ABSTRACT
BACKGROUND: Acute-on-chronic liver failure (ACLF) is a syndrome of acute portal hypertension with high short-term mortality. ACLF patients have low mean arterial pressure (MAP), systemic vascular resistance, and high cardiac output. This, in turn, leads to an increased incidence of ascites, acute kidney injury, and hyponatremia. We evaluated the role of the early addition of midodrine, which has not been analyzed to date. METHODS: ACLF patients who were started on midodrine (Gr. A) in addition to standard of care (SOC) for ascites control were included and compared with those who received only SOC (Gr. B). The aim was to assess the hemodynamics, ascites control, diuretic-related complications, and mortality at 1 month. RESULTS: Forty-five ACLF patients (Gr. A-21; Gr. B-24) were included in the pilot study. At inclusion, the baseline characteristics were similar among the groups. The dose of midodrine was 22.5 (7.5-22.5) mg/day for 22.29 ± 8.75 days in Gr. A. Midodrine significantly improved the MAP and urinary sodium excretion. Only 33.34% of patients required paracentesis in Gr. A compared with 62.5% in Gr. B (p = 0.05). Gr. A patients tolerated a higher dose of diuretics than Gr. B. Diuretic-related complications developed in 54.2% of patients in Gr. B compared with only 23.8% in Gr. A (p = 0.03). Fourteen percent in Gr. A developed side effects to midodrine and required dose modification. Mortality at day 30 was similar in both groups. CONCLUSION: Addition of midodrine improves the hemodynamics, tolerability of diuretics, and ascites control in ACLF patients.
ABSTRACT
AIMS: We studied in-hospital predictors of mortality of acute on chronic liver failure (ACLF) in Indian patients. METHODS: Patients admitted to the intensive care unit of our institute fulfilling the definition of ACLF based on the Asia-Pacific Association for Study of Liver Disease (APASL) consensus were included. Complete history and medical evaluation to assess the etiology of underlying liver cirrhosis and to identify the acute precipitating insult of worsening liver function was done. Data was prospectively recorded and various scoring systems and individual clinical and laboratory parameters were assessed to identify predictors of 28 days mortality. RESULTS: 64 out of 240 patients screened for ACLF were analyszed in the study. Median age was 44 years and 53% were males. Alcohol was the primary cause of cirrhosis in 60.93%. Infections and active alcoholism was the main precipitating acute insult in 43% and 37% patients respectively. 28% patients had history of ingestion of hepato-toxic drugs as the acute insult. More than one acute insult was seen in 37.5% patients and type-II hepatic injury was the most common type. 28 days in hospital mortality was 43.75% and was highest in patients with sepsis (67.8%). Presence of hepato-renal syndrome and need for ventilation was associated with poor outcome. Though multiple variables were significant in predicting mortality on univariate analysis, yet on regression model only APACHE II and shock could significantly predict mortality with odds ratio of 3.18 and 9.14 respectively. Highest mortality was seen with cerebral and lung as organ failure and mortality increased as the number of organ failure worsened. CLIF-SOFA and APACHE-II scores having area under curve > 0.8 had higher ability to predict mortality. CONCLUSION: ACLF carries high short-term mortality and early intervention by liver transplantation should be considered in patients who shows high risk of mortality.
ABSTRACT
BACKGROUND: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). OBJECTIVE: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. MATERIALS: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n = 15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. RESULTS: Significant reduction of HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than controls with more explicit decline of PARP1 (P = 0.0002). Both genes were significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1 declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all the disease categories. CONCLUSION: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC.
ABSTRACT
A patient presented with symptoms of gastric outlet obstruction. On evaluation she was found to have a polypoidal lesion in the proximal jejunum on upper gastrointestinal barium series. Endoscopic evaluation showed the gastric mucosa prolapsing into the duodenum. At laparotomy, the gastric mucosa was found to prolapse into the jejunum via the duodenum. Excision of the prolapsed mucosa resulted in resolution of the patient's symptoms.