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Living donor liver transplantation (LDLT) needs "Mercedes Benz" or "J-shaped" incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to noncirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Generally diagnosis of non-alcoholic fatty disease is made on imaging, however, mild steatosis is difficult to diagnose on imaging. Liver biopsy is the procedure of choice but is not carried out as it is an invasive procedure. We describe our experience of 157 liver biopsies in living liver donors with normal body mass index (BMI) <23 kg/M2 (lean). The study was conducted at a tertiary care center in north India. Data of lean living donors who underwent a liver biopsy before donation were analyzed. Data are presented as percentage, mean, or median (25–75 interquartile range). Of 718 donors who had a liver biopsy before donation, 157 (21.8%) donors were lean (BMI < 23 kg/M2). Seventy-eight percent of lean donors had no or only one metabolic risk factor. Fifty-three (33.7%) of lean donors had nonalcoholic fatty liver (NAFL) in liver biopsy. When donors with NAFL were compared to donors with normal histology, donors with NAFL had significantly higher aspartate transaminase (26.6 ± 7.5 versus 23.7 ± 5.4, p = 0.007), alanine transaminase (33.4 ± 11.7 versus 27.8 ± 10.7, p = 0.003), and gamma glutamyl transpeptidase [25 (16–40.5) versus 18 (14–23), p = 0.003]. Only triglycerides (TGs) were statistically different among metabolic factors in lean NAFL and normal histology groups, 97 (70–161) versus 86 (62.5–114.7), p = 0.043. A total of 30% donors in the lean NAFL group had TGs >150 mg/dl as compared with 12.5% in the normal histology group, p = 0.009. Other metabolic risk factors were not statistically different. One third of lean donors had NAFL. Among all metabolic risk factors, only higher TGs levels showed a significant association with NAFL. [ABSTRACT FROM AUTHOR]

Recipients of liver transplantation (LT) remain at higher risk (adjusted for other risk factors) of de novo malignancies (DNMs). The higher risk can be attributed to the effect of immunosuppression and patient-related risk factors (age, tobacco, alcohol, etiology of liver disease). DNMs are an important cause of late mortality in liver transplant recipients. The pattern (type) of posttransplant malignancies reflects pattern in local population. The common types include skin cancers, solid organ malignancies, and post-transplant lymphoproliferative disorders. Counseling of patients about risk factors and surveillance protocols may help in the prevention and diagnosis at early stage. We also discuss the results of LT in patients with a history of extrahepatic malignancy in the pretransplant period. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). In the period March 15–June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is the only cure for patients with end-stage liver disease, which offers good long-term survival. The long-term issues after LT affecting survival are cardiovascular disease, chronic kidney disease, de novo malignancies, recurrence of original disease and immunological causes. Alcoholic-related liver disease (ALD) is one of the most common indications for LT worldwide including India. LT for ALD is associated with several unique challenges as compared with other etiologies. Long-term survival after LT in patients with ALD is affected by recidivism. Various studies have shown different predictors of relapse; the main predictors of relapse are pretransplant abstinence, psychiatric comorbidities, and lack of social support. Although several risk scores have been proposed, these scores are not validated. Studies with active involvement of psychiatrist have shown lower relapse rates. The relapse prevention strategy for reducing likelihood and severity of relapse after initial cessation of alcohol uses a combination of pharmacotherapy and cognitive behavioral approach (identifying and addressing high-risk situations for relapse). [ABSTRACT FROM AUTHOR]

The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients. [ABSTRACT FROM AUTHOR]

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation. It is associated with a high mortality rate. We describe an unusual case of hepatic mucormycosis in a living donor liver transplant recipient presenting as delayed graft dysfunction, which was successfully treated with combination of liposomal amphotericin B and oral posaconazole therapy, without surgical resection. The patient had clinical improvement with normalization of liver function tests. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder with liver transplantation (LT) being the only definitive treatment in end-stage disease. Recurrence of PSC after LT is a significant concern which can lead to graft loss. The aim of this study is to find out the disease recurrence and long-term outcome after living donor liver transplantation (LDLT) in PSC. We conducted a retrospective review of all patients undergoing LDLT for PSC at our centre. Of 2268 adult LTs from August 2004 to July 2018, 32 (1.4%) patients underwent LDLT for PSC including 6 with PSC and autoimmune hepatitis overlap. The data were reviewed to look for PSC recurrence, complications, and overall survival. All patients received tacrolimus-based immunosuppression. Data are shown as number, percentage, median, and interquartile range (IQR). The mean age of 32 LDLT recipients was 44 ± 12 years (males 22, females 10). At the time of transplantation, the mean child's score was 9 ± 1.6 and model for end-stage liver disease score was 18.9 ± 6.4. Ulcerative colitis was seen in 7 patients and none had cholangiocarcinoma. Majority of patients (n = 29) received right lobe graft and all but 3 underwent hepaticojejunostomy for biliary reconstruction. PSC recurrence was seen in 6 (20%) patients during a median follow-up of 59 (29–101) months, after exclusion of 2 patients with early mortality. A total of five patients died during follow-up, and one of these deaths was due to PSC recurrence. There were 2 perioperative deaths due to sepsis and 3 deaths on follow-up (sepsis in 2 and PSC recurrence in 1). LDLT can be performed in PSC with good overall long-term outcomes. [ABSTRACT FROM AUTHOR]

There are few data on genetic relation of the donor and outcomes in living donor liver transplantation (LDLT) recipients. We compared outcomes of LDLT between recipients of genetically related and unrelated donors in a large single-center series. The study included 1372 adult, ABO-compatible, primary LDLT recipients, who received a graft from either a first-degree relative (parent, sibling, son, or daughter; n = 756) or unrelated donor (spouse or relative of the spouse; n = 616). The mean age of the recipients with a related donor was 50.2 ± 10.8 years compared with 47.3 ± 9.3 years for recipients with unrelated donors (P = 0.000). Chronic rejection was significantly more common in the genetically unrelated donor group than in the genetically related donor group (28 [4.5%] versus 9 [1.1%]; P = 0.000) at a mean follow-up of 37 months (15–95 months). There were no significant differences in other outcomes between the 2 groups. The 12-month and 36-month survival between the unrelated and related groups was 87.6% versus 90%, and 86.3% versus 89.7% respectively (P = 0.115). The multivariate analysis revealed genetically unrelated donors (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.80–8.34, P = 0.001) and history of acute cellular rejection (OR: 3.39, 95% CI: 1.68–6.81, P = 0.001) as predictors of chronic rejection. Although chronic rejection was found to be more common in genetically unrelated donors, the patient survival after LDLT was similar. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a catastrophic illness, which is associated with high mortality in absence of liver transplantation. ALF is associated with multisystem involvement including acute kidney injury (AKI). AKI worsens the already poor prognosis of ALF. There is limited literature on impact of AKI on outcomes of liver transplantation (LT). The use of continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridging to LT. Although results suggest a somewhat lower survival in patients with ALF and AKI, LT is a life-saving option and should not be deferred in absence of other contraindications. In the current review, we discuss impact of AKI on transplant-free survival, possible role of CRRT, and role of LT in patients with ALF associated with AKI. [ABSTRACT FROM AUTHOR]

Performance status may adversely affect living donor liver transplantation (LDLT) outcomes. We present our data regarding performance status and posttransplantation survival in a large LDLT cohort. Patients with ABO incompatibility, of pediatric age, with acute liver failure, with hepatocellular carcinoma, and/or who had incomplete data were excluded. Two hundred sixty adults who had decompensated cirrhosis and underwent LDLT from January 2016 to March 2018 were included. Performance status was assessed by Karnofsky Performance Score (KPS). The data are depicted as number, mean (SD), or median (25–75 interquartile range [IQR]). The cohort included 232 males and 28 females, aged 48.3 ± 9.8 years. Etiology of liver disease was hepatitis B in 33, hepatitis C in 19, alcohol related in 120, nonalcoholic steatohepatitis/cryptogenic in 68, and other etiologies in 20 patients. The mean Child's score was 9.6 ± 1.7, Model for End-Stage Liver Disease (MELD) score was 18.0 ± 5.8, and donor age was 33.4 ± 9.9 years. Forty-one recipients died at median follow-up of 11 months. The KPS was 100 in 6 (no deaths), 90 in 53 (2 deaths), 80 in 93 (12 deaths), 70 in 69 (14 deaths), 60 in 26 (8 deaths), and 50 in 13 (5 deaths) (P = 0.003). The area under the receiver operating characteristic curve of KPS to predict mortality was 0.698 (P = 0.000, 95% confidence interval [CI] = 0.616–0.780), and the best sensitivity (63%) and specificity (67%) were achieved at KPS ≤70. The survivors and nonsurvivors had a significant difference with respect to KPS (77.6 ± 10.9 versus 69.5 ± 10.9, P 0.000), age of the patient (47.8 ± 9.4 versus 51.1 ± 11.7; P = 0.047), postoperative infections (53.8% versus 85.3%, P = 0.001), and need of packed red cells transfusion. Multivariate analysis (Cox proportional-hazard) showed KPS (hazard ratio [HR] = 0.96, 95% CI = 0.93–0.99, P = 0.007), postoperative infections (HR = 2.3, 95% CI = 1.04–5.1, P = 0.038), and recipient age (HR = 1.03, 95% CI = 1.002–1.07, P = 0.039) as predictors of mortality. Pretransplant performance status is one of the predictors of mortality after LDLT. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. In addition to the liver-related morbidity and mortality, NAFLD is now also associated with various extrahepatic diseases. Pathogenesis of NAFLD is multifactorial with limited pharmacotherapy options for the treatment of patients with NAFLD. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in the transcriptional regulation of lipid metabolism, glucose homeostasis, energy balance, inflammation, and atherosclerosis. PPAR agonists are attractive options for treatment of NAFLD as they can act at multiple targets involved in the pathogenesis of NAFLD. We reviewed the available literature on the pathophysiological role of PPARs and use of PPAR agonists in the treatment of NAFLD. Original studies and review articles available on PubMed regarding the role of PPARs in the pathogenesis and utility of PPAR agonists in the treatment of NAFLD were included in this review article. ClinicalTrials.gov and Clinical Trials Registry-India sites were searched for ongoing studies on saroglitazar. The available literature suggests that PPARs play an important role in the pathogenesis of NAFLD. Use of PPAR gamma agonists is associated with histological improvement in NAFLD. Dual PPAR agonists with no or minimal PPAR gamma activity are being explored in the treatment of NAFLD. Because of the pathophysiological role of PPARs in NAFLD, PPAR agonists are attractive options for the treatment of patients with NAFLD. Dual PPAR agonists without significant gamma activity appear promising for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy due to portosystemic shunts is a well-defined entity in patients with cirrhosis. Rarely, liver transplant recipients develop hepatic encephalopathy owing to persistence or surgically created portosystemic shunts. We present a case of post-transplant recurrent hepatic encephalopathy due to a surgically created portocaval shunt. The patient was managed by a covered metal stent placement in the inferior vena cava, thus causing functional closure of the shunt. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Patients with NAFLD are at a higher risk of developing cardiovascular disease (CVD). In fact, CVD-related mortality is more common in patients with NAFLD in comparison to liver-related mortality. This association is related to the common metabolic risk factors such as obesity, dyslipidemia, diabetes, and hypertension shared by both NAFLD and CVD, and also there is independent association of NAFLD with CVD because of risk factors such as insulin resistance, systemic inflammation, and atherogenic dyslipidemia. While there is abundant literature on association of NAFLD with CVD, there is sparse literature regarding the screening for CVD in patients with NAFLD. In the current review article, we discuss as to which patients with NAFLD to screen and how to screen for CVD. [ABSTRACT FROM AUTHOR]

While Autoimmune Hepatitis (AIH) may recur in patients after liver transplant, an AIH like presentation (positive auto antibodies, raised immunoglobulin G, raised transaminases and histology showing plasma cell rich infiltrate) may also occur in liver transplant recipients who had transplant for some other disease, called De novo Autoimmune Hepatitis (DAIH). A timely diagnosis and treatment can prevent further graft dysfunction. We report 4 cases of DAIH after living donor liver transplantation. [ABSTRACT FROM AUTHOR]

Introduction Although liver transplantation is a definitive cure for Wilson's disease (WD), there is limited data about results of living donor liver transplantation (LDLT) in adults. Material and methods 18 adults underwent LDLT for WD. The presentations before LDLT were decompensated cirrhosis ( n = 16), acute on chronic liver failure ( n = 1) and acute liver failure ( n = 1). The donors were parents ( n = 2), siblings ( n = 3), cousin ( n = 1), daughter ( n = 1), nephew ( n = 1), spouse or relatives of spouse ( n = 9) and from swap transplantation ( n = 1). All genetically related donors were negative for screening of WD. Results The study cohort comprised of 15 males and 3 females, aged 32 ± 10 years. Severity of liver disease (excluding acute liver failure patient) was as follows; Child's score 10 ± 2, model for end-stage liver disease (MELD) score 18 ± 6. The graft to recipient weight ratio was 1 ± 0.2. The ICU and hospital stay were 5.5 ± 0.9 and 15 ± 5 days. Two patients died in first month after liver transplantation, rest of patients are doing well at median 15 (8–38 months). Two patients had acute cellular rejection that responded to steroids, one had hepatic artery thrombosis and 2 had biliary strictures. Three patients had neurological symptoms; 2 of these patients had partial recovery while one had complete recovery. There was no significant difference between LDLT from genetically related or unrelated donors. Conclusion LDLT for WD in adults is associated with good outcomes. [ABSTRACT FROM AUTHOR]

Introduction Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on “real world” experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. Material and methods Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin ( n = 58), Sofosbuvir + Ledipasvir ± Ribavirin ( n = 5), Sofosbuvir + Daclatasvir ± Ribavirin ( n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). Results A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. Conclusion Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT. [ABSTRACT FROM AUTHOR]

While antibody mediated hyper-acute vasculitic rejection is rare in liver transplant recipients, acute and chronic rejection have clinical significance. The liver allograft behaves differently to other solid organ transplants as acute rejection generally does not impair graft survival and chronic rejection (CR) is uncommon. The incidence of acute and chronic rejection has declined in current era due to improved immunosuppressive regimens. Acute rejection generally improves with steroid boluses and steroid resistant rejection is uncommon. CR may improve with escalation of immunosuppression or may result in irreversible loss of graft function leading to retransplantation or death. The current review discusses diagnosis and management of acute and chronic liver allograft rejection. [ABSTRACT FROM AUTHOR]

Background Acute-on chronic liver failure (ACLF) is defined as acute insult on previous liver disease that causes sudden worsening of liver functions. Methods ACLF is characterized by high incidence of organ failure and prognosis is remarkably worse than patients with cirrhosis. Incidence of organ failures is very high despite best medical care and timely liver transplant before development of multi organ failure is associated with good survival rates. Results At present, there are no reliable score or ways to correctly identify patients who are going to recover from patients who will need transplantation. Organ failures are important part of prognosis and to define need or futility of early liver transplantation. Conclusion Asian Pacific Association for the Study of the Liver (APASL) published their recommendations regarding ACLF in 2014. Several important studies regarding course/nature of disease and transplantation for ACLF became available after 2014 APASL recommendations and still there are some unanswered areas. The current review discusses various issues regarding liver transplantation in patients with ACLF. [ABSTRACT FROM AUTHOR]

Introduction: Zinc, copper, manganese and magnesium are essential trace elements whose role in chronic liver disease and its complications is not clear. Aim: To study the concentration of these elements in patients with Chronic Liver Disease (CLD) with respect to Child-Torcotte- Pugh (CTP) scoring. Materials and Methods: This was an observational study carried out in the Department of Medicine, JSS Hospital, Mysore, India, between October 2013 and October 2015. A total of 75 patients with cirrhosis were prospectively enrolled. Severity of liver disease was assessed based on CTP score and patients were grouped into Class A, B and C. Routine investigations were done and following trace elements were assessed in allzinc, copper, manganese and magnesium. Results: The serum concentrations of zinc decreased with severity of liver disease, and the mean difference between different severity classes was statistically significant (p<0.001). There was a significant negative correlation between zinc and CTP Score (r= -0.439; p<0.001). Copper concentration was increased in patients with more severe cirrhosis and mean level difference of copper among the CTP groups were statistically significant (p<0.001). Moreover, copper showed significant positive correlation with CTP Score (r=0.385; p<0.001). The serum levels of manganese were significantly higher in patients with CTP C class in comparison to patients with CTP A and B class (p<0.05); Manganese showed significant positive correlation with CTP Score (r=0.271; p= 0.019). The concentrations of magnesium did not differ significantly between CTP class with the mean level difference not statistically significant. Conclusion: Increasing liver dysfunction alters the metabolism of trace elements towards excess of copper and deficiency of zinc. [ABSTRACT FROM AUTHOR]

Intraductal ultrasonography (IDUS) utilizes probe catheter and operates at a higher frequency (12-30 MHz). It can be passed down the biopsy channel of a side-view endoscope during endoscopic retrograde cholangiopancreatography, and it provides real-time, high-quality imaging of pancreatobiliary ducts and the surrounding structures. IDUS has been used in defining choledocholithiasis, evaluating biliary as well as pancreatic strictures or thickening, and local staging of tumor. We shall discuss the utility of IDUS in the current review. [ABSTRACT FROM AUTHOR]