Palliative Care Quality Indicators for Patients with End-Stage Liver Disease Due to Cirrhosis

Background and Aims

There are guidelines for the medical management of cirrhosis and associated quality indicators (QIs), but QIs focusing on standards for palliative aspects of care are needed.

Methods

We convened a 9-member, multidisciplinary expert panel and used RAND/UCLA modified Delphi methods to develop palliative care quality indicators for patients with cirrhosis. Experts were provided with a report based on a systematic review of the literature that contained evidence concerning the proposed candidate QIs. Panelists rated QIs prior to a planned meeting using a standard 9-point RAND appropriateness scale. These ratings guided discussion during a day-long phone conference meeting, and final ratings were then provided by panel members. Final QI scores were computed and QIs with a final median score of greater than or equal to 7, and no disagreement was included in the final set.

Results

Among 28 candidate QIs, the panel rated 19 as valid measures of quality care. These 19 quality indicators cover care related to information and care planning (13) and supportive care (6).

Conclusions

These QIs are evidence-based process measures of care that may be useful to improve the quality of palliative care. Research is needed to better understand the quality of palliative care provided to patients with cirrhosis.

     

Role of Apheresis and Dialysis in Pediatric Living Donor Liver Transplantation: A Single Center Retrospective Study

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible‐liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type‐incompatible liver transplantation was 128 and eight, respectively (P < 0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P < 0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1‐year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO‐incompatible liver transplantation, and fluid management for acute respiratory failure.     

Non-variceal Gastrointestinal Bleeding in Patients with Liver Cirrhosis: A Review

Background

Non-variceal gastrointestinal (NVGI) bleeding in cirrhosis may be associated with life-threatening complications similar to variceal bleeding.

Aim

To review NVGI bleeding in cirrhosis.

Methods

MEDLINE, Scopus, and ISI Web of Knowledge were searched, using the textwords “portal hypertensive gastropathy,” “gastric vascular ectasia,” “peptic ulcer,” “Dieulafoy’s,” “Mallory–Weiss syndrome,” “portal hypertensive enteropathy,” “portal hypertensive colopathy,” “hemorrhoids,” and “cirrhosis.”

Results

Portal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE) are gastric lesions that most commonly present as chronic anemia; acute upper GI (UGI) bleeding is a rare manifestation. Management of PHG-related bleeding is mainly pharmacological, whereas endoscopic intervention is favored in GVE-related bleeding. Shunt therapies or more invasive techniques are restricted in refractory cases. Despite its high incidence in cirrhotic patients, peptic ulcer accounts for a relatively small proportion of UGI bleeding in this patient population. However, in contrary to general population, the pathogenetic role of Helicobacter pylori infection remains questionable. Finally, other causes of UGI bleeding include Dieulafoy’s lesion, Mallory–Weiss syndrome, and portal hypertensive enteropathy. The most common non-variceal endoscopic findings reported in patients with lower gastrointestinal bleeding are portal hypertensive colopathy and hemorrhoids. However, the vast majority of studies are case reports and, therefore, the incidence, diagnosis, and risk of bleeding remain undefined. Endoscopic interventions, shunting procedures, and surgical techniques have been described in this setting.

Conclusions

The data on NVGI bleeding in liver cirrhosis are surprisingly scanty. Large, multicenter epidemiological studies are needed to better assess prevalence and incidence and, most importantly, randomized studies should be performed to evaluate the success rates of therapeutic algorithms.     

Hepatitis B Recurrence After Liver Transplantation: A Single Center Experiences and Review the Literature

Background

Despite the advances in the treatment of chronic hepatitis B virus (HBV) infection, liver transplantation (LT) remains the only hope for many patients with end-stage liver diseases resulting from HBV.

Objectives

The aim of this study was to investigate the rate of HBV recurrence in cases that had undergone LT due to the HBV related liver cirrhosis.

Patients and Methods

Forty-nine patients who underwent LT due to HBV related cirrhosis since 2001 to 2009 in Shiraz Organ Transplantation Center were enrolled in the present study. They were asked to complete the planned questionnaire and also to sign the informed consent in order to take part in this study. Post-transplant prophylaxis protocol against HBV recurrence was based on a hundred milligrams of lamivudine daily plus intramuscular injections of hepatitis B immune globulin (HBIG) with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L and 100 IU/L in the first six months and afterwards, respectively. Blood samples were obtained and checked for HBsAg, HBeAg, and the titers of Anti -HBsAb as well as Anti- HBeAb with ELISA. A quantitative HBV DNA assay was also done on all samples (GENE-RAD® Real-time PCR).

Results

There were 91.8% males and 8.2% females enrolled in the study. The duration of post-transplant prophylaxis ranged from 3 months to 8 years (mean 18.9 ± 19.3 months). HBsAg and HBeAg were positive in 24.5% and 2% of cases, respectively. Real-time PCR for HBV DNA were zero copies/mL in 91.8% of patients, none of which represented a positive value for HBV recurrence (Positive > 10,000 copies/mL). The mean Anti-HBs Ab titer was 231.7 ± 135.9 IU/L; it was above 100 IU/L in 71.4% of patients. Thirty-seven (75.5%) of the patients were taking tacrolimus plus mycophenolate mofetil, 6 (12.2%) were on cyclosporine plus mycophenolate mofetil, and 6 (12.2%) were taking sirolimus plus mycophenolate mofetil. HBsAg was detectable in seven patients taking tacrolimus plus mycophenolate mofetil (18.9%), in four patients taking cyclosporine plus mycophenolate mofetil (66.7%), and in one patient among the six who were taking sirolimus plus mycophenolate mofetil (16.7%). There was no significant statistical correlation between the presence of a positive value for HBsAg and the immunosuppression regimen or Anti HBsAb titer (P ˃ 0.05). Presence of a positive value for HBsAg was not predictive of a positive HBV DNA or its level in blood (P ˃ 0.05).

Conclusions

Post-transplant HBV prophylaxis with lamivudine and intramuscular HBIG with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L in the first six months and above 100 IU/L afterwards is effective for prevention of HBV recurrence after LT.     

Liver Transplantation for Alcohol-Related Cirrhosis: A Single Centre Long-Term Clinical and Histological Follow-Up

Background  

Alcohol-induced liver cirrhosis is one of the leading indications for liver transplantation today. Due to the general organ shortage and continuous deaths on the waiting list there has been some debate on the issue of indication and ethical problems. It was the aim of this study to critically analyse the outcome of patients with alcoholic cirrhosis transplanted at our centre with special emphasis on alcohol-recurrence frequency and long-term histological follow-up.     

Specialist Palliative Care is More Than Drugs: A Retrospective Study of ILD Patients

Background  

This study aimed to assess the palliative care needs of progressive idiopathic fibrotic interstitial lung disease (PIF-ILD) populations in two London ILD centres.     

Pulmonary Hemodynamics and Gas Exchange After Liver Transplantation in Patients with Cirrhosis

In patients with cirrhosis, discrepant findings have been reported on the evolution of pulmonary hemodynamics and gas exchange after liver transplantation. The aim of this study was to evaluate the effects of liver transplantation on pulmonary and systemic hemodynamics and gas exchange in patients transplanted for cirrhosis. Forty-three patients with cirrhosis underwent hemodynamic investigations before and one year after liver transplantation. Mean pulmonary arterial pressures did not significantly change after transplantation (from 17 ± 4 to 17 ± 3 mm Hg) whereas pulmonary vascular resistance significantly increased by 62%. Cardiac index significantly decreased by 20%. Pao₂ did not change significantly after transplantation (from 88.8 ± 13.9 to 88.5 ± 12.1 mm Hg) and PaCo₂ significantly increased by 16%. In conclusion, liver transplantation has no effect on pulmonary pressures but normalizes pulmonary vascular resistance in patients with cirrhosis without pulmonary hypertension. Moreover, it has no major effect on gas exchange in patients with cirrhosis without hypoxemia.     

Liver Transplantation for Alcoholic Liver Disease: Survival of Patients Transplanted with Alcoholic Hepatitis Plus Cirrhosis as Compared with Those with Cirrhosis Alone

From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 ±1.7 years) than nonsurvivors (53.6 ± 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p <; 0.01) but not in the AH group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 ± 0.2) than it was in nonsurvivors (0.4 ± 0.1) (p < 0.01). In patients with CIRR, the platelet count was greater in survivors (252 ± 29 vs. 86 + 11 ± 10⁹ cells/liter).
The data support the clinical impression that patients with chronic decompensated cirrhosis referred for liver transplantation had more severe complications of their liver disease than did those with AH. Survival in both subgroups was similar, but overall the survivors are nearly a decade younger than the nonsurvivors. Because the diagnosis of AH implies a briefer period of alcohol abstention, it was interesting to note that liver transplantation could be accomplished as successfully with AH as with CIRR.     

Statin Use in Patients with Cirrhosis: A Retrospective Cohort Study

Background

Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis.

Aim

Compare mortality in patients with cirrhosis on statins to those not on statins.

Methods

A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child–Pugh class. Decompensation was defined as ascites, jaundice/bilirubin >2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child–Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan–Meier curves graphed mortality.

Results

Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4 % of patients were Child–Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child–Pugh A patients had longer survival on Kaplan–Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use.

Conclusions

In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.     

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims

To evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).

Methods

Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation.

Results

On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments.

Conclusions

Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.     

Bone Marrow-Derived Stem Cells for Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis

Background: To date, studies have shown inconsistent results of treatment with bone marrow-derived stem cells (BMDSC) for patients with liver cirrhosis. This study aims to compare the efficacy and safety of BMDSC and standard therapy for liver cirrhosis.Methods: Articles from PubMed, Embase, and the Cochrane library were searched from inception to April 2018. The index included Model for End-stage Liver Disease (MELD), alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), Child–Pugh score, and all-cause mortality.Results: A total of 9 studies with a total of 424 patients with liver cirrhosis were included in final meta-analysis. BMDSC therapy was associated with lower MELD within 3 months (P = .010), while it had no significant impact on MELD after 6 months (P = .074). There were no differences between BMDSC and standard therapy for ALT within 3 months (P = .336) and after 6 months (P = .379). BMDSC did not affect albumin level within 3 months (P = .196) and after 6 months (P = .840). BMDSC reduced the TBIL level within 3 months (P = .037) and was not associated with the TBIL level after 6 months (P = .914). There were no differences between BMDSC and standard therapy for PT within 3 months (P = .167) and after 6 months (P = .484). The Child–Pugh scores within 3 months (P = .342) and after 6 months (P = .133) were not associated with BMDSC treatment for liver cirrhosis patients. Finally, the BMDSC was not associated with the risk of all-cause mortality, as compared with standard therapy (P = .622).Conclusions: BMDSC treatment for patients with liver cirrhosis could improve short-term MELD and TBIL, but not the risk of mortality, as compared with standard therapy.     

The Therapeutic Use of Analgesics in Patients With Liver Cirrhosis: A Literature Review and Evidence-Based Recommendations

Context:

Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs.

Evidence Acquisition:

An indexed MEDLINE search was conducted in July 2014, using keywords “analgesics”, “hepatic impairment”, “cirrhosis”, “acetaminophen or paracetamol”, “NSAIDs or nonsteroidal anti-inflammatory drugs”, “opioid” for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well.

Results:

Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance.

Conclusions:

No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.     

Clinical Outcomes of Patients with Liver Cirrhosis Who Underwent Curative Surgery for Gastric Cancer: A Retrospective Multi-center Study

We investigated early postoperative morbidity, mortality, and long-term outcomes in patients with liver cirrhosis (LC) who had undergone curative surgery for gastric cancer. The medical records of patients with LC who had undergone radical gastrectomy for gastric adenocarcinoma between January 1996 and September 2006 were retrospectively reviewed. A total of 57 patients were enrolled in this study. Forty-six patients (81%) were classified into Child’s class A. In 22 patients (39%) postoperative complications developed, the most common being ascites (23%), followed by wound infection and hepatic encephalopathy. Postoperative ascites occurred more frequently in patients with Child’s class B or C than in those with class A (63.6% vs 13%, P = 0.001). Massive ascites developed in 4 patients, 3 of whom had Child’s class B and underwent D2 lymph node (LN) dissection, and 1 of whom had Child’s class C and a D1 LN dissection. Postoperative mortality occurred in 5 patients (9%), with a significantly higher mortality rate for patients with Child’s class B or C than for those with class A (27.2% vs 4.3%, P = 0.045). With a median follow-up of 32 months, the estimated 5-year survival rate for all patients was 54%. Regardless of the tumor depth, overall survival was longer for patients with Child’s class A than for those with Child’s class B or C. These results demonstrated that radical gastrectomy with extended LN dissection is feasible in patients with compensated LC. For patients with moderate to severe hepatic dysfunction, however, D1 or less extensive LN dissection may be the more reasonable surgical procedure.