Fibroprogression and Cirrhosis Occurring in Living Liver Donor: First Case Report.

Background: Limited dead donor pool paved the way for living liver donation so that waitlist mortality could be reduced. With over two decades of experience in the East as well as in the West, right lobe adult-to-adult living donor liver transplantation has become an established intervention. The short-term surgical outcomes, complications and health-related quality of life are well known. There is dearth of data on long-term health of remnant liver of donors, especially after a decade of donation. Case description: A 56-year-old lady who donated her right liver lobe 11 years back for her husband with end-stage liver disease. Recipient is doing well till date. She was incidentally found to have thrombocytopenia on follow-up. Her haematological evaluation was negative for blood dyscrasias. Further evaluation demonstrated biopsy-proven cirrhosis with endoscopic evidence of portal hypertension. Aetiological workup was done, which ruled out viral, autoimmune causes as well as Wilson's disease and hemochromatosis. This donor had gained weight post-donation with body mass index of 32.4 kg/m2 and dyslipidaemia. The final diagnosis of fibro progression due to non-alcoholic fatty liver disease was made. Conclusion: We report the first case of cirrhosis developing in a right lobe living liver donor. While selecting living liver donors, extensive evaluation is done to rule out all potential aetiologies remaining silent but later could lead on to chronic liver disease. Although all other aetiologies, which could induce inflammation and fibrosis, are ruled out at the time of donation, lifestyle liver disease, especially non-alcoholic fatty liver disease, can occur in remnant liver post-donation. This case underscores the importance of regular follow-up of liver donors.

Acute Pancreatitis Complicating Liver Transplantation in a Case of Fulminant Hepatic Failure Due to Yellow Phosphorus Poisoning.

INTRODUCTION: Yellow phosphorus (YP) is a general protoplasmic poison causing hepatic, cardiac, renal, and multiorgan failure. We report an unusual case of fulminant liver failure due to ratol (YP) poisoning complicated by acute pancreatitis postoperatively after liver transplantation. CASE REPORT: A 25-yr-old man presented with alleged consumption of approximately 7 gm of Ratol paste. Serum amylase and lipase levels were 880 and 2423, respectively, and CT imaging of pancreas was normal. He developed fulminant liver failure, fulfilling King's college criteria and an living donor liver transplantation was performed. Intraoperatively fat saponification was seen at the root of mesentery. On postoperative day (POD) 13, he developed incisional wound dehiscence and he underwent laparotomy with extensive slough removal from the lateral aspect of wound. On POD 21, wound showed evidence of burst abdomen. CT abdomen revealed inflamed tail of pancreas with peripancreatic fat stranding and an exploratory laparotomy was performed again. Intraoperatively, walled-off necrotic collection was seen in the tail of the pancreas and necrosectomy was carried out. All the aforementioned re-explorations were carried out under steroid immunosuppression. He was restarted on tacrolimus on POD27. Graft function and cholestatic biochemistry improved progressively, and he was discharged and is on regular follow-up. DISCUSSION: YP is very toxic with rapid absorption and gets accumulated in liver causing acute liver failure. Acute pancreatitis in a patient after liver transplantation for fulminant liver failure owing to Ratol poisoning has not been reported in published English literature. Although clinically relevant pancreatitis is rare in ratol poisoning, despite elevated pancreatic enzymes, it is prudent to meticulously image pancreas before embarking on liver transplantation. In those with pretransplant elevation of pancreatic enzymes, it is desirable to follow up the enzyme values postoperatively.

Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity.

INTRODUCTION: Insulin resistance (IR) plays a central role in pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to correlate histopathological grading and IR in overweight/obese patients with NASH as compared with lean NASH. METHODS: Patients with NASH who underwent liver biopsy between January 2012 and December 2012 were included. Anthropometric, clinical, and biochemical features, necro-inflammatory grades, and fibrosis stage on liver biopsies were scored according to Brunt and non-alcoholic fatty liver disease (NAFLD) activity score (NAS). RESULTS: Of 42 patients, 33 (78.6%) had body mass index (BMI) ≥ 23 kg/m2 (overweight/obese) while 9 had BMI < 23 kg/m2 (lean). Mean fasting blood sugar (FBS) and HbA1c levels in overweight/obese patients with NASH were higher than in lean NASH (p < 0.05). The median homeostatic model assessment-estimated insulin resistance (HOMA-IR) among NASH patients with BMI ≥ 23 kg/m2 was higher than among those with BMI < 23 kg/m2 (3.02 [0.34-17.22] vs. 2 [0.52-5.26]; p = 0.045). However, fasting insulin levels were comparable among lean and overweight/obese patients with NASH. Metabolic syndrome could be predicted with 75% sensitivity and 85.3% specificity at a HOMA-IR cutoff value of 3.9. No significant difference was observed with regard to HOMA-IR levels with Brunt grades, Brunt staging, Brunt grades 1 and 2, Brunt scores < 2 and > 2, and NAS scores, and NAS scores < 4 and > 4. CONCLUSIONS: Although IR was significantly higher in overweight/obese patients with NASH as compared with that in lean patients with NASH, there was no difference in the correlation of HOMA-IR with histology between these groups.

Role of therapeutic plasma exchange in acute liver failure due to yellow phosphorus poisoning.

BACKGROUND: Therapeutic plasma exchange (TPE) has been utilized in various liver disorders. There is limited data on the efficacy of TPE in patients with acute liver failure (ALF). METHODS: Study group consisted of patients who underwent TPE for ALF due to yellow phosphorous poisoning (YPP) between 2015 and 2019. Demographic data and biochemical parameters were recorded before and after TPE. Overall survival and transplant-free survival (based on King's College Hospital Criteria [KCHC]) were analyzed. RESULTS: Forty-three patients underwent TPE for ALF due to YPP. Most of them were young males. Overall survival was 34 (79.06%). In our study population, 20 patients fulfilled KCHC (Group A) and 23 did not fulfill KCHC (Group B). Both the groups showed significant improvement in alanine aminotransferase, aspartate aminotransferase, and international normalized ratio (INR) after TPE (p < 0.05). In Group B, there was significant improvement in ammonia after TPE (p < 0.05) and all 23 patients (100%) survived after TPE. In Group A, 4 underwent liver transplantation (LT), 7 survived without LT, and the remaining 9 died without LT. Mean survival after completing TPE was 41.2 ± 44.5 days in Group A and 90 days in Group B. This difference was statistically significant (p = 0.001). There was statistically significant difference in post-TPE values of INR (p = 0.012) and ammonia (p = 0.011) between non-survivors and survivors. Adverse events such as hypotension (11.62%) and minor allergic reaction (4.65%) were managed conservatively. CONCLUSION: TPE is an effective procedure in ALF due to YPP, not fulfilling KCHC for LT. In KCHC fulfilled group, though it shows LT-free survival benefit, there is requirement of prospective, large volume, multi-center study to assess its efficacy.

Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality.

BACKGROUND: Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. METHODS: The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 µg/dl after SST. RESULTS: The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p = 0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p = 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). CONCLUSION: The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.

Emerging therapies for portal hypertension in cirrhosis.

INTRODUCTION: Counteracting splanchnic vasodilatation and increased portal-collateral blood flow has been the mainstay for the treatment of portal hypertension (PH) over the past three decades. However, there is still large room for improvement in the treatment of PH. AREAS COVERED: The basic mechanism leading to portal hypertension is the increased hepatic vascular resistance to portal blood flow caused by liver structural abnormalities inherent to cirrhosis and increased hepatic vascular tone. Molecules modulating microvascular dysfunction which have undergone preclinical and clinical trials are summarized, potential drug development issues are addressed, and situations relevant to design of clinical trials are considered. EXPERT OPINION: Experimental and clinical evidence indicates that molecules modulating liver microvascular dysfunction may allow for 30-40% reduction in portal pressure. Several agents could be utilized in the earlier stages of cirrhosis (antifibrotics, antiangiogenics, etiological therapies) may allow reduction of fibrosis and halt progression of PH. This 'nip at the bud' policy, by combining therapies with existing agents used in advanced phase of cirrhosis and novel agents which could be used in early phase of cirrhotic spectrum, which are likely to hit the market soon would be the future strategy for PH therapy.

Embolization of portosystemic shunt for treatment of recurrent hepatic encephalopathy.

Hepatic encephalopathy in the setting of advanced chronic liver disease, occurs following a precipitating factor and generally responds to correction of the precipitating factor and anticoma measures. We report the case of a lady with Child A cirrhosis who presented with frequent episodes of hepatic encephalopathy without any precipitating factors. She was found to be having a large portosystemic shunt. The shunt was obliterated by coil embolotherapy following which there was no further episodes of encephalopathy.