Cirrhosis affects women differently than men. Women are more likely to clear HCV spontaneously and less likely to develop advanced fibrosis from HCV when premenopausal due to protective effects of estrogen. However, postmenopausal women lose these benefits. Women also have a lower risk of progression to cirrhosis and HCC from HBV than men. Pregnancy in women with cirrhosis carries significant risks for both mother and fetus and requires close multidisciplinary management throughout.

1. Kurdistan Board GEH J Club 2016
Supervised by:
Dr. Mohamed Alshekhani
Professor in Medicine
MBChB-CABM-FRCP-EBGH

2. Introduction:
• Cirrhosis is an important public health concern with prevalence
of 0.27% adults , 27% women, lower closely related to lower
prevalence of HBV&HCV, alcohol & iron overload.
• NASH ? more prevalent in women that in men.
• knowledge of sex differences in liver disease prevalence, natural
history& treatment is important to:
• Optimize individual long-term outcomes.
• Manage unique issues in women with regard to conception,
pregnancy & postpartum care.

3. SEX DIFFERENCES :Chronic HCV
• Spontaneous clearance of the virus occurs more frequently among
women than men; 37% vs 21%.
• Female sex is also a protective factor for the progression of liver
fibrosis in premenopausal but not postmenopausal women with
HCV, through protective effect of estrogens.
• Among postmenopausal women, there was less advanced fibrosis
in those who had received hormone replacement therapy
• Other factors; lower frequency of cofactors, like alcohol use&
HIV.
• Tolerability of ribavirin, reduced in women due to lower Hb.
• The teratogenicity associated with ribavirin should also be
considered in every woman of child-bearing age.
• No sex differences identified in DAA therapy.

4. SEX DIFFERENCES :Chronic HBV
• Women have a lower rate of progression to cirrhosis and HCC
then men *3-6 due to higher prevalence of cofactors for disease
progression;alcohol use, iron overload, HCV
• A higher frequency of HBV flares in men compared with women,
persisted even after adjustment for confounders; age, HBV DNA
level, fibrosis stage and presence of precore &basal core promoter
variants.
• Reactivation of HBV following HBeAg seroconversion happen
more often in men than in women , may contribute to the higher
prevalence of HBV-cirrhosis & HCV in men.
• Treatment for HBV do not differ for men vs women, except ULN
for ALT are 19 U/L for women, 30 U/L for men.
• Women with ALT >38 U/L (2 times ULN)& persistently elevated
HBV DNA are potential candidates for antiviral therapy.
• For women with cirrhosis, antiviral therapy is recommended if
HBV viremia is present, regardless of ALT.

5. SEX DIFFERENCES :Alco LD
• Women consume less alcohol than men, drink less frequently,
&less likely to be hazardous drinkers.
• Women who drink alcohol develop more liver problems than
men. Because women express less gastric alcohol dehydrogenase&
have less fat tissue&less total water than men, so smaller volume
of distribution of alcohol.
• The level of alcohol intake for liver damage 7-13 drinks / week for
women & 14- 27 drinks / week for men, so women should keep
alcohol intake <1 drink / day or 7 / week& If have another cause
for chronic liver disease;HCV or HBV,abstinence recommended.
• Women tend to do better after outpatient treatment & achieve
more sustained abstinence then men & lower mortality
• No sex difference in the treatment of alcohol dependence with
pharmacologic agents (acamprosate / naltrexone).

6. SEX DIFFERENCES :NAFLD
• NAFLD appears to be less common in white women but not in
black & Hispanic women.
• Among women; advancing age, postmenopause,more features of
MS linked with presence of NAFLD.
• ? Sex differences in the natural history of NAFLD.
• Age & hepatic inflammation were predictors of fibrosis, but not
female sex.
• Greater severity of liver fibrosis in men vs premenopausal
women, not postmenopausal women,due to sex hormones.
• HRT reduce ALT in women & oral contraceptives users had
50% lower NAFLD, no longer significant after adjusting for
obesity.

7. SEX DIFFERENCES :Prognosis
• Female inconsistency associated with mortality in cirrhosis with a
reduced risk of mortality in patients with compensated cirrhosis.
• Heterogeneity in treatable causes of cirrhosis, different times to
diagnosis/or difference in adherence to cirrhosis management are
influencing outcomes in women versus men with cirrhosis.
• Women have higher wait-list mortality than men, due to
creatinine) underestimating severity of renal dysfunction &
women are shorter than men&smaller grafts are less available.
• Post-transplant graft & patient survival do not differ, with
exception of HCV: women have more severe recurrent
disease,with a 23% higher risk of advanced fibrosis after 3 years
• Women are also at higher risk of CKD post-transplant.

8. SEX DIFFERENCES :PHT comps
• Rates of complications are comparable in women & men.
• The development&progression of esophageal varices, portal
hypertensive gastropathy, ascites,spontaneous bacterial
peritonitis, encephalopathy are not affected by sex.
• GAVE/ portopulmonary hypertension, diagnosed more frequently
in women than men, reflect the higher prevalence of AI diseases.
• In cirrhosis, GAVE does not appear to a sex predilection.

9. SEX DIFFERENCES :HCC
• A lower risk of HCC in women than men due to protective effects
of estrogen.
• Higher testosterone level increase the risk.
• HCC diagnosed at an older age.
• Higher alpha-fetoprotein.
• More likely to have smaller unifocal & well-differentiated HCC
• A significantly longer survival than men after diagnosis ,may be
women were more compliant with surveillance.

10. SEX DIFFERENCES :Infertility
• A frequent anovulation or irregular ovulation, secondary to
hypothalamic-pituitary dysfunction& alteration in hepatic sex
hormone metabolism.
• Sexual dysfunction, as reduced sex frequency& satisfaction, was
more prevalent in women with endstage liver disease than in men.
• Increased age &more severe liver disease were related to lower
sexual frequency &satisfaction.

11. SEX DIFFERENCES :contraception
• Despite decreased fertility, undesired pregnancies can occur &
contraception must be discussed with premenopausal women.
• There was no restriction on the use of any hormonal
contraception &in women with severe, decompensated cirrhosis,
the risks usually outweigh the benefits.
• For IUD use caution is warranted, as SBP association reported.
• Barrier methods can be used, but failure rates are limiting.

12. SEX DIFFERENCES :Pregnancy
• The incidence of cirrhosis in pregnant women is very low, 1/ 6000
pregnancies.
• Pregnancies in women with cirrhosis carry higher risks for the
mother/ fetus ,so multidisciplinary team that includes a liver
specialist &high-risk obstetrician are essential throughout the
pregnancy & postpartum period.

13. SEX DIFFERENCES :Pregnancy
• Possible exacerbation of portal hypertension &its clinical
consequences as early as the sixth week& peak bet 30t-
34th week
gestation, due to normal physiologic changes of pregnancy.
• Significant maternal complication occurred in 10% of
pregnancies, included variceal bleeding, significant ascites& HE.
• For EV aggressive approach to prophylaxis is advised & for acute
variceal bleed during pregnancy, the endoscopic management is
similar to that in non-pregnant patients; EBL until obliteration.
• Octreo/vasopresin category B, decrease placental perfusion & an
increase risk of placental abruption.
• TIPS described during pregnancy, with negligible radiation
exposure with women survived&1 fetus died from premature
delivery, not considered TIPS-related.

14. SEX DIFFERENCES :Pregnancy
• Labor management is dependent on the degree of PHT.
• For women with known varices, caesarian delivery suggested, to
minimize the risk of variceal bleeding related to excessive
straining & ncreased intravariceal pressure with vaginal delivery.
• Very few cases of VH at the time of delivery reported & CS
delivery carries risks, including bleeding from injury to
abdominal wall collaterals, postoperative ascites, & poor wound-
healing issues&postop risk of worsening decompensation.
• Some experts suggest vaginal delivery by senior obstetrician,with
second stage of labor kept short / excessive fluid overload should
avoided& CS reserved for obstetric indications.
• For sedation, gentle intravenous labor analgesia can be given,&
epidural analgesia safety depends on the coagulopathy severity.
• Postpartum women with portal hypertension should also be
vigilantly watched for possible uterine hemorrhage.

15. SEX DIFFERENCES :Pregnancy
• Cirrhosis was associated with more risk of preeclampsia, preterm
delivery, low birth weight, small for gestational age&neonatal
death.

22. Macronodular cirrhosis

23. Micronodular cirrhosis