The natural history of cirrhosis has usually been conceptualized in the context of progression from compensated cirrhosis to subsequent stages of decompensation. While this unidirectional concept is the most common pathophysiological trajectory, there has been an emerging understanding of a subgroup of patients which undergo recompensation. While literature mostly based on transplant waitlist registries have indicated towards such a population who experience disease regression, the overall literature about this entity remains inexplicit. An effort to generate consensus on defining recompensation has been attempted which comes with its own nuances and limitations. We summarize the available literature on this emerging yet controversial concept of recompensation in cirrhosis and delve into future implications and impact on real-life practice.

Chronic liver diseases (CLD) is one of the leading causes of morbidity and mortality. The overall life span of patients with CLD has increased and so is the number of surgical procedures these patients undergo. Pathophysiological and hemodynamic changes in cirrhosis make these patients more susceptible to hypotension and hypoxia during surgery. They also have a high risk of drug induced liver injury, renal dysfunction and post-operative liver decompensation. Patients with CLD planned for elective or semi-elective surgery should undergo detailed preoperative risk assessment. Patients should be evaluated for the presence of clinically significant portal hypertension and cirrhosis. In the absence of both cirrhosis and clinically significant portal hypertension, patients with CLD can undergo surgery with minimal or low risk. Various risk assessment tools available for patients with advanced CLD are-CTP score, MELD Score, Mayo risk score, VOCAL-Penn score. A Child class C and/or Mayo risk score >15 in general is associated with high risk of post-operative mortality and elective surgery should be deferred in these patients. In patients with Child class, A and MELD 10-15 surgery is permissible with caution (except liver resection and cardiac surgery) while in Child A and MELD <10 surgery is well tolerated. VOCAL-Penn score is a new promising tool and can be the better alternative of CTP, MELD, and Mayo risk score models but more prospective studies with large patients\' population are warranted. Certain surgeries like Hepatic resection, intraabdominal, and cardiothoracic have higher risk than abdominal wall hernia repair and orthopedic surgery. Laparoscopic approaches have better outcomes and less risk of liver failure than open surgery. Minimally invasive alternatives like colonic stent placement in case of obstruction can be considered in high-risk cases. Perioperative optimization and management of ascites, HE, bleeding, liver decompensation, and nutrition should be done with multidisciplinary approach. Patients with cirrhosis undergoing high risk elective surgery can develop liver failure in post-operative period and should be evaluated and counseled for liver transplantation if not contraindicated.

UNASSIGNED: Autophagy is a process that allows the degradation of detrimental components through the lysosome to maintain cellular homeostasis under variable stimuli. SQSTM1 is a key molecule involved in functional autophagy and is linked to different signaling pathways, oxidative responses, and inflammation. Dysregulation of autophagy is reported in a broad spectrum of diseases. Accumulation of SQSTM1 reflects impaired autophagy, which is related to carcinogenesis and progression of various tumors, including hepatocellular carcinoma (HCC). This study investigated SQSTM1 protein expression in HCC and its relation to the clinicopathological features and the likelihood of tumor recurrence after radiofrequency ablation (RFA).
UNASSIGNED: This study included 50 patients with cirrhotic HCC of Barcelona Clinic Liver Cancer stages 0/A-B eligible for RFA. Tumor and peritumor biopsies were obtained just prior to local ablation and assessed for tumor pathological grade and SQSTM1 expression by immunohistochemistry. Patients were followed for one year after achieving complete ablation to detect any tumor recurrence.
UNASSIGNED: Serum alpha-fetoprotein level (U = 149.50, P = 0.027∗) and pathological grade of the tumor (χ2 = 12.702, P = 0.002∗) associated significantly with the tumor response to RFA. SQSTM1 expression level was significantly increased in HCC compared to the adjacent peritumor cirrhotic liver tissues (Z = 5.927, P < 0.001∗). Significant direct relation was found between SQSTM1 expression level in HCC and the pathological grade of the tumor (H = 33.789, P < 0.001∗). On follow-up, tumor and peritumor SQSTM1 expression levels performed significantly as a potential predictor of the overall survival, but not the disease recurrence.
UNASSIGNED: SQSTM1 expression could determine aggressive HCC, even with reasonable tumor size and number, and identify the subset of HCC patients with short overall survival and unfavorable prognosis. SQSTM1 expression could not predict post-RFA intrahepatic HCC recurrence. SQSTM1 may be a potential biomarker and target for the selection of HCC patients for future therapies.

UNASSIGNED: There is no \"gold standard\" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis.
UNASSIGNED: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period.
UNASSIGNED: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores.
UNASSIGNED: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.

Hyponatremia is the most common electrolyte abnormality in patients with decompensated cirrhosis on Liver Transplantation (LT) waiting list. Most of these patients have dilutional or hypervolemic hyponatremia secondary to splanchnic vasodilatation. Excessive secretion of the antidiuretic hormone also plays an important role. Hypervolemic hyponatremia is commonly associated with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. Although uncommon, the use of diuretics and laxatives can cause hypovolemic hyponatremia that is characterized by the striking absence of ascites or pedal edema. Clinical features are often nonspecific and depend on the acuity of onset rather than the absolute value of serum sodium. Symptoms may be subtle, including nausea, lethargy, weakness, or anorexia. However, rarely patients may present with confusion, seizures, psychosis, or coma. Treatment includes discontinuation of diuretics, beta-blockers, and albumin infusion. Hypertonic saline (3%) infusion may be used in patients with very low serum sodium (<110 mmol/L) or when patients present with seizures or coma. Short-term use of Vasopressin (V2) receptor antagonists may also be used to normalize sodium levels prior to LT. However, all these measures may be futile, and LT remains the definite treatment in these patients to improve survival. In this review, we describe the classification, pathogenesis of hyponatremia, and its clinical implications in patients with cirrhosis. Approach to these patients along with management will also be discussed briefly.

UNASSIGNED: Diagnosis and management of tuberculosis (TB) in patients with cirrhosis remains challenging. We studied the clinical spectrum, diagnosis, and management of TB along with the assessment of the diagnostic utility of various laboratory investigations in this cohort.
UNASSIGNED: A retrospective review of records of patients with cirrhosis (July 2017 and December 2019) was done. Out of 30 patients with cirrhosis and TB, 20 patients with pleural/peritoneal TB (cases) were compared with 20 consecutively selected spontaneous bacterial peritonitis (SBP) controls. Composite of clinical, laboratory, radiologic features and response to antituberculosis therapy (ATT) was taken as the gold standard to diagnose TB.
UNASSIGNED: Extrapulmonary TB (EPTB) (n = 23, 76.7%) was more common. Overall, 9 (30%) patients presented with ATT-induced hepatitis. Patients with pleural/peritoneal TB had less severe hepatic dysfunction as compared to SBP group with significantly lower CTP [8 ± 1.5 vs. 9 ± 1.7 (P = 0.01)], MELD [16.3 ± 5.8 vs. 20.2 ± 6.6 (P = 0.02)] and MELD-Na [18.8 ± 5.9 vs. 22.5 ± 7.1 (P = 0.03)] scores. Median ascitic/pleural fluid total protein [2.7 (2.4-3.1) vs. 1.1 (0.9-1.2); P < 0.0001] and adenosine deaminase (ADA) levels [34.5 (30.3-42.7) vs. 15 (13-16); P < 0.0001] were significantly higher in the TB group. Total protein levels had a sensitivity and specificity 81% and 93.3%, respectively, at cut off value of >2 g/dl with an AUROC of 0.89 [(0.79-0.96); P < 0.001] whereas ADA levels at cutoff >26 IU/L showed 80% sensitivity and 90% specificity to diagnose pleural/peritoneal TB with an AUROC of 0.93 [(0.82-0.97); P < 0.001]. Only 11 (36.7%), and 8 (26.6%) patients showed positivity on GeneXpert and mTB-PCR, respectively. Patients with Child-Turcotte-Pugh scores of ≤7 and 8-10 tolerated well two and one hepatotoxic drugs, respectively.
UNASSIGNED: EPTB is more frequent in patients with cirrhosis. Relatively lower cutoffs of ascitic/pleural fluid total protein and ADA may be useful to diagnose EPTB in patients with high pretest probability. Individualized ATT with close monitoring and dynamic modifications is effective and well-tolerated.

UNASSIGNED: Spontaneous bacterial peritonitis (SBP) heralds increased mortality in cirrhosis, mandating strategies for prophylaxis. Norfloxacin has been the recommended choice for SBP prevention. However, its use has raised concerns about antibiotic resistance. Rifaximin has been suggested as an alternative. We investigated the efficacy of rifaximin against norfloxacin in primary and secondary prophylaxis of SBP.
UNASSIGNED: In this open-labeled randomized trial, patients with either advanced cirrhosis having ascitic fluid protein levels (<1.5 g/l), Child-Pugh score ≥9 points, serum bilirubin ≥3 mg/dl or impaired renal function (primary prophylaxis group), or those with prior SBP (secondary prophylaxis group) received either norfloxacin (400 mg once daily) or rifaximin (550 mg twice daily). All patients were followed for six months, with the primary endpoint being the development of incident SBP.
UNASSIGNED: 142 patients were assessed for eligibility, of which 132 met the enrolment criteria; 12 were lost to follow-up, while 4 discontinued treatment. In patients on primary prophylaxis, occurrence of SBP was similar (14.3% vs. 24.3%, P = 0.5), whereas in secondary prophylaxis SBP recurrence was lower with rifaximin (7% vs. 39% P = 0.004). Rifaximin significantly reduced the odds for SBP development in secondary prophylaxis [OR (95% CI0.14 (0.02-0.73; P = 0.02)]. Patients receiving rifaximin as secondary prophylaxis also had fewer episodes of hepatic encephalopathy (23.1% vs. 51.5%, P = 0.02). 180-day survival between the arms in either group was similar (P = 0.5, P = 0.2).
UNASSIGNED: In comparison to norfloxacin, rifaximin significantly reduces incident events of SBP, as well as HE when used as a secondary prophylaxis, whereas for primary prophylaxis both have similar effects (NCT03695705).
UNASSIGNED: ClinicalTrials.gov number: NCT03695705.

Chronic liver disease (CLD) is one of the leading causes of disability-adjusted life years in many countries. A recent understanding of nuclear bile acid receptor pathways has increased focus on the impact of crosstalk between the gut, bile acids, and liver on liver pathology. While conventionally used in cholestatic disorders and to dissolve gallstones, the discovery of bile acids\' influence on the gut microbiome and human metabolism offers a unique potential for their utility in early and advanced liver diseases because of diverse etiologies. Based on these findings, preclinical studies using bile acid-based molecules have shown encouraging results at addressing liver inflammation and fibrosis. Emerging data also suggest that bile acid profiles change distinctively across various causes of liver disease. We summarize the current knowledge and evidence related to bile acids in health and disease and discuss culminated and ongoing therapeutic trials of bile acid derivatives in CLD. In the near future, further evidence in this area might help clinicians better detect and manage liver diseases.

OBJECTIVE: Multiple definitions of sarcopenia exist and the acceptable criterion that best predicts outcome is lacking. We estimated the prevalence of sarcopenia based on four criteria and assessed their utility in predicting mortality in cirrhotics.
METHODS: In a prospective observational study, consecutive Asian patients with cirrhosis underwent testing for handgrip strength (HGS) and estimation of skeletal muscle index (SMI) using computed tomography at the third lumbar vertebra. Sarcopenia was defined based on the Western cut-off (WC; SMI < 50 cm2/m2 for men and <39 cm2/m2 for women), Asian cut-off (AC; SMI < 36.5 cm2/m2 for men and 30.2 cm2/m2 for women), European Working Group on Sarcopenia in Older People-2nd meeting (EWGSOP2) definition incorporating low HGS (<27 kg for men and <16 kg for women) with low SMI (defined by the WC), and EWGSOP2 definition with low HGS and low SMI (defined by AC). Risk factors for mortality were assessed using multivariate Cox-proportional hazards.
RESULTS: We included 219 patients with cirrhosis (168 men; mean age 42.6 years) with 50.2% patients having decompensation. Alcohol was the commonest aetiology (33.3%). The prevalence of sarcopenia was highest with the WC (men: 82.1%; women: 62.7%). There was a weak concordance among all criteria (Fleiss\' kappa 0.23, 95% confidence interval [CI] 0.10-0.37). Overall, 12-month survival was 86.1% (81.1-91.3%) over a median (interquartile range) follow-up of 12 (6-15) months. Ascites (hazards ratio [HR] 6.27 [95% CI 1.6-24.1]; P < 0.007) and SMI (HR 0.92 [0.85-0.98]; P = 0.021) were independent predictors of mortality. The 12-month mortality rate was higher in patients with sarcopenia, irrespective of criteria (log rank P < 0.05). Low HGS and low SMI (defined by AC) was the best for predicting mortality (HR 3.04 [1.43-6.43]; P = 0.004).
CONCLUSIONS: A weak concordance exists amongst various diagnostic definitions of sarcopenia. Sarcopenia diagnosed by a combination of low HGS and population-specific SMI cut-off (AC) best predicts mortality.

UNASSIGNED: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on outcome of cirrhosis patients in post-hospitalization period are limited.
UNASSIGNED: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge.
UNASSIGNED: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score.
UNASSIGNED: Cirrhosis patients with (n=92) or without (n=92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P=0.520), over a similar duration of follow-up [186 (86-271) vs 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed re-hospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P=0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group.
UNASSIGNED: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.