patients underwent attempt for EUS-AG (mean age 54.8 ± 12.1 years; female 44.4%). Most common primary cancer was pancreatic cancer in 42.1% (23/54) patients. Indication was palliative in 34 (62.9%) patients and PBD in 20 (37%) patients. Level of block was distal in 35 (64.8%) and proximal in 19 (35.1%) patients. Technical success of EUS-AG was 88.7% (47/53). Clinical success was seen in 95.7% (45/47) patients. Median number of days of hospitalization postprocedure was 1 day. No procedure-related severe adverse events were seen. Of 20 patients who underwent EUS-AG as PBD, 19 had technical success (95%) with clinical success in 94.5% (18/19). Surgery was performed in 11 patients, of whom 10 patients underwent successful PPPD (one intraoperative liver metastasis). Two patients had Clavein-Dindo III/IV complication post-PPPD, with one mortality within 30 days of surgery. CONCLUSION: EUS-AG is safe and effective after failed ERCP in both preoperative and palliative setting.

A survey of clinical practices among oncologists regarding hepatitis B screening in patients with cancer.

Background & objectives: Screening for hepatitis B prior to the initiation of chemotherapy in patients with cancer is recommended by all major hepatology and oncology societies. This study was aimed to determine the screening practices for hepatitis B among oncologists from India and their experience with hepatitis B reactivation. Methods: A questionnaire-based survey was conducted among oncologists attending the Evidence-Based Medicine Conference at Tata Memorial Centre, Mumbai, India. The questionnaire was developed in keeping with the recent guidelines for hepatitis B reactivation on chemotherapy, with questions regarding demographics, years in practice and hepatitis B screening practices and management. There was 78 per cent response rate to the questionnaire. Results: Most respondents were <35 yr of age (69%), with < five years of experience (39%), practicing in an academic institution (81%). Seventy four per cent respondents always screened their patients with cancer for hepatitis prior to chemotherapy, whereas 19 per cent in special settings and seven per cent never screened; 96 per cent respondents used hepatitis B surface antigen (HBsAg) as a screening test, while 17 per cent also used antibody to hepatitis B core antigen. Sixty one per cent respondents used entecavir or tenofovir for prophylaxis; 70 per cent continued prophylaxis till 6-12 months after completion of chemotherapy, while 21 per cent continued only till the end of chemotherapy. Interpretation & conclusions: More than 25 per cent of the oncologists were not screening their patients with cancer for viral hepatitis prior to cancer-directed therapy, and only 17 per cent of the oncologists used the recommended tests for screening. Better training of oncologists regarding viral hepatitis screening and management is needed.

Pulmonary Renal Syndrome: Experience from Tertiary Centre in Mumbai.

INTRODUCTION: Pulmonary Renal Syndrome (PRS), is characterized by diffuse alveolar haemorrhage (DAH) and glomerulonephritis (GN), occurring simultaneously. It has high mortality and dialysis dependence at one year, if not timely diagnosed and aggressively treated. OBJECTIVES: To study etiology and short term outcome of PRS in India. MATERIALS AND METHODS: This study included patients of PRS seen in a tertiary care center in Mumbai, by one consultant from 1997- 2013, analyzed retrospectively and from January 2014 to December 2015 collected prospectively from six medical units, intensive care unit, nephrology and respiratory units. Patients with DAH (haemoptysis, breathlessness and x-ray chest with bilateral alveolar shadows with sparing of apices) and glomerulonephritis (Proteinuria, heamaturia, hypertension with or without raised serum Creatinine) were included in the study after carefully excluding other causes of haemoptysis and breathless like tuberculosis, pulmonary oedema, pneumonia, ARDS. During prospective enrollment of patients, in all admitted patients with haemoptysis, urine examination was carried out to specifically look for proteinuria and red blood cells in urine, same was also followed in those admitted for breathlessness with chest x-ray suggestive of alveolar haemorrhage. Patients were extensively investigated for etiology and were treated with steroids and pulse cyclophosphamide (after ruling out infectious etiology). Supportive care with ventilator or dialysis was given as per usual indications. Palsmapheresis was initiated in those with serum Creatinine ≥ 5.7mg/dl. Rituximab was used in refractory cases, as per treating physicians' choice. Final outcome was death or discharge. RESULTS: There were 25 patients of PRS (13 retrospective, 12 prospective), with following etiology : Granulomatosis with polyangiitis (GPA) 7, Microscopic polyangiitis (MPO) 4, Churg Strauss Syndrome (EGPA) 1, Goodpasture's syndrome 1, lupus 5, leptospirosis 5, dengue 2. All were given steroids, 18 (72%) were given pulse Cyclophosphamide (barring those with leptospirosis and dengue), ventilator support in 14 (56%) patients (8 invasive, 6 non-invasive), haemodialysis 3, plasmapheresis 1, Rituximab 2. Seventeen (68%) patients survived, mortality was high in those requiring invasive ventilator. CONCLUSION: Most common etiology of PRS is ANCA positive vasculitis in India. With high degree of suspicion for DAH in patients presenting with haemoptysis, breathlessness and alveolar opacities in chest x-ray and carefully investigating by simple urine examination for evidence of GN, timely diagnosis of PRS can be made. With timely appropriate treatment survival is 68%. Patients with PRS due to leptospirosis or dengue have features suggestive of underlying disease (like icterus with raised bilirubin but < 200U SGOT/SGPT, subconjunctival haemorrhage, typical rash of dengue with thrombocytopenia).